Infinity Pharmaceuticals, Inc. (INFI) CEO Adelene Perkins on Q4 2021 Results - Earnings Call Transcript

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Infinity Pharmaceuticals, Inc. (NASDAQ:INFI) Q4 2021 Earnings Conference Call March 29, 2022 4:30 PM ET

Company Participants

Jayne Kauffman - Senior Executive Coordinator

Adelene Perkins - Chairman & CEO

Robert Ilaria, Jr - Chief Medical Officer

Larry Bloch - President & Treasurer

Conference Call Participants

Anupam Rama - JPMorgan

Ted Tenthoff - Piper Sandler

Kevin DeGeeter - Oppenheimer

Soumit Roy - Jones Research

Kalpit Patel - B. Riley Securities

Robyn Karnauskas - Truist Securities

Operator

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 Results. 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 for follow. Please be advised that this conference is being recorded at Infinity's request.

Now I would like to introduce your host for today's call, Jayne Kauffman. Please go ahead.

Jayne Kauffman

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 Adelene Perkins, Chief Executive Officer and Chair; Larry Bloch, President; and Robert Ilaria, Jr., Chief Medical Officer. We'll open the call for Q&A following our remarks.

The press release issued today details our results and is available on our website at infi.com. Please 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. 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 Adelene.

Adelene Perkins

Thanks, Jayne, and thank you to everyone for joining us today to review Infinity's key 2021 accomplishments and 2022 goals.

Even against the challenging backdrop of a global pandemic, geopolitical tensions and deteriorating capital markets, Infinity was able to make meaningful progress during 2021 and is well positioned to weather future storms. The 4 foundational pillars necessary to create great value are all in place with a differentiated drug, good clinical data, an augmented leadership team and a strengthened balance sheet. Building on these in 2022, we are now poised to initiate the first eganelisib registration study, expand eganelisib clinical evaluation in multiple additional solid tumor indications and establish the best path forward to continue to fund and maximize the value of eganelisib for patients and shareholders.

Before turning to 2022, I'll review the 4 foundational pillars, which are enabling us to optimize the value of eganelisib, our first-in-class drug that reprograms max stages in the tumor microenvironment to reduce immunosuppression and activate 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 disclosed positive results in 5 solid tumors across SITC 2020, San Antonio Breast Cancer Symposium in 2020 and 2021 as well as ASCO GU 2021. These presentations included data in 3 different combination regimens in multiple lines of therapy and tumor types, including metastatic triple negative breast cancer, or TNBC; metastatic urothelial cancer, or UC; ovarian cancer as well as checkpoint inhibitor resistant squamous health cancer of the head and neck and melanoma; all settings where checkpoint inhibitors have provided more limited patient benefit to date.

These data validate eganelisib's potential to increase the effectiveness of current standards of care including in the PD-L1 negative patient population for whom checkpoint inhibitors alone are particularly ineffective. The encouraging results across 5 distinct tumors are impressive in their own right, and yet the totality of the data are even more compelling in light of the consistent patient benefits seen across multiple settings.

Improvements in both median progression-free survival and median overall survival further underscore the promise of eganelisib to drive the next generation of immuno-oncology combination therapy. On today's call, we'll focus specifically on the data from 2 of these studies in patients with frontline metastatic TNBC from our MARIO-3 study and 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 of eganelisib has enabled us to strengthen another foundational pillar, our team. In 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 Ilaria, Jr;, our Chief Scientific Officer, Dr. Stéphane Peluso; and our former Chief Medical Officer and now Board member, Dr. Brian Schwartz.

In addition, today, I am very pleased to announce the addition of Sujay Kango to our Board of Directors. Sujay was most recently the Chief Commercial Officer at Acceleron prior to its acquisition by Merck late last year and previously served as Infinity's Executive Vice President and Chief Commercial Officer. Sujay will be providing important commercial and strategic insights as a member of our Board, which is very timely as we initiate our first registration study for eganelisib of this year.

And last but not least, in 2021, 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 2022, we have the resources required to initiate our registration trial in frontline metastatic TNBC and expand our development of eganelisib through our MARIO-P study this year. Altogether, we are very encouraged that even in the face of global uncertainty and market volatility, Infinity's future is bright.

