Q2 2021 Compugen Ltd Earnings Call

And axis and differentiating us in the tissue space is the only company targeting and the clinical setting PV array G ticket and PD, 1 as part of our free pathway hypotheses.

On today's call I'm pleased to have the opportunity.

Unknown Executive: and differentiating us in the TIGIT space as the only company targeting, in a clinical setting, PVRIG, TIG, and PD1 as part of our three pathway hypothesis. On today's call, I am pleased to have the opportunity to remind you of our strategy, provide an update on our most recent data, our views on important developments in the field, and what's to come for the remainder of 2021. We believe that the foundation that underlies our success at Comptigen is our science and our people.

And remind you of our strategy provide perspectives on our most recent data our views on important developments in the field and what's to come for the remainder of 2021.

We believe that the foundation that underlies our success it's competition is our.

Our science and our people.

We were the first to identify PV, our IGN ILD or 2 as novel checkpoint and.

Unknown Executive: We were the first to identify PVRIGN ILD2 as novel checkpoints, and we published on TIGIT the same year as Genente. Both PGRIG and TIGIT are key parallel and complementary inhibitory pathways in the DEM axis, which also intersect with the well-established PD1 pathway. While TIG and PGRIG pathways share similarities, we observed key differences between the two with respect to their expression pattern and their ligand expression pattern on immune cells and two more times. Furthermore, our recent data shows that PVRIG is expressed similarly to P1 and TIG in stem cell-like memory and exhausted T cells, an important cell population with a potential role in mediating anti-tumory effects.

And we published on TG, the same year as Genentech.

Both PDR IGN ticket, a key parallel and complementary inhibitory pathways in the denim X.

<unk>, which also intersect with a well established PD 1 pathway.

While ticket and PV or a G pathways share similarities.

We observed key differences between the 2 with respect to their expression pattern and their ligand expression pattern on immune cells and tumor types.

Furthermore.

Recent data shows that P. D. R. I G is expressed similarly to PD, 1 and <unk> in stem cell like memory and exhausted T cells and important cell population with the potential role and mediating antitumor effect.

However, recently.

Unknown Executive: However, recently, Iranofir, our VP of Research and Drug Discovery, presented scientific data showing that PVRIG has a more dominant expression pattern on early differentiated stem-like memory T cells than TG10 PD1, further pointing to the possibility that PVRID may act different We believe that the future of immunoncology will be driven by a combination approach, Research from Compugents suggest that the PVRIG TIG and P21 pathways have different dominance in different tumor types and patients, implying that to induce effective immune antitomor responses, certain patient populations may require the blockade of different combinations of these three pathways. To test this hypothesis, Comfegent has established a biomarker and biology-informed clinical program, which aims to evaluate different combinations of these axis members across tumor types.

Iran and fear, our VP of research and drug discovery presented scientific data showing that PD are AG has a more dominant expression pattern on early differentiated stem stem like memory T cells, then ticket and PD 1.

Further pointing to the possibility.

The PV array G May act differently.

We believe that the future of immuno oncology will be driven by combination approaches.

Research from computer and suggest that the PV or a G. T G and PD 1 pathways have different dominance in different tumor types and patient.

Implying day to induce effective immune antitumor responses certain patient populations may require the brocade of different combinations of these free pathways.

To test this hypothesis cartilage and has established a biomarker and biology and formed clinical program, which.

To evaluate different combinations of these excess members across tumor types.

We're focused on maintaining our first mover advantage and the Clinique and <unk>.

Unknown Executive: We're focused on maintaining our first mover advantage in the clinic as the only company with monotherapy, doublet, and triplet combination clinical studies evaluating the Dinaaxis players, PVRIG and TIG as well as PD1. We believe these programs, augmented by our first-in-class anti-PVRIG antibody Com 701, uniquely position Compugent with innovative and potential first to market doublet and triplet therapy. Our most recent data from the Phase 1 Dose Escalation and Expension Cohort of Com 701 as monotherapy and in combination with Nivalimab presented at ASCO this year are important for several reasons.

Only company with monotherapy doublet and triplet combination clinical studies evaluating the denim X is players PV array G.

And ticket as well as PD 1.

We believe these programs and cord by our first in class NTP V or a G antibody comps and no 1 uniquely positioned compu Jen with innovative and potential first to market doublet and triplet therapies.

Our most recent data.

Data from the phase 1 dose escalation and expansion cohorts of concert and the 1 as monotherapy and in combination with <unk> volume up presented at Astro. This year are important for several reasons.

These preliminary data showed durable responses and disease control.

Unknown Executive: These preliminary data show durable responses and disease control in patients who exhausted all prior treatment options, which may have meaningful effects. Notably, these responses were in tumor types typically not responding to immune checkpoint inhibition. Com701, in combination with Nivalumab, resulted in a disease control rate of 67%. This included a complete response in a patient with Analsquemone who had prior treatment with Nivolumum and a partial response in a patient with microsatellite-stable colorectal cancer. These are two more types of cancer, typically unlikely to respond to checkpoint inhibitors, and at the time of reporting, we saw responses up to and beyond one year.

In patients who have exhausted all prior treatment options, which may have meaningful effect.

Notably these responses were in tumor types typically not responding to immune checkpoint inhibitors.

Comps have and no 1 in combination with new volume.

Control resulted in a disease control rate of 67%.

This included a complete response in a patient with honest squamous cell carcinoma, who had prior treatment with any volume up.

And the partial response in a patient with microsatellite stable colorectal cancer.

<unk> is our tumor types typically unlikely to respond to checkpoint inhibitors and.

And at the time of reporting we saw responses up to and beyond 1 year.

Moreover, our potential differentiation.

Unknown Executive: Moreover, our potential differentiation comes through the addition of an anti-tigyth antibody to this doublet regimen in our ongoing triplet combination study and combining anti-PVRIG with anti-Tig in a newly initiated NPD1 independent study. These data are also important as they demonstrate signals of antitumor activity in a com-7-1 monotherapy setting, in patients who have exhausted all available standard therapies and in tumor types typically not responding to immune check Com 701 resulted in a disease control rate of 47%, including one partial response.

And through the addition of and.

And TPG to antibody to this doublet regimen.

And our ongoing triplet combination study.

And combining NTP, Gary G with NTT, Jade and our newly initiated anti PD 1 independent study.

These data are also important as they demonstrate.

The uniqueness of antitumor activity in a calm 7.1 monotherapy setting in patients who have exhausted all available standard therapies and in tumor types typically not responding to immune checkpoint inhibitors.

Comps have and no 1 resulted in a disease control rate of force.

207%, including 1 partial response.

It is also important to note that comes in and no..1 was well tolerated with no DLT with mono therapy or in combination with the volume month.

Unknown Executive: It is also important to note that Com 701 was well tolerated with no DLTs when administered monotherapy or in combination with Nivalum. This is a critical component of our ability to move forward with our differentiated combination approach.

This is a critical component of our ability to move forward with our differentiated combination.

Nation approach.

This preliminary data are also important as they included our first initial pharmacodynamic biomarker data, which indicated treatment with comps and no 1 lead to immune activation.

Unknown Executive: These preliminary data are also important as they included our first initial pharmacodynamic biomarker data, which indicated that Com701 led to immune activation. We also showed that antitumor activity was observed in selected PD1 low PVRL2 positive patients, suggesting Com 71 treatment may drive antitumor immunity even in patients with a less inflamed tumor microenvironment. I will come back to this data and a broader biomarker strategy later in the call.

We also showed that antitumor activity.

Pvt was observed in selected PD, 1 low PBR and 2 positive patients, suggesting comes off and on treatment may drive antitumor immunity, even in patients with less inflamed tumor microenvironment I will come back to the data and a broader biomarker strategy later.

Is it comparable.

College and execution in the clinic has been impressive in a short time, we have gone from our first clinical launch and data presentation to a comprehensive clinical program with the opportunity to truly differentiate us in the denim and tissue space, including.

Unknown Executive: Comptogen execution in the clinic has been impressive. In a short time, we have gone from our first clinical launch and data presentation to a comprehensive clinical program with the opportunity to truly differentiate us in the digital world. denim and digit space, including the ongoing cohort expansion of Com 701 in combination with Nivalum, and the triplet study of Com 701 with Nivalumab and Bristol-Mere Scrib Thetic Inhibitor, for which we just announced the initiation of the cohort expansion study.

The ongoing cohort expansion of comps and the 1 in combination with the volume up.

The triplet study of <unk>, 7 and 1 would be volume up and Bristol Myers Squibb digitally inhibitor.

For which we just announced initiation of the cohort expansion study.

The dose.

Unknown Executive: The dose escalation of Com 902, our wholly-owned TIGI inhibitor, and the recently initiated Doublet Study of Com-902 and Com-701, initially evaluating the safety and tolerability of the combination at both of the recommended doses for expansion in patients who have exhausted all available standard of care therapies, i.e., all comers.

Dose escalation of come and I know to our wholly owned <unk> inhibitor.

And the recently initiated doublet study of Cop 902, and come 7 and 1 initially evaluating the safety and Tolerability of the combination.

