Q4 2023 Cardiff Oncology Inc Earnings Call
Yeah.
Operator: Welcome to the Cardiff Oncology 4th Quarter and Full Year 2023 Financial Results and Corporate Update Conference Call. At this time, all participants are in a listen-only mode.
Welcome to the car to phone calls the fourth quarter and full year 2023 financial and corporate update conference call. At this time all participants are in listen only mode. After the speaker's presentation there'll be a question and answer session to ask a question. During the session you will need to press star one on your telephone.
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Operator: Please be advised that today's conference is being recorded. I would now like to turn the conference over to Lawrence Watts of the Gilmartin Group. Please go ahead.
Please be advised that today's conference is being recorded I would now.
Like to turn the conference over to Lawrence, What's the Gilmartin group. Please go ahead.
Lawrence Watts: Thank you all very much. Joining us on the call today from Cardiff Oncology are Chief Executive Officer Mark Erlander, Chief Medical Officer Dr. Farouk Binabar, and Chief Financial Officer James Levine. During the conference call, management will make forward-looking statements, including, without limitation, statements related to guidance, results, and the timing of data readouts for on-vanity clinical trials. Such forward-looking statements are based on the company's current expectations and inherently involve significant risks and uncertainty.
Thank you operator.
Joining us on the call today from Cardiff Ecology, Chief Executive Officer, Mark Erlander Chief.
<unk> Medical office desktop preferred sandbox and Chief Financial Officer, Jay Levine.
During this conference call management will make forward looking statements, including without limitation statements related to guidance results from the timing of data Readouts for <unk> clinical trials.
These forward looking statements are based on the company's current expectations, apparently involve significant risks and uncertainties.
Actual results and the timing of events could differ materially from those anticipated in such forward looking statements as a result of these risks and uncertainties.
Factors that could cause results to be different from these statements include factors. The company described in the section titled Risk factors.
Annual report on Form 10-K for the year ended December 31, 2023 filed with the SEC earlier today.
Lawrence Watts: Our actual results and the timing of events could differ materially from those anticipated in such forward-looking statements as a result of these risks and uncertainties. Factors that could cause results to be different from those expressed include those the company describes in the section titled risk factors in our annual report on Form 10-K for the year ended December 31, 2023, filed with the SEC earlier today. Cardiff Oncology undertakes no duty or obligation to update any forward-looking statements as a result of new information, future events, or changes in its expectations. Slides for today's investor call can be found on the home page and the events and presentations tab of the Cardiff Oncology website at www.cardiffoncology.com. With that, I will turn the call over to Chief Executive Officer Mark Erlander.
Got it oncology undertakes no duty or obligation to update any forward looking statements as a result of new information future events or changes in its expectations.
Slides for today's Investor call can be found on the homepage.
Some presentations tab of the Cardiff oncology website at Www dot caught up oncology dot com.
With that I will turn the call over to Chief Executive Officer, Mark Allen.
Thank you. Thank you.
Good afternoon, everyone and thank you for joining the call.
We have some very important new clinical data to share on the call today.
Which we think is highly relevant to our current first line metastatic colorectal cancer program.
You may be aware last year, we made a highly consequential decision to shift our CRC program from the second bar to the first line study.
The three factors that drove our decision.
First was the clinical signal from our second line in CRC trial.
Well, it's a new mechanism of action, we discovered or an answer to.
With a strong support from the FDA for the first slide clinical staff to acquire.
What's new today is that.
For the first time, we are releasing data from our <unk> trial.
Adding powerful support to our first line strategy.
And as we'll discuss what's different with <unk>.
Some of the clinical data is that independents, it's randomized and his perspective.
You'll hear more about each of these attributes today by the.
I Hope you agree that for example data add substantial support.
First of all.
Scott.
Yes.
Slide two shows the three topics, we'll cover on today's call.
We'll talk briefly about 2023, and what a transformational year. It has been for Cardiff oncology and for the clinical development of our drug pump answered yet.
Secondly, as I mentioned will share clinical data from our randomized second line on some of the truck.
And then Simon will talk about our financial position that we disclosed today in our call.
<unk> 10-K.
On slide four we show the highlights of our significant announcements we made in 2023.
We provided our NCIC clinical update where we announced the discovery of a novel mechanism of action for advanced Chip, which was previously unknown.
And the critical level that place and hit one alpha pathway, particularly faster utilization of channels.
Mark Erlander: Thank you. Thank you. Thank you, Lawrence. Good afternoon, everyone, and thank you for joining us.
Data, we presented some evidence complementary mechanisms of action.
So with that which we will refer to as critics.
Mark Erlander: We have some very important new clinical data to share on the call today, which we think is highly relevant to our current first-line metastatic colorectal cancer program. As you may be aware, last year we made a highly consequential decision to shift our NCRC program from the second line to the first line setting. There were three factors that drove our decision.
Could explain the strength of our clinical data and then CRC.
And after discussing the clinical and the underlying mechanism with the FDA in June of last year, we received strong support for the decision to move our program to our slides.
Further we announced the Pfizer Pfizer like program.
Providing cheap.
Execution for the clients in terms of our floor.
At the time, we make all the decisions we were already enrolling patients in the example trials in the second line setting.
So in August we announced we would discontinue the trial to focus our efforts and resources on the larger patient population and the significant unmet need in the first line setting.
Mark Erlander: The first was the clinical signal from our second-line MCRC trial. Second, was the new mechanism of action we discovered for advanced... And the third was strong support from the FDA for the first-line clinical development plan. What's new today is that, for the first time, we are releasing data from our Ensembl data, adding powerful support to our first-line strategy. And as we'll discuss, what's different with the Ensembl clinical data is that it's independent, it's randomized, and it's prospective. You'll hear more about each of these attributes today, and by the end, I hope you've agreed that Ensembl's data adds substantial support to our first-line program. So, let's get started.
In September of last year, we held the second update call to announce data for our programs outside of them CRC from our second line pancreatic cancer trial, we announced four additional partial responses from the 21 basin and steam we can provide an update on those four patients by sharing that three of the four initially.
Responses were confirmed.
Stan.
We also announced our decision to ship for pancreatic program to a first line setting with an investigator initiated trial, combining <unk> with standard of care Jim for Brexit.
Finally, we announced new data from our refractory extensive stage small lung cancer investigator initiated trial.
We observed a confirmed PR among the first seven patients importantly.
