Q3 2021 Calithera Biosciences Inc Earnings Call
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Ladies and gentlemen, this is the operator today's conference call will begin shortly I tell that Tanya line someone can be placed on hold thank you for your patience.
Ladies and gentlemen addresses the operator that these conference call will begin shortly until that time. Your line. So it can be placed on hold thank you for your patience.
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Ladies and gentlemen, thank you for standing by and welcome to the County stay around Bioscience says a third quarter earnings conference call. At this time, all participants I know listen only mode. After the speaker's presentation. There will be a question and answer session to ask a question.
And drink assertion you will need to press star one on your telephone keypad. If you require any further assistance. Please press Dora the girl I would not allowed to hand to conference over here a speaker today Tiffany one. Thank you. Please go ahead ma'am.
Thank you operator, good afternoon, everyone and welcome for a third quarter 2021 conference call. Joining me today are Susan Melon out found your President then yeah, Yeah, <unk> <unk> Chief Medical Officer.
This afternoon, we issued a press release, which included an overview of a third quarter 2021 financial and operational adult which can be accessed your website I can let their dot com.
We begin I would like to remind you that today's discussion will include statements that exceed your expectations plans and plastics that constitute forward looking statements for purposes of the safe Harbor provision under the private security is litigation Reform Act of 1995.
Actual results may differ materially from those indicated for these forward looking statements as a result of various important factors, including those discussed in the risk factor section of a periodic filings with the M T.
In addition, any forward looking statements represent how he's only as of today and should not be relied upon as representing a b as in any subsequent date, while we may I'd like to thank these forward looking statements at some point in the future. We specifically disclaim any obligation to do so even if I view change. Please note that this call is being recorded and with.
I'll turn the call over to Susan.
Thanks, Stephanie good afternoon, everyone and thank you for joining us today on our third quarter 2021 conference call and a special welcome today to email Kyrgiakos, who is joining us in his new role as Chief Medical Officer <unk>.
It will be presenting later in this call we could not be more excited to embark on this next chapter with animals.
Speaking of the next chapter last month, we strengthen our precision oncology pipeline with the acquisition of September 30th and Microvolt Nick from Takeda.
As a reminder, <unk> visit dual towards one two inhibitor that targets the keys survival mechanism and keep one nerve to mutated tumors, which has the potential to be the first treatment for nurses mutated squamous non small cell lung cancer.
As the next generation torque inhibitor <unk> provide dual inhibition of the tour, one and talk to complexes and has demonstrated durable single agent responses and clinical benefit in patients with relapsed refractory nurse two mutated squamous non small cell lung cancer with a well tolerated safety profile.
My provoked myth is a second cheeseburger with the potential to be a best in class drunk and non hodgkins lymphoma as well as the first to market therapy for patients with D. L. D. C. L. This tumor is harbert My D 88, or C. D 79 mutations.
My vote Nip has shown compelling singularly connectivity and relapsed refractory NHL patience and completed phase one to study.
We plan to initiate Jake to study are both dependent searches and my vote <unk> in the first quarter of 2022.
Additionally, last week, we announced the decision to discontinue the keepsake trial of tell Glenn staff non squamous non small cell lung cancer. Following an interim analysis of 40 patients we.
We have no plans to continue the development of telephone step internally at this time.
We remain committed to developing targeted therapies for patients with difficult to treat cancers with the advancements of both the <unk> and biomarker defined population exclaims non small cell lung cancer and the two sludge be seldom former respectively.
Last week at the North American Cystic fibrosis conference, we presented interim data from the safe on V study of C V 280 arginase inhibitor.
And the presentation, we've reported the television to 80 with well tolerated and showed linear pharmacokinetics and robust goats related pharmacodynamic effects. Additionally, we start encouraging trends in disease, biomarkers, including increased fractional exhaled nitric oxide or tino and decreased sweat core I.
The current data to substantiate the proposed mechanism as a rational approach for treating C F.
Poster can be found on our website.
Finally, as we can closed on Friday, you have promoted Emily <unk> from Vice President and head of clinical development to succeed keep the Orford S. T M O N.
In addition, we have strengthened our board of directors with the addition of Keith.
I would like to take this opportunity to thank you for his contributions over the last seven years and to congratulate emel uhm his promotion.
Animal there's been a part of our team for the last four years and was an integral part of the diligence Jean did evaluated depending <unk> and my vote <unk> prior to our acquisition of these assets.
