Q4 2021 Atreca Inc Earnings Call
Good day, and thank you for standing by welcome to the <unk> fourth quarter and full year.
Financial results conference call at this time, all participants are in listen only mode. After the speaker presentation. There will be a question answer session to ask a question and session you will need to press star one on your telephone if you like any further assistance. Please press star zero to hand, the conference over to your speaker today.
Alex Greene head of Investor Relations. Please go ahead.
Thank you operator, and thank you to those joining us today, we're pleased to be hosting our year end conference call and webcast, including updated data from our ongoing phase <unk> trial.
Joining me for prepared remarks are John <unk>, CEO and Dr. Jonathan.
On your Vice President Research also on the line after chemotherapy.
Fair enough.
Third cross.
Well it would be available.
For those joining by phone.
Presenting slides as part of this program.
The webcast.
The presentation section of our Investor Relations website at IR <unk> com.
Archived replay of todays webcast and the accompanying slides will be available on our IR site following.
Yes.
During today's call, we'll make forward looking statements based on current expectations. These statements are subject to a number of risks and uncertainties and our actual results may differ materially for a description of risks and factors that could affect our future financial the financial results.
Please refer to the disclosure in the accompanying slides our most recent forms 10-K 10-Q and the reports that we may file on form 8-K Securities Exchange Commission. All our statements are made as of today March three 2020.
Based on information currently available to US we can give no assurance. These statements will prove to be correct. We undertake no duty to update these statements except as required by law I will now turn it over to John John .
Thank you Alex before discussing the agenda I'd like to briefly address the purpose of this call.
On the Herc 101 trial results with regard to see.
Under our clinical strategy will providing updated data along with our year end earnings.
To provide enrollment updates and our earnings reports going forward, we do not yet planned to host regular quarterly conference call and future data presentations will be timed around the key clinical milestones, we expect to present further updates in the second half of the year.
On today's call.
Jonathan will present data from the Trc 101, monotherapy timber listen that combination cohorts and are ongoing.
Phase one b trial evaluating each of our Super one participants.
Solid tumor cancers.
Led by an update on our clinical strategy.
I will then discuss our financials and milestones.
The line for Q&A.
Top line summary is at Herc 101 has demonstrated anti tumor activity in participants with Trc 101 target expression, including responses by resist.
Monotherapy in combination with <unk>.
And it was well tolerated at all doses and dosing.
Dosing frequency for that.
So for each of the major points turn the primary objective.
Objected to the phase <unk> study to evaluate safety, we're pleased to share that the herc we're one.
So far has been well tolerated.
And the combination.
Including at the highest dose study of 30 milligrams per kilogram.
On a once every two weeks.
Three week dosing schedule.
As a reminder, the Trc 101 targets a novel rapid nucleoprotein.
We continue to see this.
An association between target expression and anti tumor activity.
We are now validated platform drive target as well as the diagnostic participant selection, which we are proceeding with integrating into the trial protocol.
The more we're excited to report that as the synergies and heavily pretreated participant group, we're seeing responses and stable disease.
The reduction in tumor burden across multiple cancer types and participants treated with monotherapy and combination therapy.
We believe that these data showed that our first clinical candidate.
Validate the ability of our platform to identify potentially therapeutic antibodies recognizing novel targets.
Now I'll turn it over to Jonathan to discuss the data.
Thanks, John .
Thank you to everyone joining the call today.
Before we discuss the data.
I will review the trial design the baseline characteristics of participants treated.
The analysis.
As a reminder, and as shown on slide six.
The basket trial with multiple ongoing and planned expansion cohorts.
I will begin with Herc 101 administered as a monotherapy every three weeks for Q3 W.
Dose escalation portion completed last year with no dose limiting toxicity observed any cohorts.
We will be presenting data from a large number of participants involved in the Q3 W. Cohorts from the every two week dosing.
Our Q2 W monotherapy cohorts as well as the tempo of lithium that combination cohort.
