Q4 2020 IGM Biosciences Inc Earnings Call
Ladies and gentlemen, please continue to hold your conference call will begin momentarily.
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Thank you for your patience. Please continue to hold your conference call will begin momentarily.
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Good day, everyone and welcome to the IGN Biosciences fourth quarter and full year 2020 financial results call. Today's call is being recorded at this time I'd like to turn the call over to Ms, but to hear chief.
Shall officer by channel.
Thank you operator, welcome and thank you for those of you joining us today to discuss <unk> fourth quarter and full year 2020 financial results.
With me this afternoon to discuss the financial results and to provide a general corporate update.
Fred Schwarzer, Chief Executive Officer, Bruce Kite, Chief Scientific Officer, Dan Chen Chief Medical Officer, and Lisa Decker Chief Business Officer.
Please note that we will be making forward looking statements on this call, including statements about <unk> plans expectations and forecast and about future events.
Actual results may differ materially as a result of various risks and uncertainties, including those discussed in the company's most recent annual report on form 10-K, as well as its other filings with the SEC.
Any forward looking statements represent <unk> views as of today March 32021, only and the company disclaims any obligation to update these statements except as required by law.
Following this call a replay will be available on the company's website www dot IGN bio dot com with that I will now turn the call over to Fred.
Thank you Misbah.
Good afternoon, everyone. Thank you for joining us on this call to discuss our fourth quarter and full year 2020 financial results.
Before we begin is my great pleasure to introduce Lisa Decker as our new Chief business Officer.
Lisa brings a wealth of life Sciences business development experience to IGN and I'm very pleased to welcome her to our executive team.
Yeah.
2020 was an important year for <unk> yeah.
Among our milestones last year, we presented the first clinical data from our phase one trial of IGN twenty-three twenty-three or.
Our bi specific I G M antibody targeting CD 20, and CD three.
And these were presented at the Ash 2020 annual meeting.
We were highly encouraged by these initial data from both an efficacy and safety perspective.
We continue to make good progress through our IGN twenty-three twenty-three dose escalation cohorts and we are pleased with the safety and efficacy profile that we've seen so far.
We look forward to completing enrollment in the phase one dose escalation and the initial expansion cohorts.
Establishing a recommended phase two dose for this.
Sure.
And provide an operational update on this ongoing trial.
'twenty 'twenty. We also began clinical development of our gem eight four for for our I G. M. D. R. Five agonist antibody, which we believe may have application in the treatment of a broad range of cancer types.
As Dan will shortly describe we have now cleared the second dose cohort in our monotherapy dose escalation protocol and we are ready to expand into higher dose cohorts in combination therapy.
Bruce will describe some of the exciting preclinical data we've generated concerning IGN eight four for four in combination with Brent up had a clinical stage a pop ptosis drug which is synergistic with IGN eight four for four and to which we obtained exclusive global rights earlier this year.
Finally, as Bruce will also described we are very excited about the prospects for IGN $73 50 for our targeted IL 15 immune cell stimulating antibody as well as our broader pipeline.
We plan to file an IND for IGN $73 50 for towards the end of this year and to file an IND for our CD 38 by CD three T cell engage your candidate next year.
With that I'll turn the call over to Dan who will discuss IGN twenty-three twenty-three and IGN eight four for four and the current state of our clinical trials.
Thank you Fred as Fred mentioned, 'twenty, 'twenty was a particularly exciting and important year for us as we presented our first clinical data from IGN 'twenty through 'twenty three in non Hodgkin's lymphoma at the 2020 Ash annual meeting we continue to make rapid progress with both of our clinical.
Cam's IGN 'twenty through 'twenty, three and I G. M 80 for 44 and by end of 2021 we hope to file a 90 to begin the clinical development of <unk> 70 354.
I'd like to first discuss our lead clinical program I jammed 'twenty through 'twenty three as a reminder, the ongoing phase. One study is a global multicenter open label dose escalation trial intended to assess the safety pharmacokinetics and preliminary efficacy of intravenous IGN.
23 23 assets.
Single agent in patients with relapsed and refractory b cell non Hodgkin's lymphoma.
Since the Ash 2020 presentation. We've now cleared the 50 350 600 titration dose escalation cohorts and we are currently opened to enrollment for the 51000 milligram cohort, which is our planned top titration dose.
We are very encouraged by the safety and efficacy signals that we continue to see in our clinical trial and we expect this program to continue to progress quickly in clinical development.