This has been a transformational your <unk> as we prepare to close out 2021 and enter 2022, we look forward to exciting times ahead.
We will begin the new year with a keen focus on precision oncology and two new highly compelling clinical development programs we.
We plan to initiate that tastes just studying <unk> tip and my vote <unk> in the first quarter and look forward to updating all of you on our progress and with that I will pass the call over to M. O for additional details on a clinical programs.
Thank you Susan and thank you for the kind words I'm truly honored to accept the role let's do them all in one express my sincere gratitude for his leadership in membership over the last several years and thrilled to continue a partnership of going forward to rejoin the board of directors I'm happy to update you today, what are clinical programs and look forward to meeting all of you over to the next level.
I'd like to start today by providing some additional detail around the data we presented last week on C. D. Two lady or novel or a large we submitted for the treatment of 65 <unk>.
Last week at the northern can see a conference we presented data on the first 24 subject ongoing <unk> Ghost escalation trial in adults will see these 24 subjects were enrolled across the first three dose levels 50 milligrams 102 hundred milligrams B I D with 18, receiving C D. Two lady fixed receiving placebo.
The study population comprised of blood spectrum, mostly appeal genotype, including subjects with nonsense mutation.
Notably 91% of the subjects were already off here too I'm largely to therapy with like have to whore Kelly <unk>.
<unk> have you had it will tell her to safety profile across all three dose of them and all 18 subjects receiving C. D 280 complete it treatment without interruptions or furniture. This information changes enforced that's pretty volume in one second or F. E V. One for assessing the sushi airplanes and a pulled analysis of treatment versus placebo showed a positive trend an S U V.
One compared to placebo C. B 280 demonstrated linear pharmacokinetics with plasma exposure increases proportionately with those.
We can continue to target. In addition in plasma was achieved at the 100 milligram dose.
Stephen Tweedie also demonstrated where both of them with the dynamics with rapid insignificant those proportionately increases in plasma arginase, which is a key drive every night is off by production increase their way or no production was reflected by a friend showing an increased inflectional it fell nitric oxide or female and subject shoot them at T V. Two eight.
<unk> chloride Ah markers C. A P. R function showed a trend towards decreasing and C. O C D. Two it'd be treated subject.
Which is consistent with previously reported preclinical data showing that Arginase division enhances you have to your function and human Bronco like with yourself together be slomka dynamic and buy them off the data to substantiate the overall mechanistic rationale for C V. Two Lady again yeah.
Any sort of newly acquired program.
We plan to initiate these days to study in the first quarter of 2022 that will strengthen the existing data on September 30th as a mono therapy in patients with relapsed refractory squamous non small cell lung cancer harboring R. Two mutation and further value you just want a pet the activities and coupon mutated and nerve to keep on wildlife exclaimed. This phone call.
It's a lung cancer also in the first quarter of 2022, we plan to start a phase two study is taking a bit of a Michael Bolton as mono therapy and patients with relapsed or with Leslie guilty C. L. Both with and without the Mighty 88 or city center mutation. The S. P. C data there'll be January that phony studies over the course of the next 12 to 18 months or intended.
To inform and support the initiation of Registrational trials. The both of these molecules in the specific Baltimore ticket find populations of non small cell lung cancer and D. O V feel that we're interested in with that I'll pass it over to Stephanie for an update on our financial.
Thank you M O <unk>. Good afternoon, everyone can you don't financial results for the current <unk> were included in today's press release I will briefly review our results on this account.
Revenue was 618 million for the three months I need September 30th 2021 and represents the milestone payment received in September and dry inside collaboration Green.
Alright, and the expenses were 11.6 million and started putting the 20th June one compared to 18.29 in the third quarter is 2020. The decrease was primarily driven by decreases and tell <unk> I'm looking to get programs, partially offset by investments in early stage research.
Expenses were $623 million in the third quarter 2021, compared to 4.7 million in 2020, the increase was primarily related to increase legal expenses.
At last with the third quarter, 20th 21 wasn't $11.2 million cash and investments totaled $84.5 million on September 30th 2021.
70 $445 million after the upfront cash payment just a qaeda in October as mentioned during the cheese steak there to call on Friday, we expect with the scheme continuation six study to result in cost savings between 10 and $15 million. We also expect our cash and investments will be sufficient to me Ah current operating plan and.
220, 23, and with that I will not return the call back to season.
Thank you Stephanie and with that operator, we're happy to open the lines for questions.