I'll now turn the call over to Rob to review the data that supports this bright future for the studies we're initiating this year as well as potential future development path. Rob?

Robert Ilaria, Jr

Thanks, Adelene. I'm thrilled to be part of Infinity at this exciting time, guiding the design and execution of the first registration-enabling study for eganelisib and laying the foundation of the next stage of development with MARIO-P.

While approved immuno-oncology drug 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 with eganelisib, a highly specific small molecule inhibitor of PI3 kinase gamma to reprogram macrophages in the tumor microenvironment and enhance immune activation.

The strength and consistency of eganelisib data across multiple indications and treatment settings, including PD-L1 negative subgroups, provide solid evidence that eganelisib 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-3 trial, a single-arm study in advanced metastatic triple-negative breast cancer. The strategic objective was to characterize the safety and efficacy of the addition of eganelisib to atezolizumab, marketed as Tecentriq and nab-paclitaxel marketed as Abraxane in metastatic TNBC compared to the benchmark IMpassion130 study.

We reported safety data from 50 patients and efficacy data from 44 evaluable patients with a data cutoff of October 2, 2021. Tumor reduction was observed in 92.8% or 13 out of 14 patients with PD-L1 positive tumors and 85.2% or 22 out of 27 patients with PD-L1 negative tumors. In patients with PD-L1 positive tumors, the median PFS in MARIO-3 was 11 months compared to 7.5 months reported for tezelizumab and nab-paclitaxel in the IMpassion130 benchmark study, a 47% relative improvement.

In patients with PD-L1 negative tumors, the median PFS was 7.3 months compared to the 5.6 months reported IMPassion130, a 30% relative improvement. The MARIO-3 safety profile was consistent with expectations for the 3 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-L1 negative and positive metastatic TNBC patients, and we 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, our randomized Phase II study in platinum refractory immune checkpoint inhibitor naive advanced or metastatic urothelial cancer patients. In the PD-L1 negative patient population, which represented the majority of the attempt to treat patient population, we observed a median overall survival of 15.4 months with the combination of eganelisib of nivolumab compared to 7.9 months on the nivolumab control arm, with a hazard ratio of 0.60, which reflects a 40% lower probability of death on the eganelisib combination arm.

These findings are consistent with data presented earlier last year that showed at the 1-year landmark 59% of patients received the eganelisib plus nivolumab arm remained alive compared to 32% in the nivolumab control arm. Although the date of MARIO-275 and MARIO-3 are both strong and mutually supportive eganelisib as a strong potential as a TME modulating drug, we've made the decision to prioritize metastatic TNBC as our initial registration-enabling study. Due to the greater unmet need, particularly in PD-L1 negative patients, we're still receiving chemotherapy alone as the standard of care.

Towards that end, we plan to initiate MARIO-4, a randomized double-blind registration study in frontline metastatic TNBC by the end of this year with PFS and OS as key study endpoints. All patients will receive the MARIO-3 triplet of eganelisib and checkpoint inhibitor and chemotherapy, which will be compared with standard of care, which is either chemotherapy alone for PD-L1 negative patients or chemotherapy and a checkpoint inhibitor for PD-L1-positive patients.

We are now preparing for our end of Phase II 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 II clinical data in 2, mostly PD-L1 negative tumor indications, have been bolstered by uniquely strong translational, or TM data package, with support that eganelisib delivers on its intended mechanism of action. At the San Antonio Breast Cancer Symposium this past December, we presented data from paired tumor biopsies in MARIO-3, showing an increase in the M1 to M2 ratio, reflective of macro Phase III program, an increase in immune activation and an increase in PD-L1 expression in both PD-1 negative and PD-L1 positive patients compared to baseline.

These findings in tumors are consistent with what we had observed in peripheral blood gene expression analysis for MARIO-275 that showed enhanced immune activation of the eganelisib and nivolumab combination compared to the nivolumab control arm. Armed with these very encouraging clinical and TAM data in 2 solid tumor indications, one of my highest priorities since joining Infinity is to quickly identify other opportunities for eganelisib to advanced cancer treatment, particularly in areas where immune checkpoint inhibitors have had more of limited success.

