Q4 2021 Jounce Therapeutics Inc Earnings Call
[music].
Good morning, ladies and gentlemen, and welcome to the Johnson European export quarter, and full year 2021 earnings conference call.
At this time all participants are in a listen only mode.
Later, we will conduct a question and answer session and instructions will follow at that time.
As a reminder, this conference is being recorded at the company's request.
I will now turn the call over to your host Eric Glover with Jones Therapeutics. Please go ahead.
Yeah.
Thank you operator this is airtel vice president of Investor Relations at Jounce Therapeutics, Good morning, and welcome to the Jounce Therapeutics fourth quarter and full year 2021 financial results Conference call.
This morning, we issued a press release, which outlines the topics that we will plan to discuss today. The release is available in the investors and media section of our website at Www Dot Jounce, TX dot com speak.
Speaking on today's call will be our CEO and president Dr. Richard Murray, who will review our pipeline progress and key milestones followed by our CMO, Dr. Beth <unk>, who will provide an update on our clinical activities are.
Our CFO Dr. Dimitri Peter Shine.
We will then discuss our discovery programs and lastly.
Our CFO Kim Drapkin will review, our fourth quarter and year end financial results. We will then open the call for your questions before we begin I would like to remind everyone that today's discussion will include statements about our future expectations plans and prospects that constitute forward looking statements.
For the purposes of the Safe Harbor provisions under the private Securities Litigation Reform Act of 1095 actual results may differ materially from those indicated by these forward looking statements as a result of various important factors, including the risk factors discussed in our SEC filings.
In addition, any forward looking statements represent our views only as of today March 'twenty.
2022, and should not be relied upon as representing our views of any subsequent date.
While we may elect to update these forward looking statements at some point in the future. We specifically disclaim any obligation to do so if our views change with that I'll now turn the call over to rich.
Thanks, Eric Good morning, and thank you for joining today.
2021, with an important year of remarkable execution for us a challenge as we advanced our two wholly owned proof of concept stage clinical programs.
<unk> 864 and <unk>.
Advance our fifth internally derived development candidate into IND, enabling studies and continue to drive exciting new programs from our discovery engine.
We anticipate 2020 to be a pivotal year as we look to report clinical data from our Nate and select and advance our discovery pipeline.
Our teams continue to stay focused on making a significant positive impact on the lives of cancer patients.
Especially in the setting where patients have few therapeutic options.
On that particular note.
As the use of PD, one inhibitors continues to grow and expand into earlier lines of therapy, including non metastatic settings.
<unk> and scope of the PD, one inhibitor resistant market continues to grow.
While recognizing the important impact of PD, one inhibitors more patients are resistant to the therapy benefit from.
In many tumor settings only next option for these patients is either chemotherapy does not particularly effective foreign experimental therapy.
We believe PD one inhibitor resistance.
And one of the most challenging problems as well as opportunities in <unk>.
Research.
Scientific data continues to Mount that specific immune cell sites myeloid cells. As an example may be key to the mechanisms a PD one inhibitor resistance.
This highlights the importance of our translational science platform.
Whereby we are able to interrogate and deconstruct the complexity of all the immune cell types and human tumors, allowing for a systematic way to prioritize discrete cell type associated mechanisms.
As such our efforts into the myeloid system have led us to the low receptor or Iot bandwidth.
With low <unk> in the lead.
Gtx 80, 64 lots the function of low <unk> or Iot for on tumor associated macrophages and other myeloid cells and aims to convert immuno suppressive macrophages.
Anti tumor state and initiate T cell responses.
We believe it may create a bridge between the innate and adaptive immune systems.
This is something T cell checkpoint inhibitors cannot do alone.
In science tells US It may result in the potential to reverse PD one inhibitor resistance.
We stay true to our initial scientific mission of investigation discovery and development of therapies that target different cell types in the tumor microenvironment.
In our growing pipeline reflects this differentiated approach.
We believe this is the best way to bring a positive impact to the particular challenges that cancer patients space.
As we reflect on the highlights of 2021.
We began the year with the initiation of the trial of Gtx, 80, 64, and dose escalation as monotherapy and in combination with our PD one inhibitor some of Allomap for penni.
In advanced solid tumors.
In April we presented preclinical data at ACR.
Supported our thesis that <unk> 864 has the potential to reverse PD one inhibitor resistance.
In June at <unk>, our teams presented trials in progress posters.
To date as well as our phase III select clinical trial.
Also in June we earned our first milestone payment of $25 million under the Gilead license agreement with the FDA clearance of the IND GFS 18, 11, formerly <unk> 11.
An anti <unk> antibody.
We also announced continued pipeline expansion with the addition of two new programs targeting low before.