As a reminder to ask a question you will need to pass Dar one on your telephone keypad I can have a one if you have questions. Please crestar one on your telephone keypad.
The sand violent compiled a cute any roster.
Your first question comes in the lineup Rogers song from cast please your lifestyle dolphin.
Great. Thank you for taking the question.
A couple from me the first one is so besides those two faced to plan for the choose a new asset would you <unk> <unk>.
Additional kind of mechanistic I'll pick any need for work to better characterize yeah M O a and a unique properties for the best and collapsed potential even the targeted indication.
I'm not sure yet.
Thanks for the question Yeah. So I think the answer is yes in the sense that for both of these molecules I think the key theme is that the clinical data are already there and compelling in terms of the fact that they.
Both have single Asian activity demonstrators and be specific population.
I'd say the mechanistic the oboe mechanism for the second editor is probably much clearer in terms of the fact that it's the <unk> caused an old transduction pathway and lymphoma. That's been well studied both of my D. D N and C. D. Seven nine B there have been published report on the connection between New York too and.
12, one two any squamous non small cell lung specifically, although the exact detailed is the mechanism or not known uhm, but but there's clearly rationale supporting that 12, one two is activated and upregulated in the context of nerve to activation squame. So yes, we will do some further <unk>.
A relation of that but I think.
The fact that we are running a clinical trial also allows us to do translational work in that regard and and corroborate the mechanism and hypotheses using that work as well.
That's great. Thanks for the comment and maybe just for the C F data <unk>.
So understanding you have the kind of punishing initial face one day that maybe just what are the key elements you will be looking for for the trauma full face one data to make that go no go decision 40th program.
No great question. So I think the data so far are very encouraging and that the molecule has a very well tolerated safety profile and from a P. C. P. D standpoint, behaving very nicely Uhm and lastly from a biomarker standpoint, where these are the key downstream biomarkers of the pharmacy to have it looks like they're all headed in the right direction. So the mechanistic rash.
Now I think it's so far corroborated by the data as far as next steps. Obviously, you know real continuing dose escalation. The current cohort, which is 443 hundred milligrams isn't rolling and expected to complete by the end of the year per protocol, we have the option to go to another dose level go up another dose level.
Perjury dose escalation design and so the idea is we want to get a full characterization of the molecule P. K P. D profile and define the entire dose range in terms of safety P. K P D and biomarker once we do that the next step would be more those finding type study where.
We would pick doses from dose escalation, where we think you know, they're both faith and therapeutics in order to define what the dose would potentially be for full development and we do have the option to increase the dosing duration to 28 days and look at efficacy and a more robust fashion. So that would be the next step that would be.
<unk>.
Got it so the for the full data most day for the safety and the P. K P D not necessarily for the advocacy and the next step you will start to looking at the advocacy for the for development.
<unk>.
Okay got it okay, maybe just the one last question <unk> Uhm, so that I think you mentioned.
You also try to discovers some kind of synthetic be salty compost, maybe just tell us about the what is the history of that discovery platform and any C. N a G with previous focus.
Kind of <unk> <unk> order metabolism passed away intend on discovery.
Sure no problem. So uhm are synthetically salary targets are not specifically designed to be in the tablet them. We've really moved away from metabolism and looked at a whole series of <unk>. So we're interested in target.
Being pairs of jeans, where.
One thing is to leave it in a tumor in inhibition of the activity of the other team is the basis for a drug.
And two we branch pretty far from where we started and it really puts more to the dreadful we check that in my vote and have been <unk>, where it's clear that they play roles and signal transduction pathways. For example that are important and unimportant in specific.
Biomarker defined population.
No parallel genius like boiling it down to the simplest case you have jeanane yenching be it can be as missing in you and hit the teenage then you know that they're very related in this tumor uhm can't survive without cheese.
That's the basis for where we've gone into technically savvy and we expect to discuss some of wherever selling some of the targets at in 2022.
Got it that's very helpful. Okay. So that's all for me. Thank you for taking my questions.
<unk>.
<unk>.
Your next question comes into line I'll sneak App from last Spargo Your <unk> your line and I'm, hoping.
Great. Thank you. Thanks for taking my questions, maybe a coupla on C. D. Two H you just coke with I think the original go see plan was to go from 200 milligrams to 400 milligrams, but could they did you reported lost.