Participant enrollment is ongoing at 30 milligrams per kilogram in the Q3 W. Monotherapy combination cohorts and then 10 milligrams per kilogram in the Q2 W monotherapy cohort.
We've treated participants are five dose levels, ranging from 0.3 to 30 milligrams per kilo.
Most of our analysis. However, we will be focusing on participants who received 310 or 30 milligrams per kilogram of Herc 101, which we view to be more pharmacologically relevant in the Europe III at one milligram per kilogram doses.
Now I'd like to review the eligible indications for the study.
For monotherapy enrollment limited to participants with tumor types displaying greater than 50% immunoreactivity to <unk> 101 preclinical studies.
Tumor types.
Slide.
Enrollment in the temporal this combination cohort.
London is limited to patients that have progressed on or after treatment with an anti PD, one or anti PD.
PD one agents.
Alright that stable disease, but the treating physician has determined that the participant needs additional treatments.
Compared to the indications eligible for monotherapy.
Set of tumor types in the combination cohort was extended to include dose in December was not approved.
Also displayed greater than 30%.
<unk> <unk> hundred one in preclinical studies.
These indications are also listed on the slide.
Primary objective of the trial to determine the safety and Tolerability of the Trc 101, when administered as a monotherapy or in combination.
With key additional objectives of determining a recommended dose for expansion.
Measuring initial clinical activity.
Characterize predicted Pharmacodynamic biomarkers blood.
Tumors.
As we previously discussed and as shown on the bottom of the slide we're also evaluating a separate competition.
Pegylated licensed civil Doxorubicin.
Just on the growing understanding of the potential mechanistic synergy chemotherapy with <unk> 101.
The preclinical model doxorubicin.
Target expression in tumors, which we believe could contribute to the clinical activity of the company.
On slide seven with an overview of the baseline characteristics to participants enrolled both monotherapy arm and in the combination fromer.
As of the data cutoff date of February 15, 2022.
47 participants enrolled overall.
36 on the Q3 W. Dosing schedule eight Q2 W dosing schedule and three in the combination.
As you can see.
Asia participants was 58 years with most having E com performance status one.
Nearly half of the participants on colorectal cancer, which is not surprising given the scale of unmet need in that indication.
We've recently instructed our clinical sites to prioritize enrollments of patients with other tumor types.
We can get a more complete profile of <unk> 101 furnace early stage trial.
Finally, the supply title indicates.
Dissipates enrolled in this study and for the most part in heavily pretreated.
With a median of five prior lines of therapy.
About half of participants received at least one prior line of checkpoint inhibitor therapy.
As a reminder, prior exposure to anti PD, one or anti PDL one.
Eligibility requirements for the temporal lithium that combination.
In this presentation, we will be reviewing safety and response data.
Overall response and target lesions responses.
For the sake of clarity launched upon the pertinent analysis.
On slide eight.
Turning to the safety of 47 total participants who received at least one dose of study drug.
36 were evaluable for each store.
Pretreatment tumor biopsy.
As a reminder, each sport as a composite score target expression that captures the proportion of cells.
As well as the intensity is outstanding.
Separately of the 47 total participants thank you Sir.
<unk> 38 were administered dose of at least three milligrams per kilogram.
Although there may be some activity at lower doses as we've said.
We believe that it is more relevant to focus on the higher doses to the efficacy assessments.
Up to 38 participants treated at those dose levels, we can.
Currently have post baseline radiographic tumor reached to 32.
Those 32, we also have each score assessments for 25 participants.
A word on the final road this chart.
Of the data cutoff date, one of the 25 participants with tumor lesions itch score assessment did not have their overall response data entered into the database.
Thus the response, an H score set includes only 24 participants.
Please note that both the H score in response to omit participants who may have that data in the future.
Because for instance, they are still on treatments or their biopsy assay.
Also note that certain figures such as in waterfall those firewalls.
Participants in monotherapy and combination cohorts are grouped together.
