Infinity Pharmaceuticals Inc (INFI) 2020 Q2 法說會逐字稿

Ladies and gentlemen, thank you for standing by. Welcome to Infinity Pharmaceuticals conference call to discuss the company's operations and financial results for the second quarter 2020. My name is Shannon, and I'll be your operator for today's call. (Operator Instructions) Please be advised that this call is being recorded at Infinity's request.

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

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

The press release issued this afternoon details our results and is available on our website at infi.com. We have also submitted our 10-Q to the SEC, but the filing is pending resolution due to technical issues at EDGAR that are impacting us and other companies. 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 second 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'd like to turn the call over to Adelene.

Thanks, Jayne, and thank you to everyone for joining us today. Our goal at Infinity has been to execute on a robust clinical development plan for eganelisib, also known as IPI-549. We are evaluating eganelisib across different treatment settings and indications to evaluate its potential to improve outcomes for cancer patients by reprogramming macrophages in the tumor microenvironment from a pro-tumor to an antitumor function.

Last quarter, we've provided an update regarding the impact of COVID-19 on our clinical programs and stated that we would provide updated guidance on our second quarter call. While we and our peers are managing the still evolving COVID-19 situation, we're in a much better position to project the magnitude of the impact on our trials and time line.

We'll provide more specific updates during the call, but I'll first briefly review updated guidance across our trials. I'll start with MARIO-275, our randomized controlled Phase II study in collaboration with BMS, in which we are evaluating eganelisib in combination with Opdivo in patients with advanced urothelial cancer.

As we announced in May, we reduced the dose of eganelisib from 40 milligrams to 30 milligrams daily and are now evaluating the safety and efficacy of the 30-milligram dose for patients enrolled through May. We are pleased to report that the 30-milligram dose is well tolerated, and we will continue to evaluate the patient benefit of this dose combination through the end of the year, which will inform next step.

Our next update is on MARIO-3, our Phase II study in collaboration with Roche/Genentech in which we are evaluating the combination of eganelisib 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 are on track to present preliminary data from MARIO-3 at the end of this year. We also expect to complete enrollment of the renal cell cancer cohort by the end of the year and enrollment in the TNBC cohort of the trial by the end of the first quarter of 2021.

For MARIO-1, our Phase I/Ib study in collaboration with Bristol-Myers Squibb, evaluating eganelisib in combination with Opdivo in patients with advanced solid tumors, we intend to present data that may inform additional development path by the end of this year.

In addition to these Infinity-sponsored trials, our collaborator, Arcus Biosciences is running another study in patients with TNBC. This is a Phase Ib study evaluating eganelisib in a novel checkpoint inhibitor-free regimen that includes their dual adenosine receptor inhibitor, AB928 and Doxil in patients with relapsed/refractory TNBC. The study is proceeding well, and we look forward to future updates to market.

While the situation with COVID-19 continues to evolve, we are monitoring it carefully to proactively address any impacts on site initiations, enrollment, patient treatment and protocol compliance, with the ultimate goal of ensuring our patients have continued access to treatment with no or minimal disruption.

Before we move to the more detailed clinical update, I'd like to introduce Dr. Brian Schwartz, who joined Infinity in a consulting Chief Physician role in April. Brian's deep experience in oncology drug development has been invaluable in the generation and interpretation of data across our trials. We are delighted to have him on the team and are fortunate to have his insight and guidance. Prior to Infinity, Brian has an impressive track record of successful drug development, most recently having served as Chief Medical Officer at ArQule up until its acquisition by Merck in December of 2019.

With that, I'll now transition the call over to Brian, who will provide our clinical updates.

Thank you, Adelene. I'm excited to be collaborating with the team at Infinity.

