Q4 2021 Infinity Pharmaceuticals Inc Earnings Call
[music].
Okay.
Yeah.
Ladies and gentlemen, thank you for standing by welcome to the Infinity Pharmaceuticals conference call to discuss the company's operations and full year 2021 financial result, my.
My name is crystal and I'll be your operator for today's call.
At this time all participants are in a listen only mode.
There will be a question and answer session to follow.
Please be advised that this conference is being recorded and incentive units or class.
Now I would like to introduce your host for today's call Jayne Kauffman. Please go ahead.
Thank you Crystal and good afternoon, everyone welcome to today's call to discuss our recent business progress and review of our full year 2021 financial results and company highlights on the call with me today are Abilene Perkins, Chief Executive Officer, and Chair, Larry Bloch, President and Robert Lauria Junior.
Our Chief Medical Officer.
Well open the call for Q&A following our remarks.
The press release issued today details our results and is available on our website at <unk> Dot com.
Note that during this call we may make forward looking statements about our future expectations and plans, including clinical development objectives, the therapeutic potential of our product candidates, our strategic plans and strategies and financial projections are.
Our actual results may differ materially from what we project today due to a number of important factors, including the considerations described in the risk factors section of our annual report on Form 10-K for 2021 and in other filings, we make with the SEC.
These forward looking statements represent our views only as of today and we caution you that we may not update them in the future whether as a result of new information future events or otherwise now I'd like to turn the call over to Abilene.
Thanks, Jayne and thank you to everyone for joining us today to review and pin. These key 2021 accomplishment in 2022 goal.
Even against the challenging backdrop of a global pandemic geopolitical tension and deteriorating capital market and kidney was able to make meaningful progress during 2021 and is well positioned to weather future storms.
The four foundational pillars necessary to create great value are all in place.
With a differentiated drug.
Good clinical data.
Augmented leadership team.
And a strengthened balance sheet.
Building on these in 2022, we are now poised to initiate the first analyst registration study.
Expanded analysts clinical evaluation in multiple additional solid tumor indication.
And establish the best path forward to continue to fund and maximize the value of the Gander listed for patients and shareholders.
Before turning to 2022 I'll review, the four foundational pillars, which are enabling us to optimize the valleys again with them or first in class drug that reprograms macrophages in the tumor microenvironment to reduce the immune suppression and activate an immune attack against cancer.
The power of this unique mechanism has been underscored by robust clinical and translational data presented over the last 18 months.
We just close positive results in five solid tumors across 15, 2020, San Antonio breast cancer Symposium in 'twenty, and 'twenty and 2021 as well as <unk> 2021 .
These presentations included data in three different combination regimens in multiple lines of therapy in tumor types, including triple metastatic triple negative breast cancer or T. N V C.
Static urothelium cancer, or UC ovarian cancer as well as checkpoint inhibitor resistant squamous cell cancer of the head and neck and melanoma, all settings, where checkpoint inhibitors have provided more limited patient benefit to date.
These data validate again atlas's potential to increase the effectiveness of current standards of care, including in the PD L. One negative patient population for whom checkpoint inhibitors alone are particularly ineffective.
Encouraging results across five distinct tumor type are impressive in their own right.
Yet the totality of the data are even more compelling in light of the consistent patient benefit seen across multiple settings.
Improvements in both median progression free survival and median overall survival further underscore the promise civic analysts it to drive the next generation of immuno oncology combination therapy.
On today's call will focus specifically on the data from two of these studies in patients with frontline metastatic T. N D C from our Mario three study in patients with second line metastatic UC from our Mario 275 study.
In addition to having a first in class drug with good data the broad potential began listen it has enabled us to strengthen another foundational pillar our team.
2021 we expanded our clinical and scientific leadership and are already benefiting from the experience and momentum being driven by our Chief Medical Officer, Dr. Robert Laurie Junior our Chief Scientific Officer, Dr. Stefan Colusa L and a former Chief Medical Officer, and now Board member Dr. Brian Schwartz.
In addition, today I'm very pleased to announce the addition of <unk>.
