Q3 2023 Oncolytics Biotech Inc Earnings Call
Good morning, and welcome to Uncollected biotech third quarter 2023 conference call. All participants are now in a listen only mode. There will be a question and answer session at the end of this.
Paul.
Please be advised that this call is being recorded at the company's request.
I'd now like to turn the call over to Jon Patton Director of Investor Relations and Communications. Please go ahead.
Thank you operator, and good morning, everyone.
Earlier this morning on Craigs issued a press release, providing recent operational highlights and financial results for the third quarter of 2023, a replay of today's call will be available on the events section of the unpredictable site approximately two hours after its completion after the Max and company management, we will open the call for Q&A.
As a reminder, various remarks made during this call contains certain forward looking statements relating to the company's business prospects and the development and commercialization of Peloria right.
Statements regarding the company's mission strategy and objectives can these beliefs as to the potential mechanism of action and benefits of television right. There's the cancer Therapeutics, a clinical pipeline I believe that we are on track for licensure, enabling studies anaesthetic breast cancer and metastatic pancreatic cancer.
<unk> plans expectations regarding their leases or additional results and our updated irrespective.
Pinnacle studies.
These business development plans and strategies and other statements related to anticipated developments and the company's business. These statements are based on management's current expectations and beliefs and are subject to a number of factors, which involve known and unknown risks uncertainties and other factors not under the company's control that may cause actual results performance or achievements of the company to be materially different.
Results performance or expectations implied by these forward looking statements.
Any forward looking statements on credit spreads as an expectation or belief as to future results such expectations or beliefs are expressed in good faith beliefs have reasonable basis, but there can be more assurance that these statements are expectation I believe will be achieved these factors increase yourself, just kind of a pending clinical trials.
It's associated with intellectual property protection financial protection actions by regulatory agencies and there's other factors detailed in the company's filings with SEDAR and the SEC critics does not undertake any obligation to update these forward looking statements, except as required by applicable law.
Now I'll bring on CEO, Dr. Matt Coffey for his overall highlights.
Introduce the rest of the management team, who will be speaking today Matt.
Thank you John I'll open by saying that athletic has made substantial progress since our last quarterly update and I wanted to say thank you for joining us for today's call to hear about these operational highlights and third quarter 2023 financial results.
During the call today are Chief Medical Officer, Tom <unk>, our global head of business development and you've got a thorough our chief financial Officer, Kirk look and I will present, an update on our clinical program.
To summarize the data we presented at ESMO and other recent and upcoming medical meetings.
That's how recent data readouts and other opportunities bolster our business development efforts and potential.
Outlined our upcoming milestones and provide you with our outlook on our cash runway and summarize third quarter financial results.
Then well open the call up for questions.
Our clinic intends to deliver on its mission to improve the survival of patients with cancer by investigating the novel immunotherapy Palo railroad or pillar as we will refer to it in carefully selected indications and treatment regimes that will leverage its unique mechanism of action to provide the most meaningful clinical benefits.
This is measured by improvements in overall survival and progression free survival supported by an improved T cell profile.
The data presented at the European Society for medical oncology or ESMO from the pancreatic and colorectal arms at the Goblet study are a highlight of 2023.
I'd like to underscore a few observations and Tom will take you through the detailed results.
First.
We have now met the Simon two stage success criteria in two consecutive goblet cohorts evaluating <unk> in patients with first line pancreatic in third line colorectal cancer.
Importantly, this was the third indication, where we've seen pellet combined with a seasonal as the map provided encouraging results in patients.
These are breast cancer with the aware study plus pancreatic in third line colorectal cancer and the goblet study.
Also continue to see the combination of Impella in chemotherapy, providing response compared to historical controls demonstrating its potential as an immune therapy backbone.
Additionally, we're seeing expansion of tumor infiltrating lymphocytes or til clones correlated with tumor response, and a strong correlation between T cell clone expansion and improvements in the tumor microenvironment or <unk> consistent with pellets differentiated mechanism of action.
Critically pellet treatment continues to be well tolerated, which is important as we continue to evaluate additional indications and potential oncology treatment combinations and finally in addition to meeting the success criteria for both the pancreatic and colorectal cancer cohorts. The data are compelling, especially for pancreatic cancer, where we saw objective response rates.
Progression free survival rates and rates of overall survival that exceed historical control trials.
Taken together these data show, how Palo <unk> mechanism of action facilitates synergy with both chemotherapy and checkpoint inhibitors in multiple indications.
Furthermore, the results expand that dataset that forms the basis of a potentially compelling product profile for pillar and give us additional confidence in advancing our clinical program.
We will use the results of both Gaba segments presented at ESMO combined with our analysis of the current treatment paradigm in competitive landscape to map out our next steps for registration studies.
As we review our clinics third quarter, along with the Companys recent operations I believe there are three key take home messages.
First.