From a safety perspective, we have not yet experienced a dose limiting toxicity and we have not seen any cytokine release syndrome to date at either the 300 milligram or 600 milligram doses.
We are very excited by our ability to dose at these higher levels without Saticon released syndrome.
So far we have also not seen any sign of neurotoxicity at any dose in any of the patients treated in our clinical trial. Overall, we believe we are well on our way to demonstrating a best in class safety profile.
Of the 25 patients we have treated only to have experienced cytokine release syndrome beyond grade one one case of which was described in our ash presentation.
Those two patients had some striking similarities in that both had prior treatment with car T cell drug and also had circulating peripheral b cells.
The more recent patients had been treated with an experimental car T drug which has since been removed from clinical development.
And interestingly testing of samples showed that the patient had non detectable levels of circulating car T. Prior to treatment with IGN 'twenty through 'twenty three.
But then had detectable levels of this experimental car T circulating following treatment with IGN twenty-three twenty-three.
This event occurred at a first dose of 50 milligrams and this 50 milligram for Astellas has not demonstrated crs of any grade in any of the other 12 patients who also received 50 milligrams as a starting dose while the numbers are still small we believe that there may be something.
Special about the combination of prior car T treatment and circulating b cells. As a result, we plan to adjust our dosing scheme for that relatively small subset of patients who have previously received car T drugs and have circulating b cells. However, we do know that we can achieve both efficacy.
And low grade Crs in post car T patients with circulating b cells. In this regard the only other patients we have treated with both prior car T and circulating b cells with a day L. P. C. L patient who is now in a complete response this patient had only grade one crs.
As to our overall safety profile, we are very encouraged by the fact that to date, we have not had a case of Crs beyond grade one except in that very small subset of patients who had both prior car T treatment and circulating b cells at baseline.
We believe we are on track to develop a drug that oncologists can use with confidence we have been very pleased to note that some of our complete response patients did not have any crs, which demonstrates that crs is not a prerequisite to efficacy.
We have also been very pleased to note that we have seen an exceptionally low rate of Crs in those patients who do not have circulating b cells.
With respect to efficacy we are excited by the fact that we've seen additional complete and partial responses since our ash presentation, including amongst some of the patients that were described in the ash presentation as well as in patients only dosed more recently as you can tell from the <unk>.
That some of these additional and new responses, where patients covered by the ash presentation. We are seeing deepening of responses over time.
We are also very excited by the fact that some of our more recent responses have been very quick to develop we look forward to discussing these responses in more detail later this year.
Now that we have cleared the 5600 milligram dose cohort, we are enrolling to our 51000 milligram escalation dose cohort and two expansion cohorts at 50, 150, 350, 600 milligram dose levels and we expect that determine our recommended.
Phase two dose and schedule this year.
We are also making plans to begin clinical testing of single agent IGN twenty-three twenty-three in situations, where there is low CD 20 expression in the disease, such as chronic lymphocytic leukemia, and multiple myeloma and we are planning on combination therapy with IGN 'twenty.
<unk> 23.
In looking at combinations with standard of care and novel therapies in any channel.
Our success with IGN twenty-three twenty-three makes us very excited about aggressively moving our T cell engage your pipeline forward in both hematologic and solid tumor applications as Bruce will describe shortly we expect to be able to begin clinical testing of our CD 38.
And C D $1 23 T cell engage your molecules for multiple myeloma and acute myeloid leukemia, respectively in the relatively near future.
We are also focused on beginning to test our T cell engage your platform in the clinic against solid tumors, which we believe will be a particularly good way to utilize the features of this technology now turning to I G. M 80 for 44 R. I G. M. D. R. Five agonist antibody. It also continues to make good progress.
Progress in dose escalation.
As a reminder, the ongoing phase one study is a multicenter open label trial to evaluate I G. M 80 for 44 intravenously administered as monotherapy and in combination with chemotherapy in patients with relapsed or refractory solid tumors or non Hodgkin's lymphoma.
First two dose levels of the monotherapy escalation portion of this trial have now been completed without a dose limiting toxicity.
We are currently recruiting to our third monotherapy dose escalation cohort, which is three milligrams per kilogram.
And our first chemotherapy combination cohort.
To date, I Jam $84 40 for it looks safe and tolerable and hasn't shown any signs of hepatic toxicity with single or repeat dosing.