In support of this mission, we will initiate a platform study called MARIO-P to evaluate the clinical benefit of eganelisib 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?

Larry Bloch

Thank you, Rob. This past year has been a foundational year for eganelisib and Infinity as we prepare for eganelisib's first registrational study as well as prioritize initiation of additional clinical studies in indications where eganelisib has the largest potential benefit for patients.

In early 2021, based on the strength of eganelisib data across multiple solid tumor indications, including metastatic TNBC and metastatic UC, Infinity raised $92 million to enable our continued execution on our strategic development plans for eganelisib, including the commencement of our first eganelisib registrational study. This Infinity having total cash and cash equivalents and available for sale securities of $80.7 million at December 31, 2021, compared to $34.1 million at December 31, 2020.

Research and development expenses for the year ended December 31, 2021, was $31.6 million compared to $26.8 million for the same period in 2020, and this increase is 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 to support continued development of eganelisib.

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 expense is 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 $0.53 compared to a net loss of $40.5 million or basic and diluted loss per common share of $0.68 for the same period in 2020. If this 2022 financial guidance remains unchanged, and we continue to expect net loss for 2022 to range from $45 million to $55 million and end 2022 with the year-end cash and cash equivalent ranging from $25 million to $35 million. And Infinity's 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 eganelisib in our first eganelisib registrational study as well as a platform study in other solid tumor indications. We're truly excited about the continued advancement of eganelisib's clinical program to lay the foundation for initiation of potential future registration studies. In parallel, we will leverage eganelisib's unique of action and differentiated clinical data to evaluate and execute on the best path forward to fund its ongoing development and maximize the value of eganelisib 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?

Question-and-Answer Session

Operator

[Operator Instructions] And our first question comes from Anupam Rama from JPMorgan. Your line is open.

Anupam Rama

Larry, I want 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 eganelisib sort of the OUS rights or regional partnerships as a potential source of nondilutive capital? And how do you think about maximizing that from a timing perspective?

Larry Bloch

So thanks, Anupam. So from a business development perspective, we certainly feel that we not feasible to slice and dice a analyst to buy indications. The way you think about it in terms of geography is certainly the way we look at it. But ultimately, because of the breadth of the potential indications that eganelisib can reach across the broad swath of solid tumors, PD-1 low and PD-1 high, we think ultimately, a strategic collaboration that's global is probably going to be more advantageous than a regional collaboration because of the complexity of the potential clinical development path forward.

Operator

Our next question comes from Ted Tenthoff from Piper Sandler. Your line is open.

Ted Tenthoff

So don't take this wrong way, because it's not intended to be impertinent in any way. I get a sense for what's going into a ranging MARIO-P and MARIO-4? Specifically, what's taking so long? I'm thinking of, like, not meant to be confrontational, but what are the steps that are being required there? Obviously, drug supply, things like that, but what's really going into preparing to launch those 2 studies?

Adelene Perkins

Yes. So thanks, Ted, for the question. And 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 while we're not in a position to describe all of it yet as we are designing the trial and planning for to operationalize it, lots and lots of decisions about exactly the patient population, inclusion and exclusion, the endpoints, whether there's 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 and has the input from global regulatory authorities, we'll be sharing it. It's just simply premature to do so until we've finalized it. So the old analogy about the come along the top of the water, but the paddles going rapidly underwater. The team is rapidly doing all the things underwater. It just may not be as visible until we can describe what that final trial design is.

And Rob, I'd see if you have anything to add?

Robert Ilaria, Jr

Well, I guess one thing I will mention is time, I guess, quickly in certain respects, we just presented our updated data at the San Antonio Breast Cancer Symposium in December. And 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 in the 10-month range. And then we really moved from looking at that data, reacting to that data and to expand on what Adelene was saying, it does take a lot of pieces were 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 going to do. We only recently identified the 4 tumor types we want to do for MARIO-P platform study. So I think that's a good start, too. 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.

