Q3 2022 Compugen Ltd Earnings Call
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Okay.
Ladies and gentlemen, thank you for joining us today welcome to <unk> third quarter 2022 results conference call. At this time all participants are in a listen.
Only mode, an audio webcast of this call is available in the investors section of Combi agenda website, Www Dot Dijon Dot com as a reminder, today's call is being recorded.
I would now like to introduce E von Naughton head of Investor Relations and corporate Communications you bought please go ahead.
Hi, Amit and thank you all for joining us on the call today, joining me from <unk> are Dr. <unk>, <unk>, President and Chief Executive Officer, Dr. Henry Envoy, Chief Medical Officer, Dr. Terry around O'hare Senior Vice President of research and drug discovery, and Alberto Sessa Chief Financial Officer.
Before we begin we would like to remind you that during this call. The company may make projections or forward looking statements regarding future events isn't this outlet development efforts under potential outcome. The company's discovery platform anticipated progress sometimes results in timelines for our programs financial and accounting related matters as well as statements regarding.
And your cash position.
We wish to caution you that such statements reflect only the company's current beliefs expectations and assumptions, but actual results performance or achievements of the company may differ materially.
For you to the SEC filings for more details on these risks, including the company's most recent annual report on form 20-F filed with the SEC on February 28 2022.
The company undertakes no obligation to update projections and forward looking statements in the future with us and I'll turn it over to you and us.
Thank you John Good morning, and good afternoon, everyone and welcome to our third quarter 2022 uptake for <unk>.
Shafter, Great city contracts in Boston last week, where we had to Owen's presentation.
In the first nine months of the year, we have continued to execute and meet our guidance, we presented clinical data from the MSS CRC expansion cohorts at TCT last week.
And in three weeks' time, we'll present clinical data from the two ovarian expansion cohort at ESMO I O.
During our first orders presentation of safety doctoral imagine overman from MD Anderson presented encouraging overall response rate following treatment with comfort and align in combination with the volume up in heavily pre treated metastatic MSS CRC patients.
Hard to treat tumor type.
Typically not responsive to immunotherapy.
Over 70% of the patients on this study had liver metastases.
He kind of these patient population who are resistant to treatment.
Sponsors in these patients with liver Mets is a key differentiator for <unk> seven to one and a unique achievement.
On the safety side, there were no serious adverse events deemed by the investigator as related to study drug.
During our second oral presentation at 60.
Iran presented data showing that concept into one in combination with the volume up.
I've seen potent immune modulation in the two MSS CRC patients with liver Mets, who responded to treatment, suggesting that the clinical responses were observed in such a cold tumor type.
At least to a concert or no unmitigated effect.
He also presented data showing immune modulation in platinum resistant ovarian cancer patients treated with comps up in the one monotherapy.
These data in an additional called tumor type typically not responsive to immunotherapy is further supported by encouraging data in platinum resistant ovarian patients treated with dual and triple combination therapy blocking PD, our AG and PD one.
We and without blocking T J.
We're looking forward to presenting this data at ESMO I O in December .
I'm excited.
Totality of hard data suggests.
It comes down to one maybe acreage effect and this is specifically encouraging.
It is observed in hard to treat non responsive tumor types.
The combination of our translational data from patients tumor center.
Along with our preclinical and clinical data suggest that the increased infiltration of T cells to the tumor microenvironment.
Following blockade of PD L I D.
May be needed to sensitize, the tumor to ticket and PD one blockade.
We believe that a triple blockade of the DRAM axis unleashing. The three pathways may result, in turning costumer like MSS, CRC and platinum resistant ovarian cancer.
More responsive to such immune checkpoint inhibitors.
As a result, we're planning a triple combination study in anesthesia CRC patients.
Our own potential first in class come seven one in.
In combination with our own potential best in class anti T. J come they know too and an anti PD one.
Our anti T. G commingled too was engineered to reduced expertise functionality with the potential to enhance antitumor activity.
We believe this is the optimal design to pursue clinically and look forward to seeing how this plays out in the clinic.