<unk> was at 300 milligrams. So what was the rationale to go to 300 and it'll give them that your code is continuous plasma division or <unk> 100 milligram, Ohio, So what do you hope to achieve by doing.
About 300.
Great Great question. So I think that's a two part question. So in regards to the decision to go to 300, instead of going straight to 400.
Being that we were at the top end of the dose range. Despite the fact that we haven't seen any of the L. PS received related we end the data safety monitoring committee together decided that it would be better to get the 402 steps rather than one and I think that's primarily driven by you know the idea of a creek clinically the T on trying to get to US which is your recycling ambition.
That's measured by this market called you and a lot of gas it could have sort of a more number in your profile and and while we have not seen clinically relevant give me a cycle inhibition or disruption in this study. We just thought it was the best approach in order to do that P. Two steps and that also gives you the opportunity to be better more granular get a grandma.
Characterization of the P. K P. D profile. So that was the reason we decided to go 304 hundred with regard to your second question around why go higher than that goes where you see full plasmin target ambition.
Main reason is there's two reasons one is that we continue to see the P. D effect with regard to arguing increases. According even above doses were were saturated with targeting plasma and given that arginine is the key driver of an O production. The thinking is as long as you're getting those those related improvements in arginine that are expected to drive up I know.
<unk> you could continue to go up as long as your safety is okay and the second reason is that plasma. In addition doesn't necessarily <unk> translate to inhibition within the Airways and so the assumption is that you're driving up to stomach arginine levels that you might be higher doses to make sure that side of action in the Airways are.
Cheap at high doses and that's reflected by the fact that we're seeing friends and female which is a reflection of inhibition of the target <unk> within the lungs and so that's the other thing we're targeting.
Alright.
So as you couldn't you know just totally help on that then do you think you would see a plateau of the effect on pina.
That's a good question I don't know if we know the answer to that yet and so you know we know that these patients at baseline has diminished and no production their baseline pinos are lower than the normal population and so you know we are clearly seeing a trend in female going up and female has a wide dynamic ray.
And it's also highly valuable read out so I don't think we know the answer to that but again I think we could we could get more data on that as we continue to do exactly.
Okay.
And then I know collection of Sputum is affected by Covid and this trial is there anything you can say you will be able to set about microbial burden in these patients.
Yeah. That's a great question and we had we do have an exploratory endpoint looking at quantitative sputum colonization. The the yield at samples has been relatively poor I think it was primarily impacted by the fact that the study was enrolling doing COVID-19 and there were a lot of like level of restriction gun and.
Do sputum collection of these patients and so unfortunately, the the level of student data. We have is not there, but I think what's reflective of the benefit is number one again the trend in fino in that we're seeing a positive trend and nephews, you want as well and you know even with mechanism being primarily antimicrobial that's a <unk>.
Flexion of the fact that you know when you when you do eliminate pathogens in the airway and reducing inflammation I do see benefits with a doctor early functions. So we're all encouraged by the fact that we're seeing the biomarkers heading the right direction.
Okay, and then maybe just a couple of quick questions on the new New program. So so it's a kind of cell types of understood <unk> keep to trial, but then I could you also mentioned continue to evaluate I'm, sorry enough too and then continue to evaluate no.
Two and Keith so those two separate cohorts are two separate trials.
No. There are two separate so we'll evaluate those patients separately as separate groups in the same study and the idea here is that the data we already have from the seats have study that was completed shows you know there was a pretty compelling differentiate a signal in Europe too and you know.
No evidence of a moderate signal and keep one and so we want a number one can look at the nerve to population individually look at keep one separately also look at the question of whether wildlife patients also have that <unk>.
Would respond so we'll be looking at all of those in the context of this study.
Okay, Great and and then the middle than to need Uhm Hill looking at patients who hampers mutations.
<unk> <unk> <unk> <unk> patients, who don't have those mutations.
Will that be split evenly and then just in relation to 79 P. M. I D 88 to those mutations tend to co occur without the genetic paramount to see you in a double or triple as I'm coma.
Right. So the first question answered. The first question is yes, we will be looking at both of those and an equal number.
<unk> two separate court is the idea because we think number one can be existing data already show that there's a signal potentially going outside of that my duty, 18th and 19 location and there's strong preclinical data indicating.
Includes an increase poverty a single agent response within that mutational subsidy as well as early trends in the clinical data until your second question with regard to call mutations I think sorry, just one can you repeat that second question specific exact.