However in time to event analysis is necessary to restrict analysis to uniformly treated participants.
Moving to slide nine.
<unk> 101 continues to be well tolerated with no dose limiting toxicities observed in the safety set of 47 treated participants.
Of the adverse events observed.
There remains no pattern to suggest the particular toxicity profile.
Nor were their relationships between incidents or severity of adverse events dose.
Or incidence of adverse events with target expression.
There were two grade three adverse events considered by study investigators as possibly related to treatments.
Headache small intestinal obstruction.
No participants start to come off study due to toxicity.
<unk> eight dose reduction.
Slide 10 is a waterfall bought a 32 participants in the target lesion assessment.
Including the three participants enrolled in the combination cohort indicated.
Indicated by cross hatched bars.
Participants in the queue to W. Monotherapy cohort are indicated by the checkered bars.
Looking at the three participants on the far right up the plant. We are pleased that our melanoma participants enrolled in the combination cohort achieved a complete response.
Non small cell lung cancer patients enrolled in the Q3 W. Monotherapy cohort achieved a partial response.
Other participants treated with monotherapy achieved stable disease with reduction in tumor burden, including one participants still on study with 29% reduction.
Baird.
Of note. This slide includes all participants enrolled at a relevant dose level, regardless of target expression.
Activity observed.
Was it related to target expression as shown on slide 11.
Here, we have the chart on the left showing the significant association between target expression and response in the trial.
With data from the response from each source debt 24 Evaluable participants.
But demonstrates the target expression is significantly higher than participants who experienced a complete response partial response or stable disease.
Radiographic tumor assessments versus those who have progressive disease.
We placed a horizontal line corresponding to an H score of 52 indicate analytic threshold that defines low target expresses and high charges expresses and to compare outcomes for these groups.
On the right is the <unk>.
Bar chart, Nuvaring stable disease or better responses low target expressed in purchased since shown in light blue versus high target expressed in participants in dark blue.
Delineating these populations as we have demonstrated significant differences in outcome between these two groups.
I'd also like to note that the 36 total participants enrolled thus far that were evaluable for target expression. There was an equal split between those with screams scores.
Above 50 in dose with scores below.
This distribution is roughly in line with our expectations that were based on preclinical analysis.
So we have not yet and we will not participants to generalized conclusions about target expression patterns in any specific tumor types.
As we previously stated the target expression diagnostic has now been validated and we expect to be able to screen participants based on targeted expression and future cohorts within this trial.
On slide 12, when we applied the same color scheme to identify high and low targets for instance through the waterfall plot previously shown on slide 10, we can see clearly that participants.
Significant tumor growth.
What we're predominantly low targeted expresses and the two participants who experienced resist responses and shown on the far right of the plot where both high target expresses.
Moving to slide 13.
And because our next area of focus will be to enrich participants based on target expression.
Remove low target express just from the charts.
Bars are now color according to tumor type.
As you can see we've observed activity as defined by tumor burden reduction multiple tumor types, including melanoma.
Non small cell lung colorectal breast and ovarian cancers.
So it's still too early to narrow our focus we are.
Even true on the potential of <unk> 101 in non small cell lung cancer and melanoma.
In the appendix of this presentation and provided for your reference.
Waterfall chart willing participants.
Participants enrolled at the lower dose levels, regardless of target expression.
On slide 14 is a spider plot.
<unk> curve showing time to progression.
Here, our participants with target and source of less than 50.
Showing that low target express has tended to progress on treatments.
Shorter durations of therapy.
And participants with target H scores of greater than or equal to 50 shown on slide 16.
Hi target Express says, we're more likely to tumor reduction first response assessment onward and remains on therapy longer.
As shown on the right there was a statistically significant difference in time to progression.
As a reminder, the Kaplan Meier curves limited to participants treated in the monotherapy Q3 W. Cohorts.
Here, the median time to progression in the low target expressed in group was 41 five days.
Paired with 94, five days and the high expressing group.