This is further supported by the preclinical data Astrazeneca recently presented at ACC on their PD, one ticket bispecific derived from continental too.
Also engineered to have reduced U S T function.
Moving to ovarian cancer.
We believe the encouraging data in platinum resistant ovarian cancer.
Mary further development in this indication, which opens the door for us in a much less crowded competitive landscape compared to non small cell lung cancer.
For this reason, we have decided to pursue platinum resistant ovarian cancer.
And we're now evaluating the various options for the planned non small cell lung cancer studies.
Following the disclosure of the data from the two ovarian cancer study at ESMO, we will host an investor call to describe the totality of our data and provide details on our studies.
We have a solid balance sheet with cash expected to support operations at least through the end of 'twenty 'twenty four and we're committed to this guidance and our focus on two indications with what we believe has the highest probability of success.
On that note I would like to welcome on Board, a new Chief Financial Officer.
Bert Assessor, who is with US today for his first conference call with comp again.
I'm delighted to have Alberto as part of my management team and as we continue to focus on execution.
And delivering meaningful clinical data and value to our stakeholders.
Yes.
During today's call.
Henry will start by providing an overview of the anesthesia Trc data presented at ACC.
Iran will then provide an overview of the research and translational data that he presented at C. G.
I will then send you your expectations ahead of the data in platinum resistant ovarian cancer patients, which we will present it as Mario.
Alberto will then bring you through the third quarter financials, and then we will open the coastal questions with that I will hand over to Henry.
Thank you and that I'm very happy to provide an overview of the data the doctor over months presented us as ITC 2022.
There is an urgent medical need for patients with MSS, CRC, who have very limited treatment options.
Microsatellite stable colorectal cancer, you see cold tumor type with Lee Mr. T cell infiltration, which as you know are required for immune checkpoint inhibitors to be effective.
Historically, most immune checkpoint inhibitors have demonstrated limited or no activity in certain tumors.
It's a little scary in the third line or greater mix of subjects CRC second typically regular off of me or us.
One or two.
Would show an overall response rates of 1% to 2%.
Median PFS of two months and median overall survival of six to seven months.
Most patients with metastatic MSS CRC metastasis to the lever and studies show the presence of liver metastases conflicts with lack of response to checkpoint inhibitors.
The data that we presented.
Two questions from the combination dose escalation cohort study.
I'm 20 predictions from the combination cohort expansion study.
The baseline characteristics are typical of a patient population with metastatic MSS CRC would that was two 7% of patients with liver metastasis.
Patients with heavily pre treated with a median of new therapies.
2% had prior treatment with regular afternoon you all.
One or two which is going to standard of care.
The objective response rate was 12% in the suburbs in patients with liver metastasis.
With two patients with partial responses also hot Iraq mutations.
And additional adverse broke those big factor.
Yes.
Observing responses in patients, who typically have been poor responders I would poor prognosis.
I'm highly encourage it.
The objective response rate was 90% and the 22 patients in the overall population and the disease control rate was 27, she says with true partial responses and four patients with stable disease.
Absorbing two patients with anti tumor activity, one stable disease, and one partial response for six months or longer.
Origin.
Considering that this is a hard to treat tumor types in which the patients on the study have been extensively pre treated on the median overall survival in this patient population.
He lives in six months when compared to standard of care.
In terms of 60 on Tolerability come sub into one combined with an Ebola mob showed a favorable safety profile and was well tolerated.
No patients discontinued study treatment due to the toxicity of any of the study drugs.
Notably no serious adverse events was assessed by the investigators as related to study drugs.
Good to talk to you about data combined with the mechanism of action of Cop 701 justifies. The further development of the triple blockade of the dealer boxes with P. D. R. I G G.
On PD one in this patient population.
So not as mentioned earlier, we are moving ahead with the evaluation of this triplet combination in a proof of concept study.
I would like to extend our sincere thanks to the investigators sluggish staff patients and their families participating in our clinical trials with that I will hand over to Iran.
Thank you Henry.
I'm delighted to share the robust translational research data and presented the city on Friday, which supports the death of just presented by Henry.