Cushman could mutation too cause we often hear about double and triple hit lymphomas, and so alright, alright, yeah. So.
Yeah My Dad your city 79, do not overlap phone me with the double hit phenotype. So the double hit lymphomas are predominantly in the G. C. B celebration classification, whereas the my D V D. H C D. Seven nine for the most part and the a B C classification. So there's very little overlap and that's published big based on published data.
Okay perfect. Thank you very much.
Sure.
I am showing no afraid your question check next time I would now like to turn the conference back this is send molineux.
[noise]. Thank you upgraded and thanks, all for joining us today have a good evening.
This concludes today's conference call. Thank you all for your participation you may now disconnect.
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Ladies and gentlemen, thank you for standing by and welcome to the counties that Rob Biosciences third quarter earnings Conference call. At this time all participants are in a listen only mode. After the speaker's 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 keypad, if you require any further assistance. Please press star zero I would now like to hand, the conference over to your speaker today, Stephanie Wong. Thank you. Please go ahead ma'am.
Thank you operator, good afternoon, everyone welcome to our third quarter 2021 conference call. Joining me today are Susan Molineaux, founder, President and CEO, and Dan look Rioja, Chief Medical Officer.
This afternoon, we issued a press release, which included an overview of our third quarter 2021 financial and operational results, which can be accessed through our website I can let their dot 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 materially from those indicated by these forward looking statements.
As a result of various important factors, including those discussed in the risk factor 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 will that all.
Turn the call over to Houston.
Thank you Stephanie good afternoon, everyone and thank you for joining us today on our third quarter 2021 conference call and a special welcome today, two ml Creon <unk>, who is joining us in his new role as Chief Medical Officer.
We will be presenting later in this call we could not be more excited to embark on this next chapter with emel.
Speaking of the next chapter last month, we strengthened our precision oncology pipeline with the acquisition of the patents are good and Microvolt Nick from Takeda.
As a reminder, the patent searches it's a dual torque one two inhibitor that targets the key survival mechanisms and keep one nerf two mutated tumors, which has the potential to be the first treatment for nerf mutated squamous non small cell lung cancer.
The next generation torque inhibitor, so payments or did provide dual inhibition of the torque one and talk too complex and has demonstrated durable single agent responses and clinical benefit in patients with relapsed refractory nerf two mutated squamous non small cell lung cancer with a well tolerated safety profile.
My vote is a chicken better with the potential to be a best in class drug in non Hodgkin's lymphoma, as well as a first to market therapies for patients with D. L. Bcl, whose tumors harbor might be 88, or <unk> 79 mutations.
The voting has shown compelling single agent activity in relapsed refractory NHL patients and completed phase one two studies.
We plan to initiate phase two studies of both dependent searches and Michael in the first quarter of 'twenty to 'twenty two.
Additionally, last week, we announced the decision to discontinue the keepsake trial of tell Glenn stuff non squamous non small cell lung cancer. Following an interim analysis of 40 patients. We have no plans to continue the development of telco under staff internally at this time.
We remain committed to developing targeted therapies for patients with difficult to treat cancers with the advancements of both dependents searches and my vote knit and biomarker defined populations of squamous non small cell lung cancer and diffuse large b cell lymphoma, respectively.
Last week at the North American Cystic fibrosis conference, we presented interim data from the Phase one study of C V to Eddie our arginase inhibitor.
The presentation, we reported the T V QAD was well tolerated and showed linear pharmacokinetics and robust dose related pharmacodynamic effects.
Additionally, we saw encouraging trends in disease, biomarkers, including increased fractional exhaled nitric oxide or geno and decreased sweat chloride.
Current data to substantiate the proposed mechanism as a rational approach for treating CF. The poster can be found on our website.
Finally, as we just closed on Friday, we have promoted ml kyriacos from Vice President and head of clinical development to succeed Keith Orford a CMO in.
We have strengthened our board of directors with the addition of key I.
I would like to take this opportunity to thank Keith for his contributions over the last seven years and to congratulate ml on his promotion.
I'm always been a part of our team for the last four years and was an integral part of the diligence genes evaluated dependent circuit and my vote prior to our acquisition of these assets.
This has been a transformational year for telecom as we prepare to close out 2021 and enter 2022, we look forward to exciting times ahead.
We will begin the new year with a keen focus on precision oncology and two new highly compelling clinical development programs.
To initiate the phase two studies of independents are kept in mind for vote and if in the first quarter and look forward to updating all of you on our progress.