If this is sustained we believe that that would represent a particularly important step forward for our D. R. Five targeted agent. We hope to report initial data from this dose escalation portion of this phase one trial in the second half of this year.
As you know we also obtained exclusive global rights to bear in a path and we are working towards starting in I G. M 80 for 44 plus per in a pant combination clinical study set for later this year.
On the basis of some very intriguing data. We are also looking at possible combinations of burnt a pad with other agents in our pipeline and we are very excited by these possibilities. This clinical stage asset has already established safety dose and schedule in extensive clinical testing in it.
Peers that it may be able to further enhance the benefits of several of our engineered I G. M. Approaches we are moving forward quickly to evaluate its potential for other important combinations in the clinic.
In summary, we are very pleased with the progress growth and expansion of our clinical development efforts and we look forward to sharing additional updates as milestones are achieved.
At this point I will turn the call over to Bruce our chief.
Terrific Officer.
Thank you Dan.
I'd like to stay with IGN 80 for 44 and discuss the scientific rationale behind the combination approach with <unk>.
As a reminder, barina Pan is a bi valent small molecule smack memetic that binds to and degrades inhibitors of a pop ptosis proteins known as IAP.
By inhibiting I E. P. We believe smack pneumatics can greatly strengthen the effectiveness of the apoptotic signal.
By any Pepto says trigger such as R. I G. M 80, 440 for Dr. Five specific agonist antibody.
For that reason, we believe that smack memetics can be synergistic with 80, 444, which generates a strong apoptotic signal.
We tested I G. M 80 for 44 pre clinically in combination with a number of smack the medics and the combination of AGM 80 for 44 and Burger independent was striking.
Our in vitro and in vivo models showed remarkable synergy in combination with IGN 80 for 44 for any pent showed the greatest cancer cell, killing amongst the smack memetics we tested.
Needless to say we are eager to explore this combination has potential to deliver anti tumor activity in patients with solid tumors.
Finally, with respect to 80 444, I would also like to mention that we have an interesting a ACR presentation coming up on April 10th. This next month and will provide an update on our preclinical studies.
We're also excited about IGN $73 50 for our targeted immune stimulating IL 15 antibody, which we hope will have broad oncology applications.
This product candidate demonstrates another use of a novel J chain based bi specific technology.
In this case immune stimulating IL 15 is attached to the J chain of an anti PD L. One AGM antibody.
Which serves to display the IL 15.
Passing nearby.
CD eight T cells also called killer T cells.
And to natural killer.
The NK cells.
This results in proliferation of the killer T cells, and natural killer cells, which can play critical roles in the immune system's response to cancer.
Our preclinical studies also suggest that IGN 70, 354 provides durable immunity in tumor re challenge models.
System with the formation of a long term immune memory response.
In this recent study.
The same mice, who achieved complete tumor regression with initial treatment with a murine IGN $73 50 for remained tumor free upon being challenged without the benefit from additional treatment.
With IGN $73 50 for we.
We expect to file an IND with the U S. FDA, all IGN $73 50 for towards the end of this year.
We're also very excited by our preclinical pipeline of T cell engagements against both hematologic and solid tumors.
We expect that our next T cell engagement to enter the clinic will be CD 38 ICD three.
And we plan to file an idea on that product candidate next year.
We hope that our CD 123 by Cds from your product candidate will also enter the clinic relatively soon thereafter.
We are developing a broad pipeline of solid tumor T cell engages and we hope to file IND several solid tumor T cell engages in the next few years.
Finally, we continue to make excellent progress with our manufacturing efforts.
Construction is now complete and our GMP manufacturing facility in Mountain view, California.
We are in the process of bringing this facility online.
Caring for an initial GMP run later this year.
This 14000 square foot facility is modular in design quite flexible.
Although we will continue to utilize contract manufacturers for some time, we believe that Helen GMP manufacturing facility under our control will be a very important advantage in managing our clinical supply requirements for new and existing programs.
And with that I'll turn the call over to Mr.
Thank you Bruce.
In addition to the brief financial overview I will provide on the call today, you can read additional detail on our fourth quarter and year end financial results and our press release issued prior to this call and in our 10-K, which was filed with the SEC.
We are fortunate to be in a strong financial position.
Raised gross proceeds of $230 million in a follow on public equity offering in December.
As a result, our cash and investments totaled $366 $3 million as of December 31, 2020.
In the fourth quarter, our research and development expenses were $19 6 million for.