We believe <unk> has the potential to be a differentiated and effective immunotherapy that could improve the lives and overall survival of people with cancer. This is based on positive consistent results and gastrointestinal and breast cancer, including data presented at ESMO 2023 for pancreatic cancer and colorectal cancer.
Just the tally of our clinical data set showed significant improvements in tumor response, and overall survival coupled with highly correlated to mean, a logical responses measured by an improved T cell profile in the tumor microenvironment.
Second we are proud to be making the transition to a late stage company running registrational trials with the upcoming startup of the phase III precision promise study in pancreatic cancer.
Other important development is the recently award of a 5 million U S grants from Pan Qantas support a new phase II combination study in pancreatic cancer.
This study generate sustained responses, we've seen to date in pancreatic cancer. It could result in another pellet based combination therapy in selected for inclusion in the precision promise phase III platform trial.
Third we are well positioned to advance our clinical program based on our focus on capital efficiency with a strong balance of $40 million, including $17 million U S raised it in August public offering and the over allotment plus a $5 million U S pension grants.
Before I bring Tom on I want to thank everyone on the alcoholic steam for your unwavering dedication to our mission and your fine work now I would like to turn the call over to our Chief Medical Officer Tom.
Thanks, Matt and good morning, everyone. This morning, I would like to provide an update on our clinical programs.
Take you through the recent and upcoming medical meeting presentations.
And close by providing you with an update on our next steps.
As you know we have carefully designed our clinical development program to fully explore the clinical potential of <unk> across a range of cancers and treatment combinations.
<unk> chemotherapy and checkpoint inhibitors or both.
Our therapeutic approach takes advantage of power's ability to induce anti cancer immune responses through the introduction of its double stranded RNA into the tumor cells.
This results in a range of potentially beneficial immune effects, including the induction and expansion of anti cancer T cells.
At the same time, Hello, also modifies the tumor microenvironment to make it less immunosuppressive, which allows more effective killing of the tumor by pellet induced immune responses.
Our clinical pipeline is focused on two lead indications HR positive <unk> negative metastatic breast cancer and metastatic pancreatic cancer, which are on track for licensure, enabling studies. In addition, we're also investigating pillar and metastatic colorectal cancer and metastatic anal cancer.
We are making excellent progress on the clinical development of Palo.
Starting with breast cancer. The next milestone will be a readout of survival data from the bracelet one study.
While we cannot precisely predict when these data will be available we expect to be able to report results in 2024.
In pancreatic cancer, we expect to initiate the precision promise phase III study in the first half of 2024.
This trial will compare the goblet study treatment regimen of Pella, a piece of Elysium have gemcitabine and Nab Paclitaxel with a control arm of standard of care Gemcitabine plus Nab paclitaxel in patients receiving first line therapy for metastatic pancreatic cancer.
We are very excited to be part of the precision promise clinical trial.
This innovative study was developed with guidance from the FDA to accelerate the registration of novel pancreatic cancer therapies.
Participation in the precision promise clinical trial will allow efficient evaluation of the pellet based combination therapy and will reduce the cost of development by about 50% compared to a traditional pancreatic cancer phase III study.
If successful this clinical trial is expected to support approval of the pellet based combination therapy for first line treatment of patients with metastatic pancreatic cancer.
Pending finalization of the definitive study agreements.
And based on the timing of regulatory feedback in the pace of enrollment we hope to reach the initial data readout from the precision promise study in the first half of 2025.
Jumping into recent and upcoming medical meeting reports I would like to summarize the goblet data we presented at ESMO touch on our <unk> presentation.
And briefly comment on the anal cancer cohort from the Goblet study.
Let's start with the data presented at ESMO.
As you know goblet is an open label phase one to Simon two stage signal finding study designed to evaluate <unk> in combination with the PD L. One inhibitor of diesel as you know.
With or without chemotherapy in patients with different gastrointestinal cancers.
The primary objectives of each cohort of the study are safety and either objective response rate disease control rate at week 16.
Translational data, including T cell receptor sequencing are also being analyzed.
At ESMO, we reported updated clinical results from the pancreatic cancer in third line colorectal cancer cohorts, including overall response rate disease control rate progression free survival and interim overall survival.
And the pancreatic cancer cohort a total of 13 evaluable patients with advanced or metastatic pancreatic ductal adenocarcinoma we're involved.
Patients were treated with the combination of pillar the T for lithium mab Gemcitabine and Nab Paclitaxel.
In this cohort 93% of patients had metastatic disease, mostly and deliver.
Three or more responses at week 16, we're required to meet the predefined efficacy success criteria.
Updated data from this cohort showed that eight of 13 patients had a partial response and.
And three patients had stable disease.
These data translate to an objective response rate of 62% and a disease control rate of 85%.
We are pleased to report that this objective response rate is more than twice the rate of about 25% observed in earlier randomized studies in comparable pancreatic cancer patients.