Also note that the previously referenced participants who achieved CR.
And the 29% tumor reduction all remain on study.
On slide 16 are.
Or the treatment history, and representatives <unk> scans from the participants with a confirmed complete response reported in the combination cohort.
Chart. This is the only target expressing participants treated with combination therapy for whom we presently have response data.
Participants is a 78 year old female who was diagnosed with BRAF mutated metastatic melanoma.
And progress first on anti PD, one therapy, and then on combination to proximate and tremendous before being enrolled in this study.
As the <unk> show.
Super particular left sided nodal lesions present, just a final screaming largely disappear by the week seven skin.
By the week 13 skin lesions with undetectable.
This pattern was also observed in other target and non target lesions.
We are excited to see such a robust response in the first target expressing participants treated with combination therapy.
Particularly given that at 78 years old this purchase would be an eligible for the majority of clinical trial College.
Attribution in a single arm combination trials can be challenging, but there are a few points that give us confidence that herc one on one contributed to the response observed.
First is the evidence of monotherapy activity, including in our participants with April melanoma.
Stephen this participant with a high target express Sir.
Third tumor types are enrolled in the combination cohort, including melanoma rarely respond to anti PD, one monotherapy, having after having progressed on prior PD one therapy.
While it is still early is encouraging to see the first target expressed in purchase.
With the combination.
Cheap a complete response.
Now moving to the data summary, and next steps beginning on slide 18.
We are encouraged by the results observed thus far in the phase <unk> trial of Herc one on one.
101 continues to visit antitumor activity associated with targeted expression and was well tolerated at all doses tested.
One dose limiting toxicities observed and no treatment discontinuation due to adverse events.
Hi target expression screening defined as a screening each store 50 Europa delineated a group with better outcomes.
Finally, we were gratified that the trial participants achieved a CR and remains on study and the combination cohorts and another participants achieved a PR and remains on study in the monotherapy cohort.
Overall 13 of 19, Evaluable participants with high or unknown target expression treated with <unk> 101 at doses of 310 or 30 milligrams per kilogram.
Chief stable disease or better in the heterogeneous heavily pre treated group of participants.
On slide 19 is an outline of the next steps for one on one.
First the target expression assay now have CLIA validation.
Based in part on the data presented today, we expect to begin selecting participants based on target expression and the second quarter of this year.
During the FDA review of the.
A modified protocol, we will continue to enroll participants at 30 milligrams per kilogram of <unk> hundred one monotherapy in order to obtain additional information on efficacy and Biomarkers and to further inform our clinical strategy.
On the anti PD, one combination side.
Coleman is underway and the 30 milligram per kilogram combination cohort.
We plan to report additional data from both the monotherapy and combination cohorts later this year likely in the fall once we have enrolled a sufficient number of target expressed in participants to provided substantial update.
In the interim we will continue to provide enrollment updates in our quarterly earnings reports.
As previously mentioned, we are also evaluating separate combination arm with.
With Pegylated lysosomal doxorubicin.
Pending completion and review of the Q2 W monotherapy cohorts.
I will now turn it back over to John to discuss our financials and upcoming milestones.
John Thank you Jonathan finally on slide 21, with a summary of our financials and upcoming.
Coming milestones.
21 was a productive year for the advancement of our pipeline and we are pleased to announce that we will be hosting a pre clinically focused R&D day on April 5th during which we will be discussing our phase two program as well as several other previously undisclosed antibodies against targets and antibody drug conjugate.
Come on nature and other weaponized formats. In addition to our non oncology programs.
John mentioned plan to present additional data from both monotherapy and combination cohorts and provide an update on our clinical strategy in the second half of the year.
Expect to soon be able to select participants based on target each quarter and the timing of our update will be driven by the pace of enrollment of additional target expresses.
Finally, we had $148 $1 million in cash cash equivalents and investments as of December 31, 2021, which we believe provides us runway through the first half of 2020.
