Infinity Pharmaceuticals, Inc.

Q3 2021 Earnings Conference Call

11/2/2021

spk01: 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. At this time, all participant lines are in a listen-only mode. There will be a question and answer session at the end to follow. 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, Jane Kaufman. Please go ahead.
spk06: Jane Kaufman 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 Adeline Perkins, Chief Executive Officer, Larry Block, President, Robert Ilaria, Chief Medical Officer, and Stephon Caluso, 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 INFE.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 factor section of our annual report on Form 10-K for 2020 and in other filings we make with the FCC. 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 Adeline.
spk05: Thanks, Jane. And thank you to everyone for joining us today. This is a very important time at Infinidate as we focus on three 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 the Ganylysin 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 aganalysib to advancing a registration-focused study. Third, our validation of aganalysib's unique mechanism of action in reprogramming macrophages substantiates aganalysib's potential beyond TNBC and urothelial cancer. Aganalysib 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 aganalysib to improve 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 three 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 aganalysib 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 is these are likely to be the primary endpoints for potential registration trials. We are actively engaged with key opinion leaders and regulatory authorities in 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 GAN-ELICIB in UC on January 5th 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 aganalysin versus the control arm without aganalysin. 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 aganalysip's potential beyond TNDC and UC. Over the past 12 months, we have shown very encouraging clinical and translational data on aganalysip activity relative to reference benchmarks across five different tumor types, three different combination regimens, and in multiple lines of therapy, all of which demonstrate aganalysip'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 aganalysib to drive the next generation of immuno-oncology therapies. This is particularly true given that aganalysib 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 aganalysib. There is no alternative PI3 kinase gamma inhibitor in the clinic, so as our clinical data mature favorably, the scarcity value of aganalysib increases dramatically, as does the attractiveness of our strategic options. Hence, our highest priority is to advance the three value drivers outlined above. by continuing to generate strong clinical and translational data, advance registration-enabling studies, and leverage the fundamental biologic mechanism of EGAN-ELICIT in remodeling the tumor microenvironment to improve patient outcomes across additional settings. 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. Stephan 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 Eganilisib. We could not be more pleased that Brian is continuing to contribute to INFINITY and Eganilisib from his new position on our board. We are thrilled that Dr. Robert Aloria has joined INFINITY as our chief medical officer to lead the future clinical development of Eganilisib. Rob brings an ideal background to INFINITY given his deep expertise in drug development in immuno-oncology. He joins us from BMS and Cellgene, where he led BMS's CTLA-4 program and Celgene's PD-1 inhibitor program in collaboration with BiGene. Rob's strong track record in drug development from preclinical through approval during his tenure 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 Eganilisib, 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?
spk09: Thanks, Adeline. 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 GANALYSIB, 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 a GANALYSIB's data across multiple indications and treatment settings, including PD-L1 negative subgroups, providing solid evidence that aganalysib 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 aganalysib to this exciting point in its development. Among my highest priorities since joining INFINITY is to develop a strategy for registration-enabling studies in urethral cancer and TNBC. The MARIO275 overall survival data are truly compelling, particularly given these results we're seeing 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, MARIO275 is our randomized double-blind placebo-controlled study that enrolled 49 second-line urothelial cancer patients, randomized two-to-one, to either aganalysib plus nivolumab, which is marketed as uptivo, or standard of care nivolumab plus placebo. Our strategic objective was to increase the effectiveness of second-line treatments 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 aganalysib and nivolumab compared to 7.9 months on the nivolumab control arm. The importance of overall survival was recently underscored in April ODAC meetings 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 BFS benefit translated into OS benefit with MARIO275, including PD-L1-negative patients. I would now like to give you a brief update on our MARIO3 study in advanced metastatic triple-negative breast cancer. The strategic objective was to characterize the safety and efficacy of the addition of aganalysum to atezolizumab, which is marketed as decentric, and nabpaclitaxel, marketed as Zabraxane, in metastatic TMBC. As you may be aware, Roche withdrew the U.S. Accelerate approval for tesolizumab in first-line PD-L1-positive metastatic TMBC patients during Q3 of this year. The withdrawal was required in accordance with the requirements of the Accelerate approval program after Roche's confirmatory study, using a different chemotherapy, failed to meet its primary endpoint. Notwithstanding the withdrawal, published data from the IMPASSION 130 study demonstrated that atezolizumab and nabpaclitaxel is an active treatment regimen, and this combination is still approved for first-line metastatic TMBC patients in over 70 countries outside of the U.S. Roche has been very clear