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Edited Transcript of INFI earnings conference call or presentation 30-Oct-19 8:30pm GMT

Q3 2019 Infinity Pharmaceuticals Inc Earnings Call

Cambridge Nov 10, 2019 (Thomson StreetEvents) -- Edited Transcript of Infinity Pharmaceuticals Inc earnings conference call or presentation Wednesday, October 30, 2019 at 8:30:00pm GMT

TEXT version of Transcript

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Corporate Participants

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* Adelene Q. Perkins

Infinity Pharmaceuticals, Inc. - Chairman & CEO

* Jayne Kauffman

Infinity Pharmaceuticals, Inc. - Senior Executive Coordinator

* Jeffery L. Kutok

Infinity Pharmaceuticals, Inc. - Senior VP & Chief Scientific Officer

* Lawrence E. Bloch

Infinity Pharmaceuticals, Inc. - President

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Conference Call Participants

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* James Francis Molloy

Alliance Global Partners, Research Division - MD of Equity Research and Biotechnology & Specialty Pharmaceuticals Equity Research Analyst

* Kevin Michael DeGeeter

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

* Matthew Alexander Bannon

JP Morgan Chase & Co, Research Division - Analyst

* Nicholas M. Abbott

Wells Fargo Securities, LLC, Research Division - Associate Analyst

* Soumit Roy

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

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Presentation

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Operator [1]

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Ladies and gentlemen, thank you for standing by. Welcome to the Infinity Pharmaceuticals conference call to discuss the company's financial results for the third quarter 2019. My name is Bridget, 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.

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

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Thank you, Bridget, and good afternoon, everyone. Welcome to today's call to discuss our recent business progress and review our third quarter 2019 financial results. With me here today are Adelene Perkins, Chief Executive Officer; Larry Bloch, President; and Dr. Jeff Kutok, our Chief Scientific Officer.

We will open up the call for Q&A following our remarks. The press release issued this afternoon details our results and is now 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 third quarter of 2019, 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.

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

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Thanks, Jayne, and thank you to everyone for joining us today. I'd like to start off today's call by highlighting the important clinical progress we have made this past quarter with the initiation of 2 additional clinical studies with IPI-549. We're very pleased by our advancement of IPI-549 into new indications, combinations and earlier lines of therapy as part of a thoughtful clinical development strategy designed to reveal the potentially transformative impact of reprogramming macrophages with IPI-549.

Successful clinical trial execution has been a key priority for Infinity in 2019, and we are very pleased that progress with MARIO-1 and the initiation of 3 new trials with IPI-549 over the past few months has enabled our announcement today of important milestones expected in 2020.

First, we expect to complete enrollment of MARIO-1 by year-end 2019 and to present clinical and translational data in 2020 from this Phase I/Ib study in collaboration with Bristol-Myers Squibb, evaluating IPI-549 in combination with Opdivo in patients with advanced solid tumors.

Second, in 2020 we expect to complete enrollment in and present data from MARIO-3, our Phase II study in collaboration with Roche/Genentech. MARIO-3 is a Phase II study of IPI-549 in combination with Tecentriq and Abraxane as a frontline treatment in patients with triple-negative breast cancer and in combination with Tecentriq and Avastin as a frontline treatment for patients with renal cell cancer.

Third, in 2020 we also expect to complete enrollment in MARIO-275, our global randomized Phase II study in collaboration with Bristol-Myers Squibb, evaluating IPI-549 in combination with Opdivo in patients with advanced urothelial or bladder cancer.

In addition, we announced earlier this quarter that our partner, Arcus Biosciences initiated a Phase I collaboration 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.

These trials are representative of our commitment through data-driven approach for the clinical development of IPI-549. Our trials are informed by our clinical and translational data and learnings from MARIO-1 as well as clinical and translational data that we've been fortunate to access from our partners. We believe this rational data-driven approach has enabled the best clinical path forward to maximize potential of IPI-549.

It's a particularly exciting and important time for Infinity for 2 reasons. The first is due to our expected completion of enrollment in MARIO-1, MARIO-3 and MARIO-275 to presentation of data from MARIO-1 and MARIO-3 by the end of 2020.

