U.S. Markets close in 3 hrs 23 mins

Edited Transcript of INFI.OQ earnings conference call or presentation 11-May-20 8:30pm GMT

Q1 2020 Infinity Pharmaceuticals Inc Earnings Call

Cambridge Jul 8, 2020 (Thomson StreetEvents) -- Edited Transcript of Infinity Pharmaceuticals Inc earnings conference call or presentation Monday, May 11, 2020 at 8:30:00pm GMT

TEXT version of Transcript

================================================================================

Corporate Participants

================================================================================

* Adelene Q. Perkins

Infinity Pharmaceuticals, Inc. - Chairman & CEO

* Jayne Kauffman

Infinity Pharmaceuticals, Inc. - Senior Executive Coordinator

* Lawrence E. Bloch

Infinity Pharmaceuticals, Inc. - President

================================================================================

Conference Call Participants

================================================================================

* Anupam Rama

JP Morgan Chase & Co, Research Division - VP and Analyst

* James William Birchenough

Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst

* Kevin Michael DeGeeter

Oppenheimer & Co. Inc., Research Division - MD & Senior Analyst

* Nicholas M. Abbott

Wells Fargo Securities, LLC, Research Division - Director & Associate Analyst

* Soumit Roy

JonesTrading Institutional Services, LLC, Research Division - VP & Healthcare Analyst

* Wayne Wu

B. Riley FBR, Inc., Research Division - Equity Research Associate

================================================================================

Presentation

--------------------------------------------------------------------------------

Operator [1]

--------------------------------------------------------------------------------

Ladies and gentlemen, thank you for standing by, and welcome to the Infinity Pharmaceuticals conference call to discuss company's operations and financial results for the first quarter 2020.

My name is Elaine, 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.

--------------------------------------------------------------------------------

Jayne Kauffman, Infinity Pharmaceuticals, Inc. - Senior Executive Coordinator [2]

--------------------------------------------------------------------------------

Thank you, Elaine, and good afternoon, everyone. Welcome to today's call to discuss our recent business progress and review our first quarter 2020 financial results. On the call with me today are Adelene Perkins, Chief Executive Officer; and Larry Bloch, President. We'll open up the call for Q&A following our remarks.

The press release issued this morning 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-Q for the first quarter of 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 would like to turn the call over to Adelene.

--------------------------------------------------------------------------------

Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [3]

--------------------------------------------------------------------------------

Thanks, Jayne, and thank you to everyone for joining us today. I'd like to start off today's call by recognizing the unprecedented circumstances we are facing at Infinity and throughout the entire life-sciences community with the ongoing COVID-19 pandemic. While COVID-19 has created new challenges that we are facing together as a community, it has also highlighted the dedication, commitment and innovation that is allowing the continued advancement of desperately needed treatment for patients.

We remain committed to our clinical approach, which is designed to demonstrate the potential benefit of IPI-549 treatment for the patients in our trials, who have some of the most challenging cancers with poor prognoses. It is imperative that they have continued access to treatment and that the development of promising new therapies continues. I'm particularly proud of our team at Infinity, along with our collaborators and investigators, for continuing to prioritize the safety of our patients and team while still enabling our progress in the clinics to continue.

As a reminder, our clinical program for IPI-549 has multiple ongoing trials, including: MARIO-275, our randomized, controlled Phase II study in collaboration with BMS, evaluating IPI-549 in combination with Opdivo in patients with advanced urothelial or bladder cancer; MARIO-3, our Phase II study in collaboration with Roche/Genentech, to evaluate the combination of IPI-549 with Tecentriq and Abraxane as a front-line treatment in patients with triple-negative breast cancer, or TNBC, and in combination with Tecentriq and Avastin as a front-line treatment for patients with renal cell cancer, or RCC. We also have MARIO-1, our Phase I/Ib study in collaboration with Bristol-Myers Squibb, evaluating IPI-549 in combination with Opdivo in patients with advanced solid tumors.

In addition to these Infinity-sponsored trials, our collaborator, Arcus Biosciences, is running a Phase I study, evaluating IPI-549 in a novel checkpoint-inhibitor-free regimen that includes their dual adenosine receptor inhibitor, AB928, and Doxil in patients with relapsed/refractory triple-negative breast cancer.