For the full year 2020, R&D expenses were $65 million Jenny.
General and administrative expenses for the fourth quarter of 2020 were $5 $1 million and $18 $3 million for the full year of 2020.
Our net loss for the fourth quarter of 2020 was $24 $6 million or a loss of 79 cents per share.
For the full year of 2020, our net loss was $81 $4 million or a loss of $2 65 per share.
Turning now to the financial guidance for 2021, we expect our full year 2021, GAAP operating expenses to be between $175 million and $185 million. This.
This includes estimated noncash stock based compensation expense of approximately $25 million.
We also expect to end 2021, with a balance of over $200 million in cash and investments, providing IGN with an expected cash runway into the second half of 2022.
With that I'll now turn the call back over to Fred.
Thank you Misbah.
In closing I would like to thank all of the employees of <unk>, Jim for their work over the past year.
All of our principal investigators and their teams and their institutions and most importantly, the patients and their families.
All of whom have made the progress we've described today possible.
All of us at I G M sincerely hope that the accomplishments of the past year represent a critical first step in the process of bringing new and important treatments to patients.
We appreciate your interest in IGT M and we look forward to keeping you all informed as to our progress.
With that operator, I'd like to open the call for questions.
Thank you Sir.
As a reminder to ask a question you would need to press star one on your telephone to withdraw your question. Please press the pound key.
Please standby, while we compile the Q&A roster.
I show our first question comes from the line of Stephen Willey from Stifel. Please go ahead.
Yes, good afternoon, guys. Thanks for taking the questions.
Was.
Was wondering if you could maybe provide a little bit more color just around the 50 Meg.
Dose cohort patient receiving 23 23.
In terms of the severity.
Of Crs that was observed specifically in that patient I understand the context of.
Our prior car T in circulating T cells, but if you could just let us know.
What the greatest severity of Crs from that patient was that would be helpful.
Sure.
I'll turn that question over to Dan. Thanks, Fred Thanks, Steve Yeah. So you know.
I think one of the keys here is that the vast majority of patients that have been treated or arent, showing crs or aren't showing crs greater than grade one and in fact of the 13 patients that have been dosed at 50 milligrams.
The other 12 haven't even demonstrated a grade one crs. So I think that has put us in a pretty strong position in terms of the safety and tolerability of IGN in 'twenty three 'twenty three now it is interesting that this one patient receiving 50 milligrams.
Did experience a higher grade of Crs by S. T. C. T that was a grade three event for the patient was well managed well tolerated through it and again I think one of the.
Really important parts for the development of 'twenty three 'twenty three is that we've been able to very specifically.
Identify and isolate of a very small subset of patients prior car T with circulating b cells that seem to behave differently and that allows us to relatively easy easily just implement a different way to treat and manage those patients. We do think it's important to still treat.
Those patients as you know the the prior car T. Prior B cell patient population also includes another patient that had a.
A D L. Bcl patients that had a complete response to IGN 'twenty three 'twenty three in that patient only experienced a grade one crs so essentially just fever.
And so I think where we've come to know is we've implemented titration dosing.
The vast majority of those patients have done well without even experiencing even grade one C. R. S.
And we've identified just a very narrow subset of patients with whom we can manage those patients differently and will likely just increased pretreatment steroids slow infusion and maybe even fractionate their first dose to make sure that you know we don't have.
Have other high grade Crs events.
Yes understood.
And it sounds like the the.
<unk> of the deal Bcl patient now, becoming I guess or SCR is incremental could you just maybe talk a little bit about.
I guess, how soon post the ash presentation.
Sure.
That previous P. R. I guess flip to a CR and I guess.
I ask the question Ali just because there's a lot of interest regarding just the kinetics of response that you guys have been seeing in the clinic.
Yeah, I'm going to actually take your broader question here.
Which is you know.
We're seeing a host of new responses, that's obviously really important to our program as we continue to dose escalate and expand our experience. So we've seen additional see ours P. R's and interestingly, we do see you know different patterns of response. So some of these patients seem to evo.
All over many weeks and I think you've seen that we described all from several of those.
At Ash, including you know patients evolving into their CR at 24 weeks for example, so half a year to two two CR. That's obviously a slower response pattern.
We've also started to see the complete opposite of that meaning very fast CR. So.
You can imagine how that may look on on a first scan.
And and so we see that diversity and I think it's important for us to continue to think through different the different mechanisms.