The second is that in parallel with our generation of data across a wide range of indications in combination with best-in-class emerging standards of care, we are witnessing an explosion in the appreciation among the medical and scientific communities for the importance of tumor macrophage-directed immuno-oncology therapies. With meaningful data expected from IPI-549 study starting in 2020, Infinity is positioned to become a leader in the burgeoning field of macrophage-targeted immunotherapy.

We're inspired by the ability to leverage our extensive research and groundbreaking discoveries in the tumor macrophage field to bring IPI-549 forward for patients in need of better therapeutic options. At Infinity, we're deeply committed to advancing our science and clinical programs to serve patients and are very appreciative of the patients and their families for participating in our studies designed to demonstrate potential benefit of IPI-549 treatment.

With that, I'd like to turn the call over to Jeff to speak to the status of our clinical development plan in more detail.

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Jeffery L. Kutok, Infinity Pharmaceuticals, Inc. - Senior VP & Chief Scientific Officer [4]

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Thanks, Adelene. It's incredibly exciting to be reviewing our progress in now 4 trials that are evaluating IPI-549 in a wide-ranging indications and treatment regimens. To begin, I'll provide an update on MARIO-3, our most recently initiated trial. MARIO-3 is particularly exciting to us as we are moving IPI-549 to a frontline setting.

The Phase II study includes 3 cohorts of frontline patients, one 30-patient cohort in frontline triple-negative breast cancer patients with high levels of PD-L1 tumor expression, evaluating IPI-549 in combination with Tecentriq and Abraxane.

Another 30-patient cohort evaluating the same combination therapy in frontline triple-negative breast cancer patients with low levels of PD-L1 tumor expression and a third cohort of 30 patients in frontline renal cell cancer, evaluating IPI-549 in combination with Tecentriq and Avastin. Infinity is conducting this study in collaboration with Roche/Genentech.

MARIO-3 is an exciting new approach enabled by the safety profile of IPI-549. Specifically, the safety and tolerability of IPI-549 makes possible innovative triple combination therapies in both triple-negative breast cancer and renal cell cancer patients. Our goal is to evaluate how the addition of IPI-549 can improve upon the benefits of these frontline treatment regimens in patients with real unmet need.

Tecentriq and Abraxane were approved in frontline treatment of PD-L1 positive triple-negative breast cancer patients based on the IMPassion130 study. Tecentriq and Avastin were evaluated in frontline renal cell cancer patients in the IMmotion151 study.

The multi-cohort study of 90 patients is being conducted in approximately 25 sites in the U.S. The primary analysis will be the complete response rates in both cohorts of the study, which were less than 10% in the IMPassion and IMmotion studies. MARIO-3 will be evaluating the benefit of these combinations independent of MDSC and PD-L1 status. However, we will of course be carefully monitoring how these parameters impact clinical activity as the study progresses.

We look forward to presenting our initial clinical and translational findings in 2020. I'm also pleased to share that our partner, Arcus Biosciences initiated in the third quarter, the evaluation of IPI-549 in novel triple combination therapy with their dual adenosine receptor inhibitor, AB928 and Doxil in patients with relapsed/refractory triple-negative breast cancer.

This checkpoint inhibitor-free Phase I study will initially evaluate the safety of IPI-549 with AB928 in Doxil and dose escalation. This utilization of IPI-549 in another triple therapy regimen trial is further testament to its remarkable safety profile, allowing for pioneering combinations with diverse agents in wide-ranging treatment settings. We are pleased to provide guidance today that we expect to complete enrollment in 2020 of MARIO-275, our Phase II study of IPI-549 in combination with Opdivo in patients with immunotherapy-naive, platinum-refractory advanced urothelial cancer in collaboration with BMS.

MARIO-275 is a randomized trial that investigates the effect of adding IPI-549 to Opdivo in bladder cancer patients with high and low levels, data levels of MDSCs. The trial was developed based on data from a retrospective analysis of BMS's approval study, CheckMate-275, which showed bladder cancer patients with high baseline levels of MDSCs had a shorter overall survival when treated with Opdivo as a single agent. These data, combined with our MARIO-1 data that showed the combination of IPI-549 and Opdivo treatment is associated with a reduction in blood MDSC levels, support our trial design in which IPI-549 can potentially improve outcomes for these bladder cancer patients in combination with Opdivo.