<unk> RMB, one at our R&D day.
In October we announced the completion of both the mono and combo dose escalation portions of the study.
We initiated the mono and combo expansion cohorts at the recommended phase II dose of Gtx 1064.
Currently there are eight phase III tumor specific expansion cohorts ongoing.
<unk> monotherapy and <unk> combination therapy cohort that makeup DNA trial.
It's our intention to announce a meaningful body of data from the <unk> trial this year.
We've also continued enrollment in our randomized phase two proof of concept trial of <unk> or <unk> in combination with <unk>.
The select trial is a randomized phase II study in non small cell lung cancer with a stringent biomarker selection of patients that we believe to be the most appropriate for both the <unk> and PD one inhibitor mechanisms.
It is a direct result from learnings from our clinical trials and we believe best position Io naive patients.
We expect clinical data readout from the full trial in the second half of this year.
Our discovery team has advanced our new look before program now called Gtx 14, 84 into IND, enabling studies.
And we are targeting an IND submission for this program in 2023.
Our discovery engine continues to target the low receptor family and other myeloid based targets as well as creating additional opportunities from other immune cell types.
We're also excited by our new efforts to leverage our robust discovery of highly specific antibodies into the discovery and development of rationally designed by specific and multi specific antibody formats, which may ultimately further enhanced clinical benefit.
We ended 2021 and a strong financial position and are situated to fund <unk> past the proof of concept inflection points, Nate and select Wildcat.
While continuing our robust novel discovery efforts identifying and progressing new mechanisms.
2022 is expected to be an important year for <unk> and for the patients we hope to help.
We head into the year with the momentum of both the innate and select proof of concept trials and expect data from both trials this year.
I'll now turn the call over to Beth to provide our clinical pipeline update.
Thanks, Rich and good morning.
Im extremely pleased that the progress we have made in both our <unk> and select clinical trials in 2021, and I look forward to updating you as we continue to advance both trials this year.
Let's start with the <unk> trial of Gtx 80 64.
<unk> two inhibitor.
Last year, we completed the phase one dose escalation for both monotherapy and combination with <unk>.
Selected 700 milligrams as the recommended phase II dose and initiated the phase two expansion cohorts for both mono and combination treatment in seven different indications.
Each of the expansion cohorts is a Simon two stage design.
Once we enroll the first stage of the Simon two stage cohorts must meet pre specified response criteria before further expansion.
Once the pre specified criteria has been satisfied for an individual cohort enrollment of additional patients in the second stage of that cohort may commence.
The monotherapy cohort can expand to up to 47 patients in each of the combination cohorts can expand to up to 29 patients.
We selected seven different tumor types, starting with the biology of the <unk> and focusing on those that have a high percentage of immunosuppressive macrophages.
The next steps in our indication selection process, where an examination of the unmet need and evaluation of opportunities across three major groups of patients.
The first group is PD, one inhibitor naive patients who have tumors for which they are approved PD. One PDL, one inhibitors, where some patients achieved durable clinical benefit, but there is still much room for improvement.
Does that one thing Jay PX 864 in this setting which gives us the opportunity to treat frontline patients in combination with <unk> or approved PD, one inhibitors and we are starting with PDL, one positive frontline head and neck squamous cell carcinoma and eight.
The second group is PD, one inhibitor naive patients who have tumors for which there are no PD, one or PDL, one inhibitors approved because they have generally not demonstrated much efficacy to date.
If gtx 80, 64 can reverse this type of primary resistance a combination with a PD one inhibitor could make immunotherapy a therapeutic option in this area of high unmet need.
This also represents an opportunity for Gtx 80, 64, plus our PD, one inhibitor or penny due to the lack of approved PD one inhibitors and these tumors.
Tumor types in this group that are enrolling at an eight our third and fourth line platinum resistant ovarian cancer and two subtypes of sarcoma second to fourth line undifferentiated pleomorphic sarcoma and LIFO sarcoma.
The third group is patients who are PD, one inhibitor experienced and whose tumors are now PD one inhibitor resistant.
This represents a large and growing area of unmet need in which a drug that reversed as PD one inhibitor resistance could make a great difference for patients since chemotherapy is the predominant and not very effective standard of care.
Currently for <unk>, there are no approved PD, one or PDL one inhibitors in this patient population.
The opportunity to develop two wholly owned <unk> products Gtx at $8 64, and <unk> as a combination approach.
We opened four expansion cohorts in this group in second and third line cutaneous squamous cell carcinoma.
And third line non small cell lung cancer second and third line clear cell renal cell carcinoma, and second to fourth line Triple negative breast cancer. We have recently opened a new cohort in this patient group, adding second and third line PD, one inhibitor experienced head and neck cancer.