That IGN in 'twenty three 'twenty three can engage as it induces these different responses right and I think that's one of the things that's kind of special about AGM twenty-three twenty-three remember we talk about three potential mechanisms of action that the T cell dependent killing which we know can happen fast.
Complement dependent killing which can happen really fast and doesn't even require the presence of T cells tests to engage and they interferon gamma dominant and repeatable stimulation, which we would expect to take longer. So as we look at these different response patterns. We generally are looking at it through the <unk>.
Lance of those different mechanisms of action and we continue to be very aggressive about collecting biomarkers.
Because we want to understand it but we think that this type of a depth of understanding about our drug or our technology and our platform will help with the success of <unk>.
Of that I G. M T cell engage your platform I think it is interesting to note that as we've seen these different kinetics.
You saw that at Ash, you know it seemed like as we got the higher doses, we were seeing faster kinetics of those responses and we've continued to see that pattern as we've gotten to higher doses.
Okay.
That's very helpful and I guess just lastly.
I think it was.
Thank you.
Prior guidance had suggested that maybe there was a chance for us to get.
Disclosure of the Phase one development program for 'twenty through 'twenty, three kind of in and around the mid year timeframe. I guess is is that possibility still on the table I think as you look at the medical conference calendar, obviously with us and then.
Just in terms of incremental patients that had been enrolled post ash I know that there seem to be a fair balance between into Lincoln aggressive lymphoma patients has that been kind of a consistent pattern, where the incremental patients that you've observed.
Or would that you've enrolled thus far and thats. It from me. Thank you.
Thanks, Dave.
So you know I would say that we continue to focus on.
Jana flying that recommended phase II dose and that would be our trigger for the next clinical presentation.
For I G M $23 23, and that's definitely on the table for middle of the year, but as you can probably recognized it's going to be data driven right. So I don't think we can sit here and promise yet exactly when it'll happen it will be based upon the data that that.
That we see in the phase one now I think it's important to note that we will focus on that next clinical presentation at a future scientific or clinical meeting, but obviously additional operational updates could also happen.
At forums outside of medical meetings, such as such as this one.
In terms of the histology have you as you've noted we're enrolling a full range of.
Different types of histology as with non Hodgkin's lymphoma in the phase one and it's part of our belief that.
That and a CD 20, directed T cell engage or like IGN 'twenty three 'twenty three.
Is likely to have similar types of activity across a broad range of CD 20 expressing malignancies.
Obviously, our numbers are still small if the.
The numbers of patients with the different histology as or even smaller.
And so I would reserve any further.
Further our characterization until we have greater experience.
But in general I think we continue with the belief that that a drug like AGM twenty-three twenty-three should work relatively similarly in the different histology.
Great. Thanks for taking all the questions and congrats on the great year.
Yeah.
Thank you I share. Our next question comes from the line of Michael Schmidt from Guggenheim. Please go ahead.
Oh, Hey, guys. Thanks for taking my questions I had a couple more for Dan maybe just to clarify some of the new information. So did I hear you correctly in saying that you have from now 20 patients treated in total and if that's the case I would assume that the D O bcl patients.
With this.
Case of grade three Crs had already been assessed at ash is that correct.
Thanks, Michael So our total number of pick treated patients on the IGN $23 23 phase one is 25 patients.
So it continues to increase as we both dose escalate, but remember we also have dose.
Dose expansion cohorts enabled right. So as you know I mean, we've already seen see ours at the 5100 dose level and even in that patient on the 30 milligram level. So clearly we have strong activity at dose levels that we've already cleared.
And that gave us the confidence to go ahead and start to expand those doses as we think forward to the recommended phase two dose recommendation recommendation and decision right. So if you already see ours at lower doses. You know as you look forward to that decision that you're going to want a pretty good under.
Standing of the activity safety at that lower dose that was already generating see ours and so that's partially responsible for the number of patients dose.
Okay understood.
And for your second question about was this.
50 milligram patients at Ash. The answer is no that was subsequent to ash.
Okay understood.
Yeah.
I guess, how do you.
How do you think about.
You know too.
And to find the recommended phase two dose I think I heard you mentioned net.
1000 milligram dose.
Top titration the top planned titration dose in the phase one I.
I guess do you have plans to going beyond that she did not see.
And TD or DLT then.
How do you think about detailing the.
The recommended phase two dose.
Yeah. So.
1000 is our planned top dose so where were right around the corner from completing the planned dose escalation as you know we would certainly be open to going higher if the data suggested we should I don't know that day.