Additional efficacy results as of the data cutoff of September 18, 2023.
So the median duration of response of five seven months.
Median progression free survival of seven two months.
In the interim median overall survival of $10 six months in an interim 12 month overall survival rate of 46%.
Like the objective response rate outcome. These results compare favorably to those reported in prior clinical trials.
Moving to the translation of results our updated data showed that steady treatment resulted in the expansion of T cell clones, including new and pre existing tumor infiltrating lymphocytes hotels imports.
Importantly, and consistent with prior studies expansion of til clones appears to correlate with tumor response.
No safety signals were identified in this or any of the goblet cohorts consistent with our other studies.
The updated results confirm that the pellet combination therapy outperforms historical controls and provides strong support for advancing pillar into the phase III precision promise study.
Next is the goblet colorectal cancer cohort.
Which <unk> in combination with the teaser lives. He may have been the chemotherapy trustworthy interpersonal also known as task 102 was evaluated in heavily pretreated patients who received two prior lines of chemotherapy for metastatic colorectal cancer.
Stage one of this cohort enrolled 15, evaluable patients of whom four achieved stable disease at week 16, indicating that this arm of the study also met its prespecified success criteria.
Overall, six patient showed stable disease for a disease control rate of 40%.
It is important to note that this is the second goblet study cohort in a row that has met its success criteria further supported the pillows ability to synergize with the diesel as you know.
In addition, translational data from this arm of the study demonstrated that pillar increased the tumor expression of PDL, one as well as the expansion of new T cell clones in the blood.
Therefore, these data confirm that pellet is taken up by tumor cells and is able to stimulate T cell expansion, even in heavily pretreated colorectal cancer patients.
These results are encouraging given that exhaustion of tumor infiltrating lymphocytes resolving from the late stage of the disease and from extensive prior chemotherapy.
Limit their ability to expand in response to treatment.
Moving onto city, we presented the translational data from the aware one breast cancer studies in an abstract.
With the full data from the posts are expected later today.
You may recall with the aware one study evaluated <unk> plus left resolved with and without <unk> in patients with HR positive <unk> negative breast cancer.
Data presented at ACR in 2021 showed that this combination acted synergistically to up regulate PD lone expression on tumor cells and enhanced infiltration of T cells into the tumor.
The study data presented at <unk>. This year includes imaging mass cytometry or IMC to study samples at the single cell level.
From patients who receive power letrozole in acute leukemia.
IMC technology makes it possible to evaluate tumor immune responses and cellular interactions in the tumor microenvironment in much more detail.
The results.
Reported this year at city provide further support for pellets mechanism of action.
By demonstrating its ability to increase cytotoxic T cells into tumor.
In addition, the data show that pillar up regulated PD lone expression in tumor tissue.
Potentially making tumors more amenable to checkpoint inhibitor therapy, such as strategic lose Ya man.
With the game changing availability of checkpoint inhibitors and the recognition that many patients progress where do not respond to checkpoint inhibitor treatments.
A great deal of effort being made in the biopharmaceutical industry to find and test treatments that can turn a patient who would likely not respond to checkpoint inhibitor therapy into one who would.
This may be achieved by making the tumor microenvironment more immunologically active that is to say hot and attribute palla is demonstrated in several different cancers.
I should note that the synergy of pillar with a T cell as you might have in breast cancer as demonstrated in the aware. One study is what prompted uncle index to select a T cell lithium at this as a checkpoint inhibitor to combine with pellet and the goblet study of gastrointestinal cancers.
Finally, I will touch on the anal cancer cohort or the goblet study.
This was also designed to Simon two stage study in stage, one we will enroll 10 evaluable subjects eligible for second line or later therapy.
Who are treated with a combination of pillar and a T cell as you map without chemotherapy.
Who are more responses are required to meet the pre specified success criteria and advance to stage two of the study.
We expect to report interim results from this cohort, including preliminary objective response rate.
In Q4 of 2023 these.
These results will help to shape, our future development pathway for this program.
Everyone at <unk> is genuinely pleased bechtel is consistent.
Clinical success and a series of difficult to treat cancers, which also includes HR positive <unk> negative metastatic breast cancer is reported at Astro last June.
These clinical successes are strongly supported by the translational research results that further solidify pellets immunologic mechanism of action and make us optimistic that tullow has the potential to be a highly effective immunotherapy for people with different cancers.
Before I hand, the call over to Andrew.
I'd like to take a moment to thank all of the patients caregivers clinical investigators study site teams and our many collaborators for their efforts and dedication to advancing pillar for the benefit of cancer patients.
Drew.
Thanks, Tom as discussed the positive and consistent data Readouts. We've seen this past month for gastrointestinal cancers, along with a bracelet one data from Moscow continue to keep us engage with existing and new potential Biopharma partners.