Mark Erlander: Slide three shows the three topics we'll cover on today's call. First, I'll talk briefly about 2023 and what a transformational year it has been for Cardiff Oncology and for the clinical development of our drug, Contagion. Secondly, as I mentioned, we'll share clinical data from our randomized second-line ensemble trial. And then, finally, we'll talk about our financial position that we disclosed today in our Forum 10 case.
First clinical data generated using on Bachelor Jim as a single agent.
Looking at the range of our announcements in 2023.
We believe a year was a truly transformational for Cardiff oncology.
The second I'm sorry.
My voice.
Sorry.
CA CFO, Jamie two critical remarks on the call.
Available for Q&A at the end of the call. Thank you.
March.
On slide five we transition to our second item on the agenda, the new clinical data we're announcing today.
Call that our NCIC program includes three clinical trials and we want to very clearly discussed what's significance in each one.
Mark Erlander: On slide four, we show the highlights of the significant announcements being made in 2020. In August, we provided our NCRC clinical update, where we announced the discovery of a novel mechanism of action for our advancer type, which was previously unknown, and the critical role that it plays in the HIF-1-alpha pathway in inhibiting vascularization of tumors. The data we presented, showing evidence for complementary mechanisms of action, formed an answer to it, and assuming that, which we will refer to as BAS, could explain the strength of our clinical data in the MCRC. And after discussing the clinical underlying mechanism with the FDA in June of last year, we received strong support with a decision to move our program to the first-line test. Further, we announced our partnership with Pfizer through its Pfizer Ignite program, which means providing a cheat.
The phase one two trial and K Ras mutated NCIC generated the initial signal of efficacy on which we base our <unk> clinical development program and the trial is now complete.
Based on the strength of the preliminary data from the single arm Phase <unk> trial, we proceeded with our originally designed next step of our clinical development program by implementing the second line ensemble trial, which would provide randomized data comparing <unk> plus standard of care to standard of care alone. However is the fee.
<unk> data matured, we saw a powerful an unexpected positive signal from the data we identified a subgroup of patients specifically those who have not had prior treatment with bev in the first line setting that achieved higher response rates.
What would have been expected.
As we state on slide eight.
We discussed our findings, including both the phase one two clinical data and the new mechanism of action I mentioned at the start of the call with the FDA, which led to their strong support for us to discontinue the ensemble trial and shift our clinical program for the first line setting.
<unk> is a randomized first line RAF mutated NCIC trial for which we just announced the first patient was dosed and Pfizer ignite is providing clinical execution.
Mark Erlander: There is a clinical execution for the CARB-004 trial. At the time we made all these decisions, we were already enrolling patients in the ensemble trials in the second-line setting. So, in August, we announced we would discontinue the trial and focus our efforts and resources on the larger patient population and the significant unmet need in the first-line setting. In September of last year, we held a second update call to announce state-of-the-art programs outside of NCRC.
As you see on slide nine today, we are sharing new clinical data from the car to 003 ensemble trial.
We had enrolled 23 patients in ensemble prior to making the decision to discontinue this trial.
While we closed the trial to new enrollment those patients who are already enrolled continued treatment per protocol and the majority of the patients enrolled remain on the trial today.
As Youll see there are important findings in the ensemble clinical data that validate our decision to shift to the first line.
I'll now turn the call over to Dr. Bruce <unk>, our Chief Medical Officer to review, our clinical data as a reminder, Dr. <unk> is a medical oncologists with 35 years of experience, who led the colorectal cancer program at UCLA and it was heavily involved in the Registrational trial that led to the approval of <unk> in metastatic colorectal cancer.
Mark Erlander: From our second line paper at a cancer trial, we announced four initial partial responses from the 21 patients, and today we can provide an update on those four patients by sharing that three of the four initial responses were confirmed on a subsequent scan. We also announced our decision to shift our pancreatic program to a first-line study with an investigator-initiated trial combining advanced attempt with standard of care. Jim, goodbye.
Thank you Jamie and thank you Mark.
It's my pleasure to present, the new randomized clinical data from our guidance with the ensemble trial.
On Slide 10, you can see the ensemble trial design.
This trial enrolled second line Ras mutated metastatic colorectal cancer patients with Unresectable, but measurable disease.
Patients are randomized across three arms one.
One was the control arm, where patients received standard of care.
Chemotherapy, consisting of poultry plus better.
Mark Erlander: Finally, we announce new data from our refractory extensive stage small lung cancer investigator machine trial, where we observed a confirmed PR among the first seven patients. Importantly, this is the first clinical data generated using onbanser.giv as a treatment. Looking at the range of our announcements in 2023, you can believe that the year was truly transformational for Cardiff Oncology. I'm just going to take this break for a second. I'm sorry, but I am losing my voice.
And the two experimental arms patients received a buildup one month's or live in each of the first five days.
Following the full treaty Bev infusion.
One of them included a penny milligram daily dose at one one.
Yes included a 30 milligram daily dose of one month.
The primary endpoint was objective response rate.
And the dosing schedule was the same as in a phase one b two trial.
Looking at the enrollment at the top of Slide 11, you can see that at the time down sample trial, we'll just can view.
<unk> basically had been randomized across three arms.
Importantly, one patient was never treated because of patient withdrew consent and loved the trial prior to receiving any therapy.
This review is the treated patient population.
Evaluable for safety with 22 patients only.
Mark Erlander: So I'm going to ask my CFO, James, to continue with his remarks on the call. I'll be available for Q&A at the end of the call. Thank you.
Also one additional patient withdrew consent.
Another trial before receiving any post baseline scan.
So 'twenty one on the <unk> patients.
Evaluable for efficacy.
Both patients who loved the trial randomized to the control arm and both web exposed so their withdrawal from the trial does not impact any of the conclusions drawn from the data on the following slides.
James E. Levine: On slide 5, we transition to our second item on the agenda, the new clinical data we're announcing today. Recall that our MCRC program includes three clinical trials, and we want to very clearly discuss what's significant in each one. The Phase 1b2 trial in KRAS-mutated MCRC generated the initial signal of efficacy on which we based our MCRC clinical development program, and the trial is now complete. Based on the strength of the preliminary data from the single-arm Phase 1b2 trial, we proceeded with our originally designed next step of our clinical development program by implementing the second-line ensemble trial, which would provide randomized data comparing vancitive However, as the Phase 1b2 data matured, we saw a powerful and unexpected positive signal from the data.
On slide 12, I'd like to define exactly what we mean by Bev naive and better exposed.
And our second line Mci patients trials enrolled patients would have already received first line therapy.
That may or may not have included.
