Q3 2023 Agenus Inc Earnings Call
Earnings Conference call.
Q3 2023 earnings conference call.
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After the Speakers' remarks, there will be a question and answer session.
After the speakers remarks, there will be a question and answer session.
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Thank you.
Zach Armen you may begin your conference.
Thank you operator, and thank you all for joining US today today's call is being webcast and will be available on our web site for replay.
Thank you, operator, and thank you all for joining us today. Today's call is being webcast and will be available on our website for replay.
I'd like to remind you that this call will include forward looking statements, including statements regarding our clinical development regulatory and commercial plans and timelines as well as timelines for data release and partnership opportunities among other updates.
I'd like to remind you that this call will include forward-looking statements, including statements regarding our clinical development, regulatory, and commercial plans and timelines, as well as timelines for data release and partnership opportunities, among other updates.
These statements are subject to risks and uncertainties and we refer you to our SEC filings available on our website for more details on these risks.
These statements are subject to risks and uncertainties, and we refer you to our ITC filings available on our website for more details on these risks.
Joining me today are Dr. Garo, Armen, Chairman and Chief Executive Officer, Dr. Stephen, Though Dave Chief Medical Officer, Dr. Tatiana <unk> strategic advisor and Christine <unk>, Vice President of Finance.
Joining me today are Dr. Gero Harmon, Chairman and Chief Executive Officer, Dr. Steven O'Day, Chief Medical Officer, Dr. Tadd Yancy, Chief Strategic Advisor, and Christine Klask, Vice President of Finance.
After Robin Taylor, Chief commercial officer, where he will be participating in the Q&A session.
Dr. Robin Taylor, chief commercial officer, we will be participating in the Q&A session.
Now I'd like to turn the call over to Garo to highlight our progress and speak to our outlook for the remainder of the year Carol.
Now, I'd like to turn the call over to Garrow to highlight our progress and speak to our albumists for the remainder of the year. Garrow.
Thank you Zack.
Ladies and gentlemen, as we gather today or do your earnings call.
Ladies and gentlemen, as we gather today for the earnings call.
Let's reflect on the remarkable patient outcomes from our book kind of fill in that trial.
Let's reflect on the remarkable patient outcomes from our book and still
As underscored by a leading experts and researchers.
as underscored by our leading experts in research.
Witnessing.
We're witnessing sustained benefits in treating some of the most challenging cancer.
<unk> benefits, increasing some of the most challenging cancers.
Based on these observations and fortis takeoff cancer patients.
Based on these observations and for the sake of cancer patients, our urgent mission is to set a new benchmark in cancer care, providing patients with longer term, potentially pure good benefit, with some patients experiencing treatable capsid-
Urgent mission is to set a new benchmark in cancer care, providing patients with longer term.
Thankfully pure could benefit.
With some patients experiencing treatment bulk activities.
Our box therapy is showing promise across various cancer stages and cuts.
Our butt therapy is showing promise that goes to various cancer stages and types.
Benefit seen in some of the most treatment resistant.
with benefits seen in some of the most treatment resistant so-called
So called cold tumors.
In addition, recent data presented at our corporate events in Madrid during the ethanol.
In addition, recent data presented at our corporate event in Madrid during ASMO.
Video back to potential.
reveal what potential in earlier stages of cancer where remarkable rapid responses were observed with the possibility to prevent significant treatment related morbidities including the potential need for colostomy.
In earlier stages of cancer.
Were remarkable rapid responses were observed.
With the possibility to prevent significant treatment related morbidities.
Including the potential need for colostomy.
Moving forward, we're concentrating on three key priorities.
Moving forward, we're concentrating on three key priorities.
Submitting our first biologics license application.
Submitting our first Biologics license application will correct OK.
Colorectal cancer.
Prioritizing other clinical programs with the potential for rapid approval.
prioritizing other clinical programs with the potential for rapid approval.
And importantly, tomorrow reallocating resources to achieve our goals.
and importantly, smartly allocating resources to achieve our goal.
Accordingly, we are gearing up our first basketball BLA submission.
Accordingly, we're gearing up our first bulk BLA submission in mid-2024 with a focus
In mid 2024.
With a focus on late stage colorectal cancer.
That's the entity will delve deeper into this topic shortly.
The cliente will delve deeper into this topic shortly.
The cancer community, then here's the abdomen rapid enrollment in our phase two clinical trial in MSS CRC.
The cancer community's enthusiasm and rapid involvement in our Phase 2 clinical trial in MSF-CRC highlights an urgent, unmet need.
Highlights and urgent unmet need.
The address please.
We have started a compassionate use program.
We've started a compassionate youth program.
With the ammo broadening it into an expanded access program next year.
with the aim of broadening it into an expanded access program next year.
With very limited options to treat patients with advanced colorectal cancer.
With very limited options to treat patients with advanced colorectal cancer, the positive trend and lasting responses in our studies strengthen our conviction in both
The positive trends and lasting responses in our studies.
Since then our conviction in <unk> potential.
Our top priorities obtaining.
Our top priority is obtaining Bell's approval in MSS TRC in order to allow patients access to this important IO treatment, offering them new hope, which does.
<unk> approval in MSS CRC in order to allow patients access to this important I O treatment.
Offering them new hope.
<unk> does not exist today.
Our second area of focus is advancing our prioritized clinical programs, which include refractory pancreatic cancer.
Our second area of focus is advancing our prioritized clinical programs, which include respiratory pancreatic cancer.
And new adjuvant setting in CRC.
And new argument setting in CRT.
Macro they will detail.
Dr. Odey will detail the exciting data that showcases bus potential in these cold solid waters along Duwap disQuickway to 2000 Luke
Exciting data that showcases bus potential in these solid tumors.
In addressing our financial capabilities.
In addressing our financial capabilities to drive our objectives, we're already taking and continue to take steps to contain costs.
Our objective.
We're already taking and continue to take steps to contain costs.
These facts are important, particularly given the current challenging environment in the biotech sector.
These steps are important, particularly given the current challenging environment in the biotech sector.
Our immediate prospects for additional cash infusion.
Our immediate prospects for additional cash infusion.
That does not involve stock issuance.
that does not involve stock issuance includes a milestone payment for
They include a milestone payment from.
One of our partnered programs.
Expected by the end of December 2023.
expected by the end of December 2023, that's this year.
This year.
In addition to this expected milestone we are in the process of the sale of two non strategic assets.
In addition to this expected milestone, we are in the process of the sale of two non-strategic assets.
And pursuing the partial sale of milestones and royalties due to <unk> from our partnered programs.
and pursuing the partial sale of milestones and loyalties due to a genesis from our partner program.
The three that are expected to close by the end of the first core catalog 2024.
These three sales are expected to close by the end of the first quarter, half of 2024.