That I will pass the call over to M O for additional details on our clinical program.
Thank you Susan and thank you for the kind word I'm truly honored to accept the role of CFO and want to express my sincere gratitude.
For his leadership and Mentorship over the last several years and I'm thrilled to continue our partnership with going forward as he joins the board of directors I'm happy to update you today on our clinical programs and look forward to meeting all of you over the next several months.
I'd like to start today by providing some additional detail around the data we presented last week on <unk>, our novel oral arginase inhibitor for the treatment of cystic fibrosis.
Last week at the North American CF Conference, we presented data on the first 24 subjects in the ongoing phase one dose escalation trial in adults with.
These 24 subjects were enrolled across the first three dose levels 50 milligrams 100 milligrams and 200 milligrams B I D with 18, receiving CVT Lady and fix receiving placebo. The study population comprised a broad spectrum of see FTR genotype, including subjects with nonsense mutation.
Notably 91% of the subjects were already off to a modulator therapy with a catheter heart Keller Becker here.
Do you have a well tolerated safety profile across all three dose levels and all 18 subjects, receiving PD to 80 completed treatment without interruption or premature discontinuation changes enforced that's pretty volume in one second or F&B. One we're assessing the safety endpoint in a pooled analysis of treatment versus placebo showed a positive trend in F&B.
One compared to placebo CB 280 demonstrated linear pharmacokinetics with plasma exposure increase in proportionately with dose.
Police and continuous target inhibition in plasma was achieved at the 100 milligram dose.
He'd been trading also demonstrated robust pharmacodynamic effects with rapid and significant dose proportional increases in plasma arginine, which is a key driver of every nitric oxide production increase their annual production was reflected by a friend showing an increase in fractional exhaled nitric oxide or pheno in subjects treated with CB two eight sweat.
Ride a marker USTR function showed a trend towards decreasing Mcf CB 280, <unk> treated subjects.
Which is consistent with previously reported preclinical data showing that arginase inhibition and yet your function in human bronchial epithelial cells.
Together these pharmacodynamic biomarker data substantiate the overall mechanistic rationale for C. D to 80 you can.
Turning to our newly acquired program.
Plan to initiate a phase II study in the first quarter of 2022 that will strengthen the existing data onto the 10th circuit as a monotherapy in patients with relapsed or refractory squamous non small cell lung cancer harboring <unk> two mutation and further evaluate its monotherapy activity and coupons mutated and nerve to or keep on wildfire squamous non small cell.
A lung cancer also in the first quarter of 'twenty two we plan to start a phase II study is a sick inhibitor minor voting as monotherapy in patients with relapsed or refractory GERD D. C L. Both with and without commodity 88, or seven argumentation. The efficacy data that will be generated from these studies over the course of the next 12 to 18 months are intended to.
Inform and support the initiation of Registrational trials for both of these molecules into specific biomarker defined population of non small cell lung cancer and D. L. D. C. L. A that we're interested in with that I'll pass it over to Stephanie for an update on our financials.
Thank you Emily.
Good afternoon, everyone you don't financial results for the current quarter were included in today's press release I will briefly review our results on this call.
Revenue was $6 8 million for the three months ended September 30 of 2021 and represents the milestone payment received in September and our inside collaboration agreement.
R&D expenses were $11 6 million in the third quarter of 22, one compared to $18 2 million in the third quarter of 2020. The decrease was primarily driven by decreases in his Hello, Glenn is that I'm not going to get programs, partially offset by investments in early stage research.
G&A expenses were $6 3 million in the third quarter 2021, compared to $4 7 million in 2020. The increase was primarily related to increased legal expenses net loss for the third quarter 2020, one was $11 2 million cash and investments totaled $84 5 million at September 30 of 2021.
Or $74 5 million after the upfront cash payment to Takeda in October as mentioned during the keepsake data call on Friday, we expect with this team.
Continuation of the Q six study to result in cost savings between 10 and $15 million. We also expect our cash and investments will be sufficient to meet our current operating plan into 2023.
With that I will now turn the call back to Susan.
Thank you Stephanie and with that operator, we're happy to open the line for questions.
Yeah.
As a reminder to ask a question you will need to press star one on your telephone keypad I can everyone. If you have questions. Please press star one on your telephone keypad.
Please stand by we'll compile the Q&A roster.
Your first question comes from the line of Roger song from Jefferies. Your line is now open.