Our Bev naive patient is simply a patient described therapy did not include Bev.
These patients.
So these patients would have received only ballparks chemotherapy in the first line treatment.
We're coming into a second line trial.
In our second line on Sandler trial.
One of our 21 patients evaluable for efficacy.
Nate.
We referred to the other 14 evaluable patients in our trial is bev exposed.
Brian first line therapy included.
In addition, the full Fox chemotherapy.
So the critical question, we had as we worked down some old trial data mature over the past six months.
Well the high response rates with sulfur Bev naive patients in our phase <unk>.
Alon drop.
We observed in the ensemble randomized trial.
And Im excited to show you the results over the next slide.
Slide 13.
Is the waterfall plot with shows each patients' best response to therapy over the course of their treatment.
James E. Levine: We identified a subgroup of patients, specifically those who had not had prior treatment with BEV in the first-line setting, that achieved higher response rates than what would have been expected, as we state on slide 8. We discussed our findings, including both the Phase 1b2 clinical data and the new mechanism of action I mentioned at the start of the call with the FDA, which led to their strong support for us to discontinue the ensemble trial and shift our clinical program to the first-line setting. Cardiff-004 is our randomized, first-line, RAS-mutated MCRC trial for which we just announced that the first patient was dosed. And Pfizer-Ignite is providing clinical execution.
As you can see the answer to my question the <unk> patients receiving an uncertainty with full period plus about once again have the most robust response to treatment.
Now allow me to walk you through what this slide is showing.
Starting from the top of the slide you can see that we have segregated the 21 evaluable patients into two groups.
So the seven Bev nave patients are on the left.
<unk> been explored that makes those patients are on the right.
With each of these cohorts within each of these calls.
We further divides the data into its third line patients who received <unk> plus standard of care for Judy.
And the control arm patients on portfolio plus about without on uncertain.
Looking at the graph.
The bars above the line represent tumor growth.
And the bars below the Midland represent tumor shrinkage.
<unk> colored bar represents an objective partial response.
James E. Levine: As you see on slide 9, today we are sharing new clinical data from the Cardiff-003 Ensemble. We had enrolled 23 patients in Ensembl prior to making the decision to discontinue this trial. While we closed the trial to new enrollment, those patients who are already enrolled continue treatment according to protocol, and the majority of the patients enrolled remain on the trial today. As you'll see, there are important findings in the Ensemble clinical data that validate our decision to shift to the first line. I'll now turn the call over to Dr. Peruz-Kabinovar, our Chief Medical Officer, to review our clinical data. As a reminder, Dr. Kabinovar is a medical oncologist with 35 years of experience, who led the colorectal cancer program at UCLA, and who was heavily involved in the registrational trial that led to the approval of FEV in metastatic colorectal cancer. Thank you, Jamie, and thank you, Mark.
Meaning the patient at 30% or greater reduction in the tumor sites.
A light Red bar represents progressive disease, which is an increase of more than 20% in the tumor size.
And the yellow bar represents stable disease, which was between these two numbers.
At the bottom of the slide you can see that those are one months.
One third of it.
Received by each experiment around patients either patient either 20 milligram 30 milligram.
Shown in blue boxes above the patient number.
And the pull through digital patient number is.
Clinical trials type number.
As you scan from left to right on the waterfall plot.
You can see that the three patients with the greatest tumor shrinkage.
Our bev nave patients receiving <unk> plus.
Plus standard of care.
This is highly encouraging and consistent with what we would have expected based on our prior phase <unk> trial data.
On the next few slides, we'll park this waterfall plot intersections and draw additional conclusions.
As you all are on slide 14.
You can see that for the Bev nave patients. The only objective responses were observed we observed in patients that received standard of care plus online.
Given this is a randomized trial. It is also important to point out that we did not see any responses in the control arm of Bev nave patients that received standard of care alone without online survey.
In addition by looking at the first three digits after each patient number.
Dr. Farouk Binabar: It's my pleasure to present the new randomized clinical data from a Cardiff 0-0-3 ensemble trial. On slide 10, you can see the ensemble trial design. This trial enrolled second-line grass-materiated metastatic colorectal cancer patients with unreflectable but measurable disease. Patients are randomized across three arms. One was a control arm where patients received standard of care chemotherapy consisting of Colferi plus Bell. In the two experimental arms, patients received a dose of 1,1-SERDIV in each of the first five days following the Colferi Plus Dab infusion. Additionally, one arm included a 20 milligram daily dose of 1,1-sertab. The other arm included a 30 milligram daily dose of 1,1-sertab.
You can see that is bev naive patient was enrolled at a different trial site.
So that's the Bev naive funding is not the result of any bias coming out of a single trial site.
Specifically in the bedroom nave patients that did respond one patient received.
Online said that demonstrated a 44% reduction in the tumor site.
And the second patient had a 43% reduction.
Importantly, both of these patients have confirmed partial responses.
And we see this largely responses at both.
90, milligram 30 milligram dose of one side of it.
The third Bev nave patients who received online sedative.
At a 20% reduction in the tumor site.
Which is very.
Very close to the 30% threshold to qualify for a partial response.
I would like you to keep your especially if you don't mind I'll provide more detail in the next two slides.
On.
<unk>.
We are focused on the 14 patients in the boat exports cohort and.
And you can see that in both the experimental and control arms. There were no objective responses observed.
And certainly the size of the effect appears to be less than what we see in the Bev nave cohort.
Dr. Farouk Binabar: The primary endpoint was objective response rate, and the dosing schedule was the same as in our Phase 1B2 trial. Looking at the enrollment at the top of slide 11, you can see that at the time the on-sample trial was discontinued, 23 patients had been randomized across the three arms. Importantly, one patient was never treated because the patient withdrew consent and left the trial prior to receiving any therapy.
And on Slide 16, you can see that the bev nave and Bev exposed control arm patients.
Appeared to have very similar responses to the standard of care therapy.
On slide 17, we are looking at the Spider plots on the Bev naive patients.
You can see that on the left our patients in the experimental arm.
The <unk> lines and the Florida allow you to see the trajectory of the two patients with confirmed partial responses.
The plot on the right shows the Bev nave control arm patients.
Who did not receive <unk>.
Importantly, the two controllers patients with tumor shrinkage at the two months scam. Both subsequently progressed at four months and left the trial.
Now on slide 18, I'd like to provide some context around the patient as I mentioned earlier.