To put this concept into one in combination with the volume up in MSS CRC patient associated with potency immune activation and tumor microenvironment. We also show a delta supporting Julich expression of <unk> on the other differentiator to stimulate the immune system, which are key players in driving T simply fruition in the tumor microenvironment.
Well sure translational data from 13 patients with a stomach MSS CRC.
As I mentioned.
This comes to the new one in combination with the volume up with associated with potency Most division.
Ultimately in the toothbrush and two partial responses, who should have been more positive and activation in the tumor microenvironment.
Such magnitude.
Vision for a triple brocade is not typical for consumer like emphasis here.
<unk>.
The clearly one observation.
No responding patients may.
I suggest that it's purely because of the dinner mixes barely untreated antibody my tip the balance towards enhancing its division and subsequent further improve clinical outcomes.
This is supported by our preclinical and clinical data across our studies.
Also presented translational data in patients with another consumable document resistant ovarian cancer. So we should just comfortable.
Jeremy.
Also here treatment was associated with immune activation in the tumor.
Government.
There is pressure to biopsy of one patient who had a durable partial response to comfortable on monotherapy children engine desert with no T cells in the tumor environment instead of a negative for PDL one.
Commscope in one and just a robust interest in and therefore demo in the peripheral blood.
These patients from who didn't have post reason biopsy.
Also here the Caribbean Division soon also in non responding patients with all of your brands you Blockheads may suggest that affordable access my tips.
Balance towards enhancing clinical antitumor activity.
Superstar brocade in a vertical so patients will be presented by us.
Finally on the research side, we describe the unique attributes of <unk>.
Provides biological rationale for these antitumor activity.
Activity of conserving the warm and indications are typically not responsive to checkpoint inhibitors.
Using cutting edge technologies and competition that analysis, we showed that <unk> compared to checkpoints PD, one and <unk> is uniquely and dominantly express an early differentiated stem like memory T cells in tertiary lymphoid structures.
These cells could drive police force of antitumor T cells burst, but maybe inhibited dominated by people.
Therefore.
Unleashing dislocated, but it comes to the norm.
Appreciate the drive systems is a jewel macro environment and in doing so making culture words like MSS CRC is presumed resistant ovarian cancer or responsive to anti PD ones and potentially the digits, especially the cross talk of these three buzzwords.
With that I'm now turning back to Alex.
Thank you Ron and Henry.
Moving now to setting expectations ahead of the platinum resistant ovarian cancer data, which we were present it as my Oh on December eight.
We will present preliminary data, including overall response rate duration of response safety and very niche is translational data from 20 patients with platinum resistant ovarian cancer, who were treated with comes with a new one in combination with <unk> volume up.
And 20 patients who were treated with come 71 in combination with the volume up and BMS antique T J.
We're excited to be seeing encouraging data following dual and triple blockade of the DRAM axis in these patients.
Effective treatment option for patients with platinum resistant ovarian cancer, a limited specifically standard of care in patients with platinum resistant ovarian cancer is single agent chemotherapy and responses ranged from 8% to 12%.
With median progression free survival of three to four months and overall survival of around one year.
Also immune checkpoint inhibitors as monotherapy and as part of immunotherapy combination has demonstrated limited activity in this patient population.
Also here P. R. A G unique biology.
And then other checkpoint.
Have potential to generate different outcomes.
Finally, we plan to host an investor call. Following the data presentation at ESMO Io on December eight.
During this call we will discuss the data presented at that conference, including in platinum resistant ovarian cancer patients and non small cell lung cancer.
The merger static non small cell lung cancer data, we will present his long term follow up off a very small number of patients already presented at the ESCO in 2020 one treats.
Treated with comfort and the one we do without any volume up.
In the call. We will also provide details on our planned studies and we plan to share initial findings and progress on these studies during 2023.
We're also making progress on our preclinical pipeline and are very excited about our lead program called FIFO suite, which has first in class potential.
We will elaborate more on this program during the end of the year and vessel calls in early 2023.
I will now hand over to Alberto.
Thank you on that I am delighted to be onboard and excited with the opportunity to work closely with you and to come to an experienced management team to ensure the company will continue to execute and deliver value to our stakeholders.