Addition of a PD, one inhibitor experienced head and neck cancer cohort will add valuable insights to our understanding of the tumor microenvironment and the role of <unk> 64 in both PD, one inhibitor nave and experienced patients with the same tumor type and will also address an area of high unmet need.
<unk>.
This PD one inhibitor resistant category of patients represents a growing and severe unmet need and opportunity for both of our antibodies in combination to continue to approval upon positive results and follows an initial clinical signal from the third party antibody.
Staying true to our focus on high unmet need and a Nate we have decided to close the triple negative breast cancer cohort for now.
Pace of enrolment in TN BC has been much slower than any other cohort and investigators have told us that they no longer have many patients who meet the eligibility criteria for Nate.
This is due to a change in the treatment paradigm cincinnatus started related to the unexpected withdrawal of to centric frontline accelerated approval in the U S and approval of <unk> in second and third line triple negative breast cancer.
With the addition of the PD, one inhibitor experienced head and neck cohort. We maintained four cohorts focused on PD, one inhibitor experienced patients with a high unmet need.
We have included all three categories of patients in our expansion cohorts to determine the best opportunities for <unk> 64 to make a difference for patients with cancer.
As part of the trial, we will be evaluating Pharmacodynamic biomarkers and will also be collecting data on archival and pretreatment tumor samples to identify potential predictive biomarkers.
The findings will help US guide further development and are an important part of Jones's philosophy of providing the right immunotherapy for the right patients.
We are pleased with the pace of enrollment and are on track to prepare a preliminary data from <unk> in 2022. Therefore, our intention is to obtain sufficient enrollment and clinical data prior to providing specific guidance on data timing in 2022.
We are frequently asked about the scope of data that we expect 2%. This year from our <unk> trial, our intention is to provide a robust meaningful and interpretable data package. This will include.
Complete phase, one monotherapy and combination dose escalation data, including the respective safety PK PD biomarker and preliminary efficacy data.
In addition, we expect to include safety and preliminary efficacy pharmacodynamic and potential predictive biomarker correlative data from at least the first stage of the Simon two stage for multiple phase two expansion cohorts, both on an individual cohort basis and in across cohort analysis.
Yes.
Now onto our other phase III programs, Oprah and the select trial, a randomized phase II proof of concept trial of both our Iqos agonist. We are studying <unk> in combination with <unk> compared to <unk> alone and approximately 75 biomarker selected patients with metastatic non small cell.
Lung cancer, who are PD, one inhibitor naive and have progressed on a platinum based chemotherapy regimen.
A key feature of this trial is the predictive biomarker selection of patients utilizing <unk> and AT&T gene signature that includes genes relevant to both PD one CD eight.
Iqos CD four T cell biology.
Only patients with a value above the biomarker thresholds are enrolled and the trial is powered to show the statistical superiority of <unk>, plus a PD one inhibitor <unk> versus <unk> alone.
As a reminder, the primary endpoint is the change from baseline in tumor size averaged over 918 weeks.
We chose this endpoint because we believe it may be a better predictor of overall survival than resist response criteria in early studies and because as a continuous variable. It provides the opportunity for statistical significance with a smaller number of patients than the categorical variables of resist.
It is also uniquely suited to immunotherapy and which durable tumor reductions can lead to long term clinical benefit.
We will provide more insight into interpretation of the primary endpoint as we get closer to data readout.
We will also be reporting secondary endpoints, including overall resist response rate progression free survival overall survival and duration of response to help with interpretation of the data in the context of more familiar endpoints.
A positive result in select May lead to biomarker directed development in multiple potential tumor types.
We look forward to reporting the clinical data from select and providing guidance on next steps for Volcker anticipate in the second half of 2022.
As many of you know select is enrolling in Russia and countries in eastern Europe , including Ukraine.
We have some active patients and sites in Ukraine and are in regular contact with our steady personnel and Ukraine are.
Thoughts are with the patients their families and those who provide their care as they navigate this tragic situation in the Ukraine.
Our first priority is to make sure that patients are able to receive their study treatment.
As of now we do not believe there will be an impact on timing of the select data readout, but there may be an impact on the data if patients are not able to complete all planned study visits.
We will continue to monitor the situation very closely.
I would like to take a moment to thank our valued investigators and most importantly, the patients who put their trust in our medicines to make a difference in their lives.
I would also like to thank our team at <unk> and their dedication to advancing these critical programs. We look forward to reporting on our continued progress this year.
With that I will now turn the call over to Dmitry to discuss our ongoing discovery efforts dmitry.
Thanks Beth.
We focus on the utilization of our translational science platform to address the problems that patients with cancer are facing today.
Namely resistance to T cell checkpoint inhibitor therapy.