On our previous financial results call I mentioned the process of bringing some of these relationships all the way through fresh and can take time.
We are thrilled to be selected by precision promise for the adaptive phase III platform trial with the combination of pellet Gemcitabine and Nab Paclitaxel in a teaser ledger mapped in pancreatic cancer.
Initial pancreatic data from that treatment combination from cohort one of the goblet study.
It was announced around this time last year, but bank selected for precision promise and receiving grant from paying Ken to explore Palo with modified fill ferredoxin pancreatic cancer only came to light late this past summer.
There was a rigorous vetting process with multiple meetings over many months with experts and key opinion leaders from paying Ken. So we're thrilled to have proven palace potential to a well respected global panel of experts.
The opportunity was palette modify infill fair enough could be potentially very meaningful.
Standard of care for pancreatic cancer hasn't changed much for several decades with most patients receiving either modified Fullfare Knox art Gemcitabine, plus Nab paclitaxel as their first line metastatic treatment options.
Ah Palo based combination with Gemcitabine and Nab Paclitaxel will be evaluated in the precision promise phase III study, which covers one of the treatment options for pancreatic cancer patients.
If pallet can also showed similar signs of efficacy when combined with modified pill fair enough with.
With or without a checkpoint inhibitor than <unk> could capture significant first line patient population and provide thousands of pancreatic cancer patients with an improvement over the currently available treatment options.
Keep in mind, our BD goals remain the same.
<unk> secured global clinical and commercialization partnership with a leading Biopharma company under optimal charts.
We already have relationships with companies like Pfizer, Merck Roche insight and others.
A number of our studies, including Goblin and bracelet, one have been conducted clinical collaborations with these large pharmaceutical companies.
Collaborations have provided us with important validation support.
Including the agents used in the treatment combinations.
Working collaboratively and continuously updating them on our clinical progress enables them to become increasingly comfortable with pallet its mechanism of action and its potential to improve the lives of cancer patients, which we believe will serve us well in any partnering discussions.
I try to remind our shareholders that we can't predict the timing of any potential partnership will be thorough as we navigate the best possible outcome for <unk> and its shareholders. We hope to secure single licensing deal for both our breast cancer pancreatic cancer programs allows us to minimize clinical and commercial risk.
Providing upside through upfront payments milestones and royalties.
As we continue to report encouraging data across multiple indications and with multiple cancer treatments, we intend to create competition among potential partners and foster continued interest.
We plan to provide additional updates as appropriate and look forward to enhancing <unk> value proposition.
Now I'll hand, it to Kirk for a review of our financials Kirk.
Thanks, Andrew.
This morning, I'd like to provide an update on our cash balance.
Our financial runway and provide you with a high level review of our operating results for the third quarter of 2023.
As a reminder, all figures are in Canadian dollars unless otherwise stated.
First I'll touch on our financial position cash balance and financial runway.
I'm pleased to report, we closed the third quarter with $40 million in cash and cash equivalents.
During the quarter. Despite the continued challenging capital market environment, we successfully closed a public offering securing over $21 million.
Yeah.
Along with the prudent use of our at the market facility in the first half of the year, we have raised over $30 million in 2023.
With the recently announced 5 million U S. Dollar grant from Pan Ken We've continued to maintain a financial runway that exceeds 12 months.
With respect to our operating results on clinics continues to demonstrate remarkable fiscal responsibility.
We aim to maximize our resources ensuring that each dollar spent contributes to our R&D efforts as we move our breast and pancreatic cancer programs towards approval.
Our research and development expenses for the third quarter of 2023 were $5 8 million compared to $3 7 million for the same period in 2022.
The change, mainly reflecting higher manufacturing expenses as we scale up our production process and work to comply with changing environmental standards.
Specifically during the quarter, we completed the scaled up engineering production along with the associated batch testing.
General and administrative expenses for the third quarter of 2023 were $5 2 million and this compares with $2 4 million for the same period in 2022.
The change was mainly associated with higher Investor relations activities, along with a portion of the transaction costs associated with our public offering allocated to G&A expenses.
Net loss for the third quarter of 2023 was $9 9 million or <unk> 14 per share on $69 8 million weighted average shares outstanding this.
This compares with a net loss for the third quarter of 2022, a $4 4 million or <unk> <unk> per share.
Finally, with our prudent financial management combined with our ability to secure funding in this tough equity capital market, we are well positioned for 2024 and achieving our development milestones.
With my financial review complete I will now hand, the call back to Matt for concluding remarks, Matt.
Thank you Eric.
In closing I want to come back to our three key take home messages.
First we believe Palo has the potential to be a differentiated and effective immunotherapy that have improved the lives and overall survival of people with cancer.
Second we are proud to be making the transition to becoming a late stage company running Registrational studies with the start of the phase III precision promise study in pancreatic cancer on the horizon.