The potential proceeds from these four transactions are estimated at approximately $200 million in total.
the potential proceeds from these four transactions.
I estimate it at approximately $200 million in total.
With our cash balance at the end of Q3.
without cash balance at the end of Q3, alone with these four plain transactions.
Loan with the bold claim transactions.
We believe we are sufficiently funded through the end of 2024.
We believe we are sufficiently funded through the end of 2024.
In addition to these planned transactions. We're also in advanced discussions for a potential structured financing for Bob <unk>.
In addition to these planned transactions, we're also in advanced discussions for a potential structure financing for MacDowell.
As well as a potential corporate collaboration with a large pharma or biotech company.
as well as a potential corporate collaboration with a large pharma or biotech company.
That ends my formal remarks introductory remarks, and now I'll be handing it over to Dr. <unk> to shelf life on our latest findings and Paypal face Steven.
That ends my formal remarks, introductory remarks, and now I'll be handing it over to Dr. O'Day to shed light on our latest findings and data updates. Steven?
Thank you Garo.
Together with our investigators and key opinion leaders, we presented uptake from the box style development program at a corporate event posted during the Madrid ESMO Congress.
Together with our investigators and key opinion leaders, we presented updates from the BotBowl development program at a corporate event hosted during the Madrid ESMO Congress in October .
<unk>.
I will now briefly describe these data update beginning with colorectal cancer.
I'll now briefly describe these data updates, beginning with colorectal cancer.
We updated our phase one b cohort of 70, evaluable patients with Bard and dial in refractory MF stable colorectal cancer without active liver metastasis.
We updated our phase 1B cohort of 70 evaluable patients with BOT and BAL in refractory MS-stable colorectal cancer without active liver metastasis.
This is the target population for a fully enrolled phase two study and the population in which we have received fast track designation from the FDA.
This is the target population for our fully enrolled phase two study and the population in which we've received fast track designation from the FDA.
The research confirmed overall response rate was 24%.
The Rhesus confirmed overall response rate was 24%.
The duration of response was not reached with 59% of responses ongoing.
The duration of response was not reached with 59% of responses ongoing. And now a median follow-up updated to 12.3 months.
And now a median follow up updated to 12 three months.
These patients showed a 12 month overall survival rate of 74% approximately twice that reported for standard of care.
These patients showed a 12-month overall survival rate of 74%, approximately twice that reported for standard of care.
With longer follow up the median OS previously reported at 29 months is now no longer reached.
With longer follow-up, the median OS previously reported at 20.9 months is now no longer reached.
Importantly, the OS curves plateau continues to emerge and strengthen as the data matures with the longest patient now alive at three and a half years and three other patients who are alive beyond 21 months.
Importantly, the OS curve plateau continues to emerge and strengthen as the data matures, with the longest patient now alive at three and a half years and three other patients who are alive beyond 21 months.
We plan to file our initial BLA in this indication in mid 2024.
We plan to file our initial BLA in this indication in mid-2024.
Next we presented data from an investigator sponsored trial at Weill, Cornell and which 12 patients with CRC were treated with one dose of bot and two doses about in the neo adjuvant therapy window of opportunity setting.
Next, we presented data from an investigator-sponsored trial at Weill Cornell in which 12 patients with CRC were treated with one dose of BOT and two doses of BAL in the neoadjuvant therapy window of opportunity setting.
Surgery was performed on average only four weeks after the initiation of immunotherapy.
Surgery was performed on average only four weeks after the initiation of immunotherapy.
All three MSI high colorectal patients had complete or near complete pathological responses.
All three MSI high colorectal patients had complete or near complete pathologic responses.
And even more importantly, six out of nine patients with MF stable colorectal cancer had pathological responses of 50% or greater including two complete pathological responses.
And even more importantly, 6 out of 9 patients with MS-stable colorectal cancer had pathologic responses of 50% or greater, including 2 complete pathologic responses.
None of the 12 patients had tumor growth during the treatment interval and no surgeries were delayed due to immune related toxicities.
None of the 12 patients had tumor growth during the treatment interval, and no surgeries were delayed due to immune-related toxins.
These results represented an important opportunity to move into earlier lines of therapy with curative intent.
These results represent an important opportunity to move into earlier lines of therapy with curative intent.
And change the treatment paradigm for MF stable colorectal cancer potentially avoiding the morbidity of late line therapies.
and change the treatment paradigm for MS-stable colorectal cancer, potentially avoiding the morbidity of late-line therapy.
In second line pancreatic cancer, we have treated six patients with a combination of both <unk> and <unk>.
In second line pancreatic cancer, we have treated six patients with a combination of Botanfilamab, Gemzar, and Abraxane triplet.
Saar at our Brac same triplet.
All six patients had progressed following first line metastatic <unk> therapy at all six have liver metastasis.
All six patients had progressed following first-line metastatic full furanox therapy, and all six had liver metastasis.
For the six patients have achieved marked and sustained tumor marker reductions.
Four of the six patients have achieved marked and sustained tumor marker reduction.
Two of the four patients have already achieved partial responses at 16 weeks with target lesion reduction of minus 47%, which has been confirmed and minus 37%, which is pending confirmation scan.
Two of the four patients have already achieved partial responses at 16 weeks.
with target lesion reduction of minus 47%, which has been confirmed, and minus 37%, which is pending confirmation scans. And both responses.
And both responses are ongoing.
Two other patients showed stable disease at their first eight week scans with tumor reduction of minus 20, and minus 13% and they remain on study awaiting 16 week scan.
Two other patients showed stable disease at their first eight-week scans with tumor reduction of minus 20 and minus 13 percent, and they remain on study awaiting 16-week scans.
Our randomized phase two study is currently enrolling in a data update is anticipated in the first half of 2024.
A randomized phase 2 study is currently enrolling and a data update is anticipated in the first half of 2024.
Our other phase III trial is in refractory metastatic melanoma, including PD, one refractory as well as PD, one see Chile for refractory disease.
Our other phase two trial is in refractory metastatic melanoma, including PD-1 refractory as well as PD-1 CTLA-4 refractory disease.
In our phase one expansion cohort of 10 patients.
in a phase 1b expansion cohort of 10 patients.
Both <unk> alone showed a 30% objective response rate and 60% disease control rate and these refractory patients.
Bowdoin-Cilinab alone showed a 30% objective response rate and 60% disease control rate in these refractory patients.
In the phase two study the boat and fill a mab monotherapy cohort is now fully enrolled and the boat fill nab valves still a mab combination cohort is enrolled with approximately 30 patients.
In the phase two study, the botan-silamab monotherapy cohort is now fully enrolled, and the botan-silamab-valve-silamab combination cohort is enrolled with approximately 30 patients.
Data update is anticipated in the second half of 2024.