We believe that our ability to dissect the tumor micro environment at the molecule level using immune cell type specific gene signatures will lead us to targets that may be important for overcoming resistance to checkpoint blockade.
The growing body of data points to suppressive myeloid cells, including tumor associated macrophages and their contribution to resistance to PD, one or <unk> directed therapies.
Gtx, 80, 64, which targets immune suppressive macrophages and other myeloid cells in the <unk> serves as an example of our patient centric biomarker driven approach in discovery and through development.
This approach is key to the value generating programs we are pursuing.
We are very excited about our discovery activities and have announced our most recent advancement having selected Gtx $14 84 is our newest development candidate.
IND, enabling studies are well underway and we hope to submit an IND next year.
Gtx $14 84 binds to and inhibits Lula are before <unk> three another little RB family member that is highly expressed on some of the key myeloid cells, including myeloid derived suppressor cells and <unk> dendritic cells, the orchestrate immune suppression.
In the Tms, including resistance to checkpoint inhibitors.
The <unk> target is distinct from other <unk> family members with respect to its ligand specificity as well as temporal and spatial pattern of expression on immune cells.
Therefore, we see this program as complementary to our ongoing efforts to target <unk> with Gtx 80 64.
Our pipeline of mono specific little RV targeted antibodies is further strengthened by the ongoing efforts to develop a potent and specific blockers oral <unk> one.
An inhibitory receptor that is expressed not only on myeloid cells were also on certain subsets of T and NK cells.
Having these high quality building blocks to target three important members of the little RB family.
Has enabled us to explore multi targeted approaches pre clinically by leveraging our knowledge and growing expertise in <unk> biology.
We are confident that the <unk> family as well as other targets that we're currently pursuing represent attractive opportunities in immuno oncology with a potential to improve upon and restore responsiveness to PD, one or <unk> inhibitors.
I will now turn the call over to Kim for a discussion of our fourth quarter and year end 2021 financial results Kim.
Thank you Dmitry.
We reported in this morning's press release, we ended 2021 with cash cash equivalents and investments totaling $220 2 million compared to $213 2 million as of December 31, 2020.
The increase in cash and cash equivalents and investments was primarily due to the receipt of $90 9 million in net proceeds from the follow on public offering and sale under our aftermarket offering program completed in the first quarter of 2021.
And receipt of a $25 million milestone from Gilead in the third quarter of 2021 offset by operating expenses incurred.
Turning to the P&L license and collaboration revenue was $26 9 million for the full year 2021, compared to $62 3 million in 2020.
Revenue recognized during 2021 was related to the Gilead milestone achievement and completion of revenue recognition related to the Gilead upfront license fee.
Revenue recognized during 2020 was related to the Gilead upfront license fee.
Research and development expenses were $89 million for the full year 2021, compared to $78 7 million in 2020.
The increase in research and development expenses in 2021 was due to $5 1 million of increased expenses, primarily associated with manufacturing activities for our development programs $2 9 million of increased employee compensation costs.
And $2 6 million of increased clinical and regulatory expense, primarily attributable to our EMEA and select clinical trial.
General and administrative expenses were $29 million for the full year of 2021 compared to $28 8 million in 2020.
The increase in general and administrative expenses for full year 2021 was primarily attributable to increased administrative costs.
Net loss was $90 9 million for the full year 2021, resulting in basic and diluted net loss per share of $1 82.
Compared to the net loss of $43 8 million for the full year 2020.
Resulting in basic and diluted net loss per share of $1 24.
The increase in net loss and net loss per share was attributable to increased operating expenses and reduced revenue recognized under the license agreement with Gilead during the year ended 2021 as compared to 2020.
Based on our current operating and development plans, we reiterate our financial guidance for 2022.
We continue to expect gross cash burn on operating expenses and capital expenditures for the full year 2022 to be approximately $115 million to $130 million.
Given the strength of our balance sheet, we expect existing cash cash equivalents and investments to be sufficient to enable the funding of our operating expenses and capital expenditure requirements through the third quarter of 2023.
We continue to have the financial flexibility to drive our innovative immunotherapy pipeline, while efficiently executing against our strategic plans and goals.
With that I'll hand, the call back to rich for final comments.
Thanks, Tim.
The combination of our experienced team innovative science and financial resources puts us in a strong position to move beyond the next set of inflection points and continue to execute our strategic plans.
<unk> continues to focus on patients first and we're proud of the Io pipeline, we're building to address the growing unmet medical need faced by cancer patients.
In summary, we look to address multiple large market opportunities driven by our productive discovery engine.
Built a compelling pipeline with next generation Io agents and continue to develop additional therapies addressing the significant unmet needs of cancer patients.