C. J can go to our board of directors.
So Jay was most recently the chief commercial officer at Exceleron prior to its acquisition by Merck late last year and previously served as Infinity Executive Vice President and Chief Commercial Officer.
T J will be rough providing important commercial and strategic insights as a member of our board, which is very timely as we initiate our first registration study for again a list of this year.
And last but not least in 2020 , one we strengthened our balance sheet, having raised $92 million in the first quarter of last year.
With over $80 million on our balance sheet at the beginning of 'twenty 'twenty. Two we have the resources required to initiate a registration trial in frontline metastatic T N D C and expand our development of a catalyst to our Mario Peace study this year.
Altogether, we are very encouraged that even in the face of global uncertainty and market volatility.
<unk> future is bright and.
I'll now turn the call over to Rob to review the data that supports this bright future for the studies, we are initiating this year as well as a potential future development path.
Rob.
Thanks, Natalie I'm thrilled to be part of Infinity at this exciting time guiding the design and execution of the first registration, enabling studies toward vandalism and laying the foundation of the next stage of development with Mario P.
While approved immuno oncology drugs have led to important advances we still have much work to do to fully harness the immune system to effectively combat cancer.
That's why I'm, so enthusiastic about the positive results, we are observing but again Elisa.
Specific small molecule inhibitor of <unk> kinase gamma to reprogram macrophages in the tumor microenvironment and enhanced immune activation.
The strength and consistency of the analytical data across multiple indications and treatment settings, including PD one negative subgroups provide solid evidence that again Elisabeth has the potential to be a transformative therapy in immuno oncology.
Only a few months ago at the December 2021, San Antonio breast cancer Symposium, we provided updated data from our Mario three trial single arm study in advanced metastatic triple negative breast cancer.
The strategic objective was to characterize the safety and efficacy of the addition of again with the two inches loosen them marketing centric and Nab Paclitaxel market as a black thing in metastatic team D C compared to the benchmark and passion when Dirty study.
We reported safety data from 50 patients and the efficacy data from 44 Evaluable patients with the data cut off of October 2nd 2021.
Tumor reduction was observed in 92, 8% or 13 out of 14 patients with PD lone positive tumors and 85 to <unk>.
Per cent for 22 out of 27 patients with PDL, one negative tumors.
Patients with PD Lone positive tumors. The median PFS in Mario three with 11 months compared to seven five months reported potential as a map and Nab Paclitaxel and the Impassion 130 benchmark study of 47% relative improvement.
In patients with PDL, one negative tumors. The median PFS was seven three months compared to the five six months reported the Impassion 130 study a 30% relative improvement.
Mario three safety profile was consistent with expectations for the three component drugs and did not show any new safety signals compared to the benchmark trial.
Overall, we're encouraged with the efficacy findings in both PD lone negative and positive metastatic P. M. P C patients.
Plan to provide more follow up data from this trial in the second half of 2022.
In January we reported encouraging median overall survival data from Mario 275, a randomized phase II study in platinum refractory immune checkpoint inhibitor naive advanced or metastatic <unk> cancer patients.
In the PD lone negative patient population, which was represented the majority of the attempt to treat patient population. We observed a median overall survival of 15.4 months with the combination of again, a list of interval and that compared to 7.9 months amenable map controller with a hazard ratio of 0.60.
Which reflects a 40% lower probability of death, I mean again it was a combination arm.
These findings are consistent with data percentage, where we were last year that showed that one year landmark 59% of patients received.
Again, it was a pleasant you've all map car arm remained alive compared to 32% and a roadmap control arm.
Although the data in Mario 275, and Mario three are both strong and mutually supportive again, unless there's a broad potential as a T. M. Modulating drugs. We've made the decision to prioritize metastatic team B C is our initial registration enabling studies due to the greater unmet need, particularly in PD lone negative.
Patients were still receiving chemotherapy alone that's the standard of care.
Towards that end, we plan to initiate Mario for a randomized double blind registration study in frontline metastatic T N B C. By the end of this year with PFS and OS as a key study endpoints.
All patients will receive the Mario three tripling of again of listen and immune checkpoint inhibitor and chemotherapy, which will be compared with standard of care, which is either chemotherapy alone for PDL, one negative patients where chemotherapy and a checkpoint inhibitor for PD one positive patients.