in communicating its commitment to continue studying atezolizumab in TMBC and in continuing to supply atezolizumab for our ongoing MARIO3 study. The eligibility criteria for MARIO3 were designed to mirror the IMPASSION 130 study to facilitate historical benchmarking, and patients were enrolled in either a PD-L1 negative or a PD-L1 positive cohort. It's important to note that recent approvals of immune checkpoint inhibitors in combination with chemotherapy in first-line metastatic TMBC have been limited just to PD-L1 positive patients. There are no immune checkpoint inhibitor regimens approved for metastatic PD-L1 negative TMBC patients who represent the majority of TMBC patients and therefore a very significant unmet medical need. The data we presented at San Antonio Breast Cancer Symposium in 2020 provided 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 the valuable 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 observed in impassioned 130. In the patients with PD-L1 negative tumors, we reported a median PFS of 7.3 months versus 5.6 months observed on impassioned 130. Together, these results suggest that the addition of aganalysib to immune checkpoint inhibitor and chemotherapy has the potential to improve PFS for both PD-L1 positive and PD-L1 negative patients. For TMBC, the maturing MARIO3 data will be our north star in outlining our best registration path for aganalysis. 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 urethial and TMBC clinical programs to build a very strong foundation of translational data that support aganalysis fundamental mechanism of action of macrophage reprogramming. In our July KOL event update, we presented the results of a gene expression analysis from MARIO275 that showed clearly enhanced immune activation in the aganalysive nivolumab combination compared to the nivolumab control arm. From MARIO3, 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, an 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 is to determine the optimal path forward in bladder cancer and TNBC, The strong data we've generated with aganalysib in combination with both PD-L1 and PD-1 inhibitors and in checkpoint inhibitor-free regimen supports broader investigation of aganalysib across additional tumor types, including tumors for which immune checkpoint inhibitor-based treatments 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 Eganilisib in UC with our January 5th guidance for 2022. And with that, I'll turn the call over to Larry to review the third quarter financials. Larry?
spk04: Thank you, Rob. Even before our upcoming San Antonio Breast Cancer Symposium presentation later this quarter, 2021 has already been a foundational year for Eganilisib and Infinity. As we prepare for Gantt-Olesen's initial potential registration-enabling study, as well as prioritizing opportunities with the largest potential benefit for patients through additional clinical studies with the Gantt-Olesen. As Eileen outlined, we've strengthened our executive team with the return of Stefan to Infinity as chief scientific officer, in addition of 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 Gantt Alyssa. So, at September 30th, 2021, InfinityEd total cash, cash equivalents, and available for sale security is $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 the same period in 2020, and this increase was primarily related to an increase in development expenses and compensation-related expenses. General 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. And 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. If in these 2021 financial guidance remains unchanged, and we expect net loss for 2021 to range from $40 to $50 million, and to end 2021 with the year-end cash, cash equivalents, and available for sale securities balance ranging from $70 to $80 million. So we're very much looking forward to sharing our updated Marriott 3 data in first line metastatic triple negative breast cancer on December 10th in person at the San Antonio Breast Cancer Symposium. We're really pleased to have Dr. Hatem Salomon, 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 Marriott 3, presenting our data at the San Antonio Breast Cancer Symposium, where Dr. Sullivan 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, again, listed 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?
spk01: To ask an audio question, press star 1 on your telephone keypad. Again, that is star 1 to ask a question. And we'll pause for a moment to compile the roster. Your first question is from Anupam Rama from JP Morgan.
spk11: Hi, guys. Thanks so much for taking the question. Just a quick logistical question from me. I think the prior guidance was that enrollment would complete in 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? Thanks so much.
spk05: Yeah, 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 three or four 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.
spk11: Got it. Thanks so much for taking our question. Sure.
spk01: Your next question is from Kevin DeGieter with Oppenheimer.
spk02: Hey, Greg. Thanks for taking my questions. There's been some pretty well-publicized shortages of Abraxas, and I'm just curious if in this data that we'll get an update on San Antonio, your patients, for whatever reason, may have missed How is that sort of treated from a protocol and statistical perspective?
spk05: 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 trials a priority. But, Rob, you can take that.
spk09: Yeah, there is a nationwide shortage, as you mentioned, of Abraxane. However, we are supplying the drug. And, you know, so far our supplies have been fine. You know, 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've missed any doses because of not having the Abraxane.
spk04: 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.
spk02: No, great. That was super helpful. And then just in terms of the opportunities to, you know, learn more about, you know, outside of TMDC and UC, you know, should we think about, you know, investigator-sponsored studies is one avenue, you know, you may explore in 2020 or what really is the right, you know, structure to, you know, better characterize, you know, the activity that, you know, the drug more broadly while you do move forward with your registration strategies for UC and TMC.