Starting out with an update on MARIO-3. As you recall, there are 2 cohorts in this ongoing Phase II study, one evaluating eganelisib in combination with Tecentriq and Abraxane as a frontline therapy in triple-negative breast cancer patients and another, evaluating eganelisib combination with Tecentriq and Avastin as a frontline therapy for patients with renal cell cancer. The MARIO-3 multi-cohort study of 30 RCC patients and 60 TNBC patients is currently conducted at approximately 25 sites in the U.S. We have completed the formal safety running portion of both cohorts of the trial and have moved into the expansion phase of this trial in both TNBC and RCC.

Now for some exciting news from MARIO-3. We have made important clinical progress this quarter with a generation of early but highly encouraging signals of clinical activity in the TNBC cohort. We have submitted an abstract to present these preliminary data at a medical meeting this year and are looking forward to providing the first data from our expansion of eganelisib in frontline setting, particularly given the TNBC is the deadliest form of breast cancer with limited treatment options. The activity we are seeing in TNBC from MARIO-3 built on the TNBC activity seen in the late-line setting in MARIO-1, in combination with nivolumab and complements the data we are generating in the second-line setting in collaboration with Arcus with a checkpoint inhibitor-free triple combination therapy.

Moving on to the status update for the trial. On our last call, we shared that we were experiencing delays in the site initiation and enrollment for the trial. I can today provide an update that the majority of identified sites are now up and running, and we are observing an uptick in study-related activities. In terms of enrollment, despite initial delays, enrollment in RCC cohort is now progressing well with minimal disruptions. In the TNBC cohort, we are working closely with our clinical partners and the CRO to proactively address enrollment delays and are encouraged by the progress. As Adelene shared, we expect to complete enrollment in the RCC cohort this year and in the TNBC cohort by early 2021.

Moving next to MARIO-275, our controlled randomized Phase II study evaluating eganelisib in combination with Opdivo in platinum refractory IO naive patients with advanced urothelial cancer. This is in collaboration with BMS. Our last quarter call, we shared information from the first scheduled MARIO-275 independent data monitoring committee, or IDMC. The meeting reviewed safety data from the initial 42 patients treated in the study. In these 42 patients, liver enzyme elevation of Grade 3 or higher were seen in 7 patients, 5 with grade 3 and 2 with grade 4. In this -- while these liver enzyme elevations were reversible and had resolved without sequela, we implemented a dose reduction from 40 milligrams once a day to 30 milligrams QD to address these liver elevations.

As a reminder, 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 PI3K gamma with eganelisib monotherapy at doses of 20 milligrams once-daily and above. Our ultimate goal of dose reduction was to reduce these elevations, and it appears we have been successful, enabling the continued treatment of patients previously enrolled in the study. We are waiting for this data from these patients to mature, and we'll be able to use these data to inform next steps for MARIO-275 by the end of the year.

Overall, we are pleased that despite the continued challenges associated with COVID-19, patients enrolled in MARIO-275, MARIO-3 and MARIO-1 have been able to continue treatment and study visits with limited disruptions. We will continue to closely monitor the situation and work closely with our trial sites to ensure that patients maintain access to treatment as well as protocol compliance.

It is important to remember that our patients have challenging-to-treat cancers, often with poor prognosis, and we are committed to ensuring a safe, continued access to treatment. With highly encouraging early data from MARIO-3, these are exciting times in Infinity, and we look forward to continue to advance eganelisib as a unique MDSC-targeted treatment in the hopes of providing meaningful benefit to patients that expand the reach of immunotherapy across indications and treatment settings.

Before I transition the call over to Larry, I would like to thank our patients, investigators and collaborators at BMS, Roche/Genentech and Arcus, whose continued dedication has enabled our clinical progress.

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

Thank you, Brian. We are pleased that you joined us in Infinity at this really exciting time. I look forward to sharing later this year the early but encouraging eganelisib clinical data you just discussed.

Turning to our second quarter financial results. At June 30, 2020, Infinity had total cash, cash equivalents and available-for-sale securities of $42.7 million compared to $50.3 million at March 31, 2020.