MARIO-275 is a global randomized study of 160 patients being conducted in approximately 45 sites in both the U.S. and Europe. The primary objective of the study is to compare overall response rate in patients with high baseline MDSC levels, following combination treatment with IPI-549 plus Opdivo to that of Opdivo monotherapy. The study will enroll patients in either the IPI-549 plus Opdivo or Opdivo plus placebo arms in a 2:1 fashion regardless of the PD-L1 status, and will also stratify patients by MDSC status at a ratio of 2:1, high to low in both arms of the study.

Finally, we expect to complete enrollment by year-end in MARIO-1, our Phase Ib study, evaluating IPI-549 plus Opdivo and expansion cohorts of advanced solid tumor of patients with data to be presented in 2020.

MARIO-1 is focused on evaluating IPI-549 plus Opdivo in settings where patients would not be expected to respond to Opdivo monotherapy, including patients with melanoma, non-small cell lung cancer and head and neck cancer who had progressed on checkpoint inhibitor as their immediate prior therapy.

Before I transition the call over to Larry, I'd like to take a moment to acknowledge our fantastic collaborators at BMS, Roche/Genentech and Arcus.

We're fortunate to have developed impactful collaborations, allowing us to leverage data and strategic insights for the clinical development of IPI-549. We're enthusiastic about our expansion to multiple lines of therapy and novel therapeutic combinations and are grateful to our dedicated partners that help us advance our goal of providing macrophage targeted immune therapy to improve patient outcomes.

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

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Lawrence E. Bloch, Infinity Pharmaceuticals, Inc. - President [5]

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Thank you, Jeff. This year, there's been a tremendous amount of hard work to initiate multiple Phase II studies for IPI-549. And we continue to be very focused on execution to enable complete enrollment of all of our ongoing IPI-549 studies by the end of next year. Importantly, we strategically maintain worldwide rights to IPI-549, the total net sales royalty burden of only 4%, while also ensuring sufficient resources for its continued development to our clinical collaborations with Bristol-Myers Squibb, Roche/Genentech as well as Arcus Biosciences.

At September 30, 2019, we had total cash, cash equivalents and available for sale securities of $52 million compared to $63 million at June 30, 2019. R&D expense of third quarter 2019 was $7.1 million compared to $5.4 million for the same period in 2018. The increased R&D expense was primarily due to an increase in clinical and development activities for IPI-549.

General and administrative expense was $3.1 million, $3.6 million for the third quarter 2019 compared to $3.4 million for the same period in 2018.

Net loss for the third quarter of 2019 was $11.4 million or basic and diluted loss per common share of $0.20 compared to net income of $13.4 million or basic and diluted earnings per common share of $0.23 for the same period in 2018.

Our financial guidance remains unchanged. We expect 2019 net loss to range from between $40 million and $50 million, and we expect to end 2019 with a cash and investment balance ranging from between $40 million and $50 million. Based on our current operating plans, which exclude additional funding or business development activities, we anticipate that existing cash, cash equivalents and available for sale securities will be adequate to satisfy the company's capital needs for at least the next 12 months.

We really appreciate the support of our clinical investigators, patients, partners and the team of Infinity, who've enabled our progress with IPI-549 to date as well as anticipated important milestones in 2020. We're looking forward to providing updates on additional progress in upcoming conferences and our next annual 10-K call.

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

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Questions and Answers

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Operator [1]

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(Operator Instructions) Our first question comes from the line of Anupam Rama with JPMorgan.

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Matthew Alexander Bannon, JP Morgan Chase & Co, Research Division - Analyst [2]

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This is Matt on Anupam. Congrats on execution of this quarter. Just a couple from us here. So first off, you gave enrollment time line guidance for the MARIO trials. And I may have missed it, but I didn't see any time lines for the Arcus trial. So did I miss that or is it just too early to gauge patient enrollment there?

Secondly, on the MARIO-275 trial. Can you just remind us of the rationale suggesting that you may be able to see benefit in patients regardless of their MDSC status?

And then finally, how urgently are you guys looking for a new CMO? Like is it a top priority right now or has the consultants you brought in being able to get the job done?

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

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Sure, Matt. So on your first question regarding Arcus, that's a trial that's being conducted by Arcus. So it's inappropriate for us to provide guidance on that. We'll look to what Arcus provides as guidance for enrollment and so that will be driven by them.