That concludes today's prepared remarks, I'd like to thank our trial participants and their families as well as investigators and research staff and our clinical site. Thanks again to everyone for joining the conference call and webcast today with that operator could you. Please open the line for Q&A.
As a reminder to ask a question you May press star one on your telephone.
And the question press the pound key please.
Please send wireless compile the Q&A roster.
Our first question comes from the line.
<unk> Willey from Stifel you may begin.
Yes, thanks for taking the questions and congrats on the data.
Was just curious I know that you've talked about having a particular interest I guess.
Non small cell lung melanoma and.
I was wondering if you could maybe tell us what proportion of those tumor types in the refractory setting.
Meet that threshold level of H score cutoff.
And then I guess.
Second to that curious if you've looked at H score longitudinally.
In terms of just trying to understand the stability of of target expression over time during the course of treatment.
Yes.
Great Jonathan Yes, yes excellent question. So the first question about distribution page scores in melanoma and non small cell lung cancer.
Indicated we're still working with a somewhat small.
Sample size, so I would rather not.
Go too much into that at this point I think we need to see more data.
And in terms of the stability of the target over time is something that is actively being explored as we mentioned in the preclinical model <unk> modulation toward that level by chemotherapy, whether or not that is durable over time.
Is unknown to us.
But we are actively analyzing that very question.
Yeah, and I think with our.
Diagnostic strategy, we'll be collecting.
Both archival as well as fresh tissue biopsies.
Look at those exams.
Examples.
Further a mistake.
40 of target expression.
Okay, and then maybe.
Just lastly, I guess when you look at.
The differences in activity.
That's been observed between the high and low target expression I think Theres a bar chart on slide 11.
Right hand panel.
Do we know.
What proportion of those patients who have extracted clinical benefit didn't have an H score of greater than 50 received the 30 Mig per <unk> dose.
So you're saying in terms of.
So in terms of the six patients with stable disease.
Patients with stable disease on slide 11 in the bar graph.
<unk>.
The honest.
I haven't I have a number in my head.
The number but I think it's approximately eight.
Okay.
Very helpful.
Taking the questions and congrats again.
Thanks, Steve.
Our next question comes from the line of so Nathan from Kevin You May begin.
Good afternoon, and thanks also for taking my question and congrats on the activity a few questions on the patients from us.
First on the.
The CR patient with melanoma.
What was the prior response on that and that patient to date progress immediately or was there a pure CR.
So the first round of PD one treatment.
The patient progressed after.
Approximately nine months.
Precise best response.
A little bit unclear.
But it was.
There was not a lot of measurable disease treatment initiation.
And then the patient progressed.
The nine months time.
You mentioned, it's very.
Sure.
I would just say and they have received as they have been treated with both a PD one as well as.
The RAF inhibitor combination sequentially.
Right right yes.
No that's very interesting.
You mentioned in your prepared remarks, it's very rare that there is a response on re treatment with PD one in melanoma post progression.
Progressive progression do you do you know with that.
You have the response rate data.
How often does it doesn't happen.
Bob.
There are various levels of evidence CRM there've been meta analysis on this topic.
So there are there are a range of numbers that have been provided depending.
How how it's been defined but.
I can summarize in one way by saying if you just look at the guidelines the guidelines.
Entergy, New Orleans et cetera.
That is now recommended to retreat in this setting.
But I would say that if there are no bona Fide response, and we're not talking about treatment beyond progression.
So it's a primary therapy I would say that it's probably the single digits.
Got it okay, that's really helpful.
That's very helpful and then in terms of the.
The PR or CR.
I apologize if I missed this.
Are those patients still in response and.
If now what was the duration of those responses.
The CR.
Sure.
And the colorectal in the colorectal cancer patients with a 29% reduction remain on treatment. They remain on study.
Okay, and then last question on that.
The pure non small cell lung cancer patient where their prior rounds of therapy.
Okay.
Plenty of prior lines of therapy, including a platinum based doublet.