Dr. Farouk Binabar: This reduces the treated patient population available for safety to 22 patients only. Also, one additional patient withdrew consent to another trial before receiving any post-baseline scans. So 21 of the 23 patients are now available for efficacy. Both patients who left the trial were randomized to the control arm, and both were BEV exposed, so their withdrawal from the trial does not impact any of the conclusions drawn from the data on the following slide. On slide 12, I'd like to define exactly what we mean by Web9 and WebExpose.
We added 27% reduction in the tumor sites at the six month scan.
Under six months Ken.
Suspicious new metastatic lesions was noted in the patient's lung.
So the treating physician decided to discontinue on one side.
But continued treating the patient with standard of care full period plus Bev.
The lung lesion was later confirmed by biopsy to be value fewer fungal infection.
Unrelated to the patient's cancer and not a new tumor lesions.
And the patients eight one scan.
With tumors increase sufficiently for you to reconsider progressive disease.
But more importantly during this two month period between the six months eight months scandal in the tumor progressed.
The patient was not receiving any online survey, but it was only on full period plus Bev.
Dr. Farouk Binabar: In our second line, MCRT patients, trials, and those patients who have already received first-line therapy that may or may not have included Bev. A BEV-NAIF patient is simply a patient whose prior therapy did not include Bev. So these patients will have received only full-force chemotherapy in their first-line treatment before coming into our second-line trial, in our second-line ensemble form. Seven of our 21 patients evaluable for efficacy were BAP-nave. We refer to the other 14 evaluable patients in our trial as BEV exposed, meaning that prior first-line therapy included BEV in addition to full-focus chemotherapy. So the critical question we had as we worked the ensemble trial data matured over the past six months was, Will the high response rates we saw for BAP-nave patients in our Phase I, B2, single-arm trial continue to be observed in the Ensembl randomized trial? And I'm excited to show you the results on the next slide.
In summary on slide 19, I'd like to reiterate the key attribute to the <unk>.
The online sample data, but mark and Dave you mentioned at the start of the call now that you have seen all the data.
First Jonathan.
Jonathan will travel as independent events.
The second clinical trial and a different point in time than our earlier phase one <unk> trial.
Showing once again.
<unk> patients have a strong response to therapy.
Includes unnecessary to full <unk>.
Secondly on one cell.
Ensemble Trung.
The randomized drop.
Thereby removing all clinical bias.
Will we see that Bev nave patients in the control arm of <unk> plus.
Without online service had no objective responses.
And finally, the ensemble trial was prospectively designed.
Luisa above 90, finding in the phase <unk> trial, whilst from a retrospective look back at the data.
However, we have seen the Bev 90 signal before enrolling the ensemble trial, and then prospectively planned devalued the differences in response rates.
When the <unk> patients in a randomized fashion.
And importantly, when we look at the safety data that is included in the appendix of this material we.
We see that on one side and when combined with chemotherapy plus <unk>.
<unk> is well tolerated with no major unexpected toxicity was observed.
Dr. Farouk Binabar: Slide 13, is the waterfall plot which shows each patient's best response to therapy over the course of their treatment. As you can see, the answer to my question, the BEV-9 patients receiving on-one serative with full PURI plus BEV once again had the most robust response to treatment. Now, allow me to walk you through what this slide is showing.
On slide 20.
I will conclude my remarks, reminding of the new mechanism of action rediscovered for online <unk>.
And that Mark mentioned at the start of the call.
This mechanism of action explains why we believe we are seeing the clear efficacy signal and Bev naive patients.
As we discussed in detail in August.
We believe that the robust responses, we're seeing are due to a novel mechanism of action.
That we have discovered four onwards that will grow in the hypoxia response pathway.
Dr. Farouk Binabar: Starting from the top of the slide, you can see that we have segregated the 21 evaluable patients into two groups. So the seven BEV-nave patients are on the left. The 14 BevExpo patients are on the right, with each of these cohorts to further divide the data into experimental outpatients who received on one-sided plus standard of care full fury plus baroque and the control on patient, on PulseFuryPlusWeb without on-one surgeon. Looking at the graph, the bars above the midline represent tumor growth, and the bars below the midline represent tumor shrinkage. A teal colored bar represents an objective partial response, meeting the patient at a 30% or greater reduction in the tumor size. A light red bar represents progressive disease, which is an increase of more than 20% in the tumor size, and a yellow bar represents stable disease, which is between these two numbers.
It is well known.
Outgrow their blood supply and become hypoxic.
Meaning that becomes startup oxygen and nutrients.
Cumulus respond to these hypoxic stress.
By producing the hip one out of a protein.
<unk> stands for hypoxia inducible factor one alpha protein.
Which turns on hundreds of genes that allows the tumor to survive in the hypoxic environments.
One of those mechanisms in all of the tumor secreted vascular endothelial growth factor.
<unk>.
The formation of creation of new blood vessels.
To bring oxygen and nutrients to the Kansas Alf.
As you can see on slide 21.
But works by neutralizing wedge of innovating the creation of new escalates.
But on one third of the plays a role upstream of VEGF.
By inhibiting.
<unk> one alpha directly.
And thereby blocking all leads downstream effects.
This shows <unk>.
<unk> certainly been complementary in a bit.
Overnight setting.
But deploying two separate hits on the tumor angiogenic pathway.
And its survival mechanisms.
In conclusion.
In my 35 years as a medical oncologist.
I've never been as excited.
Now to see the kind of efficacy signal, we are observing across our clinical trials.
Now I'm going to hand, the call back over to Jamie to continue.
Discussion further.
Jamie.
Thank you Bruce.
We will conclude the call with a few comments about <unk>.
Turning now to slide 23, you can see the colorectal cancer is a major public health issue.
It is both a highly prevalent form of cancer and it is challenging to treat and.
Dr. Farouk Binabar: At the bottom of the slide, you can see the dose of On1Certib received by each experimental arm patient, either 20 milligrams or 30 milligrams, shown in blue boxes above the patient number. And the first three digits of the patient number are the clinical trial site number, as you scan from left to right on the waterfall plot. You can see that the three patients with the greatest tumor shrinkage observed are BAP-nave patients receiving ON1C plus standard of care. This is highly encouraging and consistent with what we would have expected based on our prior Phase 1B2 trial data. In the next few slides, we'll part this waterfall plot into sections and draw additional conclusions.
And recently there have been a number of reports that CRC is becoming more common in younger adults, thus increasing our responsibility to develop more effective therapies beyond the current standard of care.
And on the right side of the slide you can see how our decision to move from second line to first line substantially increases the number of metastatic colorectal cancer patients, who may benefit from adding <unk> to the current standard of care.