I'll begin on MARIO-275, and then I'll turn it over to Jeff. In general as we presented to date, we have seen a reduction in MDSCs in combination of 549 and Opdivo across the vast majority of patients that we've treated with a number of different tumor sites. And that is combined with the really great retrospective analysis that CMS did on MARIO-275, what was very clear that high baseline levels of MDSCs were associated with much poor outcomes. So that's a very high level. And Jeff, I'm sure you have more to add.

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Jeffery L. Kutok, Infinity Pharmaceuticals, Inc. - Senior VP & Chief Scientific Officer [4]

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Yes. So the focus of MARIO-275 is on the MDSC high patients, and we're ensuring adequate numbers of those patients by stratifying 2:1, high to low in the study, and the primary objective will be to look at response rates in the MDSC high population in the combination compared to the monotherapy Opdivo arm. We are also looking at the MDSC low patients because while they're low relative to the patients with higher levels, they're still elevated compared to normal healthy individuals. So we don't know a priority that there won't be a significant benefit in patients with lower levels of MDSCs to the combination therapy, and we're hoping to evaluate that in the study.

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

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And then I'll finish up, Matt, on your last question about new CMO. It's not an urgent priority for us right now for several reasons. One is that our trials are now designed and have been kicked off. And so we've got a really strong clinical team at Infinity, who's now implementing those trials. And of course, we still do have Sam Agresta is on our Board and is actively involved in that process with us in addition to, as you mentioned, a strong network of external CMO collab partners, consultants that we work with. So we have what we need right now. We don't feel that there's a huge hole, but of course, as we go forward, we'll be looking to see if there's just a terrific candidate that we could come in as we begin to collect and interpret this data.

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Operator [6]

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

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Kevin Michael DeGeeter, Oppenheimer & Co. Inc., Research Division - MD & Senior Analyst [7]

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Great. I want to add my congratulations. With regard to the 2020 data update for the MARIO-3 study, should we anticipate getting updates from each of the 3 arms or at least the triple-negative breast component? Just kind of how much visibility do you have on sort of the pace of enrollment in the different cohorts?

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Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [8]

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Thanks, Kevin. It's a little premature for us to provide specific guidance on which of those 3 arms we'll be presenting on and when. As the trial advances will provide more granularity, but we can't provide that granularity at this time.

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

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Okay, great. No, fair enough. And then with regard to MARIO-275. Can you just remind us again, you kind of give us a pretty broad sketch in terms of completion enrollment in 2020, but kind of -- I realize you're not providing guidance on when you expect to be able to present some data, but sort of a similar line of questioning. Should we anticipate that we'll see data on specific cohorts, perhaps before the entire data set matures? Or is your kind of current thinking that it's best to be able to present the data when each of the arms is fully enrolled and the adequate follow-up is available?

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

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Sure. So I'll remind you that MARIO-275 is a blinded study, and so we will wait until we have unblinded the study, and it's most likely that we'll present the data on the various arms because it's the value of having a controlled study. We'll be looking at how patients fare on the Opdivo-only arm as given that Opdivo is approved as a monotherapy relative to the combination of Opdivo in 549. And I believe it will be important to look at both arms, control arm and the treatment arm as well as the patients who have -- as we've stratified high levels of baseline MDSCs in low level. So my expectation is we'll be presenting that full data set at the appropriate time.

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

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And one last question for me, more of a high-level question. As you sort of alluded to at the top of the call, there has been a pickup in development of multiple different compounds and strategies targeting and regulation of macrophages to potentially enhance the breadth of response to immunotherapy. On a high level, is your expectation that these various strategies will ultimately be competitive or is there a rationale here that certain strategies may be complementary, certain macrophage regulation may be complementary in terms of expanding response specifically to PD-1s?

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

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Sure. So it's important to highlight that we have the only PI3-kinase gamma-specific inhibitor in development. So with respect to our specific mechanism of action there is today no direct competition. There is, as you referenced, a number of other programs given the excitement about macrophage modulation but most are still in early development. We're not aware of any that have randomized Phase II data. So it's a little early to know how those will stack up relative to IPI-549 and whether there's an opportunity for potential synergy between them, but we'll be watching as those other programs mature and as they start to get into the clinic.