I would now like to review the current status and updates of our studies. For MARIO-275, we were pleased to announce the U.S. FDA granted Fast Track Designation for IPI-549 in combination with the checkpoint inhibitor, Opdivo, for the treatment of patients with advanced urothelial cancer. Fast Track Designation is an important acknowledgment of both the unmet need for these patients and the potential of this regimen to improve patient outcomes.

As you may recall, MARIO-275 is our controlled, randomized Phase II study, evaluating IPI-549 in combination with Opdivo in platinum-refractory, immuno-oncology-naïve patients with advanced urothelial cancer in collaboration with BMS. The objective of this controlled study is to evaluate the potential benefit of adding IPI-549 to Opdivo monotherapy, building on the exploratory biomarker data from the BMS CheckMate-275 study, demonstrating an association between high levels of myeloid -- high baseline levels of myeloid-derived suppressor cells, or MDSCs, and lower median overall survival; as well as Infinity's MARIO-1 study showing that treatment with IPI-549 reduced MDSC levels in the majority of patients treated. These data suggest that IPI-549 has the potential to further improve outcomes beyond what we've seen with Opdivo monotherapy for this patient population.

In today's press release, we shared that we recently held the first scheduled MARIO-275 independent data monitoring committee, or IDMC, meeting to review the safety data on the initial 42 patients treated in the study. In these 42 patients, liver-enzyme elevations of Grade 3 and higher were seen in 7 patients, 5 with Grade 3 and 2 with Grade 4, one of which was newly observed and has not yet been reviewed by the IDMC. The liver-enzyme elevations from the 6 patients that were reviewed by the IDMC were reversible and have resolved without sequela. Of the 17 patients that were evaluable for efficacy, objective responses have been observed both in patients with Grade 3 and above liver-enzyme elevations as well as in patients without these elevations.

Today, we received a written communication from the IDMC, which was consistent with the safety management plan we had communicated to our sites earlier in the day, which included the continued treatment of patients now on study with additional patient monitoring and a suspension of new patient enrollment. Pending the review of additional data, our objective is to identify changes to or redesign of the protocols to support resumption of new patient enrollment in the future.

In addition to the IDMC recommendations, we instituted a reduction in the dose of IPI-549 from 40 milligrams to 30 milligrams once daily with no change to the Opdivo dose. We are comfortable with the pharmacokinetics and pharmacodynamics of the 30-milligram dose because, as previously presented, there is near complete and sustained inhibition of PI3-kinase-gamma with IPI-549 monotherapy at a dose of 20 milligrams once daily and above.

The issue we are addressing regarding AST and ALT liver-enzyme elevations is in the context of the package insert and prescribing information for Opdivo, which recommends the discontinuation of Opdivo following Grade 3 liver-enzyme elevations. This is the result of the 1% to 5% occurrence of acute autoimmune hepatitis seen with Opdivo as a monotherapy and in combination with ipilimumab. It is difficult to distinguish between the liver-enzyme elevations due to Opdivo and IPI-549. So we are taking a prudent approach in pausing enrollment of new patients while we analyze the data. Our goal is to develop a protocol amendment that ensures patient safety while enabling us to evaluate the potential benefit of IPI-549 plus Opdivo in advanced bladder cancer patients.

Now transitioning to a brief update on MARIO-3, as a reminder, there are 2 cohorts in this ongoing Phase II study. One, evaluating IPI-549 in combination with Tecentriq and Abraxane as a front-line therapy in patients with triple-negative breast cancer, and another evaluating IPI-549 in combination with Tecentriq and Avastin as a front-line therapy for patients with renal-cell carcinoma. The MARIO-3 multi-cohort study of 30 RCC patients and 60 TNBC patients is being conducted in approximately 25 sites in the U.S. While some site-initiation activities have been conducted remotely, MARIO-3's site initiation has been negatively impacted by COVID-19, and we are working to initiate additional sites over the coming months.

Independent of the impact of COVID-19, the TNBC cohort is also experiencing initial enrollment and site-initiation delays, which we are working closely with our CRO and investigators to address. By working with sites and investigators to leverage early site initiation and enrollment experience, insights can be generated to inform new site initiation and patient recruitment initiatives. Though COVID-19 has limited our access to sites over the past few months and made this work more challenging, we have identified and are implementing initiatives designed to accelerate site initiation and TNBC enrollment. Despite these challenges, a number of sites have continued to enroll patients, which is taking place on a patient-by-patient basis with investigators after carefully evaluating the ability of patients to stay on treatment and follow study protocol visits and procedures.