Importantly, we have several important catalysts coming up in 2022, and the financial strength that underlying our ability to take these through the inflection points over the next few years.
Before closing I'd like to take a moment to recognize the efforts our team makes everyday and congratulate them on the advances we've made across our pipeline in 2021.
We look forward to updating you on our programs as the year progresses.
With that we would like to now open the call for your questions operator.
Thank you, ladies and gentlemen, if you'd like to ask a question at this time.
I need to press the Star then the one key on your Touchtone telephone.
To withdraw your question you May press the pound key please standby, while we compile the Q&A roster.
No first question coming from the lineup gentle with Piper Sandler Your line is now open.
Great. Thank you very much.
Prefigure comments about what's going on around the world I hope, you're all keeping well during these crazy times.
Looking forward to a really busy year for you guys I wanted to get a little more color, let's have a focus on CNBC, but just to get a sense and make sure that I'm understanding correctly. So we now have seven cohorts that are enrolling.
And.
I appreciated the commentary about the fullness of data that you hope to present would that be at a medical meeting with that.
That would be out of the R&D day, just because it sounds like thats going to be a lot of the data package. Thank you.
Sure. Thank you very much for the question Ted.
First of all yes, we have seven combination cohorts actively enrolling and then the monotherapy cohort in ovarian cancer as well so eight total and our.
Our goal is our preferences, yes always to present at a medical meeting.
And.
We are on track for having all of the data that I described this year.
And as you mentioned it is a lot of data, it's the entirety of the dose escalation data for mono and combo, and then importantly safety efficacy and the Biomarkers for the at least the first stage of multiple expansion cohorts.
We believe it will be a meaningful body of data and our goal is to present something thats really interpretable. So that people can see oh, okay I see what this drug is doing.
Yes.
Does that answer your question.
Sorry, just to confirm did you discontinued CNBC them and does that mean.
Yes, yes.
Correct, Yeah. So we had seven combination cohorts.
And we decided to stop.
Stopped to triple negative breast cancer cohort for now and we have added.
As a PD, one experienced head and neck cancer cohort.
So.
Yes, yes, so we still have four cohorts enrolling in patients who are PD one inhibitor experienced.
<unk>.
The head and neck is actually really interesting because of the standard of care changes in treatment paradigms for triple negative breast cancer. It just didn't seem that there was quite as much of an unmet need there, but theres a huge unmet need in PD, one experienced head and neck cancer and so on.
We decided to open that.
And.
That will give us the opportunity to look at the tumor micro environment in both PD, one naive and PD one experienced patients and look in the same tumor type and be able to look at the efficacy in two different.
Lines of therapy in the same tumor types. So we think it will be really nice addition to the study.
Yes, awesome Super helpful. I understand clearly thank you.
Thank you.
And our next question coming from the line of Boris <unk> with Cowen Your line is open.
Great.
Question is on 8064 can you comment how different or similar it is to Merck's 48, 30, and what can we learn from the Merck drug.
To date in terms of their expansion.
In terms of their dose expansion arms to your strategy.
Sure go ahead.
Hi, Boris Yeah sure Yeah. So just in terms of how we look at the antibody.
Both antibodies and their properties and this is really looking at our data that we've put up on posters and presented as well as separately looking at.
Mmk 48, 30, that's been up on separate coasters.
So we continue to describe.
The antibodies as.
More similar than different in the sense that there is a particular region of the receptor that's involved within interaction with the ligands and the purpose of the antibodies of course is to inhibit that interaction. So thats very common in terms of what each of these antibodies is intended to do.
They are both IGT for these are straight up blocking antibody as we try to block this interaction not in part effector function through through the FC.
No.
We have noted in our studies as we look at.
Potency curves and where we hit the kind of plateau in terms of the dosing there may be there may be somewhat.
And maybe some maybe there could be some opportunities for differentiation there, but generally speaking we see similar property is more similar than different.
So moving to the ongoing trials.
There is a.
As we see it from the outside looking in.
Considerable continued expansion of studies off of the phase one of <unk> 48, 30, that's of course in combination with Keytruda.
And those.
Coming off that kind of phase one we're continuing into 13.
Expansion cohorts that we're that we're tracking.
In addition.
And again to us this is.
We are monitoring this carefully there is the phase two studies that now are being set up that 48 30 is kind of participating in so thats also in combination with Keytruda and there are multiple of those I believe now seven.
Im sorry, eight of those that have an arm of MK 48 30.
So there is a kind of <unk>.
Continued progression as we see it of course, we don't know the data, but we'd be looking forward to the to the future here, where we get another look at the at the Merck data as well as as well as shops.
Great. Thanks, so much for taking my question.
Our next question coming from the line of Cory customers with Jpmorgan. Your line is open.