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Operator [13]

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Our next question comes from the line of Soumit Roy with JonesTrading.

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Soumit Roy, JonesTrading Institutional Services, LLC, Research Division - VP & Healthcare Analyst [14]

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Congratulations again on setting up all the clinical trials and it's truly an exciting time. Just want to rehash the catalyst time line. I might be repeating Kevin's question a little bit. From MARIO-1, do we -- should we expect -- or do we know which cohort's enrolling better? And should we expect a larger bladder or melanoma cohort data around maybe mid-2020 or is it going to be much later?

And then for MARIO-275, I remember there was an option that you could show us interim look? Or right now, it looks like you would wait for the entire data to mature. In that case, should we expect any data from MARIO-275 in 2020? Or it will be more 2021 event?

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Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [15]

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Sure. So on MARIO-1, we will have completed -- or we expect to and are guiding that we will have completed the enrollment in all of those cohorts by the end of 2019. And so when we look to data that we'll present in 2020, our immediate focus will be prioritizing that data that could help inform and build on the momentum of 549 development in additional trials. So we'll really focus on that. It's a little premature to focus on what exact data will be presented until we've completed the trial and conducted our analysis. But beyond the near-term focus on future development that comes out of MARIO-1, we're committed to presenting a complete MARIO-1 study findings in a peer review format when we have all of that data.

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Soumit Roy, JonesTrading Institutional Services, LLC, Research Division - VP & Healthcare Analyst [16]

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Would it be reasonable to assume mid-2020 data readout from MARIO-1 or it's -- just trying to get a sense.

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

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That's reasonable. Again, until we've completed the enrollment, and it's hard to say because we have to -- we typically present data from our clinical studies at major medical meetings, and so we'll have to look at when we have that data and when that's synched with abstract submission deadlines. So we'll provide that once we have more insight there.

And on MARIO-275, we are guiding that we will complete enrollment in 2020. And so I think your hypothesis is that we will have data in 2021 is probably right. We -- if we do have an early look, we may decide to make that a pivotal study in which case we wouldn't be able to present that data so that we'd be able to include all of that in a regulatory submission. So I think our base case plan would be enrollment completion in 2020 and most likely data in 2021, but that will be future guidance.

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Soumit Roy, JonesTrading Institutional Services, LLC, Research Division - VP & Healthcare Analyst [18]

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Got it. I have 2 quick, kind of, quick question. One is, do you have any kind of non-compete restriction with -- on Roche collaboration? Or can you go out and try to investigate, 549s are all in RCC income maybe Keytruda chemo combination; or TKI combination or something like that?

And second is, given the amount of robust R&D activities going on for the next 12 to 18 months, how should we think about the R&D, SG&A expense for the fourth quarter and 2020 in general? If you can give us some guidelines?

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

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Sure. So I'll start with the first one. We do not have a non-compete with any of our collaborators. We have arm's length collaborations, where there is -- there are no restrictions on what we can do outside of those collaborations, and there's no transferal of rights or options on IPI-549 as part of those collaborations. Your second question, was it about the fourth quarter of 2020?

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Soumit Roy, JonesTrading Institutional Services, LLC, Research Division - VP & Healthcare Analyst [20]

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No fourth '19 and then overall 2020. How we should think about the R&D and the SG&A expenses?

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

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Sure. So I'll just make a high-level comment and then turn it over to Larry. As we look, we're keenly focused on the importance of managing our expenses such that we're able to generate data and have potential value inflection, and 2020 is a really important year to that end. As we've guided, we have cash for at least the next 12 months, and we'll have data by the end of 2020. So we're managing our expenses, which I'll turn it over to Larry to address. And then we're also -- if and when we decide to access additional capital, we have several levers, and Larry, you can elaborate on those as well.

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

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Little bit. Yes, so we're going to be wrapping up the enrollment for MARIO-1, which is our largest study of 225 approximate patients by the end of this year as we're ramping up the other clinical studies. And so while we haven't finalized our budget, and budget approval will occur in December. I think it's a fair estimate to assume that it's going to be very flat from 2019 into 2020 as MARIO-1, sort of, winds down and beta trials start ramping up.