Ted Tenthoff

Great. Well, I'd rather get it right. So I appreciate that.

Operator

Our next question comes from Kevin DeGeeter from Oppenheimer. Your line is open.

Kevin DeGeeter

I guess on MARIO-P, can you help us think about dose for a basket study? I mean, I guess we did see some deliveries that require adjustment 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. Just will all these patients sort of be getting the same dose? And how should we think about appropriate dosing for study?

Robert Ilaria, Jr

Yes. I mean, I think you bring up some good points. I mean, we had started the MARIO-275 5 at the 40-milligram dose of eganelisib daily and then had gone down to 30. I think we're really encouraged that 30 milligrams seems to be a winning dose because that's something we're dosing now in a triplet regimen with atezolizumab and a chemo, Abraxane.

So I think as you think about a platform study, I don't tend to think of toxicity being all that different across tumor types. So I think 30 milligram is a very solid dose for that. Now of course, as we design the study, will we decide to explore that dose a little bit? It's possible. But I think the fact that we're able to dose 30 milligram a day and a triplet bodes very well for a lot of combinations that we can do across different tumor types and across different agents.

Kevin DeGeeter

Great. And then just how should we think about sort of gates are opening sites in MARIO-P? It kind of sounds like that study may kick off before the registrational study in TNBC. I'm just wondering in a resource-constrained world, how we should think about potential pace of site opening and kind of folks of learning as we move into 2023?

Robert Ilaria, Jr

Sure. Well, as we announced, we are going to be opening these in a rolling basis. And one of the nice things about a platform study is that by focusing on specific tumor types, you can focus on specific terms of excellence that see a lot of that tumor type. And so it allows kind of almost like a cassette that you can open 1 tumor type, decide what you're going to do, what combinations are you going to look at and then move to the next module and do it kind of in a nice orderly fashion.

So I think that we would probably take a very tumor-centric approach that were probably the most logical way of doing it. And I think that's how we're envisioning doing this on a rolling basis. And of course, that is, as you mentioned, you do learn as you go in sort of an iterative process.

Operator

Our next question comes from Soumit Roy from Jones Research. Your line is open.

Soumit Roy

Congrats on the progress. Could you help us think through what we should expect from the MARIO-3 RCC cohort in second half '22? Is it like a number of patients you're we could expect to see data from would really help?

Adelene Perkins

Sure. I'll start, and then Rob can elaborate. So that study is a 30-patient study. It is single arm combining eganelisib with Tecentriq and Avastin. And what we're really -- the purpose of that study was to see proof of concept of the utility of adding again, eganelisib VEGF inhibitor. As you know, the Tecentriq and Avastin regimen is not approved in renal cell. So it's unlikely that 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 TKIs and we'd be evaluating. If we did want to go for what would the right drugs be and what would that design be.

So this is different from the MARIO-3 TNBC, where we were very much -- we've got the right modalities of drugs, and we can be moving directly to registration and the renal cells, different objective out of that study.

Robert Ilaria, Jr

Yes. For us, I mean, it was an interesting question to understand with modulating of VEGF. And again, this is not one of these oral TKIs. Bevacizumab is really a VEGF, big molecule antagonist, whereas a lot of -- as the field has moved on now to be these multiple kinases in RCC. But for us, it was getting some clinical data with a drug like the and of course, in combination with the checkpoint inhibitor. And we're looking to -- as we're reviewing that data to give an update on that later this year.

Soumit Roy

So essentially, in second, we are going to look into the 275 and MARIO-3, TNBC long-term like survival data, and that's -- that remains a main goal here, catalyst-wise -- data catalyst-wise?

Robert Ilaria, Jr

Yes, yes.

Operator

Our next question comes from Kalpit Patel from B. Riley Securities. Your line is open.

Kalpit Patel

One for the MARIO-P study. I know you're initiating on a rolling basis. But have you finalized which tumor type you will likely prioritize first? Based on the mechanistic profile of eganelisib, is there one tumor type that you would be start with first? And then are you also planning to enroll or restrict enrollment based on any underlying biomarker status where applicable maybe just focusing on PD-L1 negative patients for certain indications like lung cancer?