In early April, we provided an update regarding the potential impact of COVID-19 on our clinical programs. While the situation continues to evolve, we can confirm that the pandemic is negatively impacting new patient enrollment and site initiation across our clinical programs. Patients enrolled in MARIO-275, MARIO-3 and MARIO-1 have continued treatment and study visits with limited disruption today. Infinity is working closely with trial sites to protect the health and safety of patients and trial site personnel to enable the continued treatment of patients while maintaining compliance with protocols to ensure study integrity. We have not experienced and do not anticipate any COVID-19-related disruption to drug supply for our ongoing trials.

The patients in our trials have extremely challenging-to-treat cancers, often with poor prognoses, and we are committed to trying to ensure that they can safely continue to access treatment and that we can continue the development of drugs with the potential to provide meaningful patient benefit. We anticipate being able to provide an update on our clinical programs and financial guidance by our second-quarter webcast.

Moving next to corporate updates, we were pleased to add Dr. Richard Gaynor to our Board of Directors. Richard has a well-established track record of success, including senior roles at Neon Therapeutics and Lilly Oncology. We are thrilled to have him on board and are already benefiting from his insights. We are also proud to have established a world-class clinical advisory board that we believe will provide unmatched guidance and expertise as we advance our IPI-549 clinical programs.

Before I transition the call over to Larry, I'd like to acknowledge that it is challenging for us and you as valued stakeholders, that we're not able to provide concrete guidance on when we expect to complete enrollment or have data from our trials. While I wish I could be more specific, given the evolving circumstances, we're unable to make more definitive statements on timelines at this time, but look forward to updating you as we have additional clarity.

Finally, I'd like to take a moment to acknowledge the incredible work and commitment we have seen from our team at Infinity, our investigators and our fantastic collaborators at BMS, Roche/Genentech and Arcus, particularly during these unprecedented and challenging times. By working together, we're ensuring that our progress continues and hope these efforts lead to meaningful improvements for patients in need.

And with that, I'll turn the call over to Larry.

--------------------------------------------------------------------------------

Lawrence E. Bloch, Infinity Pharmaceuticals, Inc. - President [4]

--------------------------------------------------------------------------------

Thanks, Adelene. As we discussed on our last call, in January, we completed a $20 million asset-backed financing with BVF Partners with sole recourse and potential royalty payments due on future sales of patidegib. It's a hedgehog inhibitor, pathway inhibitor, discovered by Infinity, which we licensed to PellePharm back in 2013. And this financing enabled us to provide guidance last quarter that our existing financial resources were sufficient to fund all of our ongoing clinical programs through key data readouts.

But due to the delays related to COVID-19 pandemic as well as delays that Adelene discussed, specifically, MARIO-3 as well as the MARIO-275 suspension [of] enrollment, we no longer believe our current resources will be sufficient to fund this to this milestone. We continue to project a cash runway into the second half of 2021. We do recognize that we'll need to find additional cost savings and/or seek additional capital resources to fund IPI-549 studies through these key data readouts.

Now turning to our first quarter financial results, at March 31, 2020, we had total cash, cash equivalents and available-for-sale securities of $50.3 million compared to $42.4 million at the end of last year, December 31, 2019. And during the first quarter of 2020, as I discussed, Infinity did recognize the $20 million gross proceeds from BVF -- this is net of transaction costs -- as a liability, that will be amortized using the effective interest method over the full life of the arrangement, in accordance with accounting guidance. While I recognize this as a liability for the purpose of accounting, the company is not obligated to repay the $20 million from BVF.

Turning to R&D, our research and development expenses for the first quarter 2020 was $7.3 million compared to $5.8 million for the same period in 2019. And the increase in R&D expense in 2020 compared to 2019 was primarily due to an increase in clinical and development activities for IPI-549. G&A expense was $3.3 million for the first quarter of 2020 compared to $3.4 million for the same period in 2019. And net loss for the first quarter 2020 was $10.9 million or a basic and diluted loss per common share of $0.19 compared to a net loss of $13.7 million or basic and diluted loss per common share of $0.24 for the same period in 2019.