Both of the recommended.

As for expansion in patients who have exhausted all available standard of care therapies I E. All comers.

Once this is completed and expansion cohort of both study drugs will be initiated in patients with PD, 1 refractory or relapsed non small cell.

Unknown Executive: Once this is completed, an expansion cohort of both study drugs will be initiated in patients with PD1 refractory or relapse, non-smol cell cancer, and head-the-nexed one-mosell kercinoma, as well as colorectal cancer, and microsatellite colorectal cancer. Having completed the dose escalation of the triplet study and initiated the triplet cohort extension study, we We are considering removing randomization from the ovarian arm of the triplet study, as historical data for Nivalumab in ovarian cancer already exist, and we know these patients have a low response rate to Nivalumab.

Phil and cancer, and head and neck squamous cell carcinoma, as well as colorectal cancer microsatellite colorectal cancer.

Having completed the dose escalation of the triplet study and initiated the triplet cohort expansion study, we continue to evaluate strategies.

And <unk> to maintain our fast fast execution and first mover advantage.

We are considering removing randomization from the ovarian and arm of the triplet study.

As historical data for any volume up in ovarian cancer already exist and we know.

These patients have low response rate to new volume up.

In addition, we are considering adding and inflamed indication, possibly head and neck cancer.

Unknown Executive: In addition, we are considering adding an inflamed indication, possibly neck cancer, to broadly assess the full blockade of this axis in a tumor type that, unlike most of the other tumor types we evaluate, has an inflamed histology but still presents a low response rate to immunotherapy. And finally, our plan for the triplet includes starting the basket study when we have additional data aiming to support the link between PVRL2 expression and treatment response.

You broke it says the full blockade of these axes in.

And a tumor type that unlike most.

No. The other tumor types will evaluate has and inflamed histology, but still presents a low response rate to immunotherapies.

And finally, our plan for the triplet include starting the basket study when we have additional data aiming to support.

Most of the link between PV Air and 2 expression and treatment response.

Coming back to our biomarker strategy.

Unknown Executive: Coming back to our biomarker strategy, on which we receive a lot of questions, I thought I would take this opportunity to summarize our approach. First, we use biomarkers to select the tumor types for inclusion in our cohort of expansion studies. This was driven by our computational discovery prediction and validated in the lab on Denham Axis members' expression in two more samples, along with our initial clinical results from the dose escalation studies of Com 7-1.

On week, we received a lot of questions.

I thought I would take this opportunity to summarize our approach.

Firstly, we.

We use biomarkers to select the tumor types for inclusion in our cohorts of expansion studies.

This was driven by our computational discovery prediction and validated in the lab on denim X. Its members expression in tumor samples along with our initial clinical results.

The dose escalation studies of <unk> 7 and 1.

Our focus and the various expansion cohort studies, we initiated is on tumor types with the high level of both P. V. R. A G and PV our N 2 and.

Unknown Executive: Our focus in the various expansion cohort studies we initiated is on two more types with a high level of both PVRIG and PVRL2, and the tumor types in which we saw initial signals of antitumor activity in the dose escalation study. Such antitumor activity further supports our biomarker-informed approach and predictive discovery capability. The second part of our biomarker strategy is the identification of biomarkers for future patient selection. To achieve this goal, we are currently evaluating the correlation between the expression of the PVRIG pathway with clinical response, as well as other exploratory biomarker identification approaches.

And the tumor types, and which we sold initially cigna's prevented tumor activity and the dose escalation studies.

From Dutch antitumor activity further supports our biomarker informed approach and predictive discovery capabilities.

The second part of our biomarker strategy each day densification of Biomarkers for future patient selection.

To achieve this goal we are currently.

That is evaluating the correlation between the expression of the <unk> pathway with clinical response as.

As well as other exploratory biomarker identification approaches.

This work is being done in our ongoing cohort expansion studies and you reach tumor biopsies are collected.

Unknown Executive: This work is being done in our ongoing cohort expansion studies in which tumor biopsies are collected pre-and post-treatment. And thirdly, we have a pharmacodynamic biomarker approach where we measure immune modulation induced by Com 7-1 and combinations in peripheral and tumor patient samples obtained before and during treatment, as mentioned earlier. Our first presentation of our preliminary biomarker results at ASCO provided initial clinical evidence for the potential immune-mediated mechanism of action with Com701. After one treatment cycle, patients with Com 71 monotherapy showed the trend of increased proliferation of a factor called memory CD8 plus T cells. This is an important cell population, particularly given its high expression of PVRID and role in driving antitumor activity.

Currently pre and on treatment.

And thirdly, we have a pharmacodynamic biomarker approach, where we measure immune modulation induced by come 7 to 1 and combinations.

And peripheral and tumor patient centers obtained before and during treatment.

<unk> mentioned earlier.

Our first presentation of our preliminary biomarker results at Agco.

Provided initial clinical evidence for the potential immune mediated mechanism of action with comps of and a 1.

After 1 treatment cycle.

Patients would come to a and 1 mono therapy.

And show the trend of increased proliferation of effector memory CD 8 plus teachers. This is an important cell population, particularly given its high expression of PV array G and rolling driving antitumor activity.

In addition, we saw a significant proliferation of.

Unknown Executive: In addition, we saw a significant proliferation of NKT cells, which also plays a role in anti-chomer activity. From a cytokine perspective, levels of interferon gamma, a cytokine that plays a key role in anti-tumor activity, were upregulated following combined treatment of Com711 Plasmilum. Interestingly, these results showed a dose response trend with increasing doses of Com 701 and fixed doses of Nivolumab, suggesting that the observed increase in cytokines is derived from the combination regimen and not Nivolumab alone.

And he says which also plays a role in antitumor activity.

From a cytokine perspective.

Davis of interferon gamma and try to kind of plays a key role in antitumor activity were up regulated following combination treatment of <unk>, 7 and 1 glass and the volume up.

Interestingly. These results showed a dose response trend with increasing doses of concept and a 1 and fixed doses of knee volume up.

Adjusting the day observed increasing cytokines is derived from the combination regimen and not the volume up alone.

And we're excited to present, a case study at a school, which.

Unknown Executive: We were excited to present a case-studied ASCO, which included archival biopsy data from a patient with platinum-resistant MSS primary peritoneal cancer. This patient, with a confirmed PR who was on treatment for 18 months, was PDL1 negative prior to treatment with PVRL2 expression on both tumor and entotelial cells and an immune death of phenotype. Peripheral blood assessment in this patient showed immune activation as measured by immune cell proliferation and interferon gamma induction prior to tumor shrinking.

Which included archival biopsy data from a patient with platinum resistant and S. S primary peritoneal cancer.

These patients with a confirmed PR, who was on the on treatment for.

Many months was PDL, 1 negative prior to treatment with PBR and 2 expression on both tumor and endothelial cells and then immune desert phenotype.

Peripheral blood assessment in this patient showed immune activation as measured by.

A T cell proliferation, and interferon gamma induction prior to tumor shrinkage.

This biopsy and peripheral blood biomarker case study together with our recent finding of PV or Iga expression profile on stem cell like memory T cells.

Unknown Executive: This biopsy and peripheral blood biomarker case study, Together with our recent finding of PVRIG expression profile on stem cell-like memory T cells and it's ligand on dendritic cells, suggests a potential mechanism of action of Com 701 in driving tumor shrinkage, likely through immune activation in a patient with an immune desert, non-inflamed tumor microenvironment. These immune desert, non-inflamed patients are those who And are encouraged by these initial results, which provide the first translational indication that targeting the Dinum axis may expand the reach of immunotherapy to patients who typically do not benefit from this treatment.

Immune and each ligand on the <unk> says.

Suggest a potential mechanism of action of comp set and a 1 and driving tumor shrinkage likely through immune activation in a patient with and immune desert non inflamed tumor microenvironment.

These immune.

Third non inflamed patients.

Those who are typically considered least likely to respond to checkpoint inhibitors and we're encouraged by these initial results, which provide the first translational indication the targeting the DRAM axis may expand the reach of immunotherapy.

Desi to patient, who typically do not benefit from these treatments.

Our steady execution over the past year has propelled us to a unique first mover advantage and the only company with wholly owned clinical stage assets for both P D or a gen T G.

Unknown Executive: Our study execution over the past year has propelled us to a unique first mover advantage as the only company with wholly owned clinical stage assets for both PVRIGN teachers. Recent developments in the field are providing important validation of our three-way hypothesis, with considerable interest growing in pursuing similar approaches in evaluating the dual and triple blockade of DinaMexis members, PGRIGN TIGIT, along with PD1.

Recent developments in the field are providing important validation of our free way hypotheses with considerable interest growing in pursuing similar approaches in evaluating the dual and triple locate of denim X. These members PV origin ticket along with PD 1.

Third we believe the growing interest and deferred endorses, our overall strategy from target discovery and validation through to our clinical strategy and while others are looking to advance candidates targeting P. Very G into clinical studies with.