On slide 24.
You can see that the first line standard of care for Ras mutated Mcse consists only of chemotherapy with Bev a.
A regimen that hasnt changed in 20 years. So this large patient population is in need of new therapies directed at all Ras mutations.
Slide 25 provides the study design for our <unk> trial.
Similar to the ensemble trial <unk> 004 includes NCR C patients, whose tumors have a ras mutation and are Unresectable a key difference for <unk> 004 is that all patients are first line and therefore have not previously been exposed to about.
The trial will randomize 90 patients across three arms.
Dr. Farouk Binabar: As you call out on slide 14, you can see that for the BEV-9 patient. The only objective responses we observed were in patients that received standard of care, plus in one-third of them. Given this is a randomized trial, it's also important to point out that we did not see any responses in the control arm of BEV-9 patients that received standard of care alone without on-one service. In addition, by looking at the first three digits of each patient number, you can see that each Bev-Naive patient was enrolled at a different trial site, so that the Bev-Naive finding is not the result of any Specifically, in the BEV-9 patients that did respond, one patient received this on one side and demonstrated a 44% reduction in the tumor size, and the second patient had a 43% reduction.
First the control arm consisting of standard of care with full theory, Bev or full Fox Bev and.
And then two experimental arms looking at standard of care chemotherapy plus Bev.
And a 20 milligram or 30 milligram daily dose of on vantage at the same doses is in the ensemble trial.
Our primary endpoint for the trial will be objective response rate and the secondary endpoints or duration of response and progression free survival.
Let me provide a few additional details about the <unk> for enrollment.
Our clinical operations efforts together with Pfizer ignite are going well with a critical mass of 20 clinical trial sites activated as of today.
And as we announced we dosed our first patient.
Based on the current robust screening activity observed.
And our current enrollment projections, we expect to meet our goal of releasing data from the trial in mid 2024.
And we anticipate this initial release will include objective response rate data for approximately half the patients we expect to enroll on the trial.
Dr. Farouk Binabar: Importantly, both these patients have confirmed partial responses, and we see these partial responses at both 20 milligram and 30 milligram doses of 1,1-Serdac. Additionally, a third of naive patients who received On1's third dose had a 20% reduction in the tumor size, which is very close to the 30% threshold to qualify for a partial response. I would like you to keep this patient in your mind, as I'll provide more details in the next few slides, on slide 15. We focus on the 14 patients in the BEV-EXPOSE cohort. And you can see that in both the experimental and control arms, no objective responses were observed.
On slide 26, I will cover our third agenda item, our financial position as of December 31, 2023.
As we disclosed today in our Form 10-K filing we had $74 $8 million in cash and investments as of December 31 2023.
And our cash used in operating activities was $7 1 million in Q4 23.
Today, we have greater clarity on our expected future expenses and so we can be more precise about our forecasted cash runway spin.
Specifically, we believe that our current cash resources provide us with cash runway into the third quarter of 2025, which is beyond the expected readout from the <unk> trial.
Finally on slide 27, we summarize why the ensemble data. We released today is so relevant for our first line <unk> strategy and our ongoing partisan <unk> four trial.
Dr. Farouk Binabar: And certainly, the size of the effect appears to be less than what we see in the Bev-Naive cohort. And on slide 16, you can see that the BEV-NAIF and BEV-EXPOSE controls on patients appear to have very similar responses to the standard of care therapy. On slide 17, we are looking at the spider plots for the Web9 patient. You can see that on the left are patients in the experimental arm. The teal lines in the plot allow you to see the trajectory of the two patients with confirmed partial responses. The plot on the right shows the Bev-Naive control on patients who did not receive one-on-one service. Importantly, the two control arm patients with tumor shrinkage at their two-month scan both subsequently progressed at their four-month scan and left the trial.
First ensemble.
Second independent and randomized dataset reproducing the robust efficacy signal from <unk> plus standard of care in Bev naive patients.
And this supports our currently enrolling first line trial, where all patients are bev naive.
Secondly, no bev naive patients in the ensemble control arm showed an objective response to treatment without I've answered it suggesting on the answer to that is critical to the robust responses observed in the experimental arm.
And finally <unk>.
Of the two advantage of doses appear to be active which suggests the two experimental arms of the card <unk> 004 trial could be combined when evaluating the trial data for efficacy.
For all these reasons, we continue to believe our shift to the first line setting is the best strategy for all of our stakeholders, particularly the large number of patients 48000 per year in the U S with Ras mutated NCIC that may benefit from our new approach to treating their disease.
Dr. Farouk Binabar: Now on slide 18, I'd like to provide some context around the patient I mentioned earlier, who had a 27% reduction in the tumor size at their six-month scan. However, on this six-month scan, a suspicious new metastatic lesion was noted in the patient's lung. So the treating physician decided to discontinue one surgery but continue treating the patient with standard of care Polk Curie-Plus-Bev. The lung lesion was later confirmed by a biopsy to be a valley fever fungal infection, unrelated to the patient's cancer and not a new tumor lesion, and on the patient's H1 scan, the tumors increased sufficiently for it to be considered progressive disease.
With that we'll open the call up for questions operator.
Thank you as a reminder, if you'd like to ask a question. Please press star one one.
If your question has been answered and you'd like to remove yourself from the queue. Please press star one again.
Our first question comes from Marc Frahm with TV Cowen Your line is open.
Thanks for taking my questions and congrats on the data you are able to release.
Maybe first off just obviously just the first patient today, but.
Any sense for how much data youll be able to release in the middle of the year from that.
For trial, and then for the data today from ensemble.
Key characteristics, you can kind of provide.
Provided on the baseline like were there any differences in like left and right sightedness and things like that that might explain a little bit of the of the difference.
Dr. Farouk Binabar: But more importantly, during this two-month period between the six-month and eight-month scans, when the tumor progressed, the patient was not receiving any on-one seratives but was only on full PURI plus BAP. In summary, on slide 19, I'd like to reiterate the three attributes of the unwantsable data that Marc and Jamie mentioned at the start of the call, now that you have seen all the data, first. The Ensembl trial was independent because it was the second clinical trial at a different point in time than our earlier Phase I, B2 trial, showing once again that Bev-nave patients have a strong response to therapy that includes on-one SIRDEV with full Curie and Bev. Second, the ensemble trial was a randomized trial, thereby removing all clinical bias, where we see that BEV-9 patients in the control arm of Whole And finally, the ensemble trial was prospectively designed.