Our financial results for the third quarter of 2022 and in line with our forecast and working place.
We have a solid balance sheet assumption cash, which is expected to support operations at least through the end of 2024, and we are committed to continue delivering meaningful clinical data.
As of September 32022, with approximately $88 million in <unk>.
Cash.
Bird will approximate $118 million as of the.
December 31 2021.
The company has no debt.
For the third quarter of 2022, we reported a net loss of $11 $7 million or <unk> 14 per <unk>.
Basic and diluted share.
Compared with a net loss of $6 2 million or seven.
Basic and diluted share in the comparable period of 2021.
R&D expenses for the third quarter of 2022 were $9 $3 million compared to $8 $7 million for the comparable period of 'twenty to 'twenty one.
As a result of our decision to focus on to prioritize indications starting 'twenty to 'twenty three we expect our ongoing R&D cash expenditure to be lower than the current run rate.
This is expected to extend the personal way to at least the end of 2024.
G&A expenses for the third quarter ended September 32022 were $2 $6 million compared with approximately $2 8 million for the comparable period in 2021.
And with that we will now open the call for questions.
Okay.
This concludes.
Thank you ladies and gentlemen at this time, we will begin the question and answer session. If you have a question. Please press star one if you wish to decline from the polling process. Please press star two if you are using speaker equipment kindly lift the handset before pressing the numbers. Please standby, while we poll for your questions.
<unk>.
The first question is from Stephen Wiley of Stifel. Please go ahead.
Yeah.
Yes. Good morning, Thanks for taking the questions and congrats on the updated synergy.
Yes.
Tumor types within the original development program that you guys outlined.
Was that something last year.
Really prioritize biomarker expression I think bodes P. D. R. P BRL two.
What can you say about the expression of <unk>.
Of these biomarkers and colorectal.
Which I know was not originally included in the tumor types of interest.
And thank you Steve.
Yes, you're correct. So when we started the program and based on preclinical data and also based on expression profile seen in tumor samples taken from patients.
Asian patients on our study.
We were prioritizing.
Very in endometrial and breasts.
Breast and non small cell lung cancer and nature. When we started to see the dose escalation data. We also prioritize the MSS MSS CRC.
And I'll, just say that when we returned back to look at the CRC Dana the expression was.
Somewhat lower than that then they indications to prioritize but still high and maybe I'll ask Karen to say few words about the expression profit sofa.
The <unk>.
We setup yes.
Yes, so as I just mentioned the emphasis there differently with doughnuts expression of the <unk> pathway.
Basically every tumor that whoever assistance for MSC associates positive for people to for sure and actually is abundant expression. It is.
A bit lower than ovarian which has been a bit higher but definitely is.
Is there in all the business, we have tested and PDR. The ligand have Sujit is also high and actually MSS CRC is one of the indication with the highest expression.
While the litigation of the negative digits.
Okay. That's that's helpful and then.
Maybe you can just talk a little bit about some of the factors that you're considering.
Considering in terms of your decision to move forward into law.
Would the decision to pursue long or any other tumor types beyond colorectal and ovarian.
I have a meaningful impact on the current cash from us. Thanks.
Yeah.
So yes, so maybe first I tried to remind why we picked non small cell lung cancer. As you know this was not a part of the cohort expansion studies that we had in the combination of any of them.
And actually it was in the in the doublet change in PD, one free regimen.
But.
It's not with PD one.
And the reason we picked this indication is because we are we so to get to focusing on any indication that these immune checkpoint sensitive is responding inflamed.
And with such a different bar for us.
And we wanted to PK non inflamed won any playing one.
I have to say that we recognize the that time and we were related to data and more competitive area.
And for us to to get to <unk>.
And as data mature would be ovarian cancer.
And we so the data we understood that there is an opportunity for us to get into an area that is less competitive.
Enrollment rate would be.
Easier to address.
And the signal that we will need to present, even though ovarian cancer is it is a hard to treat tumors typing in many checkpoints are not paying and showing great team up there but still.
