Infinity Pharmaceuticals Inc (INFI) 2021 Q3 法說會逐字稿

Ladies and gentlemen, thank you for standing by. Welcome to the Infinity Pharmaceuticals conference call to discuss the company's operations and third quarter 2021 financial results. My name is Tina, and I'll be your operator for today's call. (Operator Instructions) Please be advised that this call is being recorded at Infinity's request. Now I would like to introduce your host for today's call, Jayne Kauffman. Please go ahead.

Thank you, Tina, and good afternoon, everyone. Welcome to today's call to discuss our recent business progress and review of our third quarter 2021 financial results.

On the call with me today are Adelene Perkins, Chief Executive Officer; Larry Bloch, President; Robert Ilaria, Chief Medical Officer; and Stéphane Peluso, Chief Scientific Officer. We'll open up the call for Q&A following our remarks.

The press release issued this afternoon 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 2020 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.

Thanks, Jayne, and thank you to everyone for joining us today. This is a very important time at Infinity as we focus on 3 significant value drivers for the company.

First, our evolving clinical and translational data, which we will review during today's call, suggests we have a drug with eganelisib and lay the foundation for significant additional value creation. Second, based on these data, we are making the very important transition from seeking proof of concept with eganelisib to advancing a registration-focused study. Third, our validation of eganelisib's unique mechanism of action in reprogramming macrophages substantiate eganelisib's potential beyond TNBC and urothelial cancer.

Eganelisib is distinctively well positioned as the only PI3-kinase-gamma inhibitor in clinical development to drive differentiated benefits for patients. In particular, we have shown the ability of eganelisib to approve the outcomes of its combination drug partners, particularly checkpoint inhibitors, which have historically benefited a minority of treated patients and which are increasingly dependent upon complementary combinations to improve results.

I'll now elaborate on each of these 3 value drivers. Starting with data. Last quarter, we presented data in patients with second-line metastatic urothelial cancer and in patients with first-line metastatic triple-negative breast cancer, which provides compelling evidence that eganelisib improves patient outcomes. Importantly, we are seeing this evidence on the most meaningful metrics of patient benefit, namely prolonged progression-free survival or PFS and extended overall survival or OS. And we see these benefits for patients regardless of their baseline PD-L1 status.

We are very pleased to have been invited to present updated TNBC data at the 2021 San Antonio Breast Cancer Symposium this December. As our TNBC data mature, we are especially interested in confirming whether the PFS results from this summer, which exceeded our expectations, are maintained over a longer period of time in more patients.

Prolonged PFS is particularly meaningful for PD-L1-negative metastatic frontline TNBC patients for whom no checkpoint inhibitors have been approved, which leads me to our second value driver as we turn our attention to registration-enabling studies. The strength of the PFS and OS data we have generated in TNBC and UC is particularly relevant as these are likely to be the primary endpoint for potential registrational trials.

We are actively engaged with key opinion leaders and regulatory authorities. And the design of a registration-focused study in UC and the strength of our PFS and OS data gives us confidence in our ability to meet the high bars necessary for approval. We look forward to updating you on our plans for eganelisib in UC on January 5, in conjunction with our 2022 guidance.

Our UC PFS and OS data are further bolstered by translational evidence from biopsies indicating that there is significantly greater immune activation in the treatment arm with eganelisib versus the control arm without eganelisib. So the drug is doing exactly what it was designed to do, which brings me to our third value driver, which is the breadth of eganelisib's potential beyond TNBC and UC.

Over the past 12 months, we have shown very encouraging clinical and translational data on eganelisib activity relative to reference benchmarks across 5 different tumor types, 3 different combination regimens and in multiple lines of therapy, all of which demonstrate eganelisib's power to activate an immune response. The data from each of these individual studies alone is notable and becomes even more compelling when viewing the totality of the data, where its consistency across multiple settings underscores the potential of eganelisib to drive the next generation of immuno-oncology therapies.

This is particularly true given that eganelisib is the only PI3-kinase-gamma specific inhibitor in clinical development. The only way to access the unique macrophage reprogramming achieved through inhibition of PI3-kinase-gamma is with eganelisib. There is no alternative PI3-kinase-gamma inhibitor in the clinic. So as our clinical data mature favorably, the scarcity value of eganelisib increases dramatically as does the attractiveness of our strategic options.