spk05: Thanks, Kevin. We're all delighted that you asked that question because as we mentioned in our remarks, we really, you know, 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.
spk02: Great. Thanks for taking my questions. I'll get back to you.
spk01: Your next question is from Ted Tindhoff with Piper Sandler.
spk07: Great. Thank you very much. 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 other trials that you're envisioning? Thanks.
spk05: Yeah, 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 the majority of patients with both TMBC 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 TMBC patients who are PD-L1 negative. 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.
spk09: Yeah, I think those are great points. 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 negatives and a cohort of positives. Of course, the patients that are negatives do not so well, so we find out earlier how they're doing or not doing, the positives do a bit better with standard care and, you know, adding again illicit, we'll have to see how that matures. But this is something we're being very mindful of and, again, we're really looking, you know, excited to see what these maturing data show.
spk05: 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 primetime, 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 suppressive microenvironment and a very strong scientific rationale for the use of Eganilisib in other combinations. And our chief scientific officer, Stefan Peluso, is working with the team to really prioritize what are the scientific rationales that make the most sense.
spk04: Great.
spk07: That makes sense. Yeah, go ahead, Larry.
spk04: Sorry. there's very few validated unpartnered macrophage targeting therapeutics. And so there really is a sort of a scarcity effect. And so we're, we are getting both from a corporate side and a, you know, investigator sponsored studies that a lot of the 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 again, less of a clinical footprint.
spk07: Great. Very helpful. Looking for the data in December and, um, Also, hearing more about the plans for other indications, thanks.
spk05: Thanks, Ted.
spk01: Your next question is from Nick Abbott with Wells Fargo.
spk12: Oh, good afternoon, and congratulations on a terrific quarter and, you know, on some great hires. So I guess the first one from me, and that is, do you expect to have a finalized UBC registration trial designed with regulator sign-off by the January 5th update, and are you planning on running this in both North America and Europe?
spk05: 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 had matured and looked really nicely in the PD-L1 positive patients as well. So we spent 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 paths forward. 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. 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 feedback, we're unlikely to have it completely finalized by January 5th, but we'll be able to provide an update on where we are.
spk12: Okay. And do you intend to run that trial in North America and Europe or just North America?
spk05: 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.
spk12: And then just in terms of the, I guess, regulatory strategy here, Adeline, I guess, you know, we're used to thinking of breakthrough therapy designation requests for small trials with a you know, OOR, endpoint, DOR. But here you have something like overall survival. So how do you balance that? Let's look for breakthrough therapy designation for, you know, a quick approval versus, okay, let's do kind of a, you know, Rolls Royce trial here with overall survival, potentially with, you know, earlier approval on PFS, but designed to support full approval.
spk05: 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 that unfortunately that in the settings we're studying, in particular bladder cancer, the overall survivals are not terribly long such that it's not like, you know, 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 eight-month range, which has been seen historically. So there's not a huge delay in difference between PFS and OS, but that's all going to be part of our deliberations on the trial design and our FDA discussions.
spk09: Okay. Yeah, and I think the Oh, yeah, sorry to interrupt. I was just going to say one other thing. I mean, I think from the ODAC meetings 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 endpoint like PFS for a potential accelerated approval.
spk12: Yeah. And then maybe a last one for me, and that is, so Mario3 actually has a renal cell carcinoma cohort. And I think you've guided to data 1H21. Can you just give us an update on that and, you know, perhaps what the key hurdle is for that trial?
spk05: Sure. Again, I'll start, and Rob, you can pick up. So just to remind everyone, our renal cell cohort is adding, again, elicit, centric, and Avastin. And our primary purpose there, there's a very strong mechanistic rationale to combine, again, elicit with a VEGF inhibitor. we're really looking for a proof of concept out of that study. And we haven't updated our guidance, which we'll do in early January, but it's probably mid-year 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.
spk12: Great. Thanks, Adelina, and congratulations again on terrific progress.
spk01: Thanks, Nick. Your next question is from Mike King with HC Railways.
spk03: Good afternoon, guys. Thanks for taking the question, and I'm glad I booked my SABCS reservation early. Just a couple of quick ones. I was also thinking about the same lines as Ted and Kevin DeGieter about enhancing the value of the Yann Elissib franchise as far as the value to the industry, in other words, physicians, patients, and, of course, your larger brethren. And are ISPs sufficient to get you where you need to go as far as generalizing Ganalysib's effects? Or do you think more corporate-sponsored formal IND and randomized studies are more appropriate?
spk05: Yeah, thanks, Mike. And Rob knows more about this than anyone. Of course, they serve slightly different purposes. So, you know, 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?