Unknown Executive: We believe the growing interest in the field endorses our overall strategy from target discovery and validation through to our clinical strategy. And while others are looking to advance candidates targeting PVRG into clinical studies, we remain ahead with clinical evaluation of monotherapy, dual, and triple combination regimens already in progress with Com 7-1. Part of the growing interest in the DEM axis includes a debate regarding the role of the FC domain and its relevance for antitumor activity for immune checkpoint inhibitors in general and TIG antibodies specifically.

Main head with clinical evaluation of mono therapy, dual and triple combination regimens, Oregon progress with comps and then in 1 part of the growing interest in the DRAM axis includes a debate regarding the role of the FC domain and its relevance for antitumor activity.

We were immune checkpoint inhibitors in general.

And <unk> antibodies specifically.

And while the debate for <unk> antibodies is ongoing which was a point of discussion at the recent seats at symposium on T. G.

Unknown Executive: And while the debate for Tidic antibodies is ongoing, which was a point of discussion at the recent Symposium on TIG, the consensus is that it is unclear if pre-clinical results from mice or in vitro studies, Support FC active TIG antibodies will translate to the clinic. Com 701 and Com902 were both purposefully designed by Comhagen to have reduced FC effector function, as we believe this best positions us for success in the clinic.

The consensus is that it is unclear if free.

<unk> for the reserve for mice or in vitro studies.

Support F C active T G antibodies will translate to the clinic.

<unk>, 7 and 1 and come and I know to where both purposely designed by coffee Gen..2 have reduced.

Clinically effector function as we believe these best positions us for success in the clinic.

Antibodies with F T effector function carry the risk of the depleting Seagate plus pieces, which are crucial for driving antitumor activity in the solid tumor setting.

Unknown Executive: Antibodies with FTA effect of function carry the risk of depleting CD8 plasticis, which is crucial for driving antitumor activity in the solid tumor set. Therefore, our strategy is to avoid the risk of depleting this important cell population. And our growing data support this decision with preliminary activity in the clinic with Com 7-1. In addition, recent developments in the field indicating promising phase-2 randomized descriptive data with an FC silent entity are in line with our FC reduced function approach.

And our strategy is to avoid the risk of depleting these important cell population.

And our Green data support this decision with preliminary activity and the clinic would come and 701.

In addition, the recent developments in the field, indicating promising phase 2 randomize the script.

If data with an FC silent NTT, Jake I inline with our FCA reduced function approach.

So far 2021 has been a year of execution for competition and we plan to continue this execution through the second half of the year with several milestones.

Unknown Executive: So far, 2021 has been a year of execution for Compugent, and we plan to continue this execution through the second half of the year, with several milestones still expected to come. Among these milestones will be preliminary data from our leading phase 1, 2, triple combination study, evaluating the safety, tolerability, and preliminary antitumor activity of Com 701 in combination with Bristol-Mersquib, TIG antibody, and evoluma. We remain on track to report initial data from the study in the fourth quarter of the year, which tests our triple-blockade hypothesis that blocking the three intersecting PBRID-G Tidget and PD1 pathways has the potential to synergistically enhance antiturmore immune responses in selected patient populations not responsive or refractory to PD1 blockade. This is a key differentiator for Compagent in the competitive digit space.

Script is expected to come.

Among these milestones will be preliminary data from our leading phase 1.2 triple combination study evaluating the safety Tolerability and preliminary antitumor activity of Com 7 and 1 in combination.

Asian, with Bristol Myers Squibb digit antibody any volume up.

We remain on track to report initial data from this study in the fourth quarter of the year, which tests, our triple brocade hypothesis that blocking the free intersecting PV or a G T J and PD 1 pathway has the potential to synergistically.

Enhance antitumor immune responses in selected patient populations, not responsive or refractory to PD, 1 blockade and.

This is a key differentiator for comprehend in the competitive digit space.

Our progress with the Triple combination study continues with the recently announced.

Unknown Executive: Our progress with the triple combination study continues with the recently announced initiation of the expansion cohort of the study, moving next to Com9O2. The Com902 monotherapy dose escalation study is important as it enables us to select a dose to independently evaluate multiple combination approaches with Com9O2 in the clinic. We expect to provide initial data from the Com902 dose escalation study in the fourth quarter of this year. We also strengthened our track record of success in the clinic with the on-scheduled initiation of our clinical study of Com-902 in combination with Com 7-1.

Initiation of the expansion cohort of this study.

Moving next to come and I know too.

They come and I know 2 monotherapy dose escalation study is important as it enables us to select a dose to independently evaluate multiple combination approaches with continental to in the clinic.

We expect to pre.

<unk> initial data from the continental to dose escalation in the first quarter of this year.

We also strengthened our track record of executing in the clinic with the on schedule initiation of a clinical study of common and I know 2 in combination with <unk> 7 and 1 day.

This study is the first.

Unknown Executive: This study, as the first clinical evaluation of the dual blockade of PVRIG and TIGC, is again a key differentiator for Compagin in the competitive TIGC space. As you know, we also have an ongoing collaboration with Bayer, and we are pleased with their commitment to advancing our ALDR2 program. Like PGRIG, Alder2 was first discovered by Confuge.

Evaluation of the dual blockade of PD ever again, <unk> is a game and.

Differentiator for <unk> in the competitive space.

As you know.

We also have and ongoing collaboration with Bayer and we are pleased with their commitment and advancing our LDR too.

Like P D R I G and D.

2 was first discovered by competition.

They have full responsibility for development of bottom up which is a novel first in class and <unk> and there are 2 monoclonal antibody.

Unknown Executive: Bayer has full responsibility for the development of Bapotilumab, which is a novel first-in-class anti-Aldier two monoclonal antibody. We're pleased to be able to say that involvement is accelerating in the phase one cohort expansion study, which is focused on treating patients with first line, I.O. Naive had the next quemal cell carcinoma.

We're pleased to be able to say that.

Enrollment is accelerating in the phase 1 cohort expansion study, which is focused on treating patients with first line I O nave head and neck squamous cell carcinoma.

We look forward to sharing additional updates on the progress of this collaboration in the future subject to bayer's.

Unknown Executive: We look forward to sharing additional updates on the progress of this collaboration in the future, subject to Bayer's communication policy. We're proud of our remarkable progress, excited for what to come, and remain committed to pioneering the science and clinical studies that have the potential to expand the reach of immunotherapies to patient populations who are unresponsive or refractory to current treatment. Before turning the call over to Ari, I would like to thank the team at Comptogen, our partners, investigators, shareholders, and patients. I'm incredibly proud of their ongoing commitment and dedication, which has enabled our impressive execution. And with that, I will turn the call over to Ari to review the finances.

And communication policy.

We're proud of our remarkable progress.

Excited for what's to come and remain committed to pioneering the science and clinical studies that have the potential to expand the reach of immunotherapies to patient populations who are.

Our unresponsive or refractory to current treatment.

Before turning the call over to Ari I would like to thank the team at comp again.

And we're partners investigators shareholders and patients and.

And I'm incredibly proud of their ongoing commitment.

<unk> and dedication, which has enabled our impressive execution.

And with that I will turn the call over to Ari to review the financials.

Thank you and not.

Good morning, and good afternoon to everyone.

Ari: Good morning and good afternoon to everyone. Our financial results for the second quarter of 2021, released this morning, continue to show our strong financial position as we execute across our growing clinical program. Research and Development expenses for the second quarter of 2021 were $6.8 million compared with $4.4 million for the same period in 2020. The increase in expenses reflects the continued execution and expansion of the various clinical trials phase one programs.

However, promotional results for the second.

Quarter of 2020 once released this morning.

Continued to show a strong financial position.

We execute across our growing clinical pool groups.

Research and development expenses for the second quarter of 'twenty, or 'twenty, 1 or $6 million to $8 million compared with $4.4 million for the same period.

<unk> and 2020.

The increase in expenses reflects the continued execution and expansion of the virus clinical trials phase 1 programs net.

Net loss for the second quarter of 2021 was $9.5 million or 11 cents per basic and diluted share compared with a net loss.

$6.2 million or 8 cents per basic and diluted share for the same period in 2020 as of June 30th 2021 we had approximately $111 million and cash and cash related accounts.

Paired with approximately $119 million as of March 31st 2000.

21, the company has no debt.

As a reminder, we expect our gross cash expenditures for 2020, 1 to be and the range between $40 million to $42 million without taking into consideration any potential cash inflows for the company from existing and new collaborations.

Thank you and with that we will now open the call for questions.

Unknown Executive: The net loss for the second quarter of 2021 was $9.5 million, or 11 cents per basic and diluted chair, compared with the net loss of $6.2 million, or $0.8 per basic and diluted chair for the same period in 2020. As of June 30, 2021, we had approximately $111 million in cash-related accounts compared with approximately $119 million as of March 31st, 2021. The company has no debt. As a reminder, we expect gross cash expenditures for 2021 to be in the range between $40 to $42 million without taking into consideration any potential cash inflows for the company from existing and new collaborations. Thank you, and with that, we will now open the call for questions. Thank you, ladies and gentlemen, at this time, we will begin the question and answer session.