Sure.
Hi, This is Kevin on for Corey.
Thanks for taking my question on the details on them.
Yes, we have.
Two part question on <unk>.
Or the mechanism of action.
First curious if you had.
It has a higher then lead towards a particular HLA.
And the Tam signature framework.
Our 2021 presentations demonstrated higher.
<unk> expression in PD, one non responders.
Just curious about the role of <unk> will be our two conveying resistance versus a potential varying HLA expression levels in patients driving that resistance.
Thank you.
Yes. Thanks for the question Boris this is.
This is dmitry.
So as we have presented in our posters.
64, sorry, 864 is a.
Potent disruptor of both HLA G binding to little RV too as well as more classical Hla's and we really believe this is a very important factor in restoring the ability of macrophages in other myeloid cells effectively presents antigens to T cells.
In addition to disrupting this inhibitory signaling through the <unk>.
And so we've continued to carefully study this in the labs and with respect to.
Yes.
It is elevated expression of <unk> in PD, one resistant cancers.
Have found and others have also confirmed that the ratio of <unk> to interferon gamma signature, which represents inherent inflammation in the tumor is in fact, a negative predictive marker for response to PD one L. One blockers and so our hypothesis continues to be that.
We believe disrupting.
And inhibiting the larvae two would restore responsiveness to these PD one L. One checkpoint inhibitors.
Okay, great. Thank you.
Our next question coming from the lineup, Steve <unk> from Raymond James Your line is open.
Good morning, everybody Ryan Deschner on for Steve <unk>.
I was wondering what specific types of biomarker data will be reported fleet trial later this year.
How big of an impact there.
<unk> been on enrollment.
Thats great.
Sorry can you repeat the question.
Sure wondering what specific types of Biomarkers will be reported.
Later this year.
Sure sorry.
So we have both Pharmacodynamic Biomarkers and then we also have a panel of potential predictive biomarkers some of the ones that we've already mentioned have been.
Gene signatures, such as <unk>, RB two itself or tumor associated macrophage gene signature.
Kieran signatures.
And then also we have.
<unk>.
We have IHT for example, CD 163, obviously, we'll be looking at PDL one.
So we have quite a nice panel I think it's one of the strengths that the study is that we're exploring so many potential predictive biomarkers and our plan is to do analyses of the correlation of these biomarkers with clinical outcomes.
By cohort and then in across cohort analysis.
Excellent.
Also asked if COVID-19 , yes.
So I would say.
Across the health care industry.
Hospitals are understaffed and Thats, probably the biggest impact, but we're really pleased with the rate of enrollment of the trial.
I would say in general Covid is having some impact, but it's hard to measure because the trial enrollment is going well.
That's helpful. Thank you very much and then real quick can you also comment on how.
Do you see opex evolving in 2022 relative to 2020. Thank.
Thank you.
Okay Opex. So in terms of our brand this year, we projected at a $115 million to 130. So that is an increase from the prior year, where it was.
By $110 million and that increase really relates to the expansion studies, we have going on with the <unk> as well as our efforts in CMC to make sure that that's not a mitigating factor as the trial progresses and.
And beyond that we continue to have a robust discovery athletic, but a lot of our the majority of our expenses are really in line with our priorities and the largest increase really has to do with an eight and preparing for future studies as well as the ongoing study.
Yes.
That's great. Thank you very much.
Thank you.
Our next question coming from the line of Colin Christie with Baird. Your line is open.
Yes. Good morning, Thanks for taking our questions. So following.
Following up on a previous question helpful comment on the comparison of Merck's antibody I'm curious can you speak to how.
Fury dosing PD, one in combination and how that compares to merge development plan in terms of frequency or before.
Before during or after.
Yes, sure sure so Tim of Allomap and Keytruda are both dosed every three weeks.
And we're using a dose of <unk> that in our phase one study showed complete receptor blockade. So.
Once you achieve steady state for a PD one inhibitor you have total blockade of PD of the PD, one PD lone interaction.
So theres really no difference I would say in that respect.
That's helpful and so are patients on PD, one typically for the same amount of time again semi protocols for one.
Scott receiving PD one.
Yes, that's a great question Colleen.
I believe in many trials.
PD one inhibitor is discontinued after two years with patients remain on treatment that far.
We've actually allowed patients to stay on as long as they're receiving benefit. So we have patients from iconic on over four years at this point and we have patients from the phase one trial of <unk> Allomap, who have been on well over two years. So.
Right now we allow patients to stay on as long as they're receiving benefit so there's no cutoff for the PD one treatment.
Okay, Great. That's helpful. Thank you and then for select.
Assuming data there would be positive what would next steps of development look like I think you mentioned there might be potential for other tumor types that you might go into it if you can elaborate there sure sure. So.