Our financial guidance remains unchanged. So we expect 2019 net loss to range from $40 million to $50 million, and we expect to end 2020 with the cash investment balance ranging from between $15 million and $25 million. So based on our current operating plans, which exclude additional funding or business-development activities, we do anticipate our existing cash, cash equivalents and available-for-sale securities will be adequate to satisfy our needs into the second half of 2021. But Infinity's financial guidance does not include potential funding or business-development activities, including potential $5 million milestone payment from BVF based upon PellePharm's ongoing Phase III clinical trial of patidegib topical gel in Gorlin Syndrome or any milestones from, or the sale of the company's equity interest in, PellePharm itself.

To close, I only can say we really appreciate your patience as we continue to work to understand the ultimate impacts on timelines for enrollment and data readouts, and we look forward to be able to provide an update on our clinical programs and financial guidance by our Q2 webcast.

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

================================================================================

Questions and Answers

--------------------------------------------------------------------------------

Operator [1]

--------------------------------------------------------------------------------

(Operator Instructions) Anupam Rama.

--------------------------------------------------------------------------------

Anupam Rama, JP Morgan Chase & Co, Research Division - VP and Analyst [2]

--------------------------------------------------------------------------------

(technical difficulty)

enzyme elevations were reversible. So I was just wondering if you can comment on the typical time to resolution for these events. And if you have the data off the top of your head, maybe how this compares to what you might expect from Opdivo alone? And then on MARIO-3, on the enrollment and study initiation delays, I guess do you have any theories here on the non-COVID impact? And then can you give us a sense of how many of the 25 sites are experiencing these non-COVID delays?

--------------------------------------------------------------------------------

Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [3]

--------------------------------------------------------------------------------

Sure. So Anupam, you broke up a little bit at the beginning. So -- but was your first question how long it takes for the liver enzyme elevations to resolve?

--------------------------------------------------------------------------------

Anupam Rama, JP Morgan Chase & Co, Research Division - VP and Analyst [4]

--------------------------------------------------------------------------------

Yes, that's correct. Yes.

--------------------------------------------------------------------------------

Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [5]

--------------------------------------------------------------------------------

Yes. So for the 6 patients that were reviewed, they resolved very quickly. So the patients were put on a dose hold and the resolution was very rapid and, as we said, without any sequela. So we're comfortable with the speed and the reversibility. As I mentioned, we're really focused on the challenge of differentiating from the more acute autoimmune hepatitis that's in the Opdivo label. And so that's why we're doing the pause to figure out how to make sure we can safely enroll the patients going forward.

On your second question on MARIO-3, our CRO experienced challenges with site initiation for the TNBC cohort. We're working with them to address collecting data from the sites to understand whether it's strictly operational and administrative in terms of receiving the necessary approvals to initiate the sites or whether there's any other factor at play that we need to address. So we're collecting that data now.

--------------------------------------------------------------------------------

Anupam Rama, JP Morgan Chase & Co, Research Division - VP and Analyst [6]

--------------------------------------------------------------------------------

Okay. And then if I may just sneak one more in, the press release mentioned that there's one newly observed Grade 4 AE. So just wondering when that -- when the next meeting is when that will be reviewed by the data-monitoring committee?

--------------------------------------------------------------------------------

Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [7]

--------------------------------------------------------------------------------

We don't have the next meeting scheduled yet with the IDMC. And so we are looking to have discussions with the IDMC about the additional data and analysis that we'll be collecting. And so we will probably review it at that time. In general, we have planned IDMC meetings at scheduled interval. And so this one may be reviewed when we are reviewing some of the data that we'll be collecting.

--------------------------------------------------------------------------------

Operator [8]

--------------------------------------------------------------------------------

And your next question comes from the line of Kevin DeGeeter from Oppenheimer.

--------------------------------------------------------------------------------

Kevin Michael DeGeeter, Oppenheimer & Co. Inc., Research Division - MD & Senior Analyst [9]

--------------------------------------------------------------------------------

Perhaps with regard to the liver enzyme observations, could you put those in context to the Phase Ib experience? I think, I guess, even going back to SITC maybe about 2 years ago, it was an interesting post there where you looked at about 82 patients, the rates there were somewhat elevated from some of the data we've seen from nivo alone across different histologies. But my question here is, what sort of -- the order of magnitude of the increase here is notable from the Ib, but it's not a dramatic step-up. So I just want to think -- make sure I'm appreciating, is this just sort of an ALT-AST issue? Or is there sort of other aspects of the clinical presentation of some of these 7 patients that inform the decision to pause enrollment?