A data update is anticipated in the second half of 2024.
In PDL one refractory.
In PD-L1, refractory, and non-small cell lung cancer, we reported on nine patients who were treated with a combination of bot and bowel. Five of the nine patients in the combination achieved rhesus confirmed partial responses for an ORR of 56% and a disease control rate of 89%.
Non small cell lung cancer, we've reported on nine patients who were treated with the combination of Boston about five of the nine patients in the combination achieved resist confirmed partial responses.
Or a 56% and a disease control rate of 89% approximately.
Approximately 50 patients have now been enrolled in two expansion cohorts, including PD, one refractory as well as PKI driver mutation refractory disease.
Approximately 50 patients have now been enrolled in two expansion cohorts including PD-1 refractory as well as TKI driver mutation refractory disease.
Data update is anticipated in mid 2024.
A data update is anticipated in mid-2024.
Dr. <unk> will key director of the sarcoma medical oncology Deputy Associate director for clinical research at the University of Colorado Cancer Center presented an update of Bolton filament program in sarcoma.
Dr. Brie Wilkie, Director of the Sarcoma Medical Oncology, Deputy Associate Director for Clinical Research at the University of Colorado Cancer Center, presented an update of Boten-Silliman program in sarcomas at ESMO 2023.
<unk> 2023.
In 41, Evaluable heavily pretreated sarcoma patients.
in 41 valuable heavily pre-treated sarcoma patients.
The combination of button Bell demonstrated an overall response rate of 20% a median duration of response of 19 four months and a six month progression free survival of 40%.
The combination of BOT and BAL demonstrated an overall response rate of 20 percent, a median duration of response of 19.4 months, and a six-month progression-free survival of 40 percent.
There was a differential responses observed by dose level with 29% response rate in the two milligram per kilo box cohort compared to 15% in the one milligram per kilo bought cohort.
There were differential responses observed by dose level with 29% response rate in the 2 milligram per kilo BOT cohort compared to 15% in the 1 milligram per kilo BOT cohort.
In addition, we observed promising activity in difficult to treat sub types of sarcoma, such as Leiomyosarcoma and visceral angiosarcoma.
In addition, we observed promising activity in difficult-to-treat subtypes of sarcoma, such as leiomyosarcoma and visceral angiosarcoma.
The results we've achieved in cold tumors in both the refractory setting and more recently in early disease offers hope for patients and families where current standards of care are in adequate or limited and benefit.
The results we've achieved in cold tumors, in both the refractory setting and more recently in early disease, offers hope for patients and families where current standards of care are inadequate or limited in benefit.
The robustness of our data broadly across tumor types, resulting in deep and durable responses showcases a potential groundbreaking advancement in oncology for boat and fill them out we.
The robustness of our data broadly across tumor types resulting in deep and durable responses showcases a potential groundbreaking advancement in oncology for Bowdoin-Silliman.
<unk> committed to improving patient outcomes and are grateful for the support of our team trial participants and stakeholders I am confident in the positive impact we are making and I'm excited about the future.
We remain committed to improving patient outcomes and are grateful for the support of our team, trial participants, and stakeholders. I am confident in the positive impact we are making, and I'm excited about the future.
Now I'll turn the call over to Todd to discuss our regulatory strategy.
Now I'll turn the call over to Todd to discuss our regulatory strategy.
Thank you Steven.
The landscape for MSS CRC patients who've received one to two prior lines of therapy is challenging.
Thank you, Steven. The landscape for MSS CRC patients who've received one to two prior lines of therapy is challenging.
<unk> effective options available so our focus in our development and regulatory path is to bridge that gap.
There are limited effective options available to our focus in our development and regulatory path is to bridge that.
At present, the available therapies in this setting including monotherapy with regular afternoon monotherapy with long served in the newly introduced combination of Avastin and long served offer only marginal reported improvements in survival and response rates are low with survival curves going to zero.
At present, the available therapies in this setting, including monotherapy with rigoracinib, monotherapy with Lonsurf, and the newly introduced combination of avastinib and Lonsurf offer only marginal reported improvements in survival, and response rates are low with survival curves going to zero.
Recognizing this we have developed a differentiated investigational agent with books and sell a map that has already demonstrated significant benefit over our reported results for the standard of care therapies.
Recognizing this, we've developed a differentiated investigational agent with botensilumab that has already demonstrated significant benefit over reported results for the standard of care.
With survival curve plateaus consistent with substantial long term benefit.
with survival curve plateaus consistent with substantial long-term.
In our study patients with a median of four prior lines of therapy quarter of whom had received prior immunotherapy experienced a 24% resist response rate compared to the standard of cares reported rate.
In our study, patients with a median of four prior lines of care.
a quarter of whom had received prior immunotherapy experienced a 24% resist response rate compared to the standard of care's reported rate of only three.
Of only 3%.
Importantly, our median overall survival is currently exceeding 21 months a significant leap from standard of care at 12 nine months, that's reported in the <unk> database.
Importantly, our median overall survival is currently exceeding 21 months.
a significant leap from standard of care at 12.9 months as reported in the RCAT data.
Our regulatory process is well underway.
Our regulatory process is well underway and we, as we have stated, plan to submit our 1st as characterized in our fast track designation in the middle of 2024.
And we as we have stated plan to submit our first BLA that's characterized in our fast track designation in the middle of 2024.
This application is robust it's targeted to include data from approximately 400 patients at two different doses, one milligram per kilogram and two milligrams per kilogram and will be supported by safety data from several hundred additional patients across multiple indications what we have observed broad activity.
This application is robust. It's targeted to include data from approximately 400 patients at 2 different doses, both 1 milligram per kilogram and 2 milligrams per kilogram and will be supported by safety data from several 100 additional patients across multiple indications where we have observed broad access.
And in this process, we're not leaving any stone unturned, we are conducting a comprehensive and full exploration of dose and schedule ranging from the lowest dose 0.1 milligrams per kilogram to three milligrams per kilogram and our phase one and phase two studies.
And in this process, we're not leaving any stone unturned. We're conducting a comprehensive and full exploration of dose and schedule, ranging from the lowest dose of 0.1 milligrams per kilogram to three milligrams per kilogram in our phase one and phase two studies.
Additionally, we're investigating the contribution of components of the two experimental agent bot and valve in a randomized fashion within are now fully enrolled phase III study.
Additionally, we're investigating the contribution of components of the two experimental agents, BOT and BAL, in a randomized fashion within our now fully enrolled Phase 2 study.
As we move forward, we are and we will continue to proactively engage with regulatory authorities.
As we move forward, we are and will continue to proactively engage with regulatory authority.
While we wait complete feedback from the FDA and EMEA, we have taken scientific advice from key European countries and are in the process of scheduling meetings with the <unk> and FDA Representatives.