Hence, our highest priority is to advance the 3 value drivers outlined above by continuing to generate strong clinical and translational data, advance registration-enabling studies and leverage the fundamental biologic mechanism of eganelisib in remodeling the tumor microenvironment to improve patient outcomes across additional setting.

To achieve this, we have further strengthened our clinical and scientific leadership as well as our Board of Directors. Last quarter, we announced the appointment of our Chief Scientific Officer, Dr. Stéphane Peluso, who, with prior experience at Infinity, is uniquely qualified and ideally positioned to push forward the important scientific work that is the foundation of our program.

On the clinical front, we have appointed a new Chief Medical Officer to succeed Dr. Brian Schwartz, who served as our Consulting Chief Physician and made impactful contributions in guiding our clinical programs through key data readouts that paved the way for the ongoing development of eganelisib. We could not be more pleased that Brian is continuing to contribute to Infinity and eganelisib from his new position on our Board.

We are thrilled that Dr. Robert Ilaria has joined Infinity as our Chief Medical Officer to lead the future clinical development of eganelisib. Rob brings an ideal background to Infinity, given his deep expertise in drug development in immuno-oncology. He joins us from BMS and Celgene, where he led BMS' CTLA-4 program and Celgene's PD-1 inhibitor program in collaboration with BeiGene.

Rob's strong track record in drug development from preclinical through approval during his tenures at Lilly, Celgene and BMS is critical to the top value drivers I just reviewed. Throughout his pharma career and now at Infinity, Dr. Ilaria has continued to treat patients, including for some of the indications for which we are now evaluating eganelisib, including TNBC, such that he is acutely aware of the magnitude of the need for those patients.

With that, I'll turn the call over to Rob. Rob?

Thanks, Adelene. I'm really thrilled to be part of Infinity at this exciting time. My decision to join the company was driven by several key factors. The first is that 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.

Top of my list and that of others is the ability to reverse the immunosuppressive tumor microenvironment. That's why I'm so enthusiastic about the potential of eganelisib, a highly specific small molecule inhibitor of PI3-kinase-gamma to reprogram macrophages in the tumor microenvironment and enhance immune activation.

The second reason I chose to join Infinity is the strength and consistency of eganelisib's data across multiple indications and treatment settings, including PD-L1 negative subgroups, providing solid evidence that eganelisib has the potential to be transformative therapy in immuno-oncology. Last and certainly not least is the strength of the Infinity team who've worked so passionately to bring eganelisib to this exciting point in its development.

Among my highest priorities since joining Infinity is to develop a strategy for registration-enabling studies in urothelial cancer and TNBC. The MARIO-275 overall survival data are truly compelling, particularly given these results were seen in both PD-L1 positive and negative patients. Based on the strength of these data, we're considering our next steps extremely thoughtfully with input from KOLs and regulatory authorities.

To recap, MARIO-275 is our randomized, double-blind, placebo-controlled study that enrolled 49 second-line urothelial cancer patients, randomized 2:1 to either eganelisib plus nivolumab, which is marketed as Opdivo, or standard of care nivolumab plus placebo. Our strategic objective was to increase the effectiveness of second-line treatment for patients with advanced urothelial cancer.

Towards that goal, we found that the strong disease control rate and progression-free survival data we presented at ASCO GU in February has translated into a nearly doubling of overall survival. Specifically, this past July, we reported a median overall survival of 15.4 months with the combination of eganelisib and nivolumab compared to 7.9 months on the nivolumab control arm. The importance of overall survival was recently underscored in April ODAC meeting, in which PFS findings that provided the basis for accelerated approval did not ultimately translate into OS benefit. Against this backdrop, we were delighted to see that our PFS benefit translated into OS benefit with MARIO-275, including PD-L1 negative patients.

I would now like to give you a brief update on our MARIO-3 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, which is marketed as Tecentriq and nab-paclitaxel, marketed as Abraxane in metastatic TNBC.

As you may be aware, Roche withdrew the U.S. accelerated approval for atezolizumab in first-line PD-L1 positive metastatic TNBC patients during Q3 of this year. The withdrawal was required in accordance with the requirements of the Accelerated Approval Program, after Roche's confirmatory study using a different chemotherapy failed to meet its primary endpoint.