We are now preparing for our end of phase two meeting with the FDA and for meetings with global regulatory authorities to review the design of our registration study and will provide updates on our progress later this year.
Our encouraging phase two clinical data into mostly PD, one negative tumor indications have been bolstered by an equally strong translational or T. Hem data package will support then again Elisa delivers on its intended mechanism of action.
At the San Antonio breast cancer Symposium. This past December we presented data from paired tumor biopsies and Mario three showing an increase in the M to M. Two ratio reflective of macrophage III program in.
An increase in immune activation and an increase in PD lone expression in both PD, one negative and PD, one positive patients compared to baseline.
These findings in tumors are consistent with what we get observed in peripheral blood gene expression analysis for Mario 275, then showed enhanced immune activation of the analysts would nibble map combination compared to the Novo Mab controller.
Armed with these very encouraging clinical and Tam data into solid tumor indications one of my highest priorities since joining infinity to quickly identify other opportunities for analyst to advanced cancer treatment, particularly in areas, where immune checkpoint inhibitors have had more limited success.
In support of this mission, we will initiate a platform study called Mario P to evaluate the clinical benefit of again listen in additional solid tumor indications on a rolling basis, starting in the third quarter of this year.
And with that I'll turn the call over to Larry to review the full year financials Larry.
Thank you Rob.
This past year has been a foundational year for <unk> and infinity.
As we prepare for our first Registrational study as well as prioritize initiation of additional clinical studies in indications, where <unk> has the largest potential benefit for patients.
In early 2021 based on the strength of a journalist data.
<unk> multiple solid tumor indications, including metastatic T M D C and metastatic UC.
It's in the raised $92 million to enable our continued execution on our strategic development plans for generalists, including the commencement of our first to get a registrational study.
This resulted in 70, having total cash and cash equivalents and available for sale securities of $87 million of December 31, 2021, compared to $34 1 million at December 31 2020.
Richard development expenses for the year ended December 31, 2021 was $31 6 million compared to $26 8 million for the same period of 2020 and this increase was primarily related to an increase in clinical development expenses.
An increase in compensation expense due primarily to new hires during the year and an increase in consulting expenses support continued development of the journalism.
General and administrative expense for the year ended December 31, 2021 was $14 $2 million compared to $12 4 million for the same period in 2020 and this increase in G&A expenses, primarily due to an increase in stock compensation professional services and consulting expense.
Net loss for the year ended December 31, 2021 was $45 $3 million were basic and diluted loss per common share of <unk> 53 cents.
Good to a net loss of $45 million or basic and diluted loss per common share of <unk>.
That same period in 2020.
Putting these 2022 financial guidance remains unchanged. We continue to expect net loss for 2022 to range from $45 million to $55 million and in 2022 with a yearend cash and cash equivalent.
<unk> from $25 million to $35 million and there's been these financial guidance does not include any additional financing or business development activities.
This is an execution focused year for infinity, and we are aggressively advancing the development of the catalysts that are first to get a list of Registrational study as well as a platform study in other solid tumor indications.
We're truly excited about the continued advancement of again, a list of clinical program to lay the foundation for the initiation of potential future registration studies and in parallel we will leverage <unk> unique mix of action aimed differentiated clinical data to evaluate and execute on the best path forward to fund its ongoing development and maximize the value.
The catalyst for patients as well as shareholders.
So on behalf of Infinity. We thank you for your continued support and look forward to updating you on our progress in the coming months.
At this time, we can open up the call for questions operator.
Thank you.
As a reminder to ask a question you will need to press Star and then one on your telephone to withdraw your question. Please press the pound key once again, that's star and then one to ask a question.
And our first question comes from Omnicom Rama from J P. Morgan Your line is open.
Hey, guys. Thanks, so much for taking my question Larry I wanted to follow up on a comment you just made which is you talked about the guidance not including any business development.
Strategically how are you thinking about <unk>.
O U S rights or regional partnerships as a potential source of non dilutive capital.
And how do you think about maximizing that you know from a timing perspective.