Third we are well positioned to advance our clinical programs based on our solid cash balance that gets us to key data readout milestones.
Looking ahead to the rest of the year and into 2024, we're focused on achieving the following milestones.
Later today, we will be presenting additional cellular immune data from the aware study demonstrating.
I'll pelo replication in the presence of a teetotalism mab derives the immune cells into the TMA and homes and to the infected cancer cells.
By the end of the year, we expect to provide an update on the fourth cohort from the Gaba trial in patients with anal cancer.
In the first half of 2024, we expect to announce the start of the phase III precision promise study in pancreatic cancer. This is a combination study with pella Nab Paclitaxel gemcitabine and the checkpoint inhibitor Athena lesser amount of solidifying athletics as a late stage clinical opportunity.
Also in the first half of 2024, we will initiate a new arm and the <unk> study evaluating <unk> in combination with modified self aeronautics with or without <unk> in patients with early stage pancreatic cancer supported in part by the $5 million scrap we received from <unk> Tim.
Also we expect to report survival data from the bracelet one study in patients with HR positive <unk> negative breast cancer.
The timing of report. These results is linked to the number of progression events defined as disease progression or death.
While it is not possible to predict the exact timing for survival data. We believe that may be available before the end of 2024. We are evaluating next steps for this indication and plan to provide investors with a further update on our plans in 2024.
Now before we sign off I want to thank our investors investigators and collaborators for supporting Onkelinx Im.
I'm also grateful for the patients participating in our clinical trials and our fantastic employees for their hard work.
We are dedicated to leveraging <unk> unique mechanism of action to improve the care and survival of patients with cancer and we look forward to keeping you informed about our progress.
Operator, we can now open the line for questions.
Thank you ladies and gentlemen, we will now begin the question and answer session. So do you have a question. Please press star followed by the number one on your Touchtone Tsai UBS, Hey, Tom Tom That's already in your request and your questions will be pulled into or their daily seats. So is the rest of the decline.
The polling process. Please press star followed by the number too.
If you are using a speaker phone please lift your handset before pressing any calls.
Our first question comes from the line of.
Chen from Cantor. Please go ahead.
Hi, congratulations on all the progress this quarter and thank you for taking my questions.
Wanted to ask you about bracelet, one and if theres any new data or updates that gave you incrementally more confidence that you will show some good overall survival data.
And then secondly for the goblet email data what exact data or are you planning to show in the interim are you going to put out a press release and then if you are going to show data.
What do you think will be competitive data or how do you think about what you would ideally like to see and then last question on your partnership have you started those discussions yet and Neil what ideally what kind of partner would be good for you if somebody global somebody you know involved in oncology what do you think about here. Thank you.
Sure Hi, Louise Thanks for the question.
Your first question was about breast cancer and the bracelet data.
Yeah.
You can tell we're a little bit cautious about saying when we would have the overall survival of them then.
What makes me really quite excited about the evolving data.
As we reported at ESMO around ESMO.
Patients receiving paclitaxel, none of them. Unfortunately made a progression past 12 months and for the <unk> arm were seeing 33% I believe the number was we're still actually tracking patients on the pellet paclitaxel arm, who are at or above two years now.
Without progressing.
Further and metastatic breast cancer setting this is a remarkable outcome for these patients.
But as you can tell if the patients haven't progressed. They also haven't died so we're still collecting the overall survival data. We do believe we'll have the events.
In 2024.
But as I said, we're still tracking a number of the patients on the test arm core just PFS. So that's a fabulous outcome.
<unk>.
That's why we have the confidence frankly is just because they're still participating on study in terms of the anal cancer.
What we'll be looking for there.
His response data like the rest of the goblets what the primary endpoint was objective response I hear what we need for success is two out of 10 patients or better.
And that one is really quite exciting as well because if you look at it.
Simply tabling them out with pillar there is no chemotherapy. So this is.
Pre treated patient population in the second line setting.
If we do see responses.
It would be due to the drug combination attitude lives and have more color. So no. One can make the argument why maybe it was chemo or what have you now in terms of what the objective response rate in this population.
It's going to be.
Historically around 10% to 13% insight.
<unk> recently reported on a study.
And that patient population I think it was 90 to 100 patients ballpark, where they reported that most recently they had three studies one reported a 10% response 111, 1% <unk>. So if we see anything in excess of that.
Especially if the responses are dramatic deepened lapping.
It sets us on quite a successful of course, because these are as you know.
Anal cancer and the second one has no treatment options is a clear unmet need area. So if we see anything.
I think in excess of this 13%.
We're off to the races. If you will in terms of partnering.
We are in discussions with a number of groups.
Really what everyone's looking for I think and I think the catalyst I think this is.
What we're striving for as well.
The.
The <unk> study is.
Being run with a <unk>, obviously, that's going to be generating randomized data with a substantial and I think that is potentially an inflection point.