And then as Adelene saying, in terms of accessing additional capital in the future, we always look for the most capital-efficient forms of resources. And so some things we've been doing, obviously, is to access complementary mechanisms and compare drugs from our strategic partners in these clinical studies, which is a big fraction of our overall clinical cost. And then we also have additional options to pursue, including as you may be aware, we have licensed out our hedgehog program to PellePharm, which is now enrolling their Phase III, which has breakthrough therapy designation from the FDA fo Gorlin Syndrome, which is a very aggressive form of basal cell carcinoma. And so at an appropriate time, we can consider monetizing that royalty stream as we did with Copiktra earlier this year. And then there's nonstrategic geographical licenses for 549 that we consider as well.

So bottom line is we think we're moving forward with a very capital-efficient execution on the clinical studies and don't expect -- unless we add additional studies beyond the ones that we've initiated this year and given guidance on for next year, I don't expect a significant increase in overall R&D.

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Operator [23]

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(Operator Instructions) Our next question comes from the line of Nick Abbott with Wells Fargo Securities.

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Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Associate Analyst [24]

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So the first one goes back to CheckMate-275. And I think it was about 18 months ago that retrospective analysis was presented. Are you able to call in on any analysis of the role of MDSCs in other CheckMate inhibitor trials? There's certainly plenty of them out there. Yes, I'd just like to see if there's -- if you -- if there's a lead, really in other tumors based on retrospective analysis of some of these large CheckMate inhibitor trials?

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Jeffery L. Kutok, Infinity Pharmaceuticals, Inc. - Senior VP & Chief Scientific Officer [25]

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Sure, I can take that question, Nick. This is Jeff. Yes, there is published data, particularly in the melanoma field where in metastatic melanoma, in one study that was published couple of years ago in patients who had failed a belimumab and then come on to receive nivolumab monotherapy, where there was an inverse correlation between MDSC levels and response. So the patients who have the lower levels of baseline MDCs had the better responses and outcomes in that study. So they're at least in the melanoma area and there's similar data that's been presented at meetings and other indications that show that aptitude for responses are in the patients with high levels of MDSCs to checkpoint inhibitor therapies and the patients with lower levels have better responses in multiple different indications. But data in the CheckMate-275 study was among the most robust, though that we've seen given the number of patients in the study that had their MDSC levels evaluated and the quality of the data that led to the accelerated approval.

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Lawrence E. Bloch, Infinity Pharmaceuticals, Inc. - President [26]

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This is Larry. Listen. Yes, the registration study, as Jeff said, that was very helpful as benchmarking and having access through our partnership with BMS to their confidential analysis helped us to set up the protocol in an optimal way. But to your -- the question on your question is, are there adjacent indications that have similar dynamics in terms of MDSCs being negatively correlated with good prognosis? And it's certainly the case with just in the literature, and so with positive data from MARIO-275, the next logical thing for us to do would be to consider expeditiously evaluating those other indications, including potentially melanoma, as Jeff said, with similar types of clinical approaches.

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Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Associate Analyst [27]

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Okay. And then in terms of MARIO-1, so you said that there'll be 225 patients in total. We know that for triple-negative breast and melanoma that, that was -- cohorts are going to be expanded if they pass those signed in 2 stages, and both of them did, so they now are expanded to 40, 29 patients in each. Can you tell us what the target enrollment is for each? And I know there are 7 combo cohorts. What the target enrollment is for those cohorts?

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Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [28]

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Sure. So we had 3 cohorts that were all in patients who had progressed on a checkpoint inhibitor as their immediate prior therapy, and those 3 were non-small cell lung cancer, where our target was 20 patients, squamous cell cancer of the head and neck, where our target was 20 patients. And then melanoma, as you correctly highlighted, the initial target was 20. And based on early responses, we increased that to 40. Triple-negative breast cancer, as you highlighted was also expanded to 29 patients. And then we had a cohort of patients in mesothelioma that was 10 patients and in adrenocortical cancer that was 10 patients, and in patients, all-comers MDSC high that was 20 patients.

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Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Associate Analyst [29]

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I don't have a tracker for that. Maybe so 225, and that would include monotherapy as well as those escalations?

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Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [30]

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Correct.