While we await complete feedback from the FDA and EMEA, we have taken scientific advice from key European countries and are in the process of scheduling meetings with the CHMP and FDA representatives.
<unk> are crucial as they will guard our path forward toward approval.
These discussions are crucial as they will guard our path forward toward approval.
Our goal is clear we aim to submit this package for potential approval by 2020 for mid year, and we are optimistic about the opportunity for an accelerated review, which would allow us to bring innovative solutions to patients in need as soon as we can.
Our goal is clear, we aim to submit this package for potential approval by 2024 mid year and we're optimistic about the opportunity for an accelerated review, which would allow us to bring this innovative solution to patients in need as soon as we can. Now, I'd like to turn the call over to Christine to.
Now I'd like to turn the call over to Christine to discuss the financials.
Thank you Todd.
We ended our third quarter of 2023 with a consolidated cash cash equivalents and short term investment balance of 106 $3 million. This compares to $193 $4 million at the end of last year.
We ended our third quarter of 2023 with a consolidated cash-cash equivalent and short-term investment balance of $100.63 million. This compares to $193.4 million at the end of last year.
For the three and nine months ended September 32023, we recognized revenue, which includes noncash revenue of $24 $3 million and $72 $5 million respectively.
For the three and nine months ended September 30, 2023, we recognized revenue, which includes non-cash revenue of $24.3 million and $72.5 million, respectively.
Including noncash expenses of $28 $1 million, we incurred a net loss of $64 $5 million for the third quarter.
Including non-cash expenses of $28.1 million, we incurred a net loss of $64.5 million for the third quarter.
For the nine months of 2023, we incurred a net loss of $208 $9 million, which includes noncash expenses of $82 million.
For the 9 months of 2023, we incurred a net loss of 208.9Million dollars, which includes non cash expenses of 82Million dollars. I'll now turn.
I'll now turn the call back to Gal.
Thank you Christine.
I want to express my gratitude for your support.
I want to express my gratitude for your support during this clinical phase of agenesis. Our striving cancer research
The second phase of advantages.
Our strides in cancer research.
Highlighted by both excellent Matt.
Signify potential new era in cancer care.
signify a potential new era in cancer.
I also want to express my gratitude to our employees.
I also want to express my gratitude to our employees.
I am confident in our team's dedication and our ability to achieve our milestones.
I am confident in our team's dedication and our ability to achieve our milestones.
The success of our potential and that remains our top priority.
The success of Potential Amap remains our top priority.
I assure you that our diligently manage finances.
And I assure you that our diligently managed finance.
We will ensure the necessity.
will ensure the necessity for resources to be allocated for this very important endeavor. With your continued support
Our resources can be allocated for this very important endeavor.
With your continued support.
We expect to meet and exceed our goals.
With the prospects of bringing hope and healing for those affected by cancer.
with the prospect of bringing hope and healing to those affected by cancer.
Thank you for your support once again.
Together, we are destined for a remarkable achievement for the benefit of cancer patients.
Together, we are destined for remarkable achievements for the benefit of cancer patients.
Which will in turn.
Create significant value for all of our stakeholders.
which will in turn create significant value for all of our patients.
With that I will now open the call for questions. Thank you very much.
With that, I will now open the poll for questions. Thank you very much.
At this time I would like to remind everyone in order to ask a question Press Star then the number one on your telephone keypad.
At this time, I would like to remind everyone in order to ask a question, press star then the number one on your telephone keypad.
Your first question comes from the line of Emily Bodner with H C. Wainwright. Your line is open.
Your first question comes from the line of Emily Bodner with HC Wainwright. Your line is open.
Hi, good morning, Thanks for taking the questions first one just briefly if you can comment on when we may expect to see initial phase two data for.
Hi, good morning. Thanks for taking the questions. First one, just briefly, if you can comment on when we may expect to see initial phase two data for the MSS CRC study.
For the MSS CRC study.
And then secondly, if you could talk about how youre thinking about strategy and neo adjuvant CRC.
And then secondly, if you could talk about how you're thinking about strategy in neoadjuvant CRC, are you kind of looking to evaluate broadly in CRC or just focus on MSS patients and maybe just discuss the regulatory pathway to potentially getting Bop-L approved in that setting? Thank you.
Kind of looking to evaluate broadly in CRC or just focus on NSS patients and maybe just discuss the regulatory pathway to potentially getting BOP Allison.
Thank you.
Thank you Valerie So let me answer the question broadly and I'll ask Dr. <unk> has any additional comments.
Thank you, Emily. So let me answer the question broadly, and I'll ask if Dr. O'Day has any additional comments. But so what I've said publicly is the fact that we have clearly disclosed it on the first 70 people.
So what I've said publicly is the fact that we have clearly disclosed the data on the first 70 basis not because the rest of the data isn't satisfactory, but the rest of the data that needs to be cleaned up.
not because the rest of the data isn't satisfactory, but the rest of the data needs to be cleaned up and we need a little bit of work to do, but our look at the data, both in the second cohort and in our...
We need a little bit of work to do but.
Look at the data both in the second cohort.
And in our phase II studies in.
Indicate.
We should have a sustainable response rate.
indicate that we should have a sustainable response rate, perhaps even
Actually even in improving response rates.
We disclose and analyze these data for regulatory.
as we disclose and analyze these data for regulatory.
Beyond purposes so.
That is going to be more of a regulatory decision on when to disclosing.
So that is going to be more of a regulatory decision when to disclose.
And the ideal circumstance for us will be certainly to published data.
And the ideal circumstance for us will be certainly to publish data at around the time of a potential BLA submission, to publish the data in a PDE journal.
At around the time of.
A potential BLA.
Okay.
To publish the data in <unk> that.
That would be.
Bye bye.
Now with regard to the Neo adjuvant.
Now, with regard to the new adjuvant plans, we haven't quite
We haven't crystallized of course the.
Of course, the typical response for neo-adjuvant studies is the fact that they're large studies, they take time. But we believe that depending on what patient populations we go after, we may be able to look at a subset of patients.
Typical response for you or how do you win the studies.
Is the fact that our studies it may take time, but.
But we believe that depending on what patient populations. We go after.
We may be able to look at a subset of patients.
That would be the subject of high morbidity.
that would be the subject of high morbidity with standards of care. And as you know, in these patients, even though the treatments are largely curative, they're not 100% curative.
With standards of care and as you know.
And these patients even though the treatments are.
Largely cured.
Accenture to standard of care I'm not 100%.
But it's sure a quite substantial number of patients.
standards of care are not 100% accurate, but they cure a quite substantial number of patients. But those cures come at a very high cost.
But those tours.
At a high cost to the patient.
And that includes the potential use of colostomy bags.
And that includes the potential use of colostomy bags.