And the way for us to exemplify Sting that would probably be.
Be easier as compared to non small cell lung cancer, where we would need to get to much higher numbers. So we can with encouraging data than we have in hand, we sold that each would be and then it would be better for us to switch that indications.
They did one in non small cell lung cancer, we're still evaluating our options for doing the study internally maybe at a different time lines or to do it externally.
Mr Gates or sponsored studies and we have a great relationship with our investigators and.
And when we tried to assess what type and what is the right path for Athene and also can enhance that but at this point in time it was.
Very important for us as a company to stay focused on one hand and make sure that we can meet their guidance on cash runway, but also.
He has peaked.
Vacations, where we fear and that we have and then we have highest higher probability of success and they think there's a variant.
It is included in the sand indefinitely going forward I think that in general you know we were now were going to start the studies and the work we're continuing to evaluate the data that we have obviously and and we'll make sure. We we don't claim that value on.
The table with respect to comps.
Alright, thanks for taking the questions.
Well.
The next question is from Mark Breidenbach of Oppenheimer. Please go ahead.
Hey, thanks for taking the questions.
Really appreciated ron's presentation.
With all the translational data I guess one of my my My main question is is what.
Or are you guys seeing as the best evidence that addition of its eejit antibody.
No wonder about doublet can do even better than what you're already seeing in terms of tumor microenvironment modulation and immune activation.
That you've seen with <unk>.
701.
Doublet combination and then Oh sorry.
Great question.
Yes.
Yeah.
We saw some.
Encouraging data from our <unk> four PD, one combination in microsatellite stable CRC.
I was wondering if you could take a moment to just compare and contrast, the safety profile.
Your combination comes from no one close novo combination versus versus that IL combo.
Maybe.
Highlight.
Distinct patient groups that one combination made maybe more appropriate for that thank you for taking the questions.
Thanks, Mark So for your first question, it's a very important one so I think there are a few lines of evidence to support the first the research we're doing on the Dino Onex's pre clinically doesn't it shows that if you combine PD, one digit and fever jetblue to completely unleashed genome activity.
And then he gets an optimal and enhance to selectivity lithium world in patient samples treated with the triplet. This is what we have seen it was really exciting to see that when you get the throughput you can.
Photo deficiency Bloods, and Thats, saying this is what we have done and we can see really potent immune activation with stupid blockade in patients treated with the triplet of brocade, a comfortable one responsive and one in PD one blocker.
Finally.
In a cohort of patients treated in the Mr. CLC was close to what else plus level, yes, the responding patients were immune modulator very significantly.
Also have many patients that were in England related a bit to a lesser extent reduced increase in TCE filtration things are happening in the tumor environment, but not sufficiently to drive activity probably now we do know that when you have most uses a dual microenvironment digital's done more active so what we think that in these patients that we were able to.
Revenue unity, but looking sufficient level to drive clinical activity.
Digits should enhance the new activity that will translate also to enhance clinical activity and this is exactly what we're going to test.
And marking to your to your other question with respect to other agents in Chile for Eylea.
Seven.
Thank you.
The two first it's encouraging data obviously, it's encouraging data what the what has been seen in emphasis you're saying it's great for patients.
I assume that the two major things that one needs to remember that are highly differentiated in our.
So our data is the fact that.
The safety profile.
We can elaborate on this and also the fact that we see sickness in liver Mets and again Henry related but I'll just say other than the regular studying Japan. There are all these studies are showing zero response rate in this patient population now remember that this specific patient.
Asia is actually consisting of about 70% of the population.
So that's the reason we think that that the data that we're showing very encouraging specifically and fits here for for MSS CRC patients and Henry feel free to elaborate and on the safety and <unk> and on.
The data.
Yeah. So mark. Thank you very much for your question with all the caveats of comparing across trials phase one trials and the caveats with comparing different class of agents.
There's other people that are.
In August studies that were conducted not just the one we reported recently.
2022 but sometimes you can see the member states.
Report data on all the ongoing trials.
Sure.
When we Oh.
<unk> seven to one as monotherapy.
Up to 20 milligrams per kilogram body weight.