Notwithstanding the withdrawal, published data from the IMpassion130 study demonstrated that atezolizumab and nab-paclitaxel is an active treatment regimen. And this combination is still approved for first-line metastatic TNBC patients in over 70 countries outside of the U.S. Roche has been very clear in communicating its commitment to continue studying atezolizumab in TNBC and in continuing to supply atezolizumab for our ongoing MARIO-3 study.

The eligibility criteria for MARIO-3 were designed to mirror the IMpassion130 study to facilitate historical benchmarking. And patients were enrolled in either a PD-L1 negative or PD-L1 positive cohort. It's important to note that recent approvals of immune checkpoint inhibitors in combination with chemotherapy in first-line metastatic TNBC have been limited just to PD-L1 positive patients. There are no immune checkpoint inhibitor regimens approved for metastatic PD-L1 negative TNBC patients, who represent the majority of TNBC patients and therefore, a very significant unmet medical need.

The data we presented at San Antonio Breast Cancer Symposium in 2020 provides an exciting initial snapshot of clinical response in our first 13 patients. In our KOL event this past July, we reported an update on a larger data set of 38 patients.

87% of evaluable patients exhibited tumor reductions, and we saw early but encouraging PFS data. Specifically, in patients with PD-L1 positive tumors, we observed a median PFS of 11.2 months compared to the 7.5 months that have been served in IMpassion130. In the patients with PD-L1 negative tumors, we rewarded -- we reported a median PFS of 7.3 months versus 5.6 months observed on IMpassion130.

Together, these results suggest that the addition of eganelisib to immune checkpoint inhibitor and chemotherapy has the potential to improve PFS for both PD-L1 positive and PD-L1 negative patients. For TNBC, the maturing MARIO-3 data will be our north star in outlining our best registration path for eganelisib. These data will allow us to make informed decisions about patient subgroups, such as those with PD-L1 negative tumors.

We've leveraged data from our urothelial and TNBC clinical programs to build a very strong foundation of translational data that support eganelisib's fundamental mechanism of action of macrophage reprogramming. In our July KOL event update, we presented the results of a gene expression analysis from MARIO-275 that showed clearly enhanced immune activation in the eganelisib-nivolumab combination compared to the nivolumab control arm.

For MARIO-3, we presented data of paired tumor biopsies from both PD-L1 positive and PD-L1 negative TNBC patients, showing an increase in the M1 to M2 ratio, reflective of macrophage reprogramming and increase in immune activation and an increase in PD-L1 expression in both PD-L1 negative and PD-L1 positive patients compared to baseline. While our near-term focus to determine the optimal path forward in bladder cancer and TNBC, the strong data we've generated with eganelisib in combination with both PD-L1 and PD-1 inhibitors and in checkpoint inhibitor-free regimen supports broader investigation of eganelisib across additional tumor types, including tumors for which immune checkpoint inhibitor-based treatment have had limited success.

Again, I'm thrilled to have joined the team at Infinity. And look forward to providing updated data in TNBC at San Antonio Breast Cancer Symposium and an update on eganelisib in UC with our January 5 guidance for 2022.

And with that, I'll turn the call over to Larry to review the third quarter financials. Larry?

Thank you, Rob. Even before upcoming San Antonio Breast Cancer Symposium presentation later this quarter, 2021 has already been a foundational year for eganelisib and Infinity. As we prepare for eganelisib's initial potential registration-enabling study as well as prioritizing opportunities with the largest potential benefit for patients through additional clinical studies with eganelisib.

As Adelene outlined, we've strengthened our executive team with the return of Stéphane to Infinity as Chief Scientific Officer, in addition to Rob as Chief Medical Officer as well as the transition of Brian to serving on our Board of Directors. Infinity has also strengthened our financial position through our public offering in February in which we've raised $92 million in gross proceeds to enable our continued execution on our strategic development plans for eganelisib.

So at September 30, 2021, Infinity had total cash, cash equivalents and available-for-sale securities of $90.1 million compared to $34.1 million at December 31, 2020. Research development expense for the third quarter of 2021 was $7.1 million compared to $6.1 million for the same period in 2020. And this increase was primarily related to an increase in development expenses and compensation-related expenses. General and administrative expense for the third quarter of 2021 was $3.8 million compared to $2.9 million for the same period in 2020. This increase in G&A expense was primarily due to an increase in consulting expenses, professional fees and stock compensation.