Thank you ladies and gentlemen at this time when we begin the question and answer session. If you have a question. Please press star 1 if you wish to decline from the polling process. Please press star 2 if you are using speaker equipment time and lift the handset before pressing the numbers. Please stand.

Operator: Thank you. Ladies and gentlemen, at this time, we will begin the question and answer session. If you have a question, please press star 1. If you wish to decline from the polling process, please press star 2. If you are using speaker equipment, kindly lift the handset before pressing the numbers.

Standby, while we poll for your questions.

Yeah.

Our first question is from Mark Breidenbach of Oppenheimer. Please go ahead.

Operator: Please stand by while we poll for your question. The first question is from Mark Brightenbach of Oppenheimer. Please go ahead.

Mark Alan Breidenbach: Hey, thanks for taking the questions and congrats on the progress. So, let me maybe start with a kind of sciencey one.

Hey, thanks for.

Taking the questions and congrats on the progress.

So let me maybe start with the kind of science you on.

Unknown Executive: We certainly appreciated Iran's presentation showing the fraction of PCF7 positive cells is important for response to checkpoint therapy and that there is expression of PVRIG in stem-like T cells. I guess I'm wondering if you see TCF7 as a potential biomarker for patient selection. Would you expect there to be many patients in your phase one dose escalation trials who still have stem-like T cells? And is that the kind of thing that can be simply monitored from peripheral blood without needing biopsies? Yeah, thanks, Mark.

And we certainly appreciated and ron's presentation, showing the fraction of Tcf 7 positive cells is important for response to checkpoint therapy, and and and Theres expression at P BRG and.

And I'm like T cells and again.

I'm wondering if you see P T F 7 as a potential biomarker for patient selection.

Would you expect there to be and many patients are in.

And your phase 1 dose escalation trials, who still have stem like T cells and is that the kind of thing that can be simply monitor.

And from peripheral blood without without needing biopsies.

Yeah, Thanks, Mark so.

Unknown Executive: So I think it's an interesting notion which is not relevant only to PVRG but to the field at all, the expression of TCF1. I think it might be a challenging bar mark in terms of its prevalence and expression in TME. But we are looking, in addition to the obvious suspects and the Dinam pathway, etc. We are looking quite broadly in terms of exploratory biomark identification. Obviously, TCF7 is one of them. And peripheral blood, I'm not sure it's correlated enough with the presence of the cells in blood composed tumor.

Thank you and.

And interesting notion, which is not relevant only to prevail and able to the field at all.

And with Tcf, and I think it might be challenging biomarker in terms of its at prevailing.

And industry and <unk>.

But we are looking in addition to the over suspects and the non pathway et cetera, we're looking quite broad in terms of.

Exploratory biomarker identification.

Obviously, <unk> 7 and 1 of them and peripheral blood.

I'm not sure it's correlated enough.

And the presence of the sales and blood compared to tumor.

Okay fair enough and and just in terms of what we should be expecting.

Unknown Executive: Okay, fair enough. And just in terms of what we should be expecting, as far as patient numbers for the upcoming readouts in the triple combination dose escalation study and the Tom 902 monotherapy dose escalation study, and also, might we see additional kinds of translational biomarker data compared to archival biopsies for any of these patients, or will the focus really be more on safety and efficacy in the fourth quarter

As far as patient numbers for the upcoming Readouts and from.

And the Triple combination dose escalation study and upon nano 2 monotherapy dose escalation.

And also might we see additional kind of translational biomarker data compared to archival biopsies for any of these patients or will the focus really be more on safety and efficacy and in the fourth quarter.

So.

Unknown Executive: So just, I let Henry relate to it, but just for the translational data, we're accumulating data, we're working on translational data generation from our studies. When we will have the data, we'll present it not sure that this will be ready for Q4, or maybe we'll have only very initial data. As for the expectations, Alex Henry will relate to it.

And we related but just for the.

And for the translational data and we're accumulating data we're working on the translational data generation from our studies.

And when we will have the data, we'll present and not sure that this will be ready for the Q4 and.

Well, maybe we'll have.

Only very initial data and 4 the expectation and select high River lately.

Yes, so it would be along the lines and Mark. Thank you very much for your question.

Unknown Executive: Yes, so it will be along the line, Mark, thank you very much for your question. It will be along the same lines as the subjects that we were previously enrolled in during those escalation. So an approximate range would be between the range of 15 to about 2, for dose escalation. And that's for both the triple combination and for Com902 as well. That is correct, Mark. Okay, thank you so much for the clarification, and thanks for taking the question.

Moving along the same lines of the subjects that we were previously enrolled and dose escalation, so and approximate range would be between the screen just 2000.

And that's for both the triple combination and or come down and it too as well.

And that is correct Matt.

Okay. Thank you so much for the clarification and thanks for taking the questions.

And next question is from Chris Howerton of Jefferies. Please go ahead.

Operator: The next question is from Chris Howerton of Jeffries. Please go ahead.

Chris Howerton: Excellent. Thank you so much for taking the questions. And, of course, congratulations on the progress and look forward to the end of the year here. So maybe just a couple of questions from me. One is maybe just more of a theoretical question in terms of some of the checkpoint axes. Obviously, the D&M axis is the focus for your team.

Okay.

But thank you so much for taking the questions and of course.

Unknown Executive: But there's also been some activity with Vista and the associated macrophage lineage. So I guess, you know, I'd be curious to hear your thoughts on how those may or may not synergize or work together. And then the second question I have is, you know, I know and not what you were mentioning about the strategy and the hypothesis that you have around the FC domain of your antibodies. There was a recent update from Arcus, obviously a little scant on details, but, you know, curious to hear your thoughts as to how that reads through to your programs.

Congratulations on the progress and look forward to the end of the year here.

So maybe just a couple of questions from me 1 is.

Maybe just more of a theoretical question in terms of some of the checkpoint axes Avi.

Obviously the D N. A M access is the focus for your team.

But there's also been some.

Activity with Vista, and the associated macrophage lineage, I guess I'd be curious to hear your thoughts on how those may or may not synergize our work together.

And then the second.

Question I have is.

And I know and that you were mentioning around the strategy and the.

Hypothesis that you have around the FC domain of your antibodies. There was a recent update from arc is obviously, a little scant on details, but curious to hear your.

And how that reads through to your programs. Thank you.

Okay. Thanks reasonable first for your first question I'm not sure what Vista, specifically, but if youre talking about me yellow with checkpoints and general this is something where it's a few years ago. Yes, we do think that <unk> plays an important troll and immune suppression and Jo Malone.

Unknown Executive: Thank you. Okay, thanks, Rhys. For your first question, not sure about Obitista specifically, but if you're talking about Mialud Checkpoints, in general, this is something we entered into a few years ago. Yes, we do think that Mialuduiz plays an important role in immune suppression in two-o-environments, and we have early programs on this in this area. And we are evaluating, of course, efficacy and combinations, the synergism with current pipelines, and assets.

Unknown Executive: Okay. And for the... Go ahead, sorry.

Environment and.

And we have early programs on this and these fronts.

And we are evaluating air force efficacy in combination and synergies and with current pipeline assets et cetera.

Okay.

Okay.

Unknown Executive: Yeah, you know, I just wanted to add on the FC domain question and the ARC data. So obviously, we were not surprised to see this descriptive data, positive descriptive data. We would wait to see the data itself, but remember that this is an approach that we have taken ourselves, and we believe in this approach. We selected an IDG purposely. So, you know, it was encouraging for us to see it, but we were expecting it.

No I just wanted to add for the FC domain question and day August data and.

And so obviously, we were not surprised to see this descriptive and data processing descriptive data.

Weighted.

And to see the data itself.

But remember the.

Is there an approach that we were taking ourselves and we believe and this approach we selected and I need your full and it perfectly.

So you know it was a it was encouraging for us to say, but we were expecting it.

Yeah Okay.

Unknown Executive: Yeah, okay. And then maybe, if I may, just one other quick question, you know, with respect to kind of the tumor microenvironment that you're describing, like the head and neck where it was inflamed but not necessarily responding to immunotherapy, you know, I guess what the mechanistic hypothesis there is in terms of specifically what the checkpoints are and how is it, you know, inflamed yet not. no appreciable immune response to the actual tumor. So we're moving on a few fronts, evaluating a few different hypotheses.

And then maybe if I if I may just.

Just 1 other quick question, you know with respect to kind of the.

And the tumor microenvironment that you were describing like head and neck, where it was and flame, but not necessarily responding to immunotherapy.

And you know I guess, what what is the mechanistic hypothesis there.

And in terms of specifically what the checkpoints are and how is it you know and flamed you get no appreciable immune response to the actual tumor.

So so we're we're moving and few fronts validating fjord different day part to this.

The.

Unknown Executive: As discussed in the script, the expression of PVRG and stem-like teeth, the expression of PIVR2 and nary cells, all of this makes it likely that PVRG may be a dominant checkpoint in terms of enhancing TESL priming, expansion, and thereby enabling targeting also patients who have a less inflamed tumor macro environment, and we present it in NACO preliminary data to show that we see some early signs of antit But obviously, every checkpoint should work better in a more inflamed tumor environment because the TIS are already there, so you might need to push it a bit less to get efficacy.