IV Q4 weeks as monotherapy and in combination.
I didn't come with it.
M. P M S 96 to a settlement.
We haven't reported anything.
Any toxicities.
On the eastern side.
Combined with <unk>.
And specifically if you go back into that.
Reported.
We.
We didn't report any subject coming off.
Coming off of study drug.
Toxicity.
Most come on to.
The emergence of adverse events.
We've done that we've seen that these four subjects.
Yeah.
These were grade one grade two.
None of the patients.
Likely related to the two.
Itself.
Yeah.
Overall, it's great. So toxicities and remember this is in combination with Ebola map.
I wouldn't want to elaborate.
More on the PP&E for antibodies.
Because we all know what the toxicity profile of these agents.
There has to be in that question was asked during this ITC action.
To the present, there with regards to trying to select patients for this study.
Subsequently come down.
Try to exclude patients with prior toxicities.
And from the checkpoints and specifically in their report they have.
How about almost a third of patients.
You bet.
Interestingly population.
This might possibly be released its sometimes the.
The disease, but we do see related to study drug.
<unk> related adverse events, so I'm stubborn on alone 701 in combination with Ya Com 701 in combination as a triplet.
Triplets.
It was very well tolerated.
The safety profile.
And even at the doses were selected.
We have not reported any increasingly are opposed to the profile of the drugs that we're combining with so very favorable and the investigators.
With regularly mentioned these.
Born out in the report that you see.
All the private or public issuance.
Okay. Thanks, Henry she brings to us thank.
Thank you.
Just to add one mechanistic insights for both basic and fundamental biology is still a focus.
So it really for us a major player controlling peripheral tolerance and that's why from the mouse studies all the way to the patients we see all this toxicity with <unk>.
<unk> was just shown on S. ATC that much of the activities happening in the tumor micro environment. The solid participant once we show that pizza is dominant in the structures in the tumor microenvironment and introduces a proliferating and we have shown that actually does most of the activities. The most dominant loan proliferating in the responding patient is in the tumor microenvironment.
Biological it seems that <unk> plays less of a relevant rolling this I'll turn it on and much of the sensitivity of discipline fruition at the end of June up environment.
Got it.
The next question is from Ren Benjamin of JMP Securities. Please go ahead.
Hey, good morning, everyone and thanks for taking the questions.
Gratulation as on the progress.
I guess, maybe just starting off I'm kind of curious how you guys are thinking about applications.
Roche is data at some time in 2023 Pan out kind of what are the implications for coffee Gen. And then maybe even more importantly, if you know drag it doesn't it doesn't show a survival benefit kind of what are the implications to the coffee business and then I have a follow up.
Thank you Randy.
Yes. It is.
It will have implications on comp on comp again, obviously if data is positive then great I guess that interesting to each would've resuming the industry and <unk>.
And and we will continue to be there to make sure that people understand that T. G. L. P. D. R I G.
The way to go in certain tumor types definitely not those that are not responding to PD. One blocker. So that's that's an important thing and we'll continue to add to.
To make sure that this is being heard and we're pursuing it is wet.
I say, that's my answer will be somewhat similar or if it is a magazine.
These negative yes, I guess, it's a sentiment in the market would not be that great, but he doesn't mean, they're all we're doing is not the right think we have the biology to support us.
Strong biology, we have data from patient clinical responses as well as immune and as well as data from the tumor microenvironment.
And we have that said, we have two independent effect and we're going to pursue it that's our plan. So so it is going to be probably hard there is that if the sentiment appears not there, but we are going to present. It then and we believe that we will show good positive data.
And that would be convincing I think that you know at the end of the day. It may also be somewhere.
Zone in and but still we are at any scenario, we're moving forward.
Got it.
Second question is just in terms of expectations for the platinum resistant ovarian cancer.
You you mentioned during your prepared remarks kind of where the typical objective response rate is where the typical median overall survival is can you talk a little bit about you know.
What what you're looking for what helps frame a go no go decision.
And in your mind, what do you need to see.
So.
So we would not go too much into detail when they say you know when the data would be all done we can speak about it anymore.