It involves sexual dysfunction.
It involves sexual dysfunction.
It also involves the loss.
and also involves the loss of muscle.
Muscle.
Function.
In the area of the Avenue and particularly if you are a.
in the area of the abdomen. And particularly if you are a patient in your 30s, 40s, you don't want to be subject to these morbidities. So we're going to take a little bit of time, not too much.
Patients in Europe, Turkey's Ortiz.
You don't want to be subject to these morbidity so.
We're going to take a little bit of time not too much time.
Two.
Determine exactly what the patient population in the trial design would be with the aim, albeit very rapid trial execution and potentially <unk>.
to determine exactly what the patient population and the trial design would be with the aim of a very rapid trial execution and potentially rapid outcome.
Good.
Filing and approval.
No.
I think.
So I think we'll disclose some of these details in the first half of next year.
We'll disclose some of these details in the first half of next year.
Okay, great thinking.
Your next question comes from the line of Choline Cozy from Baird. Your line is open.
Your next question comes from the line of Colleen Cussey from Baird. Your line is open.
Great. Good morning, Thanks for taking our questions and congrats on the progress for the randomized CRC study that's fully enrolled.
Great. Good morning. Thanks for taking our questions and congrats on the progress for the randomized CRC study. That's fully enrolled. Can you just give us a sense of the regulatory bar there? Does the combination need to be better than the individual drug arms and standard of care? And by what margin, if I may ask.
Can you just give us a sense of the regulatory bar there does the combination needs to be better than the individual drug arms and standard of care and by what margin.
If I may ask Todd to answer that question. Thank you.
Hi, Colleen.
They are really two questions. There one is what do we expect in terms of performance versus standard of care and the second is really what do we expect to see in terms of incremental contribution in the doublet. So just to remind everybody about the design of the trial or five arms of which one is standard of care in awkward patients or ran.
Hi, Colleen, I think there are really 2 questions there. 1 is what do we expect in terms of performance versus standard of care? And the 2nd is really, what do we expect to see in terms of incremental contribution in the doublet? So, just to remind everybody about the design of the trial or 5 arms of which 1 is standard of care. And of course, patients are randomized across these arms.
The other four arms, all have boat and sell a map, which as model therapy, we know to be active from the phase one dose escalation and two of those arms have Bolton filling up in combination with balance still amount and as we've been observing in the data set that we've been presenting for the MSS CRC patients on active liver Mets since well for the last almost 80.
The other four arms all have botanfilamab, which as monotherapy, we know to be active from the phase one dose escalation. And two of those arms have botanfilamab in combination with valfilamab. And as we've been observing in the data set that we've been presenting for the MSSDRC patients on active liver meds since, well, for the last almost 18 months.
18 months.
There is a substantial benefit in the combination and so as it relates to the first question versus standard of care standard of care for patients with one or two prior lines of therapy, it's offering a 3% overall response rate and a <unk>.
There is a substantial benefit in the combination and so as it relates to the 1st question versus standard of care standard of care for patients with 1 to 2 prior lines of therapy is offering a 3% overall response rate and a expected median overall survival of 12.9 months. That's coming from the arcade database of over 18,000 patients.
Expected median overall survival of $12 nine months, that's coming from the <unk> database of over 18000 patients and currently we're showing 24% versus 3% for response.
And currently we're showing 24% versus 3% for response.
And over 21 months before a median overall survival so.
And over 21 months for me and overall survival. So we need to be obviously meaningfully better than currently available standards of care. So looking at 3% versus 24% or 12.9 months versus over 21 months. I think it's clear to everyone that you could drive a truck through that.
We need to be obviously meaningfully better than currently available standards of care, so looking at 3% versus 24% or $12 nine months versus over 21 months I think it's clear to everyone that you can drive a truck through that now.
Now as it relates to the incremental contribution of valves still a map to Bolton still amount given our mechanism of action, which is really multifactorial first of all we have obviously, our optimized engagement with <unk> four and a receptor ligand interaction, but the backend engineering this resulting in suddenly and activation of both innate and.
Now, as it relates to the incremental contribution of BAL-Stilomab to Bolton-Stilomab, given our mechanism of action, which is really multifactorial, first of all, we have, obviously, our optimized engagement with CTLA-4 and a receptor-ligand interaction, but the back-end engineering that's resulting in suddenly an activation of both innate and adaptive immune response.
Captive immune response has created a hot meals U and we have we expect to see a substantial improvement in the combination certainly at least a doubling of response.
created a hot milieu and we expect to see a substantial improvement in the combination, certainly at least a doubling of response.
When we add belt similar math and so I think that's what we want to be able to discern.
when we add Valstilumab. And so, I think that's what we want to be able to discern. Just for comprehensiveness, we'll also remind everyone that in that same clinical trial we are looking at two active doses, one milligram per kilogram and two milligram per kilogram. And at the time of regulatory submission, we anticipate having approximately 175 patients in each of those two doses. So, we'll be able to have a robust.
For Comprehensiveness will also remind everyone that in that same clinical trial. We are looking at two active doses one milligram per kilogram in two milligram per kilogram.
And at the time of regulatory submission, we anticipate having approximately 175 patients in each of those two doses. So we'll be able to have a robust <unk>.
<unk> on the activity of the doses, one and two and also on the Tolerability of those two.
perspective on the activity of the doses, one and two, and also on the tolerability of those.
That's super helpful. Thank you and at the time of the BLA submission.
That's super helpful. Thank you. And at a time of BLA submission, would you expect to have any sort of overall survival early data from from this study?
Do you expect to have any sort of overall survival early data from this study.
Yes.
I think we would have certainly evident trend for patient benefit what we've observed pretty consistently in the phase one database, which is not small remembering about 101 patients in total there.
I think we would have certainly evident trends for patient benefit. What we've observed pretty consistently in the Phase 1 database, which is not small, remembering we've got 101 patients in total there for safety, and we have 70 patients.
For safety and we have 70 patients in the MSS CRC non active liver metastatic patient population for efficacy adjudication.
in the MSS CRC non-active liver metastatic patient population for efficacy adjudication, we are obviously seeing that responses for patients
<unk>, obviously seen.
That responses for patients.
And that response can be stable disease or better as trends leading to not only durable response, but very substantial overall survival I certainly expect that we'd be able to demonstrate a point estimates for response durability of response for patients with stable disease or better and that.
And that response can be stable disease or better is translating to not only durable response, but, but, you know, very substantial overall survival. So, I certainly expect that we'd be able to demonstrate a point estimates for response durability of response.
For patients with stable disease or better, and that that is trending toward a survival benefit. Remember also that the time of submission is not a moment in time. That's frozen because we will be required to provide updates on safety and efficacy during agency review and that will allow time for additional maturation of the data set. And again, as has been consistent since we began to show data in June of 2022, the longer the study goes, the more mature the observations have been around the durability of response and its translation to survival. So, I think we have a very, very robust.