As discussed and in the script to them and with the expression PV energy and stimulate T cell expression of fever, and 2 and their music sales. All of this makes us think that people have a G maybe domain and checkpoints and.

In terms of enhancing T cell priming expansion, and thereby enabling and targeting also.

The pushes and shoves less inflamed tumor microenvironment, and we presented and that is called preliminary data to show that we see some early signs of antitumor activity and patients, which have a PD, 1 and low less inflamed tumor types, but obviously every check when should work better and a more inflamed tumor microenvironment. Because these are already there so you might need to.

And to push it a bit less to get the efficacy and and 2 most like head and neck and even other more inflamed might also have a potential for PV energy in terms of enhancing and expanding our pizza, which already there and really seeing another break that might be day, 1 which is relevant to what your PD..1 alone is not itself and.

Unknown Executive: And tumors like head and neck and even other more inflamed might also have a potential for PVRG in terms of enhancing and expanding the TISA which are already there, releasing another break that might be the one which is relevant, if PD1 alone is not itself, and head and neck and non-smolcelang and other hot hair indications have quite a dominant expression of the pathway, FVRL2 and others. So I think we're testing, in a clinical strategy, multiple indications which fit different Valiopoteins all stemming from the same biology of PVLG and PVL2 and, and the role in Peacill Expedition. Okay, yeah, no, I get it. Okay, thank you very much, Arana, and I appreciate you taking the question.

And head and neck, and non small cell lung and other hot hotel indication, however, quite dominant expression of the of the pathway and fever, and 2 and others.

I think the we're testing and our clinical and.

And our strategy.

And there are multiple indications, which fits different so well reported.

And all stemming from the same biology.

<unk> and <unk>, 2 and <unk>.

And they're rolling diesel explain yeah.

Okay.

Yeah, no I get it okay. Thank you very much around and I appreciate everybody taking the question.

The next question and.

Operator: The next question is from Rennie Benjamin of JMP Securities. Please go ahead.

And summit Reni Benjamin of JMP Securities. Please go ahead.

Rennie Benjamin: Hey guys, thanks for taking the questions and congratulations on all the clinical progress. I guess just sticking with the Tid theme, you know, we've seen some significant BD activity, most recently, I guess, with BMA, and genus, and I just wanted to get your thoughts as to how we should be thinking about your own BD discussions and your thoughts regarding the potential to partner, or is this something that you really want to keep, you know, in-house?

Hey, guys. Thanks for taking my questions and congratulations on all the clinical progress I guess, just sticking with the tissue theme.

Seen some significant.

BD activity.

Most recently, I guess with BMS, and and Chinas and I.

It is 8 your thoughts as to you know I guess, how we should be thinking about your own.

BD discussions and and your thoughts regarding the potential to partner or is that something that you really want to keep and in house and sticking with the theme you know.

Rennie Benjamin: And sticking with the Tid theme, you know, when I think about, I think last night you had made some comments about how, you know, the strategy of having an inactive or slightly less functioning F. F.C. Fector prevents CD8 T-cell depletion. I always thought about, you know, the F.C. regions as mainly impacting NK cells. Is there, you know, something that I'm missing there or something you can, you know, help educate me on in regards to T cells and FC receptors?

When I think.

About I think and that you had made some comments about how you know.

The strategy with having a inactive or and slightly less function and that's T. Effector prevents CDA T cell depletion and I always thought about you know the F. C regions is mainly impacting NK cells is there.

I just wanted something that I'm missing there or something that you can help educate me on and in regards to T cells NFC reset.

Receptors.

Sure and yeah. Thank you Ronnie and I'll relate to that business front, and then Ron can take E S.

Unknown Executive: Sure, yeah, thank you, Rennie. I'll relate to the business front, and then Iran can take the FCNNK relationship.

And NK.

And our relationship.

So first you know.

Unknown Executive: So first, you know, Com 902 was developed at Comfigen in order to ensure that we extract the full potential of Com 701. So we're still on this path, and we want to make sure that we remain competitive on this front and that we remain flexible, owning the two arms of this denum axis.

And I know 2 was developed and and at <unk> in order to ensure that we extract the full potential of <unk> 701. So we're still on this path and we want to and make sure that we remain competitive and these front end and we remain flexible owning the 2 arms of this day and denim X.

And and as you know we just started day recently the comps of non income 902 study.

Unknown Executive: And as you know, we just started the Com71, Com902 study. Having said that, we're obviously open to discussing collaborative arrangements. This should allow us to continue to extract the potential of Com701 and to generate some differentiation for our pipeline. So we're open to discussing collaborative arrangements in the meantime. It will allow us to keep what we need for our own pipeline.

Having said that well obviously open to discuss a collaborative arrangement. This should allow us to continue its chuck the potential of 701.

And to generate some differentiation.

And for our pipelines, so we're open to discussing and.

And collaborative arrangements spending it will allow us to keep what we need for our own pipeline.

Got it.

Unknown Executive: I'll do it and then just Yeah, so about the role of FC. So there are a few assumptions why preclinically people think that TIGIT is superior when it has FC binding. I would say maybe the leading one indeed relates in a way to enhancing NK activity. So when you use the antibody, which has the capability to bind FC receptors, you enhance a few mechanisms that enhance the end of the depletion of the cells which carry the target, digit, in this case. NK activation is a major one, especially in mice. By the way, in the human tumor macroenvironment, you can see less NK than in mice, but also other mechanisms.

And then just.

Yes, so about the role of FC So and there.

A few assumptions.

And <unk> white preclinical if people think that <unk> is superior and we need to have the FC binding I will tell you and maybe the leading 1 and this relates in a way to enhance and NK activity. So when you use the antibody which have.

<unk> ability to bind FC receptors and enhance few mechanism that and hence and then of the day.

Depletion.

Tell us which clearly.

Targets digital in this case.

And <unk> activation is a major 1, especially in <unk> by the way and tumor human tumor microenvironment, you can see less indicate that in mice, but also other mechanisms and people again. Some claim that you can get the depletion of digit positive sales and since digitize.

Unknown Executive: And people, again, some claim that you can get the depletion of digitized high expression on regulatory T cells, this is desirable. However, TIGT also has high and overlapping expression on the CDAT cells, the same cells you want to unleash from the TGIT inhibitory effect. And if you're going to deplete anything, you have carried the risk also of depleting CDAT cells in addition to TREGs. And that's why we and others chose to focus on a non-fc binder to avoid the risk of depletion of the effect of CDAT cells due to enhancement of NK activity or other mechanisms of T-cell depletion inside your macroenviron. Did this answer your question?

<unk> expression and regulatory T cells. This is desirable however, digitize also high and overlapping expression on the CDA T cells. The same sales do you want to unleash from the digit inhibitory effect and if youre going to the price anything you had carried the risk also of depleting.

<unk> sales in addition.

Of the 6 and Thats, why we and others chose to focus and our non FC and binder to avoid the risk of depletion of effector T cells due to enhancement of NK activity or others and mechanisms of the test.

T cell depletion and Sergio macro environments.

This answer your question.

Yes that does.

Unknown Executive: Yep, that does. Thanks for the clarification. I guess just as a follow-up, with 902, we're expecting data from the monotherapy in the fourth quarter, and you've already started the combination study. What is the recommended dose for 902, or have you started at kind of the low end of the range when combined with 701 and our escalation?

<unk> clarification, and I guess, just as a follow up with 9 O..2 we're expecting the data from the monotherapy and in the fourth quarter.

And you've already started the combination study, which what is the recommended dose for 902 or have you started at kind of the low end of the range when combining with 701 and are escalating.

Yes, and let me. Thank you very much for your question.

Unknown Executive: Yeah, Remy, thank you very much for your question. Yes, we did start at the low end of the range for Com902 during this escalation. The disclosure will identify what the recommended dues for expansion for Com902 are.

Yes, we did start at the low end of the range for <unk> 902 during dose escalation.

B and the disclosure will identify what the recommended dose for expansion for <unk>.

Sorry, Henry and I, just want to make sure so and the fourth and the fourth quarter, we'll know if that's correct.

Unknown Executive: Sorry, Henry, I just want to make sure. So in the fourth quarter, we'll know what the record is. Gotcha. Yes. So the decision will be in the fourth quarter.

Got you, yes, some of the disclosure and the fourth quarter and that day I mentioned in our prepared remarks.

Unknown Executive: I'm not mentioned in that prepared. Got it. Okay. Thank you very much for taking the question.

Got it okay. Thank you very much for taking the questions.

Operator: The next question is from Astica, Gunawandana of Druis Securities. Please go ahead.

The next question is from Azteca, Kona wind and Uh Huh.

<unk> grew its securities. Please go ahead.

Hi, guys. Thanks for taking my questions.

Asthika Sarith Goonewardene: Hi, guys. Thanks for taking my questions. So, Anath you mentioned the cutoffs that she's from PBRL2 and PBRG expressionist selection criteria for some of the expansion cohorts. Can you tell us what the level of expression you're looking for for inclusion? And can you maybe just clarify for me, please, which studies are going to be applying this inclusion criteria? We're still studying it.