Robert Ilaria, Jr

Yes. So I think we like all 4 tumor types. And so we are still discussing which one we'd like to start with. I have to admit, I'm anxious to learn about all of them. But I think we're still working through which one we will start. I think we keep an open mind about narrowing the indications as far as restricting it to a certain PD-L1 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 encouraging things we found is the drug -- we're encouraged with our data across PD-L1 expression. So I don't think we have any priority thoughts that we're going to narrow it coming out of the gate. But -- but again, we're anxious to get started. We like all 4 of those, and we're in the midst of deciding which one we'd like to prioritize this year.

Adelene Perkins

And Kalpit, as you would know, Rob is not only enthusiastic about all, but he does have -- we just not yet in a position to provide the specific rank or prioritization. But we do have sentiments on that and are executing on that. And as soon as we're ready to share those details, we'll be happy to.

Kalpit Patel

Okay. And then one question on the MARIO-4 study. Based on the safety results that you realized to date with the triplet, does that tolerability profile in any sense, restrict the type of patients that you would enroll in MARIO-4? I'm just trying to understand if MARIO-4 the time line should be similar to what we have seen with IMpassion130?

Robert Ilaria, Jr

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 is pretty similar for the triplet compared to the doublet in IMpassion130, which actually is really gratifying because usually when you have a triplet, there's sort of a trade-off.

So I think the reason for that is we have an oral drug. It's very easy to adjust. Or if you dose hold it for a few days, it quickly washes out. So I don't really see any limitations per se. I would expect that -- of course, checkpoint inhibitors are sometimes restricted for patients who have autoimmune diseases and things like that, but I don't see anything particularly unique of anything we would restrict just because again, it lists in the mix.

Operator

The next question comes from Mike King from H.C. Wainright. Your line is open.

Mike King

Can you hear me okay?

Larry Bloch

Yes, coming through great, Mike.

Mike King

Just wanted to pick up for starters, pickup were Anupam left off, and that has to do with BD. It seems like it's not pragmatic to be able to have any kind of conclusive discussions until you know what the parameters are going to be from MARIO-4? I mean is that a reasonable thought process? Do you have to lock down the protocol so that you know what -- 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?

Larry Bloch

So that's certainly the approach we took the last time we put in place a global collaboration for a development of one of our programs. We had started our global Phase III for duvelisib. And on the heels of that, we brought in a partner. In this 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's certainly -- I think, as you to sort of makes the alignment easier to do.

On the flip side, some partners like to have some input on the actual design parameters and once it's lots and loaded, and have FDA and ex U.S. alignment on that. You don't really want to reopen that relitigate that again. So there's plus and minuses both sides. But certainly, the last time the infinity to this, we followed the track that you're recommending.

Mike King

Okay. But is it fair to say that even if you do not secure either a regional or a global partner before MARIO-4 is ready to go, you'll start the study?

Larry Bloch

Yes. We -- our guidance is we're going to be starting the study by year end, and we think that's completely consistent with the time line that Rob has laid out in terms of engagement with the regulatory authorities.

Mike King

Okay. All right. And then just a quick clarification, and I apologize I missed what are the 4 contemplated tumor types from RLP?

Robert Ilaria, Jr

The planned tumor types or soft tissue sarcoma, ovarian, prostate and non-small cell lung cancer.

Mike King

Okay. And then finally, I just wanted to ask, are you deprioritizing UC? You had a very nice signal there, and it just sounds like that once is not making the cut?

Larry Bloch

It's not -- we're -- I mean, I guess we're prioritizing TNBC. So I guess, implicitly, it deprioritizes urothelial cancer. If we had the resource to do 2 parallel registration studies, we'd love to do both of those. But given the fact that the standard of care for especially low patients in frontline metastatic TNBC, care is just chemotherapy. There is no immuno-oncology opportunity for those patients at might such a glaring unmet medical need that 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 collaboration, we would certainly like to bring your urothelial cancer up to the front as well, but we just we can't do 2 global registration studies in parallel at this time.