Net loss for the third quarter of 2021 was $10.7 million or a basic and diluted loss per common share of $0.12 compared to a net loss of $9.5 million or a basic and diluted loss per common share of $0.16 for the same period in 2020.

Infinity's 2021 financial guidance remains unchanged. And we expect net loss for 2021 to range from $40 million to $50 million and to end 2021 with the year-end cash, cash equivalents and available-for-sale securities balance ranging from $70 million to $80 million.

So we're very much looking forward to sharing our updated MARIO-3 data in first-line metastatic triple-negative breast cancer on December 10 in person at the San Antonio Breast Cancer Symposium. We're really pleased to have Dr. Hatem Soliman, a medical oncologist specializing in breast cancer at the Center for Women's Oncology at the Moffitt Cancer Center, one of our top enrolling investigators in MARIO-3, presenting our data at the San Antonio Breast Cancer Symposium, where Dr. Soliman will also be joining us at our investor event the same day to provide his perspective on a maturing metastatic triple-negative breast cancer data in the context of his experience treating patients with this eganelisib regimen.

On behalf of Infinity, we thank you for your continued support. And we look forward to engaging with you again in just about a month.

At this time, we can open the call for questions. Operator?

(Operator Instructions) Your first question is from Anupam Rama from JPMorgan.

Just a quick logistical question for me. I think the prior guidance was that enrollment was complete MARIO-3 by the end of the year. So where are you on that? And then will we get like -- I think the enrollment dynamics are up to 30 patients with PD-L1 negative. Will we get all 30 of those patients at San Antonio?

Yes. Thanks for the question, Anupam. So we are on track to have enrolled approximately 60 patients in the study by the end of the year. What we expect to present at San Antonio is, as you know, at our event this summer, we had 43 patients who were enrolled. So we will have -- all 43 will have been on -- had the opportunity to be on the study for another 3 or 4 months. So we'll have more mature data on those 43.

And for patients who have enrolled since then, we will -- all will be included in the safety database. And we will include any efficacy scans that we have on those patients who are more recently enrolled.

Your next question is from Kevin DeGeeter with Oppenheimer.

There's been some pretty well-publicized shortages of Abraxane. I'm just curious if in this data that we'll get an update on San Antonio, your patients, and for whatever reason, may have missed Abraxane doses, how is that sort of treated from a protocol and a statistical perspective?

Sure. Thanks, Kevin. I'll let Rob take this. I will just lead by saying that our partner, BMS, has been extraordinarily helpful in working with us to ensure that we have access for the patients that were treated. And they've made clinical trial as a priority. But Rob, you can take that.

Yes, there is a nationwide shortage, as you mentioned, of Abraxane. However, we are supplying the drug. And so far as our supplies have been fine. We've been able to provide drug to the current patients and the patients we're enrolling now. So there haven't been any patients who missed any doses because of not having Abraxane.

And if anything, Kevin, the fact that we have an uninterrupted supply of Abraxane and providing it for patients is just another benefit for being enrolled on the study.

Great. That was super helpful. And then just in terms of the opportunities to learn more about outside of TNBC and UC. Should we think about investigator-sponsored studies as one avenue (inaudible) for in 2020? Or what really is the right structure to better characterize the activity that the drug more broadly while you do move forward with registration strategies for UC and TNBC?

Thanks, Kevin. We're all delighted that you asked that question because as we mentioned in our remarks, we really -- based on the mechanism of action data that we've now seen in our existing studies, we really are very excited about leveraging that in other settings. And we have had many discussions with investigators about ISTs and other studies. We will -- if any of those are finalized by the time of our 2022 guidance in January, we'll share those. And if not, by then, we will throughout the rest of the year.

Your next question is from Ted Tenthoff with Piper Sandler.

Great. Sorry, my [phone] was a little choppy. So I didn't get to hear everything. But I wanted to get a sense for plans for triple-negative breast. If the data continues to be positive, what do you envision as next steps?

And then I think maybe [Derek] just asked this question, so I apologize if it's a repeat. But what about expanding beyond urothelial carcinoma and breast? What are some other ideas? And what are some of the trials that you're envisioning?

Yes. Sure, Ted. I'll start, and then I'll turn it over to Rob, who can describe our thinking in TNBC. I'll just preview, as you know, that there are -- the majority of patients with both TNBC and bladder cancer are PD-L1 negative. So that was the first group to enroll.