That is trending toward a survival benefit remember also that the time of submission is not a moment in time, that's frozen because we will be required to provide updates on safety and efficacy during agency review and that will allow time for additional maturation of the data set and again.
As has been consistent since we began to show data.
In June of 2022 the longer.
The study goes the more mature the observations have been around the durability of response and its translation survival. So I think we have a very very robust set of data to present to the agencies for their review.
set of data to present to the agencies for their review.
Got it that makes sense and on the cash guidance can you maybe just provide a little bit more color on what's included in that in terms of the ongoing and planned studies.
Got it. That makes sense. And on the cash guidance, can you maybe just provide a little bit more color on what's included in that in terms of the ongoing and planned study?
Say the.
If you can repeat the question on the latter part of your question.
Say the, if you can repeat the question on the latter part of your question.
Yes, just on the on the updated cash guidance.
Yeah, just on the on the updated cash guidance.
Got it okay. Okay. So.
I got it, I think. Okay. So, as you know, we finished the quarter with a little over $100 million.
As you know we finished the quarter with little over $100 million.
My guidance for the fourth quarter burner.
My guidance for the fourth quarter burn is approximately $40 million.
Is approximately $40 million.
Now.
Beyond that.
Now, beyond that, as we've said earlier,
We've said.
Earlier.
We will have a milestone payment.
We will have a milestone payment that is due to us by the end of this year.
That is due to us by the end of this year.
And reasonable so.
So two assets.
And we will sell two assets that are non-strategic assets. We expect that to be completed in the first half of this next
In our non strategic assets.
We expect that to be completed.
In the first half of next.
Next year.
And then.
Third party royalty transaction.
And then I turned to HathiLorel to transact.
Now of course.
Now, of course, the first two are entirely now controlled, meaning the milestone payment and the asset share.
First two are entirely in our control.
Milestone payment and the asset sales.
And the royalty transaction will require.
and the loyalty transaction will require external investment.
I know investors.
For that kind of a transaction we have done that before.
for that kind of a transaction. We have done that before. Some years ago, in fact, about five years.
Some years ago about five years ago.
We consummated the transaction for third party royalties when we had much skinnier.
we consummated a transaction for third party royalties when we had a much skinnier royalty portfolio.
Royalty portfolio at the time.
And we did this with XOMA Corporation. So we're talking about a transaction that will be multiples of that transaction for a much larger and much more attractive portfolio.
And we did this with Zoma Corporation. So we're talking about a transaction that will be multiples of that transaction.
for a much larger and much more attractive portfolio that has had some very encouraging comments.
Okay.
Very encouraging.
Comments.
Our partners.
So with those we expect to bring in approximately $200 million.
So with those, we expect to bring in approximately $200 million of cash between now
Okay.
Between now and the middle of next year that is through non stock issuance.
that is through non-stock issuance.
We have any stock issuance.
without any stock issuance, we expect to bring in approximately.
Approximately $200 million and with that it will take us well beyond the end of next year.
And with that, it will take us well beyond the end of next year.
Got it thank you.
Yes.
Okay.
Yeah.
Okay.
Yeah.
Yeah.
Yeah.
Yes.
Any other questions.
Any other questions? Mayak Manthani, your line is open.
My Ekman Toni your line is open.
Good morning, Thanks for taking our questions and helpful recap, albeit small demand data.
Good morning. Thanks for taking our questions and helpful recap of the ISMO event data. So, maybe just to clarify on the
So maybe just.
To quantify it.
Second line plus CIC Axeda approval.
Second line plus CRC-accurate approval, you know, are you able to talk to the specific guidance you may have on
Are you able to talk to.
Specific guidance you may have on the design of the Phase III continue daily study and maybe timing of initiation.
the design of the phase 3 confirmatory study and maybe timing of initiation.
Just kind of round out the updates you provided and then I will follow up.
to just kind of round out the other updates you provided, and then I'll follow.
So I'll just make a brief comment on the confirmatory study studies and then I'll ask Todd to.
So I'll just make a comment on the confirmatory studies and then I'll ask Todd to provide additional color.
To provide additional color.
With regard to confirmatory studies, we have two choices one is to do.
With regard to confirmatory studies, we have two choices. One is to do a confirmatory study in the second or third line setting.
Cemetery studies.
In the second or third line setting.
The other one is to do a confirmatory study in the first line, we have not made that decision yet.
The other one is to do a confirmatory study in the first light. We have not made that decision.
We've had discussions with the FDA.
We've had discussions with the FDA on the latter line confirmatory study. We have not yet had discussions on the first line because we're awaiting data from an ISD study, which is ongoing right now, which studies Botbao and Tupo.
The latter line confirmatory study, we have not yet had discussions on their first line because we're awaiting data.
From an Isd study, which is ongoing right now which studies.
Hum.
Yes.
And we expect that data to be available in the first quarter of next year and that will inform us better.
and we expect that data to be available in the first quarter of next year and that will inform us better which way to go, whether we go the first line or third line. Todd, would you like to add any?
Which way too low when we go to satisfy our telecom Todd would you like to add any additional color on this.
Yes, I just had a couple of points to that we already.
Uh, yeah, I just had a couple of points to that. We already, um, my act now that we have a clear understanding of how to.
Now that we have a clear understanding of how to preemptively manage short term intervene early on GI toxicity, you already have a higher level of comfort with regard to our ability to combine in the frontline with buyback you in Sally platinum based regimens of course, which are have associated Gi toxicity.
preemptively manage or intervene early on GI tuxes, you already have a higher level of comfort.
with regard to our ability to combine in the front line with 5FU and Ox Valley Platinum based regiments.
Of course, which are have associated toxicity. So that that level of comfort is rising. But at city of hope, we are conducting a study to determine what the best management paradigm would be for the combination.
So that that level of comfort is rising but at city of hope we are conducting a study to determine.
Determine what the best management paradigm would be for the combination and addition to that I think we have greater strength of evidence for incremental benefit in earlier lines of therapy derived from the preliminary data that we're seeing in the neo adjuvant setting.
In addition to that, I think we have greater strength of evidence for incremental benefit in earlier lines of therapy derived from the preliminary data that we're seeing in the neoadjuvant setting.
So I think our objective will be to optimize the development program to accelerate access for patients to a broader patient population and so there is a lot of regulatory precedent for doing a confirmatory trial in either a broader patient population than the accelerated approval indication or <unk> oriented earlier aligning.
Um, so I think our objective will be to optimize the development program to accelerate access for patients to a broader patient population. And so there's a lot of regulatory precedent for doing a confirmatory trial and either a broader patient population than the.