As well as.
Hey, another.
Microtubule.
Does taxol.
Experimental trial with tons of lids amount, but actually to have a trial emerald is about monotherapy.
Perfect. Thank you that's very interesting and congrats again on the activity.
Thanks, Joe.
Our next question comes from the line of John Newman from Canaccord, you may begin.
Hi, gentlemen, thanks for taking my questions and really interesting response data here, thanks for sharing that with us.
I'm wondering if.
I may have missed this I apologize just curious if you have disclosed the dose level.
Where you saw the response.
For non small cell lung cancer as monotherapy as well as the combination where you.
The complete response.
Okay.
Yes.
For the non small cell lung cancer patients and top line.
In.
Q3 week dosing frequency at 30 milligrams per kilogram.
For the melanoma patients who had a complete response to.
The combination of in that one.
It's 10 milligrams per kilogram of Herc 101.
Okay. Thank you.
Also just had two quick additional questions.
I'm just curious as to what type of H score cutoff, you're considering as you began enrolling.
On target expression and the second quarter.
So.
We have we are we are making proposal to.
The regulators.
So I believe that since it's subject to negotiation.
We can't be firm on it but.
That analytical thresholds of debt.
Where we're starting.
That's due in part not just because.
The response data.
The overall response.
D C IPR versus PD, but also when we look at the lesion responses. So the percent reduction because as you know stable disease can be heterogeneous.
Disease growth up to 20% or two these reduction up to 30.
30%, So we really tried to focus on.
A cutoff that wood.
Minimize those.
The <unk> growth.
More towards tumor reduction.
Okay, Great and just one more if I could sneak it in.
Just curious if you have any rough idea on timing for data from the.
<unk> and chemotherapy combination trial with <unk> hundred one thanks.
So maybe I apologize I apologize if I was not clear about this Dod has not started enrolling we plan to.
Wait until we complete the every two week monotherapy dosing and evaluate those results.
We will take it from there, but we have not started enrolling also.
Protocol.
That's real hard we just have not activated.
Okay, great. Thank you.
Okay.
Our next question will come from the line of Roger song from Jefferies. You May begin.
Great.
And congrats for the for the data in that thank you.
<unk>.
First of all maybe just to.
To clarify Jonathan if I misheard that.
So.
How many patients on the mono therapy at the higher highest dose 40 Meg per kg.
Hi, Paul.
Great.
Thank you.
I think we have a lot of different menology sets in.
Overall, though I think we're seeing.
Yes.
Roger.
Apologize the total number.
But in terms of what we presented today.
We're roughly representing <unk>.
Ultimately.
Patients overall.
With high score.
Yeah, Okay. Thank you.
Alright, and then still.
So for those.
Tell patients they have the high H score.
We know the medium prior well.
For those patients because overall, you'll have that come.
Five prime media among those outpatient with highest score what is the priority.
Yes.
So it's a great question, Roger and we are we are looking into that.
Can only tell you that.
It.
It is a relatively small data set.
We are seeing typically but there is a.
If we split the groups the median.
Prior lines.
It's slightly higher.
Score greater than or equal to 50 group.
Slightly higher.
So it's still small numbers and I think we're not.
We're not ready to say that that is a real phenomenon.
Got it yes.
Okay, maybe just a last one from that.
In terms of the next step the new wells with that debt.
Additional data in second half.
Given you're focusing on those high dose 310 and 30.
Would you be able to also determine that appear to be kind of moving forward.
The dose.
From that don't see doses.
Yes.
Also a great question in terms of the.
The dose for expansion.
As we've said we have not seen any safety signals, we don't believe thats higher doses.
I'm way mitigate any activity so.
For the time being we are going with the highest.
Tolerated dose, which in this case at the highest tested dose now.
It doesn't necessarily mean that that is a committed does for all future stages of development, but moving forward, we will probably use the highest dose that is tolerated.