And that's the first group that we'll be able to interpret the results from because they tend to progress more quickly given the historic benchmark would be Abraxane monotherapy because there is no checkpoint inhibitor at all that's been approved for the frontline metastatic TNBC patients who are PD-L1 negative. So we're likely to be able to map out our thinking on the PD-L1 negatives before the positives. But Rob can show you how he thinks about that.

Yes. I think those are great points. I mean, I think since now PD-L1 negative and positive patients are treated differently, what we'd like to see is how our data matures in both groups. That's why we designed that study to have a cohort of negative and a cohort of positive.

Of course, the patients that are negative do not so well. So we find out earlier how they're doing or not doing. The positives do a bit better with standard of care. And adding eganelisib, we'll have to see how that matures. But this is something we're being very mindful of. And again, we're really looking -- excited to see what these maturing data show.

And to your additional question, Ted, about what other studies, we are receiving a lot of inbound inquiries to do investigator-sponsored studies. We do have one underway now with Ezra Cohen. It's a window of opportunity study in patients with squamous cell cancer of the head and neck.

And our team is now prioritizing other ones. And as soon as those are ready for prime time, we will very much look forward to sharing them with you because there are many settings where there's the need for reduction in a new expressive microenvironment and a very strong scientific rationale for the use of eganelisib in other combinations. And our Chief Scientific Officer, Stéphane Peluso, is working with the team to really prioritize what are the scientific rationales that makes the most sense.

Great. That makes -- yes, go ahead, Larry.

This is Larry. Just there's very few validated unpartnered macrophage-targeting therapeutics. And so there really is a sort of a scarcity effect. And so we are getting both from a corporate side and investigator-sponsored studies had a lot of inbound interest. So we're in the process of prioritizing those, but very much look forward to expanding both the depth and the breadth of the eganelisib clinical footprint.

Your next question is from Nick Abbott with Wells Fargo.

Congratulations on a terrific quarter and on some great hires. So I guess the first one for me and that is, do you expect to have finalized your BC registration trial designed with regulators sign-off by the January 5 update? And are you planning on running this in both North America and Europe?

So thanks, Nick. Let me give you a rough sense of the cadence. So we decided it was very important to look at our overall survival data in bladder cancer to refine our thinking about the registration trial. And as you know, we got the first look at that at the end of July. And we've now had the opportunity.

We're really pleased with the OS data. We're also really pleased that it has matured and looked really nicely in the PD-L1 positive patients as well. So we said the very end of the summer and the early fall holding some ad boards. We were delighted to get input from really the world's thought leaders in bladder cancer, who have been really helpful about the best path forward.

And so based on this new data, we've revised and enhanced our thinking about the most attractive potential registrational trial. And so now we will go back. We've had interactions with the FDA before this new data. And the FDA was very helpful, very supportive. And so we're really looking forward to going back.

As you know, the interactions are an iterative process. So we will be requesting feedback on some of our revised and we believe enhanced thinking. And I would suspect that given the processing lead times for that feed that we're unlikely to have it completely finalized by January 5, but we'll be able to provide an update on where we are.

Okay. And do you intend to run that trial in North America and Europe or just North America?

Both. As you know, MARIO-275, we conducted a lot -- much of the MARIO-275 enrollment was in Europe and Eastern Europe. And the trial enrolled really well. And so we expect to go back. And we hope -- and our sites were terrific. So we hope to use many of the same sites and investigators who are really enthusiastic about the combination regimen.

And then just in terms of the, I guess, regulatory strategy here, Adelene. I guess we're used to thinking of breakthrough therapy designation request for small trials with ORR endpoint, DoR. But here, you have something like overall survival. So how do you balance that, let's look for breakthrough therapy designation for a quick approval versus okay, let's do kind of a Rolls-Royce trial here with overall survival, potentially with earlier approval on PFS but designed to support full approval?

Right. So Nick, and I'll ask Rob if he wants to add anything. I can't really get into the specifics because we're still working on the trial design. The one thing I can say is that, unfortunately, that in the settings we're studying, the -- in particular, bladder cancer, the overall survivals are not terribly long such that it's not like certain settings where you'd have to wait years and years for an overall survival endpoint.