And in a more informed way, but I think that just like Henry relate to the field and then and then and what should be seen in ovarian cancer.
Second a resistant ovarian cancer patients in general.
Not alluding to our data Henry.
Yeah. So thank you very much and in her prepared remarks.
And that's already previously mentioned.
But I think if you look at the NCC guideline.
Guidelines also.
For platinum resistant ovarian cancer is what consensus that.
What is recommended for most patients that either.
That category.
He's one of the Paragon.
Is that typically in the range of single digits inflation, and a PFS of three or four months.
So essentially what we will be expecting to see any.
Improvements in any of these parameters, including quality of life also.
Well with respect to input trials with.
It comes up in Illinois in combination with any of the other he just let them.
That's 96 or seven or in combination.
Hmm.
So as you know.
It means a lot.
Unfortunately.
Yes.
Trying to investigate.
Checkpoint activity.
This is done to ovarian cancer.
You bet.
We are encouraged by what we're seeing.
Studies are.
And those are the metrics that we would be looking for.
With respect to what standard of care with typically in this patient population.
I think they're fair metrics and the things that at least with the benchmark.
Yes.
What's been reported in.
Larger studies.
That's been conducted with chemotherapy.
As far as that I will go onto we normally disclose the data is more ideal.
Got it Okay. My final question is for Ron I guess.
We'd love to get an idea as to how the the biomarker kind of patient selection.
You know work that's being done at coffee gin is going in and I guess, where I am.
My question is going with this is you know you guys saw significant immune activation and in those two P. R's.
You know presented at Pepsi and.
But at baseline they all all the patients look you know look the same right. It's kind of like after you've after you've been treated or do you see this activation I'm kind of curious if have you been able to make any of them.
Any more headway.
Terms of selecting those patients or excluding patients that.
You know may or may not respond.
Yeah. So of course this is very important and we are doing extensive work both.
With the normal CSA is and also where sequencing the two more as we're doing.
Arco potentially capabilities to address identified maybe less obvious candidates for patient selection. So this work is ongoing one important thing to mentioned that one August biomarker that you're looking just for other checkpoints, it's working clinical PD ones and notice we don't see a real correlation as PDL one right.
So talking about the ovarian cancer responses obscene.
Any checkpoint activity responses in ovarian cancer is normally impeded once it gets above one <unk> been in the America PD, one plus digit study with do you have some responses at zero responses in PD, one Cps of zero.
We have results in.
Ovarian cancer patients in monotherapy that was PDL, one zero, who responded to consuming on monotherapy. We also have results nothing to CRC call. Some business really not inflamed tumor environment actually, especially with the highest speed in one level before treatment.
So at this point, putting one maybe because of that unique <unk> been able to work closely listening to a tumor types seems less relevant of course, we could see the Williston well why do you think all the genomics as members and this is work ongoing.
Great. Thanks for taking the questions.
The next question is from Dana Gray Bosch.
S D B Securities. Please go ahead.
Hi, Thank you for the questions I have two as well the first one for Henri I Wonder if you could talk more about the second responder with MSS CRC. I think you said are the presenter said they had on measurable liver metastasis I wonder what that means specifically and whether you had any signal.
Benefit.
Liver with the combination therapy, either radio graphic or clinical or symptomatic.
Yeah, Yeah, yeah, so that's subject.
The woman presented was a percent obviously.
Uh huh.
Had.
Bulky disease.
Yeah culminated defense also.
The investigator had to select.
All the tumors, which ones with measurable Uh huh.
And which ones will be deemed non measurable that'll be followed subjectively purchases. So they selected the ones of them.
No.
Two questions. The first one we reported previously we did see that it was.
Defense, we selected and there was a reduction.
Her receipts.
The target.
And the second piece that was presented by Dr. Hoffman those are the significant reduction.
Targeting since I was elected in the lungs.
Liberty Loosens appear stable.
They didn't get any worse.
So that's in itself is significant because that shows the number of prior therapies that are subject that previously.
That there was no progression in terms of the study.
But there was significant reduction.
When it came to the target lesions that were selected.