So and that you mentioned.

About the cutoffs.

PDL, 2 and especially net.

Electrical and criteria for some of the expansion cohorts can you.

And tell us what was the level of expression, you're looking for for inclusion and can you maybe just clarify for me, please which studies are going to be applying this inclusion criteria.

So we're still studying it we're following some sales we are following patients.

Unknown Executive: We're following samples. We're following patients' correlation to response. And this is exactly the goal of what we are trying to do to define at this stage retrospectively, which is the expression level cutoff, which could be percentages of PVRG in the tumor environment. It could be PVRL2 on tumor cells, on myeluit cells.

Unknown Executive: I mean, as others have shown for other bar markers. So we're looking at all of it, and it correlates. into response and, of course, looking for the right cutoff. So this is yet to be defined, and it will be defined based on data and correlation. Got it. And so, um, I think on our last call you mentioned that you might be looking to present some more of the biomarker data, perhaps at a conference later in 2021. Are you still untrusting for that?

Correlation to response.

And this is exactly the golar and what we are trying to do to define and this stage retrospectively.

<unk> is the expression level cutoff, which could be percentages of <unk> and the tumor environment it could be fever too.

And on tumor cells and <unk>.

Fluid sales I mean as others have shown for other biomarkers. So we're looking with all of its correlating to response and of course looking for the right cutoff. So this is yet to be defined that it will be defined based on data and correlations.

Got it and then and.

So.

I think on our last call.

Yes.

And you might have mentioned that you might be looking to present, some more of the biomarker data perhaps at a conference later in 2020.1.

And I still on track for that all of it and it's something we should expect more in 2020.2.

Unknown Executive: Or is this something we should expect more of in 2022? We didn't disclose when exactly we'll present the data. I can only comment that we are actively and aggressively pursuing sample acquisition and correlation, and then we'll present the data in the future. Ideally, we'd like to present it at a scientific conference, but we still didn't disclose when. Got right, okay. And then maybe just to tag on to Rennie's question about this dev, but maybe a person could give the other angle.

We didn't disclose when exactly we will present, the data and only comment that we are.

Actively and aggressively pursuing sample acquisition and correlation and then they will present the data and the future ideally, we would like to presented Phoenix and difficult for incest with still didn't disclose.

When.

Alright, okay.

And then maybe just.

Tiger.

Tag onto Randy's question about.

But maybe a personal and the other angle.

Unknown Executive: So given that Bristol may have acquired an asset that could have maybe some activity on Pyrgyzzi through their eugenics by specific antibody deal, I just want to get an idea of how involved and committed they are to doing the kind of data exploration with you, or it's just something that you are controlling.

And given that.

Given that Bristol may have acquired and I.

That could have maybe 700, and some activity and breakthrough ingenious bispecific antibody deal.

And I'll give an idea of how.

And committed they are to doing the kind of.

Data exploration with you or is it something that you are controlling.

So there's a few things and indeed.

Unknown Executive: So, so few things. Indeed, this licensing involved tidied by specific. The identity of the second arm is not known, and it could be various other targets. So just to make sure that it is recognized as a product opportunity, a separate product opportunity than TIGs. Having said that, I think it is pointing to the interest, increased interest, of BMS in the TIG space, and that's the only thing that I say on behalf of BMS, because obviously that's their decision-making and priorities.

And this and licensing involved and teaching Bispecific and.

And then.

And bulk density of the second.

Is not known and it could be.

Very odd.

The target.

And so just to make sure that it is a recognized and then.

And the product opportunity a separate product opportunities and painting, having said.

And.

I think there is point paying 2 day interest and increased interest of the BMS and theyre in the ticket space and that's the only thing that I've found that would be helpful and BMS, because obviously, that's there and.

They're in decision, making and priorities.

And I will tell you that and you know and protecting the public domain BMS is doing studies with their own T. J and that is part of our study says well, but they are.

Unknown Executive: And I will tell you that, and you know, it's a fact that the public domain, BMS, is doing studies with their own TIGs, that is part of our studies as well, but they are having studies conducted on their own with their own TIGs. And they are committed to collaboration with us. We're sponsoring, obviously, the study, the Triptet Study, and pushing forward, and that's critical for us because it's a leading program in our pipeline, and we want to push it forward and have the leadership on the execution. But at the end of the day, there are investments in this program, on the digit, and no competition with the bicycle.

And having studied.

<unk> and their own with their own ticket.

And they are committed to.

Collaboration with Us and we're sponsoring and go obviously the study the <unk> study and pushing forward and that's critical for us because it can be comfortable and 1 is a leading programming and our pipeline and we want to.

And to push it forward and to have the.

And then.

The leadership on the execution.

But at the end of the day, there is investments and big program on the T J, <unk> and and and no no competition with a with a bispecific.

Unknown Executive: Got it. Thanks for coming in so good for my question, guys. The next question is from Dana Graybosch of SVB Learing. Please go ahead.

Thanks for taking my question guys.

The next question is from Dana Gray box of SBB Leerink. Please go ahead.

Daina Michelle Graybosch: Hi, I have a couple questions for you. First, on the triplet, I wonder if you can clarify what cohorts you're starting to enroll in the expansion. I think initially you had planned to enroll a tumor agnostic based on PVRL2 expression. So with Aran's comments just now, I wonder if you would be ready to start to enroll that patient's set yet. And so could you just clarify exactly which ones you start enrolling in if you'll bring on other cohorts over time? And then, with that, how much is the BMS involved in making these clinical development strategic decisions?

Hi, a couple questions for me first on the triplet and Wonder if you can clarify.

What cohort and Youre, starting to enroll and the expansion.

And Michelle.

You had plans to enroll a tumor agnostic based on P. B R. L..2 expression.

And with Iran comments, just now I wonder if he wouldn't be ready to start to enroll that patient set yet.

And so could you just clarify exactly which ones you start to enroll and you'll bring on other cohorts over time.

Schilling with that how much is a BMS involved in making these clinical development and strategic decision.

Unknown Executive: Yeah, Dina, thank you very much for your question. For the second part of the question, I'll defer to Anat to answer.

Yes. Thank you very much for your question. So for the second part of the question and I'll defer to you.

So I'm not too to answer for the first part of the question.

Unknown Executive: For the first part of the question, as you recall, for the expansion cohort, we have a cohort of patients with ovarian cancer. So that includes patients with phallopian cancer, that includes patients with primaloporotin cancer, that includes patients with primal periturnal cancer, and patients with epithelial ovarian cancer. The other cohort of patients in the expansion cohort are patients with relapsed endometrial cancer. So those cohorts open through enrollment, and those are the ones that we're currently exploring right now.

As you recall.

<unk> for the expansion cohorts, we have and cohorts of patients squeeze.

And cancer. So that includes patients with <unk> cancer that includes patients who friendly per generic jensen and patients with typically and ovarian cancer.

The other cohort of patients and the expansion cohort of patients.

And so with relapsed endometrial cancer, and so those cohorts and open to enrollment and do.

So the ones that we're currently exploring right now.

And Dana for your question about cash decision, making and.

Unknown Executive: And Dana, for your question about decision-making, We're making joint decisions with Bristol Malesquib. Obviously, we are leading this program. We're looking at every bit and piece in this program, but we're making decisions in good collaboration with Bristol Merskweb. We have a very good relationship. We keep an open line of communication, and we make decisions that are good for the program together. So this is how this collaboration works. being conducted

We're making good joined decisions with the Bristol Myers Squibb, obviously, we're leading this program and we're looking at every day and beaten piece and the and this program, but we're making decisions and in good collaboration with the Bristol Myers Squibb, we have very good relationships and.

And we keep an open line of communication and we're making decisions that are good for the program together. So this is how the scrubbers and he's a bingo and conducted.

And and then so I understand that you have ovarian and endometrial and open if I recall correctly.

Unknown Executive: And then, so I understand that you have ovarian and endometra open. If I recall correctly, you had planned other cohorts in the expansion. Will those follow, or is this reflecting some strategic change as you've seen the dose escalation data? Oh, no, no, no, there's no strategic change. Oh, sorry, Henry, do you want to be

Thank you had plans other cohort and the expansion all of those follow or is this reflecting.

13th of change as you've seen the dose escalation data.

Oh, no no no and there is no strategic change Oh, sorry, and Henry you want to take it.

Unknown Executive: No, go ahead, and I can clarify. No, there is no strategic change. As we stated on, as Henry said, in the ovary, we decided that due to the low response rate and the historical data that we have, we can continue to relate to historical data and will not do the randomization. We will add the head and neck as an inflamed tumor type to this, and we'll continue with the endometrial that was planned in advance. There are three changes.

No go ahead, and they can close no theres no.

No strategic change and as we stated and as Henry said, even do vary and we decided that due to the low response rate and and the historical data that we have we can continue to relate to to historical data and we will not do the randomization.

We'll add to the head and neck and inflamed.