Accelerated approval indication or and or in an earlier line. And again, at the end of the day, the decision with regard to the design of the confirmatory trial will will require alignment with both the US and European authorities. And we're, we're basically looking at 2 potential options, at least that we would present for their for their review.
Again at the end of the day the decision with regard to the design of the confirmatory trial.
<unk> will require alignment with both the U S and European authorities and were basically looking at two potential options at least that we would present for their for their review.
Very helpful. Thank you and then on the new pancreatic cancer bulk chemo data quick could you just clarify what number of locations you are targeting in the randomized controlled cohort and if you are seeing any uptake in enrolling similar to what occurred in the colorectal cancer expansion cohort last year and total value.
Um, very helpful. Thank you. And then on the new pancreatic cancer, uh, bought chemo data. Could you just clarify what number of patients you are targeting in the randomized control cohort and
If you are seeing any uptick in enrollment, you know, similar to what occurred in the colectal cancer expansion cohort last year and and and for the relatively warmer tumors, you know, in lung and melanoma seems like you have both.
Disney Walmart deal in lung and melanoma. It seems like you have both mono and.
Mono and and what battle combination data. So, you know, there is a
Combination data.
There is.
Our team here at all.
a theme here of monobot data and combination bot data. So how are you sort of thinking across thematized?
One on board data in combination <unk> data. So how are you sort of thinking grodsky Mike died.
Where you may pursue board sign alone versus maybe combination.
where you may pursue, you know, bot standalone versus maybe combination. If there's a view on that, you could share. And I have one more financial question.
And then beyond that you could share and one more financial question.
Thank you Dr. <unk> would you like to take that first part first multipart question.
Thank you. Dr. O'Day, would you like to take that first part, the first multi-part question?
Martin can you repeat the very first part of it I have the melanoma part but.
Yeah. Myra, can you repeat the very first part of it? I have the melanoma part, but...
The Bankrate downturn, Bob Chemo data number of patients that you're targeting and the randomized controlled cohort and if you've seen any uptick in enrollment, yes like what happened in the clinic. So we have a lot of enthusiasm around the data so far with both our pis on the pancreas study, but more broadly.
The pancreatic cancer brought chemo data, number of patients that you're targeting in the randomized control cohort, and if you see any uptick in enrollment, like what happened with the...
So we have a lot of enthusiasm around the data so far with both our PIs on the pancreas study, but more broadly, KOL.
So we are expanding that and it is accruing and we plan on treating another 60 patients and randomization.
So we are expanding that and it is accruing and we plan on treating another 60 patients in randomization in the coming months. Got it.
In the coming months.
Got it.
Go ahead from the melanoma or amendment.
Terms of melanoma.
Obviously, we have single agent activity in melanoma, and a PD one PD one CTG for refractory that we've reported in our <unk> trial, we have now accrued.
Obviously, we have single agent activity in melanoma in a PD-1 CTLA-4 refractory that we've reported in our 1B trial. We've now accrued...
A large number of patients to monotherapy in both a PD, one refractory and PD one <unk> four refractory.
a large number of patients to monotherapy in both the PD-1 refractory and PD-1 CTLA-4 refractory at two different doses. And as I said today, we're combining it with BAL, and that data will be maturing, and we look forward to presenting it in 2024.
At two different doses and as I said today, we are combining it with Val.
That data will be maturing and we look forward to presented in 2024.
Got it.
Got it. And maybe for Garo, you know, this concept of structured financing or even corporate partnerships, I was just curious if there's any sort of segmentation you're thinking by indication or geographies, you know, are there any sort of constructs and deal term sheets that are more preferred versus less? If you could provide some color there, that would be helpful. And thanks all for taking the call.
Maybe legato.
The concept of structured financing or even cargo partnership I was just curious if there's any sort of segmentation you're thinking by indication geographies.
Are there any sort of.
Pawn shops and dealer balance sheets that are multiple Florida versus last if you could provide some color there would be helpful and thanks for taking my questions.
So the kinds of discussions that we're having in some of the mining in advanced stages as I said before.
So, the kinds of discussions that we're having, and some of them are in advanced stages, as I said before, really encompass both a global collaboration across all indicators.
Really encompass both a global collaboration.
Across all indicators.
And as well as specific indication collaboration for which.
specific indication collaboration for which infrastructure exists at some company.
Infrastructure exists at some companies.
To be able to segregate product.
to be able to segregate product by indication.
By indications.
That's new technology, and we've been proposed the potential option of segregating certain indications.
That's new technology, and we've been proposed the potential option of segregating certain indications that are of great importance.
A greater interest.
So we're looking at all of these options simultaneously.
certain factors. So we're looking at all of these options simultaneously and I think that a good deal
I think the.
And a good deal for us would be driven by several things number one.
would be driven by several things. Number one, the appropriateness of the collaborator, their conviction that our product could be a significant player in the immuno-oncology and broader oncology.
Appropriateness of the collaborator there Ken.
Dixon.
Our product could be a significant.
Players in the immuno oncology and broker oncology fields.
So that's number one because we believe that potentially.
So, that's number one, because we believe that Potential Amount Plus, Postal Amounts, offers performance.
I'll start with that.
Offers.
Performance advantages that we have not seen.
Any.
Immuno oncology and oncology treatment setting.
at any immuno-oncology and oncology treatment setting. So, for example, when we talk about patients that have either failed all other therapies or do not respond to other therapies, not just immunotherapy but beyond immunotherapy, these are patients that are in dire need of a product that alters them and potentially.
So for example, when we talk about patients that have either failed all other therapies or do not respond private not just immunotherapy.
Beyond <unk>.
Is that patients are in dire need of.
And product offerings to them.
And potentially curative option.
With toxicity that is transient.
with toxicity that is transient.
I think that there is a.
I think that there is a an enormous need in the field for such a.
And enormous need in the field for such a product.
Well eventually lap offer expect treatment option for patients.
And I think potential in that offers that treatment.
Now.
So given this partner must have high conviction.
Now, so given this, the partner must have high conviction that this product could be a huge win for patients.
This product can be a huge win for patients and a huge win commercially as a result.
and a huge win commercially as a result of it, that's number one. Number two, the partner needs to make the appropriate financial commitments, not just for compensating us in terms of
Number two.
Good partner needs to make the appropriate financial commitments.
Not just for compensating us in terms of upfront and milestones.
So substantial financial commitment for the development of this trial.
but also a substantial financial commitment for the development of this product.
And development has to be rapid.
As we've said before.
because as we've said before, we have seen...
We have seen.
Clear clinical activity.
In so far nine different cancers.
in so far nine different cancers. You can't lie about that. It's real.
You can't lie about that.
It's really it's been presented at major conferences.
And so of course, there are regulatory and other questions arrive.