On the breast cancer side, what we'd like to do is.
Looking at trial design very similar to the Pan can where we can get an interim look which provides us and partners with the confidence that this drug combination is active again the data that we presented two randomized studies is very compelling both of them having reached.
There are endpoints both of them being either.
Physically significant for survival is 92014.
As you can see with the confidence intervals on.
Bryce, let's say that didn't cost one it does speak to the fact that it is statistically significant even in a small group, but we want to be able to generate.
Basically additional data.
With the parties so that everyone can come in prior to the completion of the phase III very much like in the past that situation now that being said.
We've been very fortunate with our work with the Teetotalism App.
We've now got three out of three successful studies that being the aware, which.
<unk> demonstrated.
The synergy with the seasonal of amount in terms of enhancing that total score enhancing the information and improving the quality of it the data were presenting today it sits with.
With the IMC really that much more granular look up which cells are being recruited.
Where we're seeing the inflammation and this is really at the cellular level. So what we're looking at here is the infected cells and which cells are being recruited to eliminate that sells whether it be master files MTS.
CDA positive.
T memory T helper. So it gives us a very granular look of what's happening, but it is very clear. This is driving an immunological response also successful as it was.
<unk> study, which led to the <unk> study and now more recently with their.
Third line colorectal, where again, we met the primary endpoint. So it's very clear that a synergy with teetotalism admin presumably other.
Either PDL one inhibitors.
Goblets.
I mean thats. The results are positive this would be the fourth study in a row that would show synergy with a seasonal as the map. So I think for parties looking at this as a partnering opportunity.
Even though the and they're small they're cumulative consistent re.
Producible, so I think.
That will drive some of the discussions as well and as Andrew pointed to you we've always wanted to be very.
Competitive across our partnerships.
But what we are looking for is the large biopharma that can take on a global role with us.
To take the indications, where we already know we're successful that being <unk> in metastatic breast cancer, and then expand that into other areas as well I mean for US right now the goal is to get that approval. So that we can expand access across multiple indications and settings.
Can you just provide more patients with the opportunity to receive it because we really are.
Quite impressed with the results that we're seeing as of late Tom was there anything you wanted to add either on the breast side or on the anal cancer.
No other than to emphasize that.
That.
We've now seen consistent success across HR positive <unk> negative breast cancer.
We've met the success criteria, obviously in pancreatic cancer colorectal cancer.
With the Adenocarcinoma report coming up.
I think everything is.
Looking very promising.
Yeah.
Thank you very much.
Thanks Louis.
Our next question comes from the line of John Newman from Canaccord. Please go ahead.
Hey, guys. Good morning, Thank you for taking the question.
Good work on all the progress here excuse me.
Just had a question about the Pan cancer study I believe you mentioned, you'll be starting that in the first half of 2000 and for.
The phase one two study.
What I'm curious about is are you able to treat through progression with <unk>. So obviously.
If a patient is being treated with.
Chemotherapy or a PD one.
<unk> therapies are not always continued progression, but I'm wondering if you're able to do that with just <unk>.
Yeah.
I'm going to push Tom under the bus on that one Tom can you speak to the plan in terms of dosing on the modified call fair enough study.
Yes, so well so for the for the <unk>.
For the precision promise study, which is the gemcitabine and Nab Paclitaxel <unk> entities and that study could protocol.
This protocol has been.
The written and with guidance from the FDA and it's been highly vetted in that protocol. There is no treatment TACE progression right.
We're also doing the.
Adding the additional arm to the goblet study.
Where we're combining <unk> with <unk>.
Modified fulfill <unk>, plus or minus the teaser lithium and and.
And in that study, we do have the option to treat past progression.
Okay.
Yeah.
Okay, great. Thank you.
Our next question comes from the line of Sydney fully from Jones Research. Please go ahead.
Good morning, everyone and congrats on all the progress.
Going back to the presentation on the pancreatic data.
It looks like.
The.
Would the real competitive study would be the Napoli trial with <unk> T can and the Oss is come in kind of coming close to it. So I'm curious in the frontline setting.
Are you thinking the modified closer arm is a better option.
You can see a very clear benefit in a larger patient cohort, what's you're thinking like.
We are.
Rachel report put out by the way I'm looking at the Napoli study.
I would argue that that patient population since they have not had previous exposure to any chemotherapy and they were predominantly.
Not in the metastatic setting as Gerard I wouldn't say, that's an apples to apples.
Comparison.
Also it was an odd study and that is basically a derivative of a modified fullfare nox in the comparative to Nab Paclitaxel I would've thought a better comparator would've been modified.
<unk> as the comparator arm.
Jim Nab Paclitaxel basically.
The thinking is it's not as active but you don't pay a tax penalty in a way that you work with modified fall for Aeronautics I would argue that Napoli study has a few fundamental differences and flaws that make the comparison difficult.