So we could take into consideration we take into consideration that Q2 weeks schedule, which is also the highest dose which is 30, thanks for Kate.
Yes, that's right got it okay, great. Thank you. Thank you.
Final question.
Thank you Roger.
Our next question comes from the line of Tony Butler from Roth Capital you may begin.
Yes, thanks, Jonathan.
Really two questions one is.
Even if it's anecdotal do you have any evidence.
The tumor size had an effect such that.
Bulk.
Tumor, let's say a large tumor.
Have responded less well than a small tumor that's question one by the way and then second.
Then there is.
You didn't allude to or at least I didn't hear any translational data but.
Was there any substantial difference.
You know up either from biopsies on CD eight <unk> in the serum.
Especially at 30 in the responding patients even its stable disease patients.
Okay.
Okay. So.
We are actually looks.
As lesion by region as well as overall tumor burden.
Impact.
Steve.
Short term outcomes of response.
And we have not seen a difference.
Patients with lower tumor burden as well as those with higher tumor burden.
We can debate.
Impacting the outcome.
It remains to be seen because certainly the precedent in oncology.
Moving with immunotherapy.
The larger the tumor or tumor the less likely.
Overall, we stir ability likelihood of response.
Second question was on sort of the biomarkers whether from serum.
Our tumor.
We're continuing to analyze that.
Including flow cytometry.
The lymphoid and myeloid populations.
Do you need to look at cytokines.
When you mentioned the CDA T cells in the tumor premium for us.
<unk>.
We will present that data, we're not ready to present that data yet.
But it is forthcoming.
Certainly.
Yes, Theres no question, but could I ask.
At least from.
And I'm, sorry to press it more but at least from what Youre seeing are you encouraged by what you are seeing such that you want to complete that data set and think that it is.
It's really correlates to.
<unk>.
What the patients may be experiencing.
Yes, I think that we are encouraged that the data.
And some level of support the mechanistic model, but thats been proposed.
Two.
Along with what we presented last July .
Okay.
Thanks very much.
Thank you John .
Our next question is from the line of Joel Beatty from Baird you may begin.
Alright, Thanks for taking my questions and congrats on the responses. The first question is could you speak to.
Kind of broadly if you saw a dose response.
Okay looking at the active.
Activity, maybe beyond just the responses that we've seen in one patient with 30 milligrams and the other patient with 10 milligrams.
We're seeing overall dose response.
Scott.
The numbers are too small and the 310 and 30 group to say that there is a clear dose response I think once we have.
A larger group of target positive patients treated.
With comparable.
Same dose that we'll be able to really make a statement we've never really thought that there and we've always thought that there could be a good response with lower doses.
But they will probably occur with greater frequency with higher doses.
We need more patients.
Page source.
Got it I appreciate that and then maybe one more question could you share any potential to that.
And the decision from this trial.
Coming medical conferences.
Hum.
Tom.
We are certainly eager to share this data with the broader medical community in Brazil too.
So.
We are moving forward as we have done it as we've done in the past.
Probably.
<unk>, a future ask of market shares Oscar.
Great. Thank you.
I mean, we made we may present, we may present others.
50 is always one of the conferences that we find.
Very interesting to attend and participate and so that thats a high likelihood one.
Okay.
Our next question comes from the line of Joe and James HD.
H C. Wainwright you may begin.
Hey, guys. Good afternoon, thanks for taking the questions and thanks for the update today.
So my question may be too early but I wanted to link it also to some of your earlier comments today. When you look at the Spider plots on Slide 15, I was just curious first do you have any overall observations because there seems to be a bit of variability with regard to the especially over 50 expresses the H scores on.
The slopes of the curves and the different inflection points do you have any additional observations from these patients who wanted to share and then linking to the earlier comments.
I just wanted to make sure I heard you correctly.
Going forward in the future you'll be able to then generate more data to say maybe some of the rapid.
Our rapid progress or is in the over 50 might be loss of target.
Okay. So.
Going going going first to the heterogeneity of the Spider plots.