And so, of course, there are regulatory and other questions about do overall response rates translate to longer-term benefits?
Do overall response rates translate to longer term benefit.
We know they do we need to demonstrate that with numbers, but with CRA for binding antibodies and ours is a multi functional.
We know they do. We need to demonstrate that with numbers, but with CTLA-4 binding antibodies, and ours is a multifunctional, a broad-functioning molecule that binds to CTLA-4 as one of its five different activities, not just the center stage activity.
Broad functioning.
A molecule that binds the CMA for as one of its five different activity.
Not just the center stage activity.
To five different activities. So all of that means that this product needs to be rapidly developed.
So all of that means that this product needs to be rapidly developed and cross.
Across all indications.
Hey, henchmen to my quadrant Slide you will see that the opportunity for cancer.
If you pay attention to my quadrant slide, you will see that the opportunity for cancers, cancer patients is enormous.
Cancer patients is enormous.
The partnership has to be based on a commitment financial commitment for rapid development.
So the partnership has to be based on a commitment, financial commitment for rapid development.
And then of course.
Our cultural.
And of course, other cultural compatibilism.
Compatibilities.
That will allow our.
that will allow our A-team to work with
<unk>.
To work with partners 18.
To bring this into a high <unk>.
to bring this into a harmonious conclusion.
Conclusion.
Yes that makes a lot of sense, thanks for taking our questions.
Okay.
Your last question comes from the line of Kelly <unk> with Jefferies. Your line is open.
Your last question comes from the line of Kelly Shee with Jeffries. Your line is open.
Hi, This is Kelly.
Hi, this is Claire Han for Kelly. Thanks for taking our questions. So just one question for the plan for CRS.
Taking our questions.
So just one question.
Or the.
The plan for CRC.
So can you remind us what's your plan for those CRC patients pledge to live in that.
Phase three confirmatory studies specifically.
Patients with Oliver Metzger is there as an option to look at all convert patients. Thank you.
So I will I will.
A little crack it and then I'll ask a doctor or day two.
So I will take a little crack at it and I'll ask Dr. O'Day to also come in on this.
Also.
Comment on this.
So as you know.
Liver Mets.
Hey.
liver mets is a is a sort of a
Sort of a black box right now.
Okay, there's no clear answer as to why lever med patients.
There's no clear answer as to why liver medication.
This plan there is speculation about why they may not respond.
response, there is speculation about why they
And of course liver.
Privileged organ.
And of course, the liver is a privileged organ.
When a lateral.
Immuno suppressive.
with a lot of immunosuppressive
Components to it now.
Now we are looking at.
Now, we are looking at a number of ways of overcoming it. For example, if you look at our pancreatic data,
A number of ways of overcoming.
For example, if you look at our pancreatic data.
All patients.
Small number.
That had been treated.
a small number of patients that had been treated, had liver cancer.
Live events.
All patients that have responded have had their limit liver Mets.
and all patients that have responded have had their liver
We don't know if any of the other chemotherapies components are contributing to this.
We don't know if any of the other chemotherapy components are contributing.
So there's some speculation that Jim Decitabine may play a role in this we don't know yet but.
or there's some speculation that germcidia may play a role.
But I think in the next coming months.
We don't know that, but I think in the next coming months, we will have a very deliberate action.
We will have a very.
Deliberate.
Action plan.
And trying to answer this question.
and trying to answer this question with small trials, possibly ISDs that will be undertaken.
With small trials, possibly Isps that will be undertaken.
Let's see if we can translate some of what we were observed.
to see if we can translate some of what we observed in pancreatic cancer can be also actualized in CRC. But right now we're working with limited knowledge.
Cancer can be also.
Actualize.
CRC.
But right now we are.
Working with.
Limited knowledge.
But I think as you said this is an area that needs to be explored various diligently.
But I think, as you said, this is an area that needs to be explored very diligently.
Dr <unk>.
Yeah. So obviously in the refractory colorectal patient population the Io Io combination of Bob Al hazards.
Yeah, so obviously in the refractory colorectal patient population, the IO combination of bowel has its most profound signal to date in the non-active liver patients. These are patients who've never had liver metastasis or have had treated liver metastasis.
Most profound signals to date in the non active liver met patients. These are patients who've never had liver metastasis or had treated or treated liver metastasis.
But depending on the alignment of the phase III trial as Todd said.
But depending on alignment of the phase three trial, as Todd said, if we do move to first line, obviously we would treat all comers. And so we will be aligning our phase three trial with in the coming weeks and months.
We do move to first line, obviously, we retreat all comers and so.
So we will be aligning our phase III trial with <unk> in the coming weeks and months.
Thank you.
Yeah.
There are no further questions at this time, Garo Armen I'd turn the call back over to you.
There are no further questions at this time. Gero Armen, I turn the call back over to you.
Thank you very much everyone for your attentiveness to our developments.
Thank you very much, everyone, for your attentiveness to our developments. This is a very exciting time, I believe, for cancer patients.
This is a very exciting time I believe for cancer patients.
Certainly.
<unk> that are in desperate need.
certainly patients that are in desperate need of effective therapies, but not just therapies that extend their life by a month or two, at a very high cost of
Effective right now.
Not just therapies that extend their life by a month or two.
At a very high cost.
Paula <unk> life.
Potentially.
Potentially expanded live much longer with potential curative outcomes in some patients.
but potentially expand life much longer.
with potential curative outcomes in some.
And with a much much more acceptable more dignified quality of life with some gas.
and with a much, much more acceptable, more dignified quality of life.
Astro and test some of those side effects that are typical to over activation of the immune system.
with some gastrointestinal side effects that are typical to overactivation of the immune system.
They are reversible.
And I think if you look at our record.
And I think if you look at our record, our physicians.
Our physicians.
Have learned that reverse abilities and functional rapid into adventure.
that reversibility is a function of rapid intervention.
And as our trials progress from earlier stage phase one trials, we expanded cohorts of patients two phase II trials.
And as our trials progress from earlier stage phase one trials, we expanded cohorts of patients to phase two trials.
We've seen a significant improvement in the way.
we will be seeing a significant improvement in the way our transient toxicities are managed. So it's a very exciting time for patients and other than
Our <unk>.
Transient toxicities are advantage. So it's a very exciting time for patients.
And other than the.
Obligations that we need to wholesale in order to bring these products to patients.
obligations that we need to fulfill in order to bring these products to patients very rapidly. I think the future looks brighter than it has ever looked in our company's history and
<unk> rapidly.
I think the future looks brighter than ever in our company's history.
Career.
Zero and an operator in this business. So thank you very much.
career as an observer and an operator in this business. So thank you very.
Yeah.
This concludes today's conference call you may now disconnect.
This concludes today's conference call. You may now disconnect.