Fortunately the subject like we did mention relapsed to the brain.
At the same time.
The responses that we observed.
At this time, we do not.
So it's been cool.
Assessments performed better.
Does that answer your question.
It does thank you and then another one for Iran. I think somewhat similar but a different twist to one that everybody's been asking you about.
Really the mechanistic rationale for why P. B R. E. G. In MSS CRC you clearly showed the CRC responses were immune driven and I think you also clearly show the translational differentiation of PPR G. I'm wondering how do you think you could have or have you link.
Those two pieces of evidence. So do you have any translational are going back into our in vitro models plans that can help us understand and confirm the role of P. B R E G.
Z, a particularly or in the liver right.
Alright, thank you.
Yeah, Thanks, Dan so.
The study to do was to go into the neuron settings.
Canister clean a very relatively easy with the issue is that figure a gene in the mice is not the beverages are a bit different in human we don't go through all the details but in general.
<unk> is different in its biology, and specifically this voted you will discuss about the dominance and ability to block proliferation of search is a bit different than the months. So therefore, what we're doing is following the clinical samples and what we see over there is that bleeding is you mentioned that biology with the.
Professional observation figure just seems to be very dominant and probably in controlling these T cell proliferation event.
And this kind of a new modulation that we see an emphasis cirrhosis suggests the fever, the sole domain of the controlling T cell proliferation in the tumor microenvironment and also outside of it.
It can drive activity also in this kind of let's say trend indication and specifically one of the patients in which the biopsy was taken from the level, we could easily see almost completely as expect maybe from a liver biopsy.
Almost complete visits biopsy, becoming completely inflamed colon consume in the one and you put them off treatment. So we think that this unique observation suggests that people reduce dominant enough and controlling T cell proliferation to be active also in patients with MSS Youll see lieberman's, obviously also in other indications.
One follow up for me then and the data you showed with the data from patients not on this trial that patients with MSS CRC, where you looked at the tertiary lymphoid centers and the expression of PPI G where those are primary tumors are those metastatic tumors can you tell me.
We think more about those particular tumors or patients that they came from.
Yeah. They were a mix I don't think there was any anything specific we can say hey over then decide to disappoint in patient.
Patients with liver metastasis have something which is very different from the other patients with them assist you'll see it.
It seems that this is a wise observation.
For PVH biology.
So all said before associates.
Yeah.
Okay. Thank you.
The next.
The next question is from Tony Butler of Roth Capital. Please go ahead.
Thanks, very much two questions for Ron Ron.
This is back to the buyer.
Biology and mechanism.
Well.
Is.
Does expression of T V. Archie is it affected.
But.
Prior therapy in other words.
Do you have any evidence that it is.
Did she didn't really expressed <unk>.
<unk>.
Only expressed under certain conditions, that's one and number two if you looked at the tumor what happens with P. V. R. L. Two again the same question is it.
P G R O.
Constitutively expressed or.
Is it dependent on prior therapy for example, with Kim Thank you.
Okay. Thanks so.
Both the targets people agenda ligand have considered a expression of course it can be modulated. We don't have any data specifically showing if people would use moderating photo specific treatment in general if you have T cells.
Too much to environmental even if you shoot isn't doing local environments diverge you will be there and it will be normally dominant again early differentiated cells.
And for people to it might be upgraded but some chemotherapies.
Generally it has high expression and you can see it considerably before treatment and after treatment.
Thanks, Ron.
This concludes the Q&A session I will now turn the call back to <unk>, President and CEO . Dr. Cohen <unk> would you like to make your concluding statement.
Yes, thank you operator.
Thank you all for joining us today, and taking time to follow the company.
I want to thank the coffee Gen team for their dedication and commitment to the company's ambition in the third quarter.
We all know that this is not an easy time to be in the biotech space.
And the resilience of the competent team is commendable driven by our vision to transform the lives of patients with cancer and I'm very proud to be leading this vision. Thank.
Thank you.
Yeah.
Yeah.
This concludes the Compu Jan Q3 2022.
Conference call you May go ahead and disconnect.
[music].