We have that data today, so I would say today, we continue to plan to have 1000 as our as our top dose.
And in terms of making that decision. Obviously, you can have possibilities, where its black and white and very easy and you can also have shades of gray.
And.
We feel very fortunate that we're not in a position where our lowest target dose didn't show activity, we already have see ours at the lowest.
Targeted dose, which is that what we consider the 5100 milligram dose and schedule and so I think that we have a lot of interesting decisions to make number one on our decision tree will be you know what efficacy or are we seeing what are the kinetics of that efficacy what is the safe.
We're seeing but below that and you've I think you've heard us say this before we do have a really deep.
Interest in the underlying science and so that allows us that has pushed us to to build in a very aggressive biomarker.
[noise] program underneath that that clinical program and the way we fully intend to use all of the data available to us to help make that recommended phase two dose decision. So one of the things I think you've heard us be very interested in and is okay. As we go up in our in our dose you know hunter.
<unk> 300 600000.
Is there a difference in the end how T cells are being stimulated is there a difference in the interferon gamma dominant and repeatable signal do we start to engage more complement mediated killing of cancer cells and what do we want to do with that balance and I think we're.
In a.
Pretty promising position in that we get a chance to really set that dial and you know once we've completed this dose escalation, we're going to push with expansions across these doses and I like you know our chance to be able to set the dial.
Right.
But to your question, Michael just to reiterate we've not seen a dose limiting toxicity to date and so it would not be surprising if we do not see a maximum tolerated dose.
Yes, that's right, we would call that a maximal administered dose level.
Okay, and then just going back to the two cases for Crs and higher than grade one just hypothesizing I mean are you, suggesting that there's a scenario where you might.
Initially what patients who might potentially PRN.
Reactivation of preexisting car T cells.
I mean, I think you raised a really interesting scientific point.
The only two patients with the higher than grade one Crs that we've seen both fit a very very similar profile right. So.
The idea of prior car T.
Now if you overlay that on I G M $23 23, which again, we believe is a leads to a more physiologic T cell stimulation than.
Then other approaches that we're aware of right. So now you imagine you're giving this this may be more appropriate level of T cell stimulation you add in some interferon gamma could that lead to you know.
A.
A more physiologic stimulation of any existing car T.
And what does that do in a patient well here you know we recognize the manifestation of Crs and.
And we feel like we have a pretty good way to manage that REIT week and again, we can increase the levels of steroids, we can lower the dose. So that so that you can see that signal as a more mild and easily manage signal.
But I think that that that the part that really interest us is I think what you're suggesting which is what does this mean for the ability to treat patients either with prior car T or even with car T.
No and I think it has piqued our curiosity around could this type of more physiologic stimulation lead to.
A different kind of activity of car T. A different kind of stimulation of car T. And you know you can imagine how interest if we were in that in the finding that.
That we have a patient here with out detectable prior car T that we.
When we gave them IGN 'twenty three 'twenty three very acutely we were able to measure evidence of that car T. Now obviously, we didn't make that car T appear out of nowhere there was likely some.
Yeah.
Niche, where there were a few.
Persistent car T. So they must have seen and felt the effect of the stimulation with the IGN twenty-three twenty-three and this is something we fully intend to continue to interrogate.
So we don't have plan to exclude these patients from our trial, we'll just manage them in a way that we think is appropriate and we look forward to the possible discussions around how to develop I jumped $23 23 in those patients that either got prior car T or may get car T.
And I think it's a it's a really interesting line of thinking for us to to continue to work on.
Okay very interesting and then just a question on 80 444.
Good to see progress here as well in the dose escalation.
And I was just curious if you could remind us.
You know at what dose level, one might start to see clinical activity here and.
Weather.
What type of patients might be most likely to potentially respond to to DIY a bad assets.
Dan would you take that one yeah.
Yeah. So as you know we're we're very pleased to have moved quickly from having our second program AGM 80 for 44 in the clinic to clearing.
Two of the dose levels in the dose escalation, which puts US now just over halfway into the dose escalation of AGM 80 for 44. So this is a program that is moving very quickly. These were also key cohorts two to clear because they on gate a lot of additional activity. So.
Not only do we now continue on to complete the dose escalation for $84 40 for this dose cohort will be three megs per keg.
You only have one planned cohort above that but also that it and gates. The the development in combination initially with chemotherapy.