So they've got a bump so from a business of owned perspective.
We certainly feel that we.
Feasible to slice and dice again list by indications the way you think about it in terms of geography is certainly the way we look at it but.
But ultimately because of the breadth of the potential indications that again lists can reach across the Boston.
Broad swath of solid tumors, PD, one low NPL and high.
Think ultimately a strategic collaboration.
That's global is probably going to be more advantageous than.
A regional collaboration because the complexity of the potential clinical development path forward.
Got it thanks, so much for taking my question.
Thank you. Our next question comes from Ted <unk> from Piper Sandler Your line is open.
Great. Thanks, so much for taking my question too.
So don't take this runway could respond intended to be.
Important in any way.
Get a sense for what's going into arranging Mario.
More specifically.
Whats, taking so long.
Again, not meant to be competition, but what are the stocks that are.
<unk> requires are obviously drug suppliers things like that but whats really going into <unk>.
Preparing to launch those two studies thanks, so much.
Yeah. So thanks, Ted for the question I'll start and then I'll turn it over to Bob.
What's important to note is this is moving quite quickly the preparation for the launch of these studies so.
Well, we're not in a position to describe all of it yet.
We are designing the trial and planning for a top operator to operationalize that lots and lots of decisions about exactly that patient population the inclusion and exclusion the endpoints, whether there's an interim analysis.
What sites, what investigators and all of that is actively underway and as soon as the trial design and the plan is finalized.
It has the input from global regulatory authorities will be sharing it's just simply too premature to do so until we finalized it. So that you get the old analogy about you know the DUC booking com along the top of the water, but the paddles Goin' rapidly underwater. The team is rapidly doing all the things under water. It just may not be as visible until week.
Can describe what that final trial design is Robin if you have anything to add.
I guess, one thing I will mention is no time I guess it was quickly in some respects. We just presented our updated data at the San Antonio breast cancer Symposium in December when you think about it that's not very long ago, and we really wanted to wait until we had more mature follow up and that was the median duration of follow up on the 10 month range and we really mean.
Move from looking at that data reacting to that data and to expand them with Abilene was saying you know it does take a lot of pieces.
Writing briefing books planning global regulatory engagement and things like that so there's a lot going on we're on track to do the things that we say that we're gonna do we only recently identified the four tumor types, we want to do for the Mario P platform studies. So I think that's a good start to that.
So again I know, sometimes it seems like things are slow, but actually things are moving quite quickly for us and all the planning steps.
Great well I'd, rather get it right. So I appreciate that thanks, so much.
Thank you. Our next question comes from Kevin <unk> from Oppenheimer. Your line is open.
Hey, guys. Thanks for taking our question.
Mario Pete can you help us think about dose for a basket study I mean, I guess, we did see some deliveries or require adjustments downward in the protocol with regard to dose in Mario 275.
And one could imagine different tumor types having.
Different potential rates of liver tox or risk of liver tox.
Although all these patients sort of be getting the same dose and how should we think about appropriate caution for a basket study.
Yeah, I mean, I think you bring up some good points I mean, we had started the Mario 275 at the 40 milligram dose of again it was the daily and then had gone down to 30.
I think we're really encouraged that 30 milligram seems to be a winning dose because that's something we're dosing now in a triplet regimen with T.
And the chemo a black thing.
So I think if you think about a platform study I don't tend to think of toxicity being all that different across tumor types.
I think 30 milligrams as a very solid dose for that now of course as we design. The study will we decided to explore that does a little bit if possible, but I think the fact that we're able to dose 30 milligrams a day in a triplet bodes very well for a lot of combinations that we can do across different tumor types and.
And across different agents.
Great. Thanks for that and then just how should we think about sort of pace of opening sites and Mario P. It kind of sounds like.
That study may kick off before.
Registrational.
Study in CNBC I'm, just wondering in a resource constrained world.
How do we should think about.
Essentials pay some site opening and kind of perhaps folks of learning as we move into 2020 correct.
Sure.
You know as we announced we were going to be opening these in a rolling basis.
One of the nice things about our platform study is that by focusing on specific tumor types. You can focus on specific centers of excellence.