Correct per type and today's and we'll continue with that we then dmitry and that was planned in advance. So these are and 3 changes with respect to the basket arm Deca Deca and that we plan to do this is still in planning what we were saying is that.

Unknown Executive: With respect to the basket arm that we planned to do, this is still in planning. What we were saying is that we're continuing to collect data that will correlate the PBRID pathway with the treatment response, and when we will have data that can allow us to define the cutoff for the first. For enrollment, we will start this basket arm, so there's no changing plans on this front. Perfect, that's very helpful. Thank you. Okay. And then there was one more for me on Tidit.

And continuing to collect data.

And that will correlate continue to correlate the <unk> pathway with day treatment response.

And when we will have the data that can allow us to define.

And the cutoff for enrollment we will start to this basket.

So.

And there is no change and plan from these firms.

Perfect. That's very helpful. Thank you, Okay and then on.

And then 1 more for me on page 8 I think that you guys. Starting back in 2009 have had your hands and a lot of difference to the antibody.

Unknown Executive: I think that you guys, starting back in 2009, have had your hands on a lot of different Tidgit antibodies. I think you had a whole panel in your initial paper, and of course, you work with the BMS Kijit as well as Com 902. And you note that the potential differentiating element of KOM 902 is a very high affinity. As you've worked with all these different Kijit antibodies, have you noted any other potential differentiating elements? And I guess I'm asking the question, I wonder, as we see your dose escalation, data, you'll be the first SC-Type silent hide.

Thank you.

You had a whole panel and your initial.

And so paper.

And of course you.

Work with the Dms changes as well as <unk> and <unk>.

And you note the potential differentiating element of continental deals with very high affinity and.

The work of all of these different antibody have you noted any other potential differentiating allomap.

And I guess Oh.

And I am asking the question I Wonder as we see your dose escalation data you'll be the first and that's the type of silent and do it and if and you should expect anything pre clinically to show a clinically and what might we look for as we see this that and the second half our interest recorded.

Gordon.

Unknown Executive: And if you expect anything pre-clinical to show up clinically, and what might we look for as we see this data in the second half or in the fourth quarter? Yes, we did a comparison of common 902 compared to most of the leading tigid antibodies. What we saw was that indeed common 902 has a higher affinity, higher binding to effect or T cells than as good or better activity in actual functional essays. I don't believe we saw any major differences between the other antibodies, but yes, Komeno2 is a bit superior in that regard.

And we did a comparison of covenant no 2 compared to most of the leading digital antibodies worked through so that indeed commented to us.

Higher affinity higher binding to fix those T cells, and as good or better activity and actual functional assay.

No.

I.

And if we saw any day.

Major differences between the other antibodies, but <unk> is a bit superior and that in this regard.

I would say that is difficult to say at this stage if any of this will translate to clinical observations, yes, potentially in terms of dosing and PK.

Unknown Executive: I would say that it's difficult to say at this stage if any of this will translate to clinical observations. Yes, potentially in terms of dosing and PK, but in terms of efficacy, it would be difficult to say if there is going to be any difference from the other digit assets that we've seen so far.

In terms of efficacy to be difficult.

And I don't believe there was any going to be any different from the other.

And just that we've seen until now.

Okay. Thank you.

Unknown Executive: Okay, thank you.

The next question is from Stephen Willey of Stifel. Please go ahead.

Operator: The next question is from Stephen Willie of Staisal. Please go ahead.

Yes, good morning.

Stephen Douglas Willey: Yeah, good morning. Thanks for taking the questions. Maybe just to follow up on the Bristol collaborative question, so is your ability to, I guess, pursue a triplet regimen, whether it's, I guess, either with or without Nivo, using your tigit, Com 902. Is that somehow constrained by the existing Bristol collaboration? I'm just kind of curious if you see an interesting signal emerging out of the triplet. How quickly can you start to think about swapping in 902 for the Bristol Pidget?

And to serve taking the questions.

Maybe just to follow up on the Bristol collaborative question is so your ability to pursue.

Triplet regimen, and whether it's I guess, either with or without <unk>.

Using your till Ya Com 902 is that.

Somehow constrained by the existing Bristol collaboration and I'm, just kind of curious.

And do you see and interesting signal emerging out of the triplet.

How quickly can you start to think about swapping and 902 for the Bristol could you.

So come and I know too.

Unknown Executive: So Com902 is totally unrelated to the Bristol collaboration. This is an independent and independent asset. Discussing the triplet, it's a little bit more complicated because, under the collaboration that we have with Bristol-Mess Quib, there is an exclusivity for Com-7-1 plus T-D-1 inhibitors for a fixed period of time, so we will need to take this into consideration. But Com-902 is totally unrelated to the collaboration with

2 is totally unrelated to the Bristol collaboration and this is an independent and.

And independent asset.

Okay.

Discussing the triple net.

And it's a little bit more complicated because the day under the collaboration that we have with Bristol Myers Squibb.

And exclusivity for comfort and 1 for.

PD 1 inhibitors for for a fixed period of time, so we really need to take this into consideration, but to continental's, we've totally unrelated to the collaboration with Bristol Myers Squibb.

Okay. So I guess your ability to pursue a triplet.

Unknown Executive: Okay, so I guess your ability to pursue a triplet that would include Com 701, Com 902, and a PD1 inhibitor would overlap with the fact that you have exclusivity to Nivo tethered to Com 701. Is that the correct way to do it?

Gary I would include Com 701, common item, 2 and a PD 1 inhibitor.

Good overlap with the fact that you have exclusivity to levo.

Comp 701 is that the correct way.

Unknown Executive: There are some ways for us to do that with marketed PD1 inhibitors. So that could be done. Okay.

There are some and there are some ways to do it with debt and with marketed the PD 1.

Triplet and inhibitory so that could be done.

Okay, and then I guess.

Unknown Executive: And then I guess, you know, you've talked on the biomarker side about doing this, I guess, retrospective look, whether it's a function of evaluating PBRIG expression in the tumor microenvironments and or PVRL2, I guess, on various immune cell subsets. I know that Roche had kind of previously commented, I think, in one of their teacher presentations that they didn't believe that, you know, PDR, which is the tidaligants, wasn't a great surrogate biomarker in the sense that it's kind of broadly expressed on a variety of different L types.

You talked on the biomarker side.

About doing this I guess retrospective look whether it's.

Function of evaluating <unk> expression and the tumor microenvironment.

<unk>.

And or <unk>, 2 I guess on various immune cell subsets I know that Roche had kind of previously commented I think and there.

And there.

And there.

And 1 of their tissue presentations that they didn't believe that.

<unk>, which is the.

And just.

And July against wasn't a great surrogate biomarker and the sense that it's kind of broadly expressed on a variety of different cell types.

Unknown Executive: Is PVRL2 akin to PVR in the sense that it has that same broad pattern of expression? So PVR and PVR, 2, in a way, have a similar pattern of expression in terms of that they also have expression in normal tissues, but both of them are culating to your macroenvironment and are not; in some tumors, you can find higher PBR2 and some higher PVR. I think that for PVR, actually, there's also some publication, maybe due to its role also in enhancing other mechanisms for tumor-in-based Nive, etc.

As PBR 2.

<unk> 2 <unk> and in the sense that it has that same broad pattern of expression.

I wanted to go.

<unk> and pivotal.

In a way have a similar pattern, especially in terms of do have especially and also normal tissues, but both of them are regulating tumor micro environment and.

And I looked and then some tumor you can find and hire people to and somehow <unk> I think that for PV, Oh actually Theres also some.

Patient may be due to its role also and enhancing the other.

And the mechanisms for tumor and invasive et cetera. It was published also in addition to agenda in relation to other trials those specific procedures that it correlates with worst prognosis. So yes with genentech have shown for <unk> that and non small cell lung cancer that didn't seem to have.

Unknown Executive: It was published also, in addition to genetic data, in relation to other trials, not specifically TIGs, that it correlates with worse prognosis. So yes, what Janentech has shown for PVR, that in non-smolecular Salon cancer, they didn't seem to have a correlation to use it as a bar marker. It doesn't suggest a lot about PVRL2, and we're validating it ourselves. So we don't know, but there are reasons to think why PVRL2 will be different than PVR. Okay, that's very helpful. Thanks for taking the questions.

Publication to use it as a biomarker and it doesn't suggest a lot about <unk>, 2 and it will need to and we're ready to get ourselves. So we don't know, but there are reasons to think quite pivotal tool will be different and video.

Okay. That's very helpful. Thanks for taking the questions.

The next question is from Tony Butler of Roth Capital. Please go ahead.

Operator: The next question is from Tony Butler of Roth Capital. Please go ahead.

Thanks very much.

Unknown Executive: Thanks very much. Three brief questions, and let me just state them because they all relate to one another.

And 3 brief questions and let me just state them because they all relate to 1 another.

Unknown Executive: in Clintriles.gov on the triple UH,

And Clint Charles Dot Gov on the Triple.

Yeah.

Unknown Executive: You've made some comments today regarding the basket cohort or that of cohort three. So am I to understand that the notion of what defines high expression PBRL2 is not yet known? That's question one. And if it is, any color would be great.