spk09: Well, you know, I think you bring up a really good point. I mean, I think any clinical development strategy needs to be, you know, 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 a deep look into now because now that we've seen this positive signal in UC and now in T and BC, the big question is why wouldn't it work in other tumors? You know, the T and E 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 strategy so we can leverage both internal resources and external resources.
spk04: It would definitely be an and, not an or strategy. You know, it would be a registration and, you know, randomized phase two and IST strategy. be kind of all of the above in the answer.
spk03: Okay, yeah, because I mean the randomized format, you know, served you quite well. The other question is, you know, there's a company recently that got, had to withdraw another PD-1 space, but they had to withdraw or they chose to withdraw their NDA on their PD-1 antibody because of a conversion of an accelerated to a full approval for Keytruda. And I mean, we should know these things, but there's 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 Sentry, but is there anything else brewing either in trouble-negative breast cancer or UC that we ought to be mindful of as kind of a landmine?
spk05: So, thanks, Mike. You know, obviously, we're looking at what all, you know, 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, again, Elissib to a drug that has a full approval so that it would not be likely to influence us.
spk03: Okay. Thanks for taking the questions.
spk01: Thanks, Mike. Your next question is from Kalpit Patel with B. Reilly.
spk10: Yes, hi, good afternoon, and thanks for taking the questions. First, the update for TNBC, should we expect any PFS or OS Kaplan-Meier curves in that update, or is it too early for this type of analysis?
spk05: So, thanks, Kaplan. We will, for the 43 patients who were enrolled this summer, we will certainly be looking at All will have had the opportunity to be on study for another three or four 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.
spk10: 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?
spk05: So I'll answer the last part of the question and then Rob can answer 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, you can.
spk09: You know, I think whenever, you know, of course, in Mario 3, we had a triplet, you know, 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 five of eight of negatives converted positives, and all three 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 a 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.
spk10: Okay, great. Thank you.
spk01: Your next question is from Sal Midroy with Jones Research.
spk08: Hi, everyone. Thank you for taking the question, and congratulations on all the progress. I'm trying to remember if you guys have ever shown the spaghetti plot for the TNBC trial, and curious if you are seeing, like, Immuno-oncology agent type response, you know, 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.
spk05: So Rob can maybe go deeper. We have seen patients whose responses have deepened over time, but is there anything more?
spk09: You know, I think our data is very consistent with a lot of the IO agents. You know, originally, the responses were thought to be very slow in IO, and then as we got more and more experience, they seem to be very similar to chemotherapy sometimes. And so, you know, I think if you just look at our ORR, it's very consistent with a pretty prompt recess, but it is true. We have seen some deepening responses over time. You know, in a patient population of 50 to 60 patients, I think it's hard to make, you know, definitive statements about... how common all that is, but I mean, we've definitely seen some very interesting deepening responses over time.
spk08: Okay, just curious if we should be thinking with the more mature data, if we could see some of the stable disease patients could turn as responders.
spk05: 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 patients with stable disease had very long overall survival and more so on the combination arm than the treatment arm. it's very reflective of the mechanism of action of, again, ELISA, 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.
spk08: 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 Northern America or Europe.
spk04: So we always think about the sort of strategic and tactical opportunities. And, you know, we've looked at, you know, sort of sleeves off the vest things where Asian would, you know, rights wouldn't necessarily negatively impact, you know, a more strategic kind of global vibration. But right now we've really felt that the, The best value, and 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. And as you may recall, in our last major treaty collaboration, we waited until we were, you know, into a global registration study before we signed a collaboration with, at that time it was AbbVie, for like $235 million up front and $130 million milestones to do a very broad collaboration. So we think right now, especially with the recent addition of Stephan and Rob, it's really a time for us to focus on execution because we've got a lot of signals to track and follow.
spk08: Perfect. Thank you so much for taking the questions, and I'm looking forward to sending them to you, Dita.
spk05: Great. Thank you.
spk01: Thank you. At this time, I'm showing no further questions. I'd like to turn the call back over to Adeline for closing remarks.
spk05: 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 in UC and early PFS data in TNBC, which together point to the potential of aganalysib to provide durable clinical benefits for patients independent of PD-L1 status. These data are compelling, demonstrating that the addition of aganalysib to standard of care regimens has the potential to improve clinical outcome 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 regimens. 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've 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.
Disclaimer

This conference call transcript was computer generated and almost certianly contains errors. This transcript is provided for information purposes only.EarningsCall, LLC makes no representation about the accuracy of the aforementioned transcript, and you are cautioned not to place undue reliance on the information provided by the transcript.

-

-