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Nicholas M. Abbott, Wells Fargo Securities, LLC, Research Division - Associate Analyst [31]

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Okay. And then last question. It's probably a question for Jeff. Jeff, at SITC there's a poster entitled, adenosine and AMP gene expression profiles or predict response adenosine pathway therapies indicated a need for dual blockade of CD73 and A2AR with CD73 inhibitor. Obviously, there's folks on CD73 and A2AR, but in your discussions with Arcus, do you feel like they can get sufficient suppression of the adenosine pathway just within A2AR inhibitor? They don't need a combination approach?

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Jeffery L. Kutok, Infinity Pharmaceuticals, Inc. - Senior VP & Chief Scientific Officer [32]

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Yes, Nick, that's really a question that's probably best answered by Arcus. I think they feel strongly that they have an excellent inhibitor of the receptor, and we haven't really talked about combining multiple nodes in that -- inhibitors for nodes in that pathway. But it sounds like an interesting presentation.

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Operator [33]

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Our next question is from Jim Molloy with Alliance Global Partners.

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James Francis Molloy, Alliance Global Partners, Research Division - MD of Equity Research and Biotechnology & Specialty Pharmaceuticals Equity Research Analyst [34]

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I was wondering, on the MARIO-3 and the MARIO-275. I know that it's challenging to figure out when exactly enrollments will complete. But can you speak a little bit to sort of the gating factors that you're looking for? And so when you may have an idea of -- or when you might know a better sort of target date for getting completion on those trials?

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Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [35]

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So we usually look to have a reasonable portion of the enrollment complete. So we really understand the cadence of enrollment when we provide guidance. And so it will certainly be sometime in the first part of 2020, and it's possible that we can provide an update on our next call associated with our 10-K. And so that's a possible window the next time that we're having this call. And was there a second part of your question?

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James Francis Molloy, Alliance Global Partners, Research Division - MD of Equity Research and Biotechnology & Specialty Pharmaceuticals Equity Research Analyst [36]

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Just sort of the gating factors, thinking of -- I know there's currently thousands of combination trials going on. Is there any challenges that have sort of come up as the number of trials out there multiplied in finding patients through recruit into trials?

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Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [37]

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We've been very fortunate on that front and were with MARIO-1, and we believe there are several reasons for it. We -- MARIO-1 enrolled consistent with our projections. And I think there are at least 3 reasons for that. One is that we have the only PI3-kinase-gamma specific inhibitor in development, and there's just a lot of investigator enthusiasm. And if people are interested in working with this mechanism, 549 is the drug to work with. And the other is that it is a simple once-a-day oral pill, so it's very convenient for patients.

And the third is that it's been extraordinarily well tolerated, which of course, is a huge advantage in treating both late-line and early line cancer patients. So we think we have a number of things that were going for us in MARIO-1, and we believe that, that will likely carry forward in MARIO-3 and MARIO-275.

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James Francis Molloy, Alliance Global Partners, Research Division - MD of Equity Research and Biotechnology & Specialty Pharmaceuticals Equity Research Analyst [38]

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Okay. And last couple of questions. I know that you guys are very clear on your guidance for ending the year in cash flow and the run rate you have. Were you to have instead of $40 million to $50 million, were you to have $100 million to $200 million or sort of what sort of number -- what would advance more quickly or what additionally would come into play, say in 2020, with additional capital? I guess, I'll stop with that question.

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

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Sure. So what we've done in identifying the trials that we have now under way, we've been very disciplined in prioritizing those that we think are the very best. So we've got -- it leverages our clinical and translational findings to date as well as those for our partners. So we really think we're doing and have deliberately prioritized the best crowd. But of course, there are always more that you can do. And part of what we would do next would be informed by the data that we'll be generating in MARIO-1. So as we complete the enrollment in that trial by the end of this year and as we analyze that data, we would look to additional findings from that, that would help us answer your question about how would we -- we have a list today, but how might that be further refined based on additional data from MARIO-1. So stay tuned as we present data from MARIO-1, it will be with that exact eye what additional trials would be prioritized based on additional data coming out of MARIO-1.

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Operator [40]

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

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Adelene Q. Perkins, Infinity Pharmaceuticals, Inc. - Chairman & CEO [41]

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Thank you, Bridget. We're very excited about the opportunities we have with IPI-549, and we look forward to providing more updates on our enrollment completion and data in 2020. So thanks so much for joining us on today's call.

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Operator [42]

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Ladies and gentlemen, this concludes today's conference call. Thank you for participating. You may now disconnect.