In terms of Pan counts interests with modified Fullfare Nox.
There is a lot of clinicians that prefer it because there is a thinking that it is more active although recent publications.
Publications at.
Altimo.
Primarily.
Uh huh.
I'm just trying to think that the group that did it.
<unk> pardon me is the group that published it would suggest that maybe the differences that as much as you could see that being said modified filter or nox is going to be used.
As one of the frontline treatment options Pan Cam did want a study to see if it is more active if we can enhance that activity with Palo Verde I referenced to the lithium out but it is an experiment, we're very delighted pankau and provided a $5 million grant for us to do this.
But we won't know the activity until we actually.
Treated.
I believe it's going to be more active but on the flip side. It's a lot more drugs the toxicity could be unacceptable, we've never seen that before but it is possible, but it could also be that the modified fault paradox interferes with your T cell response as well because there is so many drugs president. So we're running the experiment to see what the activity looks like what's nice about that one.
Is it is a randomized protocol. So it's modified fall Fahrenheit, capella, plus or minus teetotalism out. So we will have a better look at the contribution.
But again I'm not anticipating there'd be any toxicities with pella because it is so well tolerated to date.
It seems a little bit about combinations have been well tolerated as well, but with a new drug combination, there's always that little bit of uncertainty, but certainly we have the backing of a very prestigious group like Pan cancer studied us. So the belief is it will be more active.
We'll we'll know later next year, Tom do you have anything to add about that Napoli study.
Yeah.
Yes.
Yes, terribly sorry, yeah. The Napoli study was certainly an interesting study, but it didn't really for the reasons, Matt mentioned it didn't really answer all the questions and I think the power plus fulfill <unk> study will be very interesting and it's not that.
There is a <unk>.
Obviously reason why pillar.
Should work better with Sofia in OXXO.
But we have reasons to believe that.
But it may work with fulfillment and some clinicians.
<unk> for different reasons.
Different parts of the world simply.
Preferred procured in October the Gemcitabine and Nab paclitaxel for some of their patients. So by investigating <unk> in combination with the modified fulfill remarks, we are able we would be able to cover the entire.
Pancreatic cancer first line population right. So it expands our ability to provide benefit to patients regardless.
<unk> one particular.
Perspectives on the standard of care treatment and also just to comment on the safety side, we have never combined with modified some fair enough, but in other studies, we have combined pillar.
With the components of <unk>.
So we so although you never know for sure. We don't have any reason to believe that it will be who poorly with any of the components of the fulfill the next.
Okay.
So that was very helpful.
Another question is.
Probably not and Goldman criteria, but are you looking into the <unk>.
Any biomarkers of these 13 patients.
In terms of the genetic biomarker or PDL, one levels something to explain the non responders or patients who are seeing on.
The shorter duration of response and anything you're seeing there.
The one biomarker that I'm very interested in is.
The expansion of the tumor.
Tumor infiltrating lymphocytes that we've demonstrated correlates to.
Consumer response, so for anyone not familiar with the story, we were able to and it was a question of Roche outlets actually they said is there any correlation with the existing T cells and tumor response. So we went back and again. This is all the TCR work.
We looked at the resident T cells within the tumor the pills at baseline and the reason for that is the assumption is that if you have a inflammatory cells within the tumor that are most likely directed against the tumor. So this was an auto reactive T cell that's becoming exhausted.
So we wanted to look what happens to those to those tails post treatment and what we were able to demonstrate is in the responders. Those tills, we could see those clones expanding in the blood. So we know we're actually getting into an expansion of preexisting T cells that do recognize the tumor and we can look at that as early as you know.
Two to three weeks. So we can immunologically say these patients had an exhaustive T cell clone that was useful and eliminating the tumor and the combination of a T. The lives amount of Impella, we're able to expand those populations to eliminate the tumor more effectively so it speaks to the immunological status, we can measure quickly and it appears to be reproducible. So.
I think for us it allows us really to.
Start guessing, which patients are going to have better immunological outcomes. Tom you are closer to the protocols or any other biomarkers that we're looking at.
We are so we are looking at a variety of.
Different markers, but I think to date.
As you pointed out map.
Two expansion is the one that.
It seems to be the most.
It has the best correlation with response and is also consistent with the prior literature. So I think thats, probably the most interesting one that we've identified so far.
There's some additional work being done with <unk>, if you're familiar with the literature, Dr. Anne Noonan at OSU.
<unk> has demonstrated that patients with better outcomes have lower <unk> levels.
That was in the NCI study looking at this though.
We are verifying that result, as well because that could be a selection criteria based on upholstery them up but pretty treatment. So we will have additional information for you there in that area as well.
I think nothing you're seeing on the <unk> channel.
DNA.
Damages <unk> mutations.
Well just so in pancreatic cancer, the large majority of patients somewhere in the 80 plus percent will have a K Ras mutations so.