Kim response rate.
I can start.
First of all like we said.
And on the call, we're going to be putting data out when we have approximately about half the patients enrolled in the trial.
And.
The second thing was regarding the ensemble data.
We have looked at that we haven't seen any differences.
Yes.
From the side of this but we will.
But we did not present this year.
Okay, and sorry, just on that update is that once you've enrolled the Oreo that you have mature response data on.
Quick question.
At least at least one scan after the baseline.
Okay. Okay. That's helpful.
Yes.
Thank you. Our next question comes from Joseph Catanzaro with Piper Sandler Your line is open.
Hey, everybody thanks for taking the questions and the update here.
Maybe first on the ensemble.
Data I'm wondering if you guys performed.
PFS analysis I'm looking at the swimmers plot and even sort of considering both bev naive and expose that.
Looks like there's a pretty good.
Maybe emerging PFS signal that youre seeing in this randomized data. So I'm wondering if you if you did that analysis.
And maybe what its saying thanks, and then I have maybe one follow up.
Thanks, Joe for that question.
We have no tenant rigorously we were waiting for more follow up for.
Dr. Farouk Binabar: The original Web 9 finding in the Phase 1 B2 trial was from a retrospective look back at the data. However, we had seen the BEV-9 signal before enrolling in the Ensembl trial and had prospectively planned to evaluate the differences in response rates between the BEV-9 and BEV-X post-patients in a randomized fashion. And importantly, when we look at the safety data that is included in the appendix of this material, we see that On1 Certip, when combined with chemotherapy plus BAS, is well tolerated with no major unexpected toxicity that was observed, on slide 20. I will conclude my remarks reminding you of the new mechanism of action we discovered for On1 Certip, and then Mark, as mentioned at the start of the call.
For us to look at that since a split it's a small number of patients, but we agree with you, but it looks like there is an emerging signal.
Okay. Thanks, and then.
For the for the frontline trial was there any.
The safety run in on the backbone of a full Fox just trying to get a sense of maybe historically, how the neutropenia compared.
With full thoughts relative to both theory.
And then maybe relatedly the expected split between full theory and full Fox.
As the backbone of I'm thinking back to.
Earlier preclinical data from a couple of years back.
Suggested on <unk> on <unk>, there is some cooperativity there.
Hopefully that question makes sense, yes.
Dr. Farouk Binabar: This mechanism of action explains why we believe we are seeing this clear efficacy signal in Web 9 patients, as we discussed in detail in August. We believe that the robust responses we are seeing are due to a novel mechanism of action that we have discovered for on-one-service role in the hypoxia response path. It is well known that tumors outgrow their blood supply and become hypoxic, meaning they become starved of oxygen and nutrients. Tumors respond to this hypoxic stress by producing the HIF-1 alpha protein. HIF stands for hypoxia-inducible factor 1 alpha protein, which turns on hundreds of genes that allow the tumor to survive in the hypoxic environment. One of those mechanisms involves the tumor-secreting vascular endothelial growth factor A, or VEGF-A, to promote the formation or creation of new blood vessels to bring oxygen and nutrients to the cancer.
Joe Let me first start by talking about the preclinical data we actually.
Have shown publicly that we have synergy with both solid platinum as well as a in the GKN and depot model pre clinically.
We have not seen any toxicity as well.
Your questions regarding the full Fox.
In the first in our first line trial, and then turn it over to Bruce our CMO here.
Hi, Joe So the question about regarding.
Any safety run in for the full folks.
Plus on one side of the balance for the first nine patients.
We will be well after the first 10 patients that windows.
And those patients will be evaluated by the.
Safety Review committee and won't be.
It is determined that full folks.
On one side, but there is no additional toxicity beyond what is expected of ballparks.
Then that will continue.
To accrue towards full completion of.
The full complement of the patients. So yes, there is a safety valve built into this drunk.
And we don't expect based on how <unk> partners with other chemotherapy.
Mark drugs, we don't expect any major toxicity issues and evenly.
Dr. Farouk Binabar: As you can see on slide 21, BEV works by neutralizing VEGF-A, inhibiting the creation of new vasculature, but on the other hand, it plays a role upstream of VEGF by inhibiting HIF-1 directly and thereby blocking all its downstream effects. This shows why on one serum and Bevop are complementary in a Bev9 setting by deploying two separate hits on the tumor angiogenic pathway and its survival mechanism. In conclusion, in my 35 years as a medical oncologist, I've never been as excited as I am now to see the kind of efficacy signal we are observing across our clinical trials. Now, I'm going to hand this call back over to Jamie to continue the discussion further. Jamie?
We do a lot more detail information, even though there were two patients with.
Neutropenia that was seen.
In this.
And B.
Ensemble trial.
At the lower end lower dose of 20 milligrams to 30 and then these patients that neutropenia resolved just by holding the treatment are delaying the treatment with seven and one patient seven days and another patient 10 days and those patients will continue on treatment without any of those reductions.
Okay. Thank you that's all very very helpful. Thanks, again for taking my questions.
Thank you. Our next question comes from Andrew Tsai with William Blair. Your line is open.
Great.
Thanks for taking our questions Mark I Hope you feel better soon.
I just wanted to dig a little.
Dr. Farouk Binabar: Thank you, Peru. We'll conclude the call with a few comments about Cardiff-004. Turning now to slide 23, you can see that colorectal cancer is a major public health issue. It's both a highly prevalent form of cancer, and it is challenging to treat. And recently, there have been a number of reports that CRC is becoming more common in younger adults, thus increasing our responsibility to develop more effective therapies beyond the current standard of care.
Just wanted to dig a little deeper anything on several top line results maybe on two topics.
One is on on liver metastases and maybe second on dose response, maybe I'll go first on the dose response, maybe.
Perhaps you can comment on whether you see some sort of dose response or both are active and how do we think about.
Both doses going forward.
Specifically on the liver metastases I think.
If I did the calculation right, it's about 77% of the patients have some sort of liver metastases.
James E. Levine: And on the right side of the slide, you can see how our decision to move from second line to first line substantially increases the number of metastatic colorectal cancer patients who may benefit from adding Vancertib to the current standard of care. On slide 24, you can see that the first-line standard of care for RAS-mutated MCRC consists only of chemotherapy with BEV, a regimen that hasn't changed in 20 years. So this large patient population is in need of new therapies directed at all RAS mutations. Slide 25 provides the study design for a Cardiff-004 trial. Similar to the Ensembl trial, CARDF004 includes MCRC patients whose tumors have a RAS mutation and are unresectable.