Now granted, we did have a very nice 15-month overall survival. But the control arm was in the 8-month range, which has been seen historically. So there's not a huge delay and difference between PFS and OS, but that's all going to be part of our deliberations on the trial design and our FDA discussions.

Okay.

I think the -- sorry to interrupt. I was just going to say one other thing. I think from the ODAC meeting earlier this year, it's very clear we do need to win on overall survival. So I think we're still focusing on that, but that doesn't mean you can't use an end point like PFS for a potential accelerated approval.

Yes. And then maybe last one for me, and that is so MARIO-3 actually has a renal cell carcinoma cohort. And I think you've guided to date to 1H '21. Can you just give us an update on that? And perhaps what the key hurdle is for that trial?

Sure. Again, I'll start, and Rob, you can pick up. So just to remind everyone, our renal cell cohort is adding eganelisib to Tecentriq and Avastin. And our primary purpose there, there's a very strong mechanistic rationale to combine eganelisib with a VEGF inhibitor. And so we're really looking for a proof of concept out of that study.

And we should -- we haven't updated our guidance, which we'll do in early January, but it's probably midyear when we'll have some data from the study. And if it looks positive, then we'll have to map out what's the next step.

As you look at the current regimens that have had the greatest activity in renal cell, there are other VEGFs that are approved and are doing very well. So we may then decide what would be the best checkpoint inhibitor and the best VEGF inhibitor to combine with in taking that regimen forward.

Great. Congratulations again on terrific progress.

Thanks, Nick.

Your next question is from Mike King with H.C. Wainwright.

Just a couple of quick ones. I was also sort of thinking about same lines as Ted and Kevin DeGeeter about enhancing the value of the eganelisib franchise as far as the value to the industry, in other words, physicians, patients and of course, your larger brethren. And are ISTs sufficient to get you where you need to go as far as generalizing eganelisib's effects? Or do you think more corporate-sponsored formal IND and randomized studies are more appropriate?

Yes. Thanks, Mike. And Rob knows more about this than anyone. Of course, they are -- they serve slightly different purposes. So a company-sponsored study is going to be more directed to a registration endpoint, and an IST is going to be more exploratory. But Rob, why don't you take that?

Well, I think it's -- I mean, you bring up a really good point. I mean, I think any clinical development strategy needs to be kind of a mixture of a company sponsored and IITs, and you would like that strategy to be holistic. I mean that's something we're taking a deep look into now because now that we've seen this positive signal in UC and now in TNBC, the big question is, why wouldn't it work in other tumors?

The theme is often very similar so I think this is something we're going to have to think seriously about. Like how do we do that? We want an integrated strategies, so we can leverage both internal resources and external resources.

(inaudible) on our strategy, would be registration and randomized Phase II and IST strategy to be kind of all of the above is the answer.

Okay. Yes, because I mean, the randomized format served you quite well. The other question is there was a company recently that got -- had to withdraw and other PD-1 space. But they had withdrawn or they chose to withdraw their NDA on their PD-1 antibody because of conversion of an accelerated approval to a full approval for KEYTRUDA.

And I'm just wondering -- I mean, we should know these things, but there are so many different trials going on. I just want to be certain that there isn't something out there that's lurking that you may know of where an accelerated approval has been granted. I know that Roche has withdrawn to Century. But are there -- anything else brewing either in triple-negative breast cancer or UC that we ought to be mindful of as kind of a land mine?

So thanks, Mike. Well, obviously, we're looking at what all -- what is happening in the development. As we think about future trial designs, we would -- that would be an issue if you were using a drug in your combination or in your control arm that was receiving -- that was -- that had an accelerated approval that might be withdrawn or if there was something that might be approved that would disrupt the standard of care that you're comparing with. The likely strategies we have, we would be comparing eganelisib to a drug that has a full approval, so that it would not be likely to influence us.

Your next question is from Kalpit Patel with B. Riley.

First, the update for TNBC, should we expect any PFS or Kaplan-Meier curves in that update? Or is it too early for this type of analysis?

So thanks, Kalpit. We will -- for the 43 patients who were enrolled this summer, we will certainly be looking at all will have the opportunity to be on study for another 3 or 4 months. And so we'll be looking at the updated progression-free survival for those patients. It will be PFS. We will not be having OS data at this review.