Mike King

Okay. So I guess you said -- Larry, I guess you say I don't want to put words in your mouth, but I guess you're saying that the only logical course forward for UC is in a randomized registration-directed study versus making a part of, let's say, MARIO-P, is that a fair statement?

Larry Bloch

Yes. I think we've already got randomized controlled data from MARIO-275. So sort of going back to Phase II for additional data, it seems like that would be a misuse of the opportunity, as Rob said, you want to explore additional indications through MARIO-P. And we think there's a pretty clear path forward towards the registrational study in urothelial cancer based on the MARIO-275 data we've already analyzed.

Mike King

Okay. Fair enough. And sorry, if I could just sneak in one more.

Larry Bloch

Two.

Mike King

What's that?

Larry Bloch

Go ahead.

Mike King

Now I've forgotten.

Larry Bloch

I would say successful.

Mike King

[Indiscernible] come back to me before you wrap up.

Operator

[Operator Instructions] And our next question comes from Robyn Karnauskas from Truist Securities. Your line is open.

Robyn Karnauskas

Just a follow-up on a couple of questions. So when thinking about the global partnership and you mentioned that something want to be involved in the design, some people do not. How are you weighing the terms of someone who wants to be involved in derisking the story because you're getting that off your plate versus waiting? Help us understand like how you're thinking about like the 2 auctions that you just mentioned?

And second, when you're thinking about the FDA, the update on very different lately. The surprising people with the 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 at centralized locations and big centers to get that diversification if needed, if the FDA is more critical of just doing it at specialized sites?

Larry Bloch

Rob, why don't you start with the clinical diversification question, I'd be happy to take the BD question?

Robert Ilaria, Jr

Okay. Sure. I think for diversification, you bring up a good point because the nowadays pembrolizumab in the United States and chemo is the standard of care. And so a lot of that is going on in community sites versus the centers of excellence necessarily. So I think we would be diversified in the way we did enrollment. I think we would want a core centers of excellence, but I think we would also want plenty of other community-based practices to be able to really do a great job of enrolling across both PD-L1 positive and in negative patients.

Larry Bloch

And maybe also, Robin, to your point about the sort of conservatism upon regulatory authorities. We've seen some of that just recently with discussions about PI3K delta in the hematological malignancy front. And from our perspective, we don't believe that touches on PI3K gamma at all in the -- in the solid tumor front because there's -- as far as we can tell, no overlap in terms of the toxicity profile. So we're really gratified that the -- there has been a review of both accelerated approval in immuno-oncology. We're really happy to see that we've seen a correlation between our PFS and our OS data, which was one of the big challenges, obviously, last year at the ODAC for the accelerated approval.

And we're 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 we wouldn't expect to see from the individual components. So what we will certainly want to diversify from a as Rob said, sort of a standard of care in centers of excellence versus the community centers. But from a general regulatory perspective, we think that the path we're pursuing is pretty well -- it's pretty clean.

Robyn Karnauskas

Just have a follow-up before you get to the question around the...

Larry Bloch

PD.

Robyn Karnauskas

Yes, PD. So if you want to do a more diversified trial, does require a lot more resources, a lot more expertise with some of pharma can get this done really quickly because they have all the connections and stuff in place. So how do you -- it sort of feeds in the question around doing this before you start the trial versus PD before you did the trial versus as were finding that partner?

Larry Bloch

Yes. So I would totally take your point. I'd say there's 2 parts. One is we're going to pursue our own independent path to registration as we've lined out with our guidance for having the MARIO-4 study up in in by year-end. That said, the critical thing for us is to get alignment with the FDA, we can obviously get alignment with the BD partner beforehand or afterhand. But there is some benefit, as you said, leveraging the resources of a partner.

We didn't find any 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't bolt-on from a partner to augment the resources that AbbVie putting in place independently before the fact.

Robyn Karnauskas

And I'll put another one in. So any surprises you think, regarding what the primary endpoint would be required to be for MARIO? Because I'm just thinking out of the box, how surprised what's being required over my lifespan, how it's changed over time. Do you think there's any surprises as far as the primary endpoint and what's required to show -- I know you showed a correlation between PFS and OS, but in the larger trials that can change.