Great. Thank you for taking the question.
A couple from me the first one is so besides those two phase two plan for the Q.
New assets would you conduct.
Additional kind of mechanistic and preclinical work to better characterize their MLR and a unique properties.
All the best in class.
Sure in the targeted indication.
I'm not sure yet.
Thanks for the question Yeah, So I think.
The answer is yes in the sense that for both of these molecules I think the key theme is that the clinical data are already there and compelling in terms of the fact that they.
Both have single agent activity demonstrated in these specific population I would say the mechanistic.
The overall mechanism for the sick inhibitor is probably much clearer in terms of the fact that it's a well characterized signal transduction pathway and lymphoma. That's been well studied both the Mighty 88, and and PD 719.
There have been published reports on the connection between <unk> and torque one two.
Squamous non small cell lung specifically, although the exact details of the mechanism are not known but but theres clearly rationale supporting that torque. One two is activated up regulated in the context of nerf to activation and Squame. So yes, we will do some further characterization of that but I think.
The fact that we're running a clinical trial also allows us to do translational work in that regard.
Corroborate the mechanism and the hypotheses are using that work as well.
That's great.
Thanks for the comment and then maybe just for the CF data.
So understand you have a.
And a promising initial phase one data maybe just what are the key elements you will be looking for Florida shop, a full phase one data to make that go no go decision for CF program.
No great question. So I think the data so far are very encouraging and that the molecule has a very well tolerated safety profile and from a PK PD standpoint, it's behaving very nicely.
And lastly from a biomarker standpoint, where are these are the key downstream biomarkers of the Pharmacodynamic effect, they're all headed in the right direction. So the mechanistic rationale I think is so far is corroborated by the data as far as next steps. Obviously, you know we're continuing dose escalation the current cohort, which is call. It four or 300 milligrams is enrolling and expect.
To complete by the end of the year.
Protocol, we have the option to go to another dose level go up another dose level.
Person you dose escalation.
Design.
And so the idea is we want to get a full characterization of the molecule PK PD profile and define the entire dose range in terms of safety PK PD and biomarker once we do that.
The next step would be a more.
Finding type study, where we would pick doses from dose escalation, where we think.
They're both based in therapeutics in order to define what the dose would potentially be for full development and we do have the option to increase the dosing duration to 28 days and look at efficacy and a more robust fashion. So that would be the next step that would be flat.
Got it so therefore, the full data mostly for the safety and the PK PD and not necessary for the Africa and the next step you will stop sure looking at the advocacy for development.
Correct.
Okay got it okay, maybe just one last question.
So that I think that you mentioned.
And you also try to.
<unk> discovers doesn't kind of synthetic lethality compounds, maybe just tell us about the what is the history of that discovery platform and any synergy with previous focus.
Can I have a.
Well, the termination or the metabolism pathway, our internal discovery.
Sure.
No problem.
Or synthetically salary targets are not specifically designed to be in metabolism, we've really moved away from metabolism and looked at a whole series of parallel change. So we're.
We're interested in targeting pairs of jeans wear.
One thing is to leave it in the tumor and inhibition of the activity of the other team is the basis for a drug.
And so we bring is pretty far from where we started and it really puts more to the drugs that we've just brought in.
Voting happens to Panesar camp, where it's clear that they played roles and signal transduction pathways. For example that are important and important and specific biomarker defined population.
Paralleled Jesus like boiling it down to the simplest case your teenage Nanjing be it can be as missing an you inhibit G&A then you know that they're very related and its tumor.
Can't survive without G&A.
The basis for where we've gone into typically Saudi and we expect to.
Discussed some of where we're selling some of the targets.
And in 2022.
Got it that's very helpful. Okay. So that's all from me. Thank you for taking my questions.
Thank you.
Thank you.
Your next question comes into line of sneak up from La Spargo you like your line is now open.
Great. Thank you and thanks for taking my questions, maybe a couple on CB 280 to cope with.
The original dosing plan was to go from 200 milligrams to 400 milligrams, but the data you reported.
This week was at 300 milligrams. So what was the rationale to go to 300 and given that you recorded continuous plasma inhibition of collagen.
100 milligram or higher.
Do you hope to achieve by going above 300.
Great Great question. So I think that's a two part question. So with regards to the decision to go to 300 that are going straight to 400.
Being that we were at the top end of the dose range.