--------------------------------------------------------------------------------

Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [10]

--------------------------------------------------------------------------------

So Kevin, as you mentioned, we have seen Grade 3 liver-enzyme elevations in our Phase I. What we're focused on with the MARIO-275 is the frequency of these events. So we're seeing them at a higher rate than we saw them in MARIO-1. And the reason that we're pausing enrollment is, again, because of this relatively rare but important acute autoimmune hepatitis that came with Opdivo monotherapy and the fact that we can't distinguish between the 2. So we've really got to get in and dig into the PK and the PD from the patients that we've dosed to date, to better understand that so that we can assure our goal is to reduce the frequency of the Grade 3 liver enzyme elevations. And so that's our goal. And that's a combination -- what we're doing with the patients that are on study right now, we've reduced the dose. We're doing more frequent monitoring. And so our objective is to reduce the frequency with which we're seeing those Grade 3 elevations.

--------------------------------------------------------------------------------

Kevin Michael DeGeeter, Oppenheimer & Co. Inc., Research Division - MD & Senior Analyst [11]

--------------------------------------------------------------------------------

Great. No, it makes a lot of sense. And then maybe just one more for me. And that is I appreciate the update with -- on MARIO-3 for the TNBC cohort. Can you just remind us with regard to the RSC (sic) [RCC] cohort, where you are there in terms of number of open sites? And what was the prior guidance with regard to an update on that cohort?

--------------------------------------------------------------------------------

Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [12]

--------------------------------------------------------------------------------

Sure. So our prior guidance on renal cell was that we would complete -- that's a 30-patient cohort -- that we would complete enrollment by the end of this year and have preliminary data. And we are still -- the only effect to that timeline that was unchanged but for COVID-19. And so we haven't had any delays that are not related to COVID-19, and we're really working with our sites now to try to understand how quickly they're going to be able to resume site initiation and enrollment coming out of COVID-19 so that we can quantify what we have -- provide an updated guidance that we no longer expect to complete enrollment by the end of 2020. And that the completion of enrollment and the availability of data will be pushed into 2021, but we want to be able to provide more granular timelines. But we need to do more work with our sites to understand when they hope to come out of the COVID-19 slowdown.

--------------------------------------------------------------------------------

Kevin Michael DeGeeter, Oppenheimer & Co. Inc., Research Division - MD & Senior Analyst [13]

--------------------------------------------------------------------------------

That's great. And then maybe just building on the last observation is sort of my final question. And that is, when we think about burn rate for the year, directionally it would seem that the puts and takes would be towards a lower burn rate from kind of the prior baseline expectations at a more aggressive enrollment trajectory. Larry, are there any items that might not be transparent as we think about this sort of our increase in the expense side of the spectrum, perhaps related to COVID-19 directly, that we should be mindful as we think about the flexibility you may have in balance sheet management?

--------------------------------------------------------------------------------

Lawrence E. Bloch, Infinity Pharmaceuticals, Inc. - President [14]

--------------------------------------------------------------------------------

Sure, Kevin. Thanks for the question. So yes, I think in terms of the cash management and cash burn, the first quarter tends to be one of our higher quarters because you have sort of annual bonuses, prepays and -- as well as some drug purchases for the ongoing clinical trials. So it's likely that the first quarter will be one of our highest burns.

But in terms of things that might be happening on a going-forward basis, you can obviously think about mitigation efforts that, as Adelene said, we're trying to work with those [TRO] sites to understand what the enrollment dynamics are, to understand the new [sublimation] dynamics and if there's ways that we can potentially accelerate those. And of course, those could be the -- require additional funding from us in order to try to move the enrollment and new site initiation at a more accelerated pace.

--------------------------------------------------------------------------------

Operator [15]

--------------------------------------------------------------------------------

And your next question comes from the line of Jim Birchenough from Wells Fargo.

--------------------------------------------------------------------------------

Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Director & Associate Analyst [16]

--------------------------------------------------------------------------------

It's Nick on for Jim this afternoon. First question, just going back to the announcement from 275 on the liver enzyme elevations. So this is a 2:1 randomization. So approximately 28 patients then would have been in the combination arm. Can you break down for us the incidence of these Grade 3, 4 events between the combination versus the Opdivo monotherapy?