See a lot of that tumor type until it allows kind of almost like a cassette that you can open one tumor type decide what you're going to you know what combinations are going to look at and then move to the next module.
Do it kind of in a nice orderly.
And so I think that we would probably take a very tumor centric approach that would probably the most logical way of doing it and I think that's how we're envisioning doing this in a rolling basis and of course that is as you mentioned you do learn as you go in sort of an iterative process.
Thanks for taking our questions.
Okay.
Thank you. Our next question comes from Sumit Roy from Jones Research. Your line is open.
Hello, everyone and congrats on all the progress.
Could you.
Help us think through what we should expect from the Mario three RCC cohort in second half 'twenty two is it a like number of patients you are.
We could expect to see data from.
Would really help.
Sure I'll start and then Rob can elaborate so that study is a 30 patient study.
It is single arm, combining analysts said with to centric and Avastin and <unk>.
What we're really.
The purpose of that study was to see proof of concept of the utility of adding again, a lesson to a veg F inhibitor.
As you know that to centric avastin regimen is not approved in renal cell. So it's unlikely that we would be with any proof of concept being taking that regimen forward. So we would then be looking at.
There's been great progress with other oral teekay is and.
We'd be evaluating if we did want to go for what would the right drugs be and what would that design base. So this is different from the Mario three P. N B C, where we were very much we've got the right modalities of drugs and we'd be moving directly to registration and the.
Renal cell different objective out of that study.
Yes for US I mean, you know it's a it was an interesting question to understand with modulating a veg F and again. This is not one of these oral teekay is bevacizumab is really a veg F big molecule antagonist, whereas a lot of as you know that field has moved on now to be these multiple kinases.
RCC, but for US it was getting some clinical data with a drug like Bev and of course in combination with a checkpoint inhibitor and we're looking to do you know as we're reviewing that data to give an update on that later this year.
Got it that's really helps so essentially in second half we are.
When you look into the 275 and Mario three T in BC long term.
Survival data that's that remains our main goal here catalyst choice.
Did I get at least twice.
Yes, yes.
Thank you. Thank you again for taking my questions.
Thank you. Our next question comes from carpet Patel from B Riley Securities. Your line is open.
Hi, Thanks for taking our questions.
One for the Mario piece, Neely, I know youre initiating on a rolling basis.
But have you finalized which tumor type you would likely prioritize first based.
Based on the mechanistic profile, yeah listen it is there one tumor type that you would ideally start with first.
And then are you also planning to enroll.
Tricked enrollment based on any underlying biomarker status, where applicable maybe just focusing on PDL, one negative patients for certain indications like lung cancer.
Yes.
I think we.
We like all four tumor types and so we are still discussing which one we'd like to start with you know after admit I'm I'm anxious to learn about all of them, but I think we're still working through which one we will start.
No I think we keep an open mind about.
Narrowing the indication as far as restricting it to a certain PD L. One subtype for example, particularly in unmet needs like prostate cancer or something where it's not quite so clear that would be good of course in lung cancer people do take that approach sometimes but.
One of the encourage you things. We found is the drug you know we're encouraged by our data across PDL one expression.
I don't think we have any op fiori thoughts that we're gonna narrow it coming out of the gate.
But but again, we're anxious to get started we like all four of those and.
You know we're in the midst of deciding which one we'd like to prioritize this year.
<unk> as you would know you know Robyn.
Not only enthusiastic about all but he does have we just are not yet in a position to provide.
Provide the specific rank or prioritization, but we do have a sentiment on that and are executing on that and as soon as we're re.
Ted.
Sure those details will be happy to.
Okay and then.
One question on the Mario for study.
Based on the safety results that you realized to date with the triplet no does the tolerability profile and any sense restrict the type of patients that you would enroll and Mario for I'm, just trying to understand if Mario for the timeline should be similar to what we've seen with with Impassion 130.
Yeah.
You know I think overall, we're very encouraged with the triplet safety profile. If you may recall from the San Antonio breast cancer Symposium in December the treatment discontinuation rate, that's pretty similar for the triplet compared to the doublet Impassion 130 would.