I'm just curious if you're -- what kind of what you call that war 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?

Robert Ilaria, Jr

Well, I think FDA has been very clear as other global regulators is that we'd like to -- we want to move overall survival, that's the gold standard. We want to get there. And that is our goal with eganelisib have been any new combinations of a checkpoint inhibitor and chemotherapy. So I don't -- I think that's evolved 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 TNBC, for example, there's been a very good correlation between PFS and OS. So people look at IMpassion130 in the KEYNOTE-355 study, PFS and OS benefits have really mirrored each other. So at least for MARIO-4, I don't see a lot of controversy there. I think our goals are obviously to win on overall survival. But if we can deliver like we have so far in MARIO-3 on PFS, I think that would be a very encouraging thing as well. But again, you must have that conversation with regulators.

Operator

And we do have a follow-up from Mike King from H.C. Wainright. Your line is open.

Larry Bloch

All right, Mike...

Mike King

I'm sure you were, so as I. I'm just curious about your thoughts on the -- if you've gone back and pressure tested the MARIO studies, MARO-3, 275 in light of the recent disappointment in Nektar. Now I know that's a different mechanism of action. But if you look at their melanoma study, they had many of the same or similar effects, again, in a single-arm study in combo with nivolumab, they had -- they converted PD-L1 negative tumors to PD-L1 positive. They had some other correlative biomarker data with respect to CD4, CD8 ratios, et cetera.

And so just as a kind of belt and suspenders exercise, I just wonder if you go back and kind of reexamine the data to make sure that the signals that you feel you mean from those studies are actually putting -- pointing you in the right direct?

Larry Bloch

I think we first cracked it and then let Rob add for their thoughts. I think the strongest basis of our confidence in eganelisib is the concordance of our data across all of the clinical studies that we presented from all the way back from MARIO-1 with melanoma in patients who would just and the immediate prior therapy had progressed on a checkpoint inhibitor were able to salvage them and get not just disease but objective responses to MARIO-275, where we had actual overall survival data correlated back to PFS, including the PL-1 low but not exclusively in the PL-1 low patients.

And obviously, with MARIO-3 and both PD-L1 high as well as the ARC-2 study in a 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 cautionary tail because we're not extrapolating off of off of a single study. It's really a state database over 350 patients across 5 individual studies.

Robert Ilaria, Jr

Well, and I think also, I mean, the Nektar drug was looking at an important signaling pathway and delivering it in a new way, but it wasn't a novel target in a basic sort of sense. I think when we kick the tires back and we always look at things with a critical eye as I think it's as important to do that. I mean, here, we're dealing with a very specific small molecule inhibitor of a pathway that's in mostly myeloid macrophage cells. And 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, both in a controlled way against nivolumab 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 tumor that the drug is doing what it's designed to do. And not only that, we actually see that it matters. We see clinical movement, too. So I think it's really important to both of those things.

Larry Bloch

We've seen that biomarker data is both the monotherapy, we've seen in peripheral and part biopsies as Rob said, we've also seen that like Nektar in combination with, we've also seen it in our 2 study absent a checkpoint inhibitor. So it's not -- it's the sort of the independence of the mechanism or lack of reliance on any single synergistic partner that I think is so compelling.

Operator

At this time, I'm showing no further questions. I'd like to turn the call back over to Larry for any closing remarks.

Larry Bloch

So in closing, we really feel very fortunate to be developing this promising therapy with the potential to improve the quality and length of life for people with cancer. And with our bolster balance sheet and our strengthened leadership team, including with Rob here today, we're really well positioned to focus on executing in 2022, which means initiating first analyst of registrational study and expanding the evaluation of eganelisib in additional solid tumor indications in MARIO-P. So we remain committed to realizing the value of eganelisib for the benefit of both patients and shareholders.

And in regards to that, I'd like to thank the Infinity team as well as our investigators, our trial sites as well as our investors and most importantly, our patients and their families who have all played interval roles in advancing our work to bring better patients treatments 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.

Operator

Thank you. This concludes today's conference call. Thank you for your participation and you may now disconnect. Everyone, have a wonderful day.

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