And that'll be with full theory. So this is a really important time in the development of IGN 80, 440 for I'd say all of these doses fall within likely active dose ranges and again, we are dosing across a complete range of solid tumors, we'll add on.
Non heme malignancies. Once we've completed the single agent dose escalation. So we look forward to the next few months on.
<unk>.
Of development in the phase one of of $84 40 for but right now it's full steam ahead.
And I guess high level are there other any predictive biomarkers.
When it comes to D. R. Five or are there certain types of cancers that are more responsive than others potentially.
Yeah, I mean, I think that we can look across the field and recognize that certain patients are just exquisitely sensitive to stimulation of this pathway and we think I think Bruce and his team have done an amazing job figuring out sort of the why behind that.
So if we were going after this is just a biomarker driven play or an indication specific play for development I think that we would be more focused on very specific subsets.
To us the real opportunity around Dr. Five agonism is much broader than just that narrow super exquisitely sensitive to single agent Dr. Five agonism and that's how we're playing out our development plan. So that doesn't mean, we're not going to take a look at those patients we will.
Dose expansion, but our primary focus is to understand safety and efficacy across a very broad range of cancers.
And play the census day, Sensitize Asian play right. So if you know theres only a subset of patients in cancer that are exquisitely sensitive you either go after that narrow group what you say how can I make the rest of these patient sensitive because we know Dr. Five.
<unk> is there across the broad range and we know this biology is not limited is broad in the sort of in the way that veg F as abroad target and PD, one PDL one as a broad target. So we look at D. R. Five very much through that lens and we're going to get a chance I think to play.
Two.
That understanding of the biology right. So if the first chemotherapy combination is intended to help sensitize. These patients and you know that we're very excited about the purina pet combo, because we think it does exactly that it plays too.
Biology that just it makes sense you give a death signal you take away that survival signal and I think you've seen a little bit of Bruce and his teams data around.
Just very synergistic.
Activity there.
Great Alright, well thanks for that detailed answer I really appreciate it.
Thank you I show. Our next question comes from the line of Brian Abrahams from RBC capital markets. Please go ahead.
Hey, guys. Thanks, so much for taking my questions and congratulations on all the progress.
It sounds like you'd rather encouraged by what you're observing with.
With $23 23.
I guess I'm curious as you have continued to see the data evolved how would you characterize your level of confidence that you'll be able to achieve response rates rapidity and durability akin to the other CD 23 by specifics within the currently planned dosing range.
You said.
Yes go ahead, Dan wants to take this one but rates rapidity and what was the third one.
Durability durability.
Yeah, I think theres a good questions I think that look we're very excited by what we're seeing here I think that we're well positioned I think we have the potential to be best in class I think the easiest place to see that we've always guided towards this is look the safety and Tolerability signal will come first.
And I think you've clearly seen that differentiation right like if you look at other molecules in the CD 20, CD three T cell engage a class.
They generally have a crs rate of 50 60, 70%.
I I my personal belief is we're not going to be anywhere close to those rates that are crs freight is going to be very low and you've heard us talk about I mean, if you look at what we've said about the Crs that we're seeing in dose titration.
I mean, that's a fair number of patients now in our experience and I think you've heard us describe not even cases of Crs.
And so even though our target isn't to say hey, we're going to deliver a no crs rate.
I mean, our experience in dose titration has seen very little clinical Crs and so I think we're well positioned to be clearly differentiated around safety and tolerability and that gives us confidence that this is a drug that you know outpatient.
Immunity oncologists should likely feel confident in their ability to use and while we'd need to generate more data to continue to support. This again I think the early data has put us in a very strong position here and it's one where I think that you know we've pushed that that acceleration.
And on our T cell engage your pipeline because we do feel confident now rapidity, where we're clearly now seeing rapidity of of responses. So even though I don't hold that as a <unk>.
Joel I would never say, Oh, we need to optimize the rapidity of responses that I don't think is something we're trying to achieve because rapidity may or may not be the best thing for patients right. If you have to trade off for a pity for durability of immune stimulation I would take durability.
[noise] of immune stimulation.
So.
It's not our goal, but clearly we've seen some very fast responses here and then finally durability, that's going to take time to show, but if you can if you can already show that responses evolve over time that tends to tell you that you have a drug that continues to work over time.
And even though we have only limited follow up our sense of the ability to generate durable complete responses. You know I think is off to a good start.
Got it that's Super helpful. And then I guess on the safety and Tolerability side.