<unk>.
That's kind of on the higher side have you looked at the two responders debate has delivered catastrophe.
The emerging data, suggesting that these patients are particularly hard to treat and maybe there is a yes.
Yes.
The hypothesis on the <unk>.
Mechanistic side of officer advanced Chip that's active in this population.
And.
Couple of follow ups.
Okay.
Thanks, Andy.
The dose response, if I understood your question correctly we.
We are seeing similar activity, albeit small data.
Numbers, but we are seeing similar activity between the two doses of 28 to 30 million.
That's what you were asking.
And so that's right.
From that.
That's why we're concluding that we can combine those arms together to look at efficacy.
James E. Levine: The key difference for CARDIFF-004 is that all patients are first line and therefore have not previously been exposed to BEP. The trial will randomize 90 patients across three arms. First, a control arm consisting of standard of care with PulferiBEV or FolfoxBEV, and then two experimental arms looking at standard of care chemotherapy plus BEV and a 20 milligram or a 30 milligram daily dose of Onbanser tip, the same doses as in the Ensembl trial. Our primary endpoint for the trial will be objective response rate, and the secondary endpoints will be duration of response and progression- Let me provide a few additional details about the Cardiff-004 enrollment.
And in terms of unfortunate.
As far as deliver Matt we have not.
Analyze that.
Robustly yet.
But I would say that.
In our phase two trial, which showed that there was no difference.
And the response indemnity.
Maybe patients who have liver mets versus those that didn't.
There was no.
No Division response, there irrespective of liberalism.
Yeah, So Andy just building up on what Mark just said.
And the phase one Bluetooth trial, we looked at multiple other factors trying to see whether any other features.
That would impact this.
Responses that we're seeing in.
Bev nave patients and to give you a very short answer absolutely no clinical feature appear to play a role in the.
Significant robust responses that we're seeing in the Bev naive patients. So we looked at <unk> the tumors right and left tumors. Both responded equally we looked at patients with liver without real improvement there obviously to respond well we looked at patients who had.
James E. Levine: Our clinical operations efforts, together with Pfizer-Ignite, are going well, with a critical mass of 20 clinical trial sites activated as of today. And, as we announced, we've dosed our first patient, based on the current robust screening activity observed and our current enrollment projection. We expect to meet our goal of releasing data from the trial in mid-2024, and we anticipate this initial release will include objective response rate data for approximately half the patients we expect to enroll in the trial. On slide 26, I'll cover our third agenda item, our financial position, as of December 31st, 2023. As we disclosed today in our Form 10-K filing, we had $74.8 million in cash and investments as of December 31, 2023, and our cash used in operating activities was $7.1 million in Q4-23.
Agenda did not impact the outcome so.
We think that at this point based on what we have seen with the phase two trial and that is the Bev naive T. If you will.
Ladies and significant role of the dramatic synergy that you are seeing between.
And on one <unk> plus chemotherapy.
I see that's that's very helpful. So maybe moving out of the sorry before it hit 35 megawatt so in terms of managing neutropenia for sure.
The ongoing <unk> four study are you considering doing growth factor prophylaxis for for patients.
So.
Let's see.
I think the three things that we normally would use.
Hold the dose or delay the next dose allowed the bone marrow to recover.
It doesn't recover then we use growth factors according to <unk> guidelines.
And then subsequently.
We also have the option of doing those reduction depending on which.
James E. Levine: Today, we have greater clarity on our expected future expenses, and so we can be more precise about our forecasted cash runway. Specifically, we believe that our current cash resources provide us with cash runway into the third quarter of 2025, which is beyond the expected readout from the Cardiff-004 trial. Finally, on slide 27, we summarize why the Ensembl data we released today is so relevant for our first-line MCRC strategy and our ongoing Cardiff-004 trial. First, Ensembl is the second independent and randomized data set reproducing the robust efficacy signal for advanced or two plus standard of care in BEV-98 patients, and this support is currently enrolling a first-line trial where all patients are BEV-nave. Secondly, no VEV-naive patients in the Ensembl control arm showed an objective response to treatment without unvancertization, suggesting that vancertib is critical to the robust responses observed in the experimental arm.
Which drug is cause is.
The culprit, but again going back to <unk> and others. We have not found a reason for us to.
Are those decrease.
So we have all the options that gold standard that we would normally use in managing these patients.
But at this point, we don't think its going to be a big issue.
Got it that's helpful and then so outside of CRC.
They believe small cell lung cancer and the September update with <unk> III stable disease.
Patients do you have any update on that cohort.
It's kind of the latest data.
I can say that we don't have any update.
The pie is moved to another academic institution and so that has somewhat slowed down the accrual in that particular trial.
Great. Thank you so much for taking all of our questions and congratulations on the progress.
Thank you thank you Andy.
Thank you there are no further questions at this time I'd like to turn the call back over to Jamie Levine for closing remarks.
Thank you operator this concludes our conference call and thanks again for joining US this afternoon bye bye.
Thank you for your participation. This does conclude the program you may now disconnect good day.
Okay.
James E. Levine: And finally, both of the two on vancitive doses appear to be active, which suggests the two experimental arms of the Cardiff-004 trial could be combined when evaluating the trial data for efficacy. For all these reasons, we continue to believe our shift to the first-line setting is the best strategy for all of our stakeholders, particularly the large number of patients, 48,000 per year in the U.S., with RAS-mutated MCRC that may benefit from a new approach to treating their disease. With that, we'll open the call up for questions. Operator.
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Operator: Thank you. As a reminder, if you'd like to ask a question, please press star 1 1. If your question has been answered and you'd like to remove yourself from the queue, please press star 1 1 again. Our first question comes from Marc Frahm with T.D. Cowan. Your line is open.
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Marc Alan Frahm: Thanks for taking the questions, and congratulations on the data that you were able to release. Maybe first off, just, you know, obviously, just the first patient today, but, you know, any sense for kind of how much data you'll be able to release in the middle of the year from the OO4 trial, and then, you know, for the data today from Ensembl, any characteristics you can kind of provide on the baseline, like, you know A little bit of the difference, in response. Thank you. Thank you. Thank you. I can start.
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James E. Levine: First of all, like we said on the call, we're going to be putting data out when we have approximately half of the patients enrolled in the trial. And the second thing is that we're learning the ensemble data. We have looked at that. We haven't seen any differences from the side of this, but we did have to start that. Okay, and sorry, just on that update, is it once you've enrolled or that you have mature response data on HAF where we're looking at at least one scan after the base? Okay, thanks. That's very helpful. Thank you. Our next question comes from Joseph Catanzaro with Piper Sandler. Your line is open. Hey, everybody.