Okay. And then in the July update, you showed paired tumor biopsy data, where a few patients converted from PD-L1 negative to PD-L1 positive status. Just curious, historically, are there precedents of observing this effect with just chemotherapy alone or even in combination with a checkpoint as a doublet in TNBC? And then can you remind us if you have conducted similar biopsies in the bladder cancer site?

So I'll answer the last part of the question, and then Rob can add first. In the bladder cancer, we did blood biopsies, and we shared a really nice translational analysis of the gene set enrichment. And we did the tumor biopsies in the TNBC. And so Rob?

I think whenever -- of course, in MARIO-3, we had a triplet. And so we didn't have a doublet in that exact same study. There have been reports that chemotherapy or even a PD-1 inhibitor may modulate PD-L1 expression.

I think what's unusual about our data is 5 of 8 of negatives converted positives, and all 3 positives got higher. That's pretty unusual. So we don't think this is just a carrier of whatever a PD-1 would do, for example, or chemo. We think this is probably much more significant. But again, we don't have the control admittedly, but I think seeing movement in that many patients is very impressive.

Your next question is from Soumit Roy with Jones Research.

Congratulations on the progress. Trying to remember if you guys have ever shown the spaghetti plot for the MARIO -- for the TNBC trial. And curious if you are seeing like immuno-oncology agent type response? What's the time to first response? And if it's deepening over time? Or have you seen any -- the PD-L1 negative versus positive patients reacting differently? Any color would be appreciated.

So Rob can maybe go deeper. We have seen patients whose responses have deepened over time, but is there anything...

I think our data is very consistent with a lot of the I/O agents. Originally, the responses were thought to be very slow in I/O. And then as we got more and more experience, they seem to be very similar to chemotherapy sometimes.

And so I think if you just look at our ORR, it's very consistent with a pretty prompt resist, but it is true. We have seen some deepening responses over time. In a patient population of 50 to 60 patients, I think it's hard to make definitive statements about how common all that is. But I mean, we've definitely seen some very interesting deepening responses over time.

Got it. Just curious if we should be thinking with a more mature data, if we could see some of the stable disease patients could turn as responders. And one last question is...

Can I just elaborate on that, too? Because as we presented in July, we were really pleased to see that patients with stable disease have had very long intervals of progression-free survival. And we saw the same thing in our bladder study, where stable disease -- the patients with stable disease had very long overall survival and more so on the combination arm than the treatment arm.

So it's very reflective of the mechanism of action of eganelisib, where in remodeling the tumor microenvironment, stable disease may be adequate to be driving this long-term benefit. So we're a little bit less focused on response rate. We're much more -- and it's not as meaningful for patients. So we're much more focused on PFS and OS than on response rate.

Got it. And one last question is, are you thinking about some kind of biz dev or out-licensing activity for maybe Asian market, something outside North America or Europe?

So we always think about the sort of strategic and tactical opportunities. And we've looked at sort of (inaudible) the best things where Asia would -- rights wouldn't necessarily negatively impact a more strategic kind of global vibration.

But right now, we've really felt that the best value, I think you've alluded to this, is that we can create so much more value by expanding the breadth and depth of the clinical signal. As you may recall, in our last major strategic collaboration, we waited until we were into a global registration study before we signed a collaboration with that time it was AbbVie for a [$25 million] upfront and $130 million milestones to do a very broad collaboration. So we think right now, especially with the recent addition of Stéphane and Rob, it's really a time for us to focus on execution because we've got a lot of single [track follow].

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

Thank you, and thank you, everyone, for joining us today. We're incredibly enthusiastic about the data we presented this past quarter, which includes OS data, NUC and early PFS data in TNBC, which together point to the potential of eganelisib to provide durable clinical benefit for patients independent of PD-L1 status.

These data are compelling, demonstrating that the addition of eganelisib to standard-of-care regimens has the potential to improve clinical outcomes and provide meaningful benefit to patients across a broad range of treatment settings and indications even in patients considered least likely to respond to checkpoint inhibitor regimen.

I'd particularly like to thank the Infinity team, which has grown with our new CSO, CMO and Board appointment as well as all of our investigators, trial sites and most importantly, our patients and their families, who have all played integral roles in advancing our work to bring better treatments to patients supported by the great team here at Infinity. We look forward to providing updates in the coming months, and thank you all for your continued support. Have a nice night.