Research and development expense for the second quarter of 2020 was $6.1 million, an equivalent amount for the same period in 2019. General and administrative expense was $2.9 million for the second quarter of 2020 compared to $3.8 million for the same period in 2019. The decrease is primarily related to a decrease in consulting as well as stock compensation.

Net loss for the second quarter of 2020 was $9.5 million or a basic and diluted loss per common share of $0.16 compared to net loss of $10.5 million or a basic and diluted loss per common share of $0.18 for the same period in 2019.

We expect to end 2020 with cash and investment balance ranging of between $20 million and $30 million. And based on our current operating plans, which exclude additional funding or business development activities, we anticipate our existing cash, cash equivalents and available-for-sale securities will be adequate to satisfy the company's capital needs well in the second half of 2021.

Infinity's financial guidance does not include potential additional funding or business development activities, a 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 PhellePharm.

We appreciate your continued support as we move forward with the development of eganelisib. At this time, we can open up the call for questions. Operator?

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

Looking forward to the updates in the second half of the year. So my first question is on MARIO-3 with the update later this year. In the press release, you talked about this encouraging activity -- early activity that you're seeing in TNBC. So just wondering the size and scope of the data you think we'll be getting here. And given the competitive landscape, how are you guys defining sort of early encouraging activity?

And then on MARIO-1, just a quick one on the translational data we're expecting later this year. What should we be looking for in terms of biomarkers and things of that nature to kind of underscore the antitumor activity of IPI-549?

So thanks, Anupam, and I'll turn it over to Brian to elaborate. But what I can tell you is on MARIO-3, what we've done very deliberately is design the trial to have the same inclusion and exclusion criteria as IMpassion130, which was the approval trial for Roche/Genentech in frontline TNBC with the double combination of Tecentriq and Abraxane. So while it's not a randomized trial, by matching the enrollment criteria, we're using that as a benchmark. And I can tell you that the -- they received accelerated approval in just the patients who had high levels of expression of PD-L1, and that data was a CR rate of less than 10% and an overall response rate of 59%. So that's the benchmark that we need to beat to show that 549 is contributing to -- is adding to that double combination.

We're not yet disclosing the data set that we'll have because, as Brian said in his remarks, we're working really hard to get patients enrolled. We've been really pleased at the site initiation that's taking place. So we're working hard to make that as robust to data set as possible by the end of the year, but it's too early to comment on that. And Brian, I turn it over to you.

Yes. No, I think Adelene summarized it really well. I think we look at a number of different efficacy parameters. And even though the numbers are still relatively small, when one looks at complete response, partial response and duration of therapy as well as the safety of the triple combination, we're very encouraged with the early data set, even though relatively small. So we look forward to expanding the data set and be able to share that by the end of the year. Obviously, this is an uncontrolled trial, so all the nuances go with it. But so far, the data has been quite encouraging.

Our next question comes from Andrew D'Silva with B. Riley FBR.

If you could just give a little bit of color on the (inaudible) amendment could be for MARIO-275? And then also how do you expect to be able to utilize data from existing patients that have been enrolled thus far if it doses halfway through being on?

Yes. So again, Brian can address this. I'll just lead in by saying any amendments to the trial will be data-driven. And so that's why we're watching carefully that we're encouraged by the early safety data, the evolving efficacy data, and Brian can elaborate on where we'll go with that.

Yes. So we'll have sort of 3 additional data sets that will help us define the path forward. We'll have the -- how the patients are doing, who's started out at 40 milligrams, how the patients are doing who started out at 30 milligrams that were dosed quickly to 30 milligrams in terms of both safety and efficacy. We'll have long-term data looking at the tail of the curve, which will be very important in urothelial cancer. And lastly, we'll have the opportunity to define the patient group a little bit more stringently.

As you know, checkpoint inhibitors have now and are being heavily studied in the adjuvant or the maintenance setting of urothelial cancer, so the front -- the first-line setting or patients not receiving prior checkpoint inhibitors is a changing population. So taking all those things into account, once we get that set of data, we'll be able to make a decision in terms of what is the best path forward for the trial.