The fact that we haven't seen any D. L. Keys are strictly related we end the data safety monitoring committee together decided that it would be better to get to 400 in two steps rather than one and I think that's primarily driven by.
The idea of the pre clinically the I'm trying to get to US which is urea cycle inhibition. That's measured by this marker called you and a lot of gas it.
Could have sort of a more non linear profile and while we have not seen clinically relevant.
Over a cycle inhibition or disruption in this study we just thought it was the best approach in order to do that in two steps and that also gives you the opportunity to get better more granular you get a granular characterization of the PK PD profile. So that was the reason we decided to go 304 hundred with regard to your second question around why go higher than the dose range.
The full plasma target inhibition. The main reason is there's two reasons. One is that we continue to see the PD effect with regards to the argument increases occurring even above doses, where we're saturating the target in the plasma and given that arginine is the key driver of N O production. The thinking is as long as you're getting dose dose related improvements in <unk>.
Arginine that are expected to drive up I know production you could continue to go up as long as your safety is okay and the second reason is that plasma inhibition doesn't necessarily.
Translate to inhibition with MB Airways.
And so the assumption is that youre driving a systemic arginine levels, but you might be higher doses to make sure that site of action in the Airways is achieved.
At higher doses and that's reflected by the fact that we're seeing trends in female.
Which is a reflection of inhibition of the target within the lung and so that's the other thing we're targeting.
Right.
So as you just told me up on that then do you think you would see a plateau of the effect on Ciena.
Well, it's a good question I don't know if we know the answer to that yet and so we know that these patients at baseline have diminished and O production their baseline pinos are lower than the normal population and so we are clearly seeing a trend in growing up and Pheno has a wide dynamic range.
Also highly valuable read out so I don't think we know the answer to that but again I think we could we could get more data on that as we go through.
Exactly.
Okay.
And then I know a question of speed and was affected by Covid and this trial, but is there anything you can say it will be able to say about microbial burden in these patients.
Yeah, that's a great question and we had a we do have an exploratory endpoint looking at quantitative sputum colonization.
The the yield of samples has been relatively poor I think it was primarily impacted by the fact that the study was enrolling during COVID-19 and there were a lot of like level of restriction on induced spirit and collection in these patients and so unfortunately, the level of speed and data. We have is not there, but I think what's reflective of the.
Benefit is number one again the trend in <unk> and that we're seeing a positive trend in S. E V. One as well and you know even with our mechanism being primarily antimicrobials. That's a reflection of the fact that you know when you when you do eliminate pathogens in the airway and reduce inflammation you do see benefits with regard to early function. So we're all encouraged by that.
The fact that we're seeing these biomarkers heading the right direction.
Okay, and then maybe just a couple of quick questions on the new new programs. So that's the kind of cell types are understood.
I keep two trial, but then I think you also mentioned continue to evaluate our I'm sorry enough too and then continue to evaluate those.
And Keith so those two separate cohorts are two separate trials.
No. They are two separate so we'll evaluate those patients separately.
Separate groups in the same study and the idea here is that the data we already have from the C. Type study that was completed showed.
There was a pretty compelling differentiated signal in nerf too and evidence of a moderate signal and keep one until we wanted number one can look at the nerve to population individually look at keep one separately also look at the question of whether wildfire patients also have that would respond.
So we'll be looking at all of those in the context of the study.
Okay great.
And then the middle tend to need it.
Youre looking at patients who have those mutations.
And wild type patients, who don't have those mutations.
Will that be split evenly and then just in relation to 70 now maybe it might be 88 to those mutations tend to co occur without the genetic paramount as seen in double or triple hit on polymer.
Right. So the first question answer. The first question is yes, we will be looking at both of those in an equal number.
Across two separate cohorts because the idea because we think number one.
Listing data already show that there is a signal or potentially even outside of that might be 88 to 90 being location and there is strong preclinical data indicating.
And an increased probability of single agent response within that mutational subsidy as well as early trends in the clinical data.
And so your second question with regard to Commutations.
I think so.
Sorry can you repeat that second question.
Exactly.
Co mutation too because we often hear about double and triple hit lymphomas, and so Oh right right yes.
Yeah, My dad used to be 79, do not overlap strongly with a double hit phenotype. So the double hit lymphoma are predominantly in the GCB cell of origin classification, whereas the Mighty 88 cities at night for the most part in the a B C classifications, so there's very little overlap and that's published.
Based on published data.
Okay terrific. Thank you very much.
Sure.
Okay.
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