It's really interesting I know.
There'd been a theory that the switch to complement from T cell driven killing.
At higher doses may have been part of the reason why you're you're observing such low Crs rates.
Is that still the dominant view or has that changed now that you haven't more detailed understanding of the patients experiencing Crs do you think it may be more about baseline characteristics like like prior car T and I guess I'm curious if this might steer you towards exploring higher starting doses than 50 megs.
Yeah. I mean these are good questions I think the theory around a shift to more complement dependent killing is definitely in play.
We'll need to study this better.
But with more patients and more data and more biomarker activity, but I think it's definitely stands as a potential hypothesis.
Now separately is there a sensitive subset that we should be careful with and just manage differently. I think that's probably true to and is consistent with how we look at clinical development. I mean patients are very different we need to be prepared to understand our drug in and many different types.
Have patience and be able to figure out how how to manage those patients.
As a whole and I think I feel pretty good about where we stand with that today.
Great maybe one more quick one for me I'm wondering if you had a sense yet of the extensive data we might be we might look for for eight for four four in the back half for the year in it and what for them those data may be presented.
Yes.
Yeah, So I think that.
Where we're targeting getting up through the eight for 80 440 for single agent dose escalation.
And that would largely trigger presentation of first clinical data from that program now recognize that in the background of that we're already starting the day.
The chemo combo, so any available data there could be packaged together at a later meeting.
I think it's too early to say, which meeting, but certainly we have some nice choices coming up in the second half of 2021 and.
And and.
And we'll just need to take a look at at at which ones to choose from when we have the data.
Yeah.
Makes sense. Thanks again.
Thank you.
And I sure. Our last question comes from the line of as peak at Gunwharf deemed from true. It's please go ahead.
Hi, guys. Thanks for taking my questions and squeezing me in at the end.
So I'm curious then.
How is that gamma dominant cytokine profile holding up after repeat dosing as I remember at Ash, we presented some data.
Sure.
I'd be honest with you guys present, some data that showed that it lasted.
Held up quite nicely I'm, just wondering how have you seen that with more follow up in house and then I got a couple of follow ups on.
This associations and kinetics.
Yeah, Thanks Africa so.
Interferon gamma we continue that whole concept of repeatable interferon gamma dominant T cell immune activation is still one of our primary hypotheses, it's something we incorporate into our thinking about how to best develop a drug like this so absolutely I would.
Say today, even with continued dosing upwards that we continue to believe in that and we continue to believe that that is something we want to be optimizing so as we define and select.
Our P two day.
That is one of the key pieces that that we're looking to optimize so yes that is fully in play and I'm sorry. Your two follow up questions were.
And so the patients who had the prior car T that had.
That's up to the 50 milligram dose I'm just wondering when for the last dose with the car T.
Yes that was.
It was a fair amount earlier it wasn't like within a short number of one months, we actually exclude patients with that had very recent.
Car T.
Okay.
Thank you.
And then lastly, if I can speak for them so.
What are you seeing regarding 'twenty three 'twenty This association from tumor cells.
I'm just wondering because the preclinical data that suggested that twin cities for he is really sticky.
So you're talking about the association you mean off rate and I think that one of the things. We've said is that that that off rate is.
It has been unmeasured will in some of the preclinical studies.
Going to turn it over to Bruce here, but I don't think anything in our clinical dataset has made us believe anything other than.
Then that concept being true, which is that I jumped 23, 23 binds to a CD 20, expressing lymphoma cell and doesn't come off.
That's right. Thank you Dan the.
The dissociation right for the AGM to the tumor target itself is just.
Irreversible.
There is there will be eventually.
Internalization of that antibody on the tumor cell and so obviously, we will continue to re dose, but the durability of that antibody on cells and the effect is much longer than any other bi valent I mean, sorry. It is a bi specific antibody, but they all have most have single.
Binding sites to the to the tumor antigen and so we get very durable effects in vitro and in vivo.
Great. Thank you very much guys.
Thank you. This concludes the Q&A session at this time I would like to turn the call back over to Mr. Fred Schwarzer, Chief Executive Officer for closing remarks.
Thank you operator.
Thank you to all of you for joining the <unk> Conference call. We really appreciate your interest and I, Jim and we look forward to updating you on our progress as the year progresses. The year passes shall I say thank you.
Thank you. This concludes today's conference call. Thank you for participating you may now disconnect good day.
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