Okay. Great. And then I just have a couple just questions on the guidance and the balance sheet. As far as guidance goes, your burn was reduced a little bit. Could you just give us a sense of where it's coming out, I'm assuming R&D. Could you just please let me know?

Yes. This is Larry. Thanks. You're absolutely right. It's predominantly coming out of R&D as we're addressing some of the enrollment challenges from the first half of the year with the COVID epidemic.

Okay. Perfect. And then as it relates to the royalty finance and then the (inaudible) that took place earlier this year, could you please let me know as far as (inaudible) on the balance sheet? That's essentially nonrecourse, right? You -- it's on you to be able to make the action active.

Exactly. There, it's completely nonrecourse and the repurchase cannot be forced upon Infinity.

And Andrew, I would just elaborate, that's true of both of the royalty monetizations that we did with both HCR and earlier this year with BVF. For accounting reasons, they're recorded as a liability, but there is no obligation to repay those. Those are totally and completely secured by the royalty stream.

(Operator Instructions) Our next question comes from Soumit Roy with JonesTrading.

Congratulations on pushing forward on every front. My call dropped off, so I don't know if this question has been asked already. I'm trying to understand what was the reasoning behind the -- for MARIO-275, the reasoning behind using the 40-milligram per QD dose when you could see a target saturation at 20 milligram. Was there a reason why you didn't want to use 30 and moved up to 40 and using it at 30? Is it -- are we compromising on some efficacy side?

Maybe I'll take...

Brian will -- yes.

So as you know, in oncology, we tend to push the dose a little far sometimes. And I think in this case, we had data from the MARIO-1 in a bunch of other tumor types where the 40-milligram was sort of on the cusp. We soon realized in a randomized trial, what the delta is between adding the drug versus just single-agent nivolumab. So clearly, the 30-milligram is a much safer bet for patients that are going to be on the drug for a long period of time. But it's just -- I think it's a function that we often have in oncology of trying to make sure that we don't under-dose anyone. But clearly, there is good target inhibition, good PD, reviewing the data at both the 20 and the 30 milligram.

Okay. And again, if this question has been answered already, apologies for that. If the hepatotoxicity that we have seen in the MARIO-275, do you have any further color? Or is it you are seeing -- do you think this is from a synergistic effect from 549 plus Opdivo or this is something else? How are you looking through this?

So there's multiple different hypotheses. We know that each drug on its own, a single agent, has a degree of hepatotoxicity and then the combination has some degree of hepatotoxicity. We have a number of hypotheses, and that the combination together may elicit a stronger immune response. And it is primarily seen in the liver in terms of a transient type of hepatitis. That's controlled reasonably well with steroids. So it could be that, but it could be each drug's contribution. There are many different factors, and it's difficult to tease out. That's one of the reasons why we're taking our time with MARIO-275 to make sure we cover all bases. So for example, if one drug stopped, you're going to reintroduce the second drug and you're able to see does the event reoccur or not. So we'll get a much better idea in terms of what the contribution of each drug is.

Okay. So year-end, would we see some of these translational data like CD4, CD8 ratio, even in the 40-milligram patient versus the 30-milligram patient and for the MDSC level, that kind of blood work?

Correct. I mean, we have continued to connect all the biomarkers on all patients, and we'll be able to evaluate that as soon as it's ready.

And in addition, Soumit, I'll remind you that it is a controlled study. And so while we may learn something that, as Brian said, will enable us to optimize our next step, we may not be able to share that data because we've worked very hard to ensure that we retain the blind.

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

Thank you, Shannon. As I hope you can tell, we're very excited about our continued progress with eganelisib and encouraging evolving data, and we look forward to providing you additional updates in the coming months and through the end of the year. So thanks for joining us on today's call, and I hope you all have a nice evening.

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