Which actually is really gratifying because usually when you have a triple if there was a you know sort of a tradeoff.
So I think the reason for that is we have an oral drug.
Very easy to adjust or if he does hold it for a few days quickly.
Quickly washes out so I don't really see any limitation per se.
You know I would expect that you know of course checkpoint.
<unk> inhibitors are somewhat restrictive for patients autoimmune diseases, and things like that but I don't see anything, particularly unique or anything that you would restrict just because again this is in the mix.
Okay. Thanks for the color.
Thank you.
Our next question comes from Mike King from H C. Wainwright Your line is open.
Hi, guys can you hear me okay.
Yes going through great Mike.
Alright, Thanks, just wanted to pick up for <unk>.
<unk> pick up where on a palm left off and that has to do with the.
With BD.
Sure.
Seems like.
Okay.
Not pragmatic to be able to have any kind of conclusive discussions until you know.
What what the parameters are going to be.
Mario for I mean is that a is that a reasonable.
Slot process do you have to lock down the protocol so that you know.
What.
How would you how to size it how long it needs to be et cetera, before anybody can understand what the expense is going to be for the entire study.
So that's certainly the approach we took the last time, we put in place a global.
<unk>.
Collaboration for development of one of our programs. We had started our global phase III for <unk>.
Duvelisib and on the heels of that brought in a partner.
Case it was abbvie.
To complete the global registration study campaign I don't think it's necessarily a requirement to do so but it certainly I think as you allude to sort of.
It makes the alignment.
Easier to do and on the flip side some partners like to have some input on the actual design parameters and once it is locked and loaded.
FTA and ex U S alignment on that you don't really want to reopen that.
Re litigate that again, so there's plus and minuses both sides, but but certainly the last time.
To this we followed the detract that you're recommending.
Okay, but is it.
Fair to say that.
Even if you do not secure either a regional or global partner before Mario for is ready to go you will start to study.
Yes.
Our our.
Guidance is we're going to be starting the study by year end and we think thats.
Completely consistent with the timeline that Rob has laid out in terms of.
Engagement with the regulatory authorities.
Okay, Alright, and then just a quick clarification and I apologize I missed.
What are the four contemplated tumor types from <unk>.
Our L P.
The planned tumor types or soft tissue sarcoma, ovarian prostate and non small cell lung cancer.
Okay. Thanks for that.
And then finally.
Just wanted to ask are you prioritizing.
You had a very nice.
And it just sounds like that one is not making the cut.
It's not.
We're prioritizing <unk>, so I guess implicitly it prioritizes youre at the old cancer. If we had the resources to do two parallel registration studies, we'd love to do both of those but given the fact that.
The standard of care for <unk>.
Especially at <unk> low patients in frontline metastatic T N B C. So cure is just chemotherapy.
There is no immune oncology.
Surety for those patients that seemed like such a glaring unmet medical need that it was.
You know it was very hard to pass up in the context of additional resources, whether from the capital markets or from a potential future business development collaborations we would certainly like to.
Bring your fuel cancer up to the front as well, but we just can't we can't due to global registry studies in parallel at this time.
Okay. So I guess, you said, Larry I guess, youre, saying I want to put words in your mouth, but I guess you are saying that.
The only the only logical course forward for you see is in a randomized registration directed study versus.
Making a part of let's say Mario P is that or is that a fair statement.
Yeah, I think we've already got.
Randomized controlled.
Data from Mario 275, so sort of going back to phase two.
For additional data it seems like there would be a misuse of the opportunity is as Rob said he wants to explore additional.
Indications through Mario P and we think there's a pretty clear path forward towards a registrational study in Europe till cancer based on the merit to 75 data we've already.
Analyzed.
Okay fair enough and I am sorry, if I could just sneak in one more.
Sure is.
What's that.
Sure.
Sure.
Oh, no no I've forgotten.
Yes.
I would say it's successful.
Before that you were at.
Okay.
[laughter].
Yeah.
Thank you and again, ladies and gentlemen to ask a question. Please press star and then one now.
And our next question comes from Robyn <unk> from <unk> Securities. Your line is open.