I think.
We believe that well I'll, just say that we believe target is necessary, but not sufficient for <unk> hundred one activity. We believe that this is a heterogeneous group of patients some with different prior.
So tumor kinetics are tumor.
Tumor kinetics going into the trial, we would expect that variability.
And the Spider plots, Joe one thing that I that I am encouraged by is that it seems that participants.
Who have the supply.
5% reduction in overall tumor burden.
Okay.
To be relatively stable, but again the follow up is short so don't want to get too far ahead of that.
And I apologize.
There was.
I think the third part of your question.
More of a follow up on.
Either for these patients are patients that you enrolled later on that some of the say rapid progressive is even over 50 that you'd be able to assess the loss of target towards authorized your earlier comments yet.
Yeah. So.
Great question.
Again I'm going to.
I refer back to some of the preclinical mechanistic studies.
We do cover in todays talk.
We believe that the Trc 101, initiate an immune response, but ultimately involves the adaptive immune system, it's not strictly require persistent expression of the Trc 101.
<unk> tried to be asked if we can do that.
Actually will.
Lead to.
Tumor cell death disadvantage in prime right now.
For other T cell responses that can ultimately lead to tumor control so far.
Of course, we are going to be looking at patients.
We have not only on study biopsies, but we end of treatment biopsies, where we would like to be able to understand if there is resistance that emerges what are the molecular mechanisms whether the phenotypes of the.
Escape escaping tumor cells.
Got it thank you very much.
And our next question comes from the line of Kumar and Roger.
Brookline capital.
Hi, Thanks for taking my questions and congratulations on the data hub.
With regard to the hit squad.
Touched on this a little bit.
Tons of putting piece apologies.
Are there specific histology is where you are seeing.
Hi, Hi, quoting.
Some population.
Yes.
Again.
I apologize.
Just not comfortable making any broad statements about the types of target expression patterns. In this limited number of patients I really think we need to.
Through a larger.
I have a larger prevalence screen and that is actually ongoing.
To determine.
What the distributions are and especially given that these are relatively broad definitions of cancer side than we are.
Everyone's drilling down more in Molecularly defined.
I mean, I think that typically defined cancers, we imagined that there may be variations within tumor types. According to the other.
Markers, so more to come on this but suffice it to say that we are continuing to.
Enroll unselected patients and we've got a little bit more prevalent data that way and.
With our with our eligibility screen will also will also be able to determine quite a bit on the distribution of it.
Scores.
It's fair to say that now that we've treated.
A larger number of patients.
What we observed in terms of target expression its not.
<unk>.
What we initially assumed based on the preclinical observations.
Histology work that we've done previously.
50% overall for all applications.
I think theres, just not enough patients if any one indication to really be able to make meaningful distinctions between them.
Yes.
Thanks, John and the analysis.
We presented were reflected explore it has been a 50 50 split exactly.
There is a little.
Variability to the small numbers.
Okay. So when you are planning.
Enrollment in the expansion.
So that assumption is that probably will end up at about 50% screen failure rate.
Screen failure based on target expression, yes, yes.
Yes.
Obviously other things that contribute to it.
Ah patients still experience, but.
Yes.
Average, we're seeing about 50%.
Ah patients exhibiting target expression.
Okay, and finally with regard to.
Hey, Jacob target when can we expect data on that.
Yes.
As I mentioned at the outset, we're planning our R&D day for April yet.
And at that time, we expect to be able to present, a lot of new information related to the entire pipeline, but in particular, our FHA program, which I think is what you're referring to.
Thank you so much.
Thank you.
Thank you I'm not showing any further questions in the queue I'd like to turn the call back over to John for any closing remarks.
Great well, thanks to everyone for joining our call today and all the terrific questions and we look forward to providing additional updates on Herc 101 program as well as.
Our preclinical research programs in the future.
Great day.
This concludes today's conference call. Thank you for participating you may now disconnect everyone have a great day.
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