--------------------------------------------------------------------------------

Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [17]

--------------------------------------------------------------------------------

Yes, thanks, Nick. As you know, this is a blinded study and so we're not able to do a breakdown of either the AEs or of the responses, because it's really critically important that we not break the blind so that we can maintain the integrity of the study. So I'm sorry that we're not able to break the blind data.

--------------------------------------------------------------------------------

Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Director & Associate Analyst [18]

--------------------------------------------------------------------------------

Is that -- but the IDMC has.

--------------------------------------------------------------------------------

Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [19]

--------------------------------------------------------------------------------

Yes. Yes.

--------------------------------------------------------------------------------

Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Director & Associate Analyst [20]

--------------------------------------------------------------------------------

Is that correct? Yes. Okay. And then you quoted the RADAR autoimmune hepatitis for Opdivo as a monotherapy, but obviously it's higher with Yervoy, so suggesting that there's potentiation of this toxicity, since one of the hopeful mechanisms of 549 is to improve immune status. Is there a concern that you might be potentiating any signal that's from Opdivo versus something that's to do with 549 alone?

--------------------------------------------------------------------------------

Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [21]

--------------------------------------------------------------------------------

Nick, really a great question. But again, because we can't identify these adverse events and whether they're on the treatment arm or the control arm, we can't break down whether we think they're mechanistically tied to IPI-549. So I'm sorry, again, it would just require...

--------------------------------------------------------------------------------

Lawrence E. Bloch, Infinity Pharmaceuticals, Inc. - President [22]

--------------------------------------------------------------------------------

But Nick, to your point -- this is Larry -- it's an insightful question. And when we talk about evaluating the risk-benefit for patients, that's exactly what we're trying to understand in the context of a blinded study with the IDMC.

--------------------------------------------------------------------------------

Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Director & Associate Analyst [23]

--------------------------------------------------------------------------------

Okay. And then I'm interested to know if this has any impact on MARIO-3. Are you considering reducing the dose of 549 MARIO-3 since it's also a combination with a PD-1 checkpoint inhibitor?

--------------------------------------------------------------------------------

Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [24]

--------------------------------------------------------------------------------

Right. So MARIO-3, as you know, is a different combination in a different patient population. So we're really evaluating it independently, but looking very closely at both the safety and the signals of efficacy in that patient population. So we will be paying very close attention to liver-enzyme elevations, but we'll be looking at the actual data in the triple-negative and renal-cell patients.

--------------------------------------------------------------------------------

Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Director & Associate Analyst [25]

--------------------------------------------------------------------------------

Okay. And then just last one from me, and that is would you consider terminating MARIO-3 to get you through to the finish of 275 with the runway or even perhaps the -- what appears being more troublesome TNBC cohort?

--------------------------------------------------------------------------------

Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [26]

--------------------------------------------------------------------------------

We haven't made any decision -- we haven't had any discussions around how we might change our portfolio. So right now, we're really just focused on how do we continue with the trials and how do we move them forward. We haven't had any other discussions at this point yet.

--------------------------------------------------------------------------------

Operator [27]

--------------------------------------------------------------------------------

And your next question comes from the line of Soumit Roy from JonesTrading.

--------------------------------------------------------------------------------

Soumit Roy, JonesTrading Institutional Services, LLC, Research Division - VP & Healthcare Analyst [28]

--------------------------------------------------------------------------------

Could you give us a little sense of when we will get an update on the status of MARIO-275 enrollment? Is it a matter of weeks? Or this is -- we have to wait till the second-quarter earnings? Or is there a possibility we will get interim look at the data or you would wait until the entire trial reads out in 2021?

--------------------------------------------------------------------------------

Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [29]

--------------------------------------------------------------------------------

Yes, Soumit. So thanks for the question. We expect to provide the next update on the second-quarter call, which will be very end of July or beginning of August. And so in that time, we will have analyzed the data and worked on protocol amendments that would allow us to proceed, and we would -- it will provide an update on where we are in that process by the second quarter call. I don't expect that we'll be sharing any of the data from these first 42 patients that we reviewed with the IDMC. Again, because it's a blinded study I do expect that we won't have the data from the study until it's completed.

--------------------------------------------------------------------------------

Soumit Roy, JonesTrading Institutional Services, LLC, Research Division - VP & Healthcare Analyst [30]

--------------------------------------------------------------------------------

Got it. Do you look at distribution like these -- they are coming from one center? Or is there a possibility these patients have been infected by SARS-CoV-2 and causing an inflammation or it's just well distributed around from different sites?