If as we believe to spoke.
It's April to select the patients who not only we'll have a better response to a PD one inhibitor, but also have an enhanced response on top of that because of <unk>. We think there's.
A lot of opportunity in places, where PD one inhibitors are approved but there is a need for better.
Response rates and also addition of something that doesn't add any toxicity.
So we believe after select the next study will be a phase III registration study and.
We're looking at a number of different tumor types, where thats possible, obviously lung cancer would be the most obvious one going into frontline since the current study as a proof of concept study in second line Io naive patients, but we believe the data.
Because we have data on levels of tests and other tumor types.
And because we believe that the mechanism is not really that tumor specific it's really.
<unk> can be applied across a number of different tumor types that there are many different options.
Based on positive select trial.
Great. Thanks for taking my question.
Youre welcome.
Our next question coming from the line of Nick Abbott with Wells Fargo. Your line is open.
Hi, Good morning, Thanks for taking my question, so just going back to the select trial.
You mentioned the situation in Ukraine, and Belarus, there are several sites in Russia.
Given the number of size can you say what proportion of patients who enrolled from those countries.
And if you have plans to increase enrollment at sites outside those countries.
In case.
I told you know do.
Do you have to stop operations in those countries.
Sure.
I guess I think were far enough along in the steady Nick that there's not any need to open new sites or go to new countries.
<unk>.
As I said there may be this isn't we don't believe this is going to.
Second our ability to report data in the second half of the year from this study.
I would say my major concern is there may be some missing data if patients aren't able to.
To attend all of their visits but we have drugs in the countries sufficient for now and.
We think we've put really good safeguards in place and it's now just a matter of the patients getting to the sites.
Okay. Thank you.
Just for me and for you.
Can you provide us some guidance on what.
How you define success on this average change in lesion size and just to be clear then development of a new lesion or growth in the existing lesion over 25% would be defined as.
Of course of disease, even if the average Legion.
Decreases substantially.
Yes, so by resist criteria, we will we will be reporting overall response by resist criteria. So.
A patient could be classified as having progressive disease, even if they had a large reduction in their target lesions. If they had growth of a new lesion envisage that is counted as progressive disease. However, what we've heard from a lot of physicians and we've seen in some of our trials sometimes these new lesions are.
Three small they really have very little to no impact on the patient's well being and so many physicians keep patients on PD one inhibitor therapy.
After they are technically progressive.
Then you can still continue to see very long term clinical benefit so.
It's one of the reasons that for <unk>.
Early proof of concept trial like this we believe our endpoint is a better predictor and there are papers that actually support this a better predictor of overall survival than just resist response rate because that pace.
Patients would still be categorized with their total tumor burden as having us quite a nice reduction in the tumor and we believe that that's what's most important the overall tumor burden for the patient and in particularly Nio, where the responses can be so durable.
So we think it's a really good endpoint for Io.
<unk>.
Should be a better predictor of survival than just a resist response rate.
Okay.
Moving to EMEA.
Using.
I'm not sure.
You did say want to stage one and please.
Sure.
Traditional same metric.
Sure. So we are using resist response rate.
Endpoint in select would not really be that useful in a single arm study, it's appropriate for a randomized study like selective.
And we also chose it because it's a continuous variable. So it allows us to get statistical power with a much smaller sample size now in a Nate. This is our first study with this drug we are using all the traditional end points.
The Merck data using resist response rate was encouraging so we believe that that's appropriate at this stage in time.
Okay, great. Thanks, Bob.
Thank you.
Our next question coming from the line of Jack Mcdonald from Roth Capital Partners. Your line is open.
Okay.
Okay.
Good morning, Thanks for taking the question.
Just wanted to ask a couple of quick things decent updates provided I think the first but.
As you're thinking about the efficacy of <unk> 64 across the various tumor types.
The tumors were selected based on the existing myeloid cells.
So I was just kind of wondering.
How much consideration probably getting to the T cell signature became back to plan in Q1.
And then the potential to kind of achieve some southerners tumor reduction.
Yes, that's a great question sake, but thank you. So our selection of the tumor types was based on a composite ranking that included not only <unk> in the tumor associated macrophage signature, but also interferon gamma so exactly for that reason, we do believe that particularly when we're developing it in combination.
With a PD one inhibitor that that T cells are going to be important part of the equation as well.
And so we'll be looking at those predictive by all of those gene signatures also in the in our analysis of potential predictive biomarkers.
Okay. Thank you and then just a follow up here as well.
Regarding the involving treatment when youre keeping oncology I was just wondering.
How are you thinking about the benefits of even pursuing a monotherapy option versus just going forward with that.
Because I imagine that the policy better.