That is.
Unlikely to be discriminatory in that in that particular room.
Patient population.
Today's alright, thanks, so much for you.
Hum.
Thanks, Amit.
Ladies and gentlemen, just a reminder, so do you have a question. Please press star followed by the number one on your Touchtone filing.
Our next question comes from the line of Jason Mccarthy from Maxim Group. Please go ahead.
Hi, guys. This is Chad on for Jason Thanks for taking the question.
So I was just wondering in the same way you got the grant from Pan cancer on a different combo in pancreatic do you think there would be.
Similar opportunity and breast cancers say evaluating palo with the different checkpoint than was used in very slow one.
Excellent question.
Yes, we do believe that and again for people looking at the story at ESMO, We presented was.
A tripling of the objective response rate when we added pellet to Paclitaxel.
<unk>, 50% increase in the median overall survival.
And then we're tracking for overall survival.
Hazard ratio is <unk> nine so it was really quite a remarkable improvement.
When we added a valeant mab eliminated that benefit and what we've found out since in subsequently.
<unk> is the only approved checkpoint inhibitor with a non modified FC portion so for anyone.
Not familiar the FC portion.
On an antibody.
So an antibody basically it looks like the letter y or a wrench.
The part that would engage with the bolt is the F&B portion thats the portion that changes and finds the epitopes that allows you to have a selective antibody response against those specific epitopes.
The handle of the ranch.
Interacts with other immune cells.
Through MHC molecules.
Every other developed on the planet has silence that FC portion so that it doesn't engage with macro page.
And the reason for that is it can lead to.
You saw him golfman or macrophages engulf from other T cells, so as opposed to expanding a T cell response it'll.
It'll actually collapses and Theres actually publications in literature talking about how our value map treatment can actually lead to hyper proliferation that is to say it'll actually tumors grow faster. So it was a poor choice to combined with an agent like ours that relies on a T cell response and you can see this from our TCR sequencing.
The addition of <unk> caused detailed collapse.
When we spoke with partners about this they said that was unexpected outcome based on this non silent FC portion.
We still think breast cancer can benefit from the addition of a checkpoint inhibitor and especially something like Athena lithium out where it is directed against the PDL, one moiety rather than the PD, one and Thats just to say for us it's better because if we got an expression on the tumor cells itself. So we can actually direct where we want it.
So it should work with derma.
But what we've seen synergy with other PD ones that have non filer that how silent FC portions like Merck I'm, just with the growing body of evidence.
<unk> is looking really good in terms of the underlying synergies.
Yes, I think we should be looking at this in the breast cancer space and I think that becomes an important component of our lifecycle management.
For a couple of reasons I think we will be successful with just paclitaxel pillar.
Two randomized studies im very comfortable thinking that a third study is going to be as successful as the last two.
But the question is can we make it even better can we get to sleep responses.
Even better survival more objective response, so I think it makes sense to study that but the phase III is not going to look at that that will be more of a lifecycle management aspect and then the question is reimbursement.
Telecom Foundation.
It will be priced like other any other immunological therapy.
If we add a checkpoint inhibitor that will double that number again for the question of how much benefit do we have to see to ensure reimbursement of a drug combination that could be looking between three and $400000 conservatively. So it is a question we have to answer.
But it'll be answered as we're running the phase III program. So that we can say, okay, let's get the approval here's the next steps, but I agree with you wholeheartedly.
Unfortunately was a poor choice and I don't think it was reflective of the underlying synergy we see with other checkpoint inhibitors and it is something we can study and it was interesting we just had our board meeting yesterday.
And the clinical component of our discussions work.
We're running the phase Iia, where can we get other studies with cooperative groups like Pan can RTC NCI NTIC to really start bolstering studies into other pivotal indications.
And obviously checkpoint inhibitors can figure very largely into that.
Picture.
Great Yeah. Thanks for the detailed answer there and I'm, taking the question.
Congrats again on all the progress.
Thanks, Ed.
Okay.
That is our last question I'd now like to turn the call back over to Mr. Mccarthy for any closing remarks.
Thank you for that.
Thanks, again, everyone, who tuned in to hear about our progress the data presented at <unk> in pancreatic and colorectal cancer. In addition to our one abstract data presented at certainly reinforced the ability of pellets are remodeled tumor microenvironment and generate immune responses in patients even those with immune systems diminished by previous lines of therapy.
The data also adds to the portfolio are evidenced that Palo synergize with checkpoint inhibitors like diesel is about we'll continue to advance towards licensure, enabling studies in breast and pancreatic cancer and provide additional updates on our progress with that I wish everyone. A wonderful rest of your day. Thanks again, everyone I appreciate it.
Thank you, Sir ladies and gentlemen. This concludes your conference call for today, we thank you for participating and ask that you. Please disconnect your lines have a lovely day.
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