And the last question is do -- do we know which cohort from MARIO-1 end of this year we're going to see data for?

--------------------------------------------------------------------------------

Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [31]

--------------------------------------------------------------------------------

So first, on understanding whether there's a concentration of any liver-enzyme elevations at sites, that's precisely the data that we're going to be digging in. Is it looking at each of the sites where these happened? Is there anything that will explain the elevations that we've seen? And so that's really the focus, both looking at the sites, looking at the individual patients, looking at any con meds, any previous history. So we're really going to be digging in. And that's really why we've put the new enrollment on pause until we can go in and do that digging. So those are the key questions and answers that we'll try to get going forward.

And with respect to MARIO-1, as we've said, we're conscious of -- we will absolutely be presenting the full data set at some future point. Any update that we do before the study is fully completed will be tied to any additional studies that might be suggested by the data, so that if there is data that's coming out of MARIO-1 that will inform our interest in pursuing additional trials, that's the data that we'll be prioritizing for presentation until we have the whole study completed and can present the comprehensive clinical and translational data set at some future point.

--------------------------------------------------------------------------------

Operator [32]

--------------------------------------------------------------------------------

And your last question comes from the line of Andrew D'Silva from B. Riley FBR.

--------------------------------------------------------------------------------

Wayne Wu, B. Riley FBR, Inc., Research Division - Equity Research Associate [33]

--------------------------------------------------------------------------------

This is Wayne Wu on for Andy. So just a few questions from us. To start, could you give us additional color on what we should expect in terms of amendments for the MARIO-275? And are you still going to be able to utilize the data from the patients that were enrolled thus far?

--------------------------------------------------------------------------------

Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [34]

--------------------------------------------------------------------------------

So thanks for the question. I can't provide any insight on what may be in a protocol amendment because that's really going to be informed by the analysis that we'll be doing. So we have to -- some of the key questions are around the pharmacokinetics and pharmacodynamics. And one of the reasons that we paused new enrollment is that that's data that we need to go get and analyze so that will inform our suggested protocol changes. So that will really be data-driven.

And the second part of your question is, yes, because -- and that's -- will the 42 patients be included in the analysis? Yes, they will be, which is why we're being so rigorous of ensuring the study blind and not providing any data that's unblinded, either from safety or from efficacy, with respect to where those events have occurred on either the treatment arm or the control arm. So we're taking great length to ensure that you keep the blind so that those patients will be counted towards the ultimate analysis from the study.

--------------------------------------------------------------------------------

Wayne Wu, B. Riley FBR, Inc., Research Division - Equity Research Associate [35]

--------------------------------------------------------------------------------

Okay. And as it relates to the enzyme elevations we're seeing, could you please refresh our memory and let us know what you would have expected for patients on Opdivo alone, what was initially seen in MARIO-1? And also, does the pause in [the] study change your thoughts on MARIO-275's ability to be a registrational study?

--------------------------------------------------------------------------------

Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [36]

--------------------------------------------------------------------------------

So what we've seen in MARIO-275 is a higher frequency of the Grade 3 liver-enzyme elevations than we saw in our grade -- in our Phase I study. So we've seen an increase, and that's what we're really doing the detailed detective work now to understand exactly why we're seeing greater frequency. When we finish that analysis and -- our goal is to identify protocol amendments that will enable us to continue to safely dose patients so that we can evaluate what we still hope will be a benefit for these advanced bladder cancer patients of the combination of Opdivo and 549. In finding a path to go forward and in completing the study, which is our goal, if the data suggests that there's a significant benefit, we will have discussions with the regulatory authorities about what is the best path to approval. But ultimately, our goal is to seek approval in this -- with this regimen in this patient population and that will all be a function of the data that we're able to generate.

--------------------------------------------------------------------------------

Lawrence E. Bloch, Infinity Pharmaceuticals, Inc. - President [37]

--------------------------------------------------------------------------------

Yes. I think -- this is Larry. I think one thing that's worth emphasizing is that for the LFT increases that were reviewed by the IDMC, those were reversible. As Adelene said, they resolved without sequela. But the critical issue is in the context of the Opdivo, not just the liver-enzyme elevations, but the 1% to 5% occurrence of acute autoimmune hepatitis. And so that's really the context with which we're trying to analyze this data and ensure patient safety. So it's not sort of ALT-AST elevations in the abstract, but how they may or may not result in -- with Grade 3 liver-enzyme elevations or higher in acute autoimmune hepatitis.