Joseph Michael Catanzaro: Thanks for taking the questions and the update, first on the ensembles and data. I'm wondering if you guys have formed a PFS. I'm looking at the swimmer's plot, and even sort of considering both Bev Naive and Bev Exposed, it feels like there's a pretty good... and maybe merging PFS signal that you're seeing in this randomized data. So, I'm wondering if you did that analysis, maybe what it's saying. Thanks, and I have maybe one follow-up. Thanks Joe for that question. We have not looked at it rigorously yet.
Okay.
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James E. Levine: We were waiting for more follow-up for us to look at that since there was quite a small number of patients, but we agree with you that there looks like there is an aversion. Okay, thanks, and then, for the frontline trial, was there any safety running on the backbone of Folfox? Just trying to get a sense of maybe historically how the neutropenia compares, with full thoughts relative to full theory, and then maybe relatedly the expected split between Folfuri and Fulfox.
Yes.
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Dr. Farouk Binabar: As a backbone, I'm thinking back to some, you know, earlier preclinical data from a couple years back that suggested for vancirtib and renotecan that, you know, there's some cooperation there. So hopefully that question... Yeah, Joe, let me first start by talking about the preclinical data. We actually have shown publicly that we have synergy with both oxaloplatin as well as adenocutin in preclinical models, and we have not seen any toxicity as well. For your questions regarding the full FOX in our first-line trial, I'm going to turn it over to Farouk, our CMO here. Hi Joe, so the question concerns any safety run-in for the full-force Bev Plus on one-sided valves.
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Dr. Farouk Binabar: Yes, for the first nine patients, will be evaluated after the first nine patients have been dosed, and those patients will be evaluated by the... Safety Review Committee, and once it is determined that full FOX plus on one-sided plus Bev causes no additional toxicity beyond what is expected of full FOX Bev, then that arm will continue to accrue to its full completion, the full complement of the patient. So, yes, there is a safety valve built into this trial. And we don't expect, based on how, on the one side, it partners with other chemotherapy drugs; we don't expect any major toxicity. And even the I'm giving you a lot more detailed information, even though there were two patients with neutropenia that were seen in this, in the Ensembl trial. Well, it was at the lower end, a lower dose, at 20 milligrams, not at 30, and then these patients, their neutropenia resolved just by holding the treatment or delaying the treatment for seven, in one patient, seven days, and another patient, ten days.
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Dr. Farouk Binabar: And those patients still continue on treatment without any dose reduction. Oh, good. Thank you. That's all very, very helpful. Thanks again. Thank you. Our next question comes from Andy Tsai with William Blair. Your line is open.
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Andy Tsai: Great. Thanks for taking our questions. Mark, I hope you feel better soon. Just want to dig a little deeper into the Ensembl Topol results on two topics.
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James E. Levine: One is on liver metastases, and maybe second on dose response. Maybe I'll go first on the dose response. Maybe, you know, perhaps you can comment on whether you see some sort of dose response, or both are active, and how do you think about, you know, both doses going forward? Specifically, on liver metastases, I think if I did the calculation right, it's about 77% of patients have some sort of liver metastases. That's kind of on the higher side.
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James E. Levine: Have you looked at the two responders? Do they have liver metastases? And, you know, I think the emerging data are suggesting that these patients are particularly hard to treat. And maybe there's a potential hypothesis on the mechanistic side of a mandative that's active in this population.
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James E. Levine: And there were a couple of follow-ups. Okay, well, thanks, Andy, for the dose response. If I understood your question correctly, we are seeing similar activity, albeit small data numbers, but we are seeing similar activity between the two doses, the 20, 30, and 40, and the. As far as the liver met, we have not analyzed that robustly yet, but I would say that in our phase 1b2 trial, it was shown that there was no difference in the response in bed-9b patients who had a liver met versus those that didn't, It was irrespective of whether the liver was involved.
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Dr. Farouk Binabar: So, Andy, just building upon what Marc just said, in the Phase I, B2 trial, we looked at multiple other factors trying to see if there were any other features that would impact these responses that we're seeing in Bev-Nai patients, and to give you a very short answer, absolutely no clinical feature appeared to play a role in the significant robust response that we've seen in the BEV-90 patients. So we looked at the laterality of the tumors; right and left tumors both responded equally. We looked at patients with liver meds and without liver meds, and they all seemed to respond well. We looked at patients who had a gender did not impact the outcome.
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Dr. Farouk Binabar: So we think at this point, based on what we have seen with the Phase 1b2 trial, and that BEV-90, if you will, that plays a significant role in the dramatic synergy that you're seeing between BEV and Oncology plus chemotherapy. I see that it's very helpful. So maybe moving out of the sorry, actually, before we move on. So in terms of managing neutropenia in the ongoing 004 study, are you considering doing growth factor prophylaxis for patients? So these are the three things that we normally would use: hold the dose or delay the next dose to allow the bone marrow to recover. If it doesn't recover, then we use growth factors according to ASCO guidelines.
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Dr. Farouk Binabar: And then subsequently, I mean, we also have the option of doing dose reduction depending on which drug is the culprit. But again, going back to the 1B2 trial and others, we have not found a reason for us to dose decrease. So we have all three options that are standard that we would normally use in managing these patients.
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James E. Levine: But at this point, we don't think it's going to be a big issue. Got it. That's helpful. And then, so outside of CRC, the only small cell lung cancer left in the September update was 1PR3 stable disease patients. Do you have any updates on that cohort? Or is that kind of the latest data? I can say that because we don't have any updates. The PI has moved to another academic institution, and so that has somewhat slowed down the accrual of data in that particular trial.
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James E. Levine: I see. Great. Thank you so much for taking all of our questions and congratulations on the progress. Thank you. Thank you, Andy. Thank you. There are no further questions at this time. I'd like to turn the call back over to James Levine for closure remarks. Thank you, Operator. This concludes our conference call, and thanks again for joining us this afternoon. Bye-bye. Thank you for your participation. This does conclude the program. You may now disconnect. Good day. ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? [? soft music playing ???????????? [? soft music playing to the end ??????????? [? soft music playing to the end ??????????????????? [? soft music playing to the end ????????????????? ??? ??? ??? ??? ??? ??? ??? ??? www.cdc.gc.ca ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ?? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ? ?
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