Currently and comments today regarding the basket cohorts that have.

Cohort 3.

So am I to understand yet the notion of what defines high expression <unk> too.

Unknown Executive: Number two,

Not yet known that's question 1 and if it is any color would be.

You've made some maturities.

Does <unk> 2 high correlate with PDL 1.

Unknown Executive: Does PVRL is too high? correlate with PDO1 being

Unknown Executive: being positive or negative? And I guess a similar question may be, are there tumors that are actually negative? with respect to both markers. And then thirdly, and this goes back to the SITSE presentation, which was quite helpful, but, Is there? This is a question that I think I hear a lot.

Being positive or negative and I guess.

Similar question may be or their tumors that are actually net negative.

With respect to both markers.

And then thirdly.

Great.

And this goes back to the <unk> presentation, which which which was quite helpful. But.

Is there.

And and this is a question that I think I hear a lot and it's.

Unknown Executive: And it's never clear to me if there's a true correlation, but through peripheral, Effector Memory, CD8s, and even NKT. Are they actually able to be found in the periphery equal to that which is found intratumarily? That is to say, is there a direct correlation such that you don't really need the biopsy or may not need it in the future? Thank you very much.

Never clear to me.

If theres a true correlation.

But.

<unk> peripheral.

Sector memory CDA.

And even and K T.

Are they actual actually able to be found in the periphery equal to that of which is found.

Intra tumor that is to say is there a direct correlation such that you don't really need the biopsy or may not needed and the future. Thank.

Okay.

So for the first question, so what is high fever and too.

Unknown Executive: So for the first question, what is high PVRL2? So this is exactly what we're looking at. To define the cutoff, is it an age score of 100 or 200 or a percentage of immune cells expressing PVR2 or other denominators axis members? What is the cutoff that determines and correlates best with response? So this will be determined retrospectively and then tested clinically prospectively. This is for the question of what high PVRL2 is.

So this is exactly what we're looking at to define what is the cutoff is it's an H score of 100 or 200 or or or.

Percentage of immune cells expressing <unk>.

The non access and members.

What is the cutoff that determines and correlates best with response. So this will be determined retrospectively and then tested clinically prospectively.

This is for the question of what is highly volatile and about <unk> 2 versus PD L..1. So this is a very important question and fever, 2 and contrast to PDL 1 is not.

Unknown Executive: About PVRL2 versus PDL1, so this is a very important question, and PVRL2 in contrast to PDL1 is not induced by inflammation, and therefore you can find high PVL2 in PD1 positive, but also in PDL1 negative tumotypes. And that's why we pre-identified, for example, ovarian and endometrial, and other tumotypes, for which, Listen The response to PD1 is not very high, but PVRL2, and in general, the PVRG pathway is very dominant there, and that's why we're trying to attack these kinds of tumotypes.

Very good supply and inflammation and.

And therefore, we couldn't find high fever, too and PDL, 1 positive, but also and PDL 1 negative tumor types and that's why we've pre identified for example, and ovarian and endometrial and and other tumor types, which.

This is some of them the expression of PDL, 1 is not very high the response.

Responding to your 1 is not very high but delivered to and in general the Viva energy pathways very dominant there and Thats why were trying to.

Dr. These kind of tumor types and above.

Unknown Executive: About effectual memory and NKT, So the correlation between a factor memory cells proliferating in the periphery and the specific effect of clones proliferating inside your macro environment exists. I wouldn't say that we and the entire scientific community are in a place that we can rely solely on peripheral measurements, and that's why we have paired biopsies in the expansion phase of our trials to look inside your microenvironment, but there is a correlation, and in many cases you see specific genes that are proliferating peripherally, and they're also expanded into the chemical environment.

And the Fictile memory, and NK and T.

So.

And the correlation between effector memory sales proliferating and position.

And specific effector clones, proliferating insightful and macro environment exists.

Wouldn't say that we and the entire scientific community is and it plays that we can rely solely on the on the terrific.

<unk> and Thats, why we have paired biopsies and the expansion course of our trials to look.

Peripheral 2 and macro environment, but there is a correlation and and <unk>.

Many cases youll see a specific loans.

Proliferating.

Early and there are also expenses that you all macro environment and you can find a bit less of those and tumor microenvironment, but the other studies to show that through and the our presence there.

Unknown Executive: NKT can find a bit less of those in the TURMACO environment, but there are studies to show that when they are present, they are mostly correlated with good prognosis. The correlation between peripheral and intertumoral expansion of NKT, I don't believe it was investigated much. I'm not aware of any studies to correlate that, but just to mention, in addition to what it reflects about the tumor's warm environment, this kind of intense proliferation also supports that the drug Com 7-1 is active. And it does, again, this is preliminary data, but it suggests that it does what you think it should do.

Insightful correlated to it.

Mostly 2 good prognosis and the correlation with and peripheral and intra tumoral expansion of indicate D. I don't believe it was investigated much of it is I'm not aware of any studies to cover that but just mentioned in addition to what's it reflects about the tumor microenvironment this kind of and hence proliferation.

And also <unk>.

Thoughts that the drug <unk> is active and.

And it does again this is preliminary data, but what it suggests that it does what you think it should do.

Unknown Executive: It's enhanced immune cell activity, enhanced pterfone gamma. So this is another surrogate marker for drug activity in addition to the direct correlation to what is happening in your microenvironment. Maybe just to add, this is why, in many cases, also for other drugs, when you, especially in early trials, with heavily-promoted patients, you can find these kind of pharmacodynamic changes in the periphery, and they're not always correlated to response. Thank you.

And hence immune sales activity and hence their phone number so it isn't and other surrogate marker for drug activity. In addition to the direct.

Correlation is happening and to a macro environments.

And maybe just to add that this is why it may be in many cases also for other drugs. When you associated notice right and this was heavily pretreated patients you can find pharmacopeia. These kind of pharmacodynamic changes and the tumor in the periphery and they're not always correlated to response.

Thank you 1 follow up if I may though this is back to the second part of PV oral too.

Unknown Executive: One follow-up, if I may, though: this is back to the second part of PBRL2 and PDO1. But if you were able, post-therapy, if you actually drove PDL1 expression, even in PDL1 minus tumors, when you look at a tumor initially having been treated with something else, that is, in fact, a relapse or relapse patient or a resistant patient, a PDL1 minus patient that had actually been treated with Tom 701, for example, would drive PDL1 expression.

And PDL, 1, but if you were April.

Post therapy.

If in fact.

And you actually drive PD lone expression, even and PDL, 1 and minus.

Tumors when you look at a tumor initially.

Having been treated with something else, but it's in fact.

Relapse.

And relapsed patient or are resistant patient PDL.

PDL, 1 minus patient and in fact and treated with <unk> 701 for example.

And would drive PDL.

1 question is that true.

For the per diem.

Unknown Executive: Is that true? It could happen. If, if indeed, as mentioned before, the biology of PVLG and PVL2, if we are able to drive and expand this into a macro environment, then potentially, it will increase the inflammatory status of the Tio macroenvironment, and then potentially, Pidl1 could be upregulated as well as a marker to indicate this. And again, this is one of the reasons PIDL1 is a biomarker for speedyton activity because Exactly, and thank you very much.

And if indeed and as mentioned before the biology of fever, and pivoted to and if we will be able to drive and expenses and to a macro environment.

And then potentially will increase and inflammatory status of tumor environment, and then potentially good day.

And 1 could be up regulated as.

And as well as a marker to indicate and again. This is 1 of the reasons PDL, 1 as a biomarker with freedom and activity, but it's reflective of the team and I was more inflamed and has more to citizen side.

Exactly and thank you very much.

This concludes.

Unknown Executive: This concludes our Q&A session. I will now turn the call back to Confugge President and CEO, Dr. Cohen-Diog. Would you like to make your concluding statement?

Alright.

Our Q&A session and I will now turn the call back to <unk>, President and CEO, Dr. Cohen <unk>.

And I would you like to make your concluding statement.

Thank you.

To conclude we are.

Unknown Executive: To conclude, we're excited about what's to come and are proud of our remarkable progress. As always, we will seek to continue to drive the science to uncover important insights into the biology and mechanism of our candidates. And we remain uniquely positioned to unlock the promise of these potentially foundational immunotherapy candidates in the clinic for patient populations typically considered unresponsive to current treatment. Thank you for joining us today and for your continued support. Stay safe and healthy.

Excited about what's to come and are proud of our remarkable progress.

Always we will seek to continue to drive the science to uncover and important insights into the biology and mechanism with our candidate and.

And we remain uniquely positioned to unlock the promise of these potentially foundational immunotherapy candidate and the clinic.

Patient population typically.

Unresponsive to current treatment.

Thank you for joining us today and your continued support.

Safe and healthy.

Operator: Thank you. This concludes Confugent Limited's Second Quarter 2021 Financial Results Conference Call. Thank you for your participation. You may go ahead and disconnect.

Thank you. This concludes coffee and limited second quarter 2021 financial results Conference call. Thank you for your participation you May go ahead and disconnect.

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[music].