--------------------------------------------------------------------------------

Wayne Wu, B. Riley FBR, Inc., Research Division - Equity Research Associate [38]

--------------------------------------------------------------------------------

Okay. A couple more quick ones, if I may. Could you please give us an update on the competitive landscape, specifically as it relates to PI3K-gamma? Has there been any updates on the Arcus Bioscience, on their, like, preclinical candidate as well?

--------------------------------------------------------------------------------

Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [39]

--------------------------------------------------------------------------------

No. We -- what I can tell you is that we watch carefully if there are any other PI3-kinase-gamma specific inhibitors in clinical development, and we're not aware of any others that are in clinical development. We know that there are some that are in preclinical development, but we don't know what the status is of the move of those drug candidates into the clinic.

--------------------------------------------------------------------------------

Lawrence E. Bloch, Infinity Pharmaceuticals, Inc. - President [40]

--------------------------------------------------------------------------------

Yes, the 2 that we're aware of are AstraZeneca and, as you said, Arcus Biosciences.

--------------------------------------------------------------------------------

Wayne Wu, B. Riley FBR, Inc., Research Division - Equity Research Associate [41]

--------------------------------------------------------------------------------

Okay. So finally, as it relates to Arcus, does their work with the PI3K-gamma candidate change your thoughts on collaborating with them going forward?

--------------------------------------------------------------------------------

Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [42]

--------------------------------------------------------------------------------

No, we're very aware that they have an interest in this mechanism and that they have a preclinical program, and they've been very forthcoming. I think we both share an interest in seeing what's the clinical benefit of the combination that we're testing together with their dual-dosing antagonist and Doxil. So we both have an interest in generating that data.

--------------------------------------------------------------------------------

Operator [43]

--------------------------------------------------------------------------------

And you have a follow-up question from Jim Birchenough from Wells Fargo.

--------------------------------------------------------------------------------

James William Birchenough, Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst [44]

--------------------------------------------------------------------------------

Quite a couple of follow-ups, if I may. The first one is, does any of the patients with increased LFTs get steroid treatment for presumptive autoimmune hepatitis?

--------------------------------------------------------------------------------

Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [45]

--------------------------------------------------------------------------------

Yes, they have.

--------------------------------------------------------------------------------

James William Birchenough, Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst [46]

--------------------------------------------------------------------------------

And then going forward, they will get 30-milligram dose? Or is it only for patients who come -- who will come on to the trial will start at 30?

--------------------------------------------------------------------------------

Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [47]

--------------------------------------------------------------------------------

No. It's the patients who are currently on study, that we've sent a letter to the sites asking that those patients who had been at 40 are all reduced to 30. We have not yet prescribed what would be in a protocol amendment for new patients. So that's really going to be a function of us completing the analysis and determining what, if any, dose reduction is appropriate for an ongoing protocol amendment that's going to be really driven by the data that we'll collect. So it's premature for us to talk about what's going to be in a future protocol amendment at this time.

--------------------------------------------------------------------------------

James William Birchenough, Wells Fargo Securities, LLC, Research Division - MD and Senior Biotechnology Analyst [48]

--------------------------------------------------------------------------------

And then finally, should we expect a partial clinical hold will be placed on this trial?

--------------------------------------------------------------------------------

Lawrence E. Bloch, Infinity Pharmaceuticals, Inc. - President [49]

--------------------------------------------------------------------------------

So Nick, this is Larry. I think it's important to differentiate a regulatory determination. It is a sponsor -- IDMC -- so the IDMC makes recommendation, the sponsor Infinity either accepts or, in this case, we actually augmented their recommendation with the dose reduction. And to date, there has been no regulatory action on 549.

--------------------------------------------------------------------------------

Operator [50]

--------------------------------------------------------------------------------

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

--------------------------------------------------------------------------------

Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [51]

--------------------------------------------------------------------------------

Thank you for participating on the call this afternoon. We appreciate your interest in Infinity and IPI-549, and we're very committed to continuing our progress on the development of IPI-549 to -- with the goal of helping patients who really need better therapies. And so we look forward to updating you in the coming months, and hope you have a nice evening.

--------------------------------------------------------------------------------

Operator [52]

--------------------------------------------------------------------------------

Thank you for joining today's conference call. You may now disconnect your line.