Hi, guys just a follow up on a couple of questions. So when you're thinking about the global partnership and you mentioned that some people want to be long involved into the design principle do not how are you weighing. The you know the terms of someone who wants to be involved in derisking. The story youre getting that off your plate versus waiting help us understand.
How you are thinking about like the two options that you just mentioned.
When you're thinking about the FDA the FDA has been very different lately.
Surprising people with requirements for clinical trials and being more conservative.
Requiring a lot more than maybe they typically have in the past how are you thinking about.
Maybe diversifying your trial versus doing it centralized locations the big centers to get that diversification if needed. If the FDA is more critical is just doing it at.
Especially site.
Rob why don't you start with the critical diversification question I'd be happy to take the BD question, Okay sure.
You know I think for diversification you bring up a good point because you know the nowadays Pembroke lose a map in the United States and chemo as the standard of care until a lot of that is going on in community site versus the centres of excellence necessarily so I think we would be diversified in the way we did enrollment.
We would want out of core centers of excellence, but I think we would also want.
Plenty of other community base practices to be able to really do a great job of enrolling across both PD lone positive and PD one negative patients.
And maybe also robin to your point about.
The sort of conservatism upon regulatory authorities and we've seen some of that just recently with discussions about.
<unk> Delta in the Hematological malignancy front and from our perspective.
We don't believe that touches on <unk> gamma at all in the in the solid tumor front because there is as far as we can tell no overlap in terms of the toxicity profile. So we're really gratified.
There has been review of both 600 approval in immuno oncology, we're really happy to see that we've seen a correlation between our PFS or.
Our OS data, which was one of the big challenges, obviously last year at.
The <unk> for the accelerated approval and we are also very pleased as Rob said with our.
Tolerability and safety profile that even a triplet, we see no new safety signals or.
Signals that you wouldn't expect to see from the individual components. So we will certainly want to diversify from.
As Rob said sort of a.
Standard of care in centers of excellence versus the community centers, but from.
General regulatory perspective, we think that the.
Path, we're pursuing is pretty well.
It was pretty clean.
Just as a follow up for you get to the question around.
Bill.
So yes.
So if you want to do a more diversified trial doesn't require a lot more resources.
A lot more expertise with some some pharma can get this done really quickly because they have all all the connections and stuff in place. So how do you sort of feeds into the question around doing that before you start the trial versus the Arab P D.
Before you did the trial versus afterwards, and finding a partner.
Yes, so I would totally take your point I'd say, there's two parts one is what we're going to pursue or our own independent path.
Two registration you know as we've lined up with our guidance for.
Having the mirror study up and running by year end.
Said.
The critical thing for us is to get alignment with the FDA, we can obviously get alignment with the.
BD partner beforehand, or after hand, but there is some benefit as you said and leveraging the resources of a partner we didn't find the problem with doing that with Abbvie. After the fact.
And given the profile of our drug we don't expect that there's going to be.
Any things that we can bolt on from a partner.
To augment the.
Resources that Rob be putting in place independently before the fact.
So it's another one and so any surprises you think regarding what the primary endpoint would be required to be primarily because I'm just thinking out of the box how surprised they didn't what's being required over my lifetime. How it's changed over time is do you think there's any surprises as far as the primary endpoint much required to.
So I know you showed a correlation between PFS and OS in the larger trials, but that can change I'm just curious.
If you are.
Uh huh.
What are you called out more games, you're playing in your head of what the different options. The FDA is going to have for you and what would be the best case and worst case scenarios.
Okay.
Well I think you know FDA has been very clear the other global regulators is that we'd like to and we want to move overall survival is the gold standard we want to get there and that is our goal with the analysts had been any new combinations of a checkpoint hamburger and chemotherapy. So I don't I think that the.
<unk> in a good way I really think that that is a benchmark we should strive for we need to improve the survival of patients with cancer now. The big question is is there a surrogate that you can get that answer quickly and I think so far in T. N. D. C. For example, there's been a very good correlation between PFS and OS if you've looked at Impassion $130.
Keynote <unk> five study PFS and OS benefits have really mirrored each other so.