Based on what we've seen and then just also kind of a follow up to that as well and as you're thinking about the time to response for single agent versus a combo do you expect there to be a difference based on the mechanism of action.
Yes, it's an interesting question. So I think it's clear from the.
Cohorts in our study that we are placing the greatest emphasis on combination therapy, we have seven combo cohorts and one mono cohort.
We felt it was worthwhile to explore monotherapy, obviously, a significant benefit there significant clinical benefit would be a home run and would be the fastest path for us to get the drug approved as a single agent.
Also add to proof of concept. However, we really do believe the future is in combination therapy. So thats why seven of the cohorts or combination therapy with respect to the time to response.
So I don't know how that I don't have any data to suggest how that would differ between mono and combo.
But we did note that many of the responses in the MK 48 30 steady.
The first response occurred not at the first scan, but it's the second scan and that could be consistent with taking a little more time for the macrophages to actually get activated before the T cells are then activated and working.
Thanks Beth.
Thinking and then rich you know I love combos, obviously, so I've been asking about when you guys going to do more condos in with that program do you have but you also mentioned, perhaps wanting to pursue bi specifics or high.
Thanks that makes intelligent wondering.
How you're thinking about the advantage of that weren't vantages of that relative to just doing the accomplished that and then maybe you can comment on.
Some of the targets that you might consider and then maybe leveraging some.
Some additional insights how you guys go about picking the combination.
Yes sure. Thanks, Thanks for that Yeah, we're really excited about.
Using kind of what we are referring to is kind of our highly specific kind of building block binding sites from the model specific agents, which deserve their own path forward and then formatting that into.
The multi the buy multi specifics, but ones that really hit a certain kind of criteria that we're that we're shooting for so let me hand that too to dmitry to continue that answer.
Yes, thanks for the question.
This is a very active area of investigation for us.
We are exploring a variety of partners for little RB targeting arm in a multi specifics including different little RV family members, but also other both well characterized as well as novel targets in immuno oncology. So again, a very active area when we have more data.
We would be more than happy to share with you, but I think as rich said, we've established a fairly stringent criteria for the advancement of our multi specific molecules and.
This is what's being tested in the labs as we speak.
Okay.
And as a reminder, ladies and gentlemen to ask a question. Please press star one.
Next question coming from the line of Rama <unk> from H C. Wainwright Your line is open.
Okay. Thank you.
Good morning.
Couple of quick questions.
The first one is on 14 84.
Just.
Trying to think about preclinical data presentations during 'twenty two.
Should we expect anything yet.
If you are.
And the other content down.
During the year.
Also.
In terms of getting ready for the.
Our NDA filing in 2003.
What sort of.
What needs to get done still.
You'll be able to file for that.
AMD.
Yes, thanks very much for the question.
As we said, we're very excited about advancing having advanced 14 84 now into IND, enabling studies, they're all underway as you can imagine it's a fairly typical set of.
Set of studies that we're conducting assessing safety further developing our biomarker strategy and developing clinical plans for $14 84. So all of this is ongoing we do plan to present preclinical data on this molecule later this year most likely one of the four.
<unk> scientific meetings and.
Really looking forward to that.
We believe this target is important and is quite distinct from <unk> as we mentioned in our presentation. This morning.
It binds to <unk> before which is highly expressed on myeloid derived suppressor cells and <unk>.
Hello, engineered dendritic cells and signatures b cell types.
Have been detected in a significant proportion of PD one PD one non responder population. So we do believe this could be one of the mechanisms overcoming resistance to PD, one PDL one inhibitors.
Inventory.
Second question is.
On the discovery engine.
I know you have the.
You have stated that every 12 to 18 months.
But I'm just trying to understand.
<unk>.
How soon should we expect another curtain raise.
So what sort of.
Targets.
Would you be going after.
Yes, that's a great question.
So we did disclose at our R&D day last year, our case that we have also an active program targeting <unk> one we.
We briefly touched on this target this morning.
We believe it to be very exciting because it takes us outside of the realm of the pure myeloid biology into subsets of lymphoid cells T and NK cells potentially when these cells, which could be very important to anti tumor immunity. So this program is advancing well once we have further updates, we'll certainly share them with you.
And.
I think as we also said during R&D day, we continue to apply this unique approach of dissecting the tumor microenvironment using our proprietary gene.
Nature's focusing on specific immune cell subtypes and.
Sure.
Again, a little bit probably too early for us to share more at this stage, but.
Looking forward to describing these programs and exciting targets in the future. Thank you.
Thank you thanks for taking my questions.
We are currently showing no remaining questions in the queue at this time, ladies and gentlemen that does conclude our conference for today. Thank you for your participation you may now disconnect.
Okay.
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