At least for Mario for I don't see a lot of controversy. There I think our goals are obviously to win on overall survival, but you know if we can deliver like we have so far in Mario three on PFS I think that would be a very encouraging thing as well, but again you must have that conversation with regulators.
Got it okay. Thank you.
Thanks Robyn.
Thank you and we do have a follow up from Mike King from H C. Wainwright. Your line is open.
Alright, Mike.
Brian .
I'm sure you were somewhat light.
I'm just curious about.
Your thoughts on the <unk>.
Gone back and pressure tested.
The Mario studies, Mario three to 75.
The recent disappointment and Nektar now I know that's different.
Recognize them of action, but if you look at their melanoma study.
They had many of the same or similar.
And again in a single arm study in <unk>.
<unk> with the volume that they have.
They converted PD PDL, one negative tumors to PD lone positive they had some other correlative.
Biomarker data with respect to CD for CD, eight ratios et cetera, and so just as a kind of belt and suspenders exercise I'm. Just wondering if you can go back and reexamine the data to make sure that the signals that you feel you.
And from those studies are actually putting point you in the right direction.
Yeah, I'll take the first crack at it and let Rob.
For the thoughts.
I think the strongest.
Basis of our confidence in again all this is the concordance of our data across all of the clinical studies that we presented from all the way back from area, one with melanoma and.
Patients who would.
Just on there.
Immediate prior therapy had progressed on a checkpoint inhibitor were able to salvage them and get not just stable disease, but the objective responses to.
Mario 275, where we had actual overall survival data correlated back to PFS, including in the PD lone low, but not exclusively the PD lone low patients.
And obviously with Mario three in both people and lower fuel to high as.
As well as our two study checkpoint free regimen, and so we definitely would not hang our hat on any single biomarker or any single study.
But we don't see the sort of the nektar.
Example, as a as a cautionary tale because we're we're not extrapolating off of off of a single study it's really.
Safety database of over 350 patients.
You know across five individuals studies.
Well and I think also I mean the nectar.
Drug was looking at a you know an important signaling pathway and delivering it in a new way, but it wasn't a novel target in basic sort of sense I think when we kick the tires back in you know, we always look at things with a critical eye because I think it's always important to do that here.
Here, we're dealing with a very.
<unk> small molecule inhibitor of a pathway, that's in mostly myeloid and macrophage cells.
And you know we've just been really encouraged by the fact that it does what we designed it to do we've looked at it in peripheral blood.
In a controlled way gets <unk> and Mario 275, we will get tumors see the same thing. So I think we have really pretty compelling data both in peripheral blood and tumors that the drug is doing what it's designed to do and not only that we actually see that matters, we see clinical movement too. So I think it's really important to both of those things we've seen we see.
That.
Biomarker data as well.
Monotherapy.
We've seen it in peripheral and.
Appeared to have biopsies as Rob said, we've also seen that.
Like Nektar in combination with volume up we've also seen it in our two study absence of checkpoint inhibitors. So it's it's.
It's sort of the independence of the mechanism.
Or a lack of reliance on any single.
<unk>.
Synergistic partner that I think is so compelling.
Okay. Thanks for the comprehensive answer guys. Thanks I appreciate it okay. Thanks for the follow up.
Thank you.
At this time Im showing no further questions I'd like to turn the call back over to Larry for any closing remarks.
Yes.
So in closing, we really feel very fortunate to be developing this promising therapy with the potential to improve the <unk>.
Quality and length of life for people with cancer, and with our bolstered balance sheet and our strengths and leadership team.
Including with Rob here today, we're really well positioned to focus on executing in 2022, which means initiating our first again a list a registrational study and expanding the evaluation of <unk> in additional solid tumor indications and Mario P.
So we remain committed to realize the value of again, Lisa for the benefit of both patients and shareholders.
And so that I would like to thank the affinity team as well as our investigators our trial sites as well as our investors and most importantly, our patients and their families have all played.
Our roles and advancing our work to bring better patients per treatment to these patients and we look forward to providing updates in the coming months.
And thank you very much for your continued support.
Good night.
Thank you. This concludes today's conference call. Thank you for your participation you may now disconnect everyone have a wonderful day.
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