Infinity Pharmaceuticals Inc (INFI) 2021 Q1 法說會逐字稿

Ladies and gentlemen, thank you for standing by. Welcome to the Infinity Pharmaceutical's conference call to discuss the company's operations and first quarter 2021 financial results. My name is Mel, and I will 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. Ma'am, please go ahead.

Thank you, Mel, and good afternoon, everyone. Welcome to today's call to discuss our recent business progress and review of our first quarter 2021 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 the call for Q&A following our remarks.

The press release issued this afternoon details our results and is available on our website at infi.com. Please note that during this call, we may make forward-looking statements about our future expectations and plans, including clinical development objectives, the therapeutic potential of our product candidates, our strategic plans and strategies and financial projections.

Our actual results may differ materially from what we project today due to a number of important factors, including the considerations described in the Risk Factors section of our annual report on Form 10-K for 2020 and in other filings we make with the SEC. These forward-looking statements may 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. We've reached an exciting inflection point at Infinity, having generated compelling data, which demonstrates the broad potential of eganelisib to improve treatment regimen in multiple solid tumors.

We're poised to build on this momentum with a substantial update this summer on a triple-negative breast cancer data presented at the San Antonio Breast Cancer Symposium with data on at least twice as many patients, in addition to providing an update on our future plans in urothelial cancer at a planned corporate event on Tuesday, July 27.

Over the last 6 months, we've generated important clinical readouts from MARIO-1, MARIO-3, ARC-2 and MARIO-275 studies across 6 different indications, which highlight the broad potential of eganelisib's unique macrophage targeting immune modulating mechanism.

Our preclinical translational and clinical data have consistently shown that eganelisib has the potential to create at T cell inflamed tumor microenvironment from a non T-cell inflamed environment, sometimes simplified as turning cold tumors hot, activating an immune response and increasing PD-L1 expression, thus priming for an increase in the effectiveness of checkpoint inhibitors, regardless of baseline PD-L1 level.

On today's call, our Consulting Chief Physician, Dr. Brian Schwartz, will discuss next steps for our TNBC and UC programs. But before that, I'd like to briefly remind you of the data we presented over the last 6 months in chronological order and program guidance.

First, data from 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, namely melanoma and squamous cell cancer of the head and neck were presented at SITC in November 2020. These data reinforce the potential of eganelisib to overcome resistance to checkpoint inhibition, including in patients who progressed on a checkpoint inhibitor as their immediate prior therapy.

Second, data from the TNBC cohort of 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 frontline treatment in patients with TNBC were presented at San Antonio Breast in December of 2020.

These data show a highly encouraging increase in the overall response rate and disease control rate, irrespective of baseline PD-L1 status with the addition of the eganelisib to Tecentriq and Abraxane standard of care doublet, which received accelerated approval for the treatment of PD-L1 high, but not PD-L1 low frontline TNBC patients.

Third, data from our ARC-2 collaboration of Phase Ib study evaluating eganelisib and a novel checkpoint inhibitor pre-regimen that includes etrumadenant, their dual adenosine receptor antagonist and Doxil in patients with relapse/refractory triple-negative breast cancer and ovarian cancer were also presented at San Antonio Breast in December and showed an increase in response rate with the addition of the eganelisib to the novel doublet therapy in both indications.

And most recently, in the first quarter of 2021, we presented data at ASCO GU for MARIO-275, our randomized, double-blind, placebo-controlled Phase II study in collaboration with BMS, evaluating eganelisib in combination with Opdivo in patients with advanced urothelial cancer. These data show improvements in response rates, disease control rates and progression-free survival, particularly in patients with low levels of PD-L1 expression who are known to not respond well to checkpoint inhibitor alone and suggest the addition of eganelisib to standard of care Opdivo monotherapy can improve patient outcomes.

Our strong execution and steady progress have propelled eganelisib forward with signals of activity across diverse settings, including double and triple combinations in the first, second and third line and also across multiple solid tumors, which Brian will review in more detail. These data leave us increasingly confident in the potential of eganelisib to improve responses in patients with some of the greatest unmet needs in oncology.

Moving to our high-level thoughts regarding future development opportunity for eganelisib. In front line TNBC, our path forward in combination with Tecentriq and Abraxane will be a function of our maturing data, which we will be presenting on July 27 and again in the fourth quarter of 2021.

We plan to cut the data as close to the end of the first half of 2021 as possible to have much robust data set possible this summer. Additional data will be presented in the fourth quarter of this year, and completion of enrollment is on track for the second half of the year.

Our current plan in bladder cancer is to focus on the PD-L1 low population who represents the majority of second-line bladder cancer patients and are also the patients with the greatest unmet need. Checkpoint inhibitors provide little to no benefit in these patients, with some approvals being limited to the PD-L1 high patient population as with Keytruda and Tecentriq in frontline urothelial cancer.

While our data suggest eganelisib could be a benefit to all patients, regardless of PD-L1 status, we plan to initially focus on PD-L1 low patients given the magnitude of the eganelisib benefit seen in these patients over Opdivo monotherapy, such that it should be possible to demonstrate the benefit of adding eganelisib placebo in a relatively smaller number of patients, enabling a smaller registration trial, which can, therefore, be faster, unless we've started to conduct.

2021 is poised to be a year of meaningful data update and continued execution, and our strong balance sheet from the $92 million public offering in Q1 leaves us well positioned to continue executing on the development of eganelisib to demonstrate the potential of our first-in-class and wholly owned macrophage targeting therapeutics.

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

Thank you, Adelene. As Adelene mentioned, our encouraging initial data from MARIO-3 in front-line triple-negative breast cancer showed a patient benefit from the addition of eganelisib to an approved standard of care regimen, in this case, the Roche/Genentech regimen of Tecentriq and Abraxane in frontline TNBC, which received accelerated approval for use in PD-L1 positive patients.

At San Antonio Breast Conference last September -- last December, we presented efficacy data from the first 13 evaluable patients as well as safety data on 20 patients, including 7 patients who enrolled but have not received their first efficacy scan.

We were thrilled to report 100% of the evaluable patients had a reduction in their tumor volume, regardless of their PD-L1 status, with 69% had either a partial or complete response, with 100% in the PD-L1 high patients responding and 50% on the PD-L1 low patients responding.

The study has been progressing really well, and we look forward to reporting data on approximately twice as many patients as well as their initial look at durability of responses on July 27.

The accelerated approval of Tecentriq and Abraxane in PD-L1 high, front line, triple-negative breast cancer patients, subject to confirmation in subsequent studies was a subject of the recent FDA Oncology Drug Advisory Committee, or ODAC, review, which highlighted the need for better treatment for these triple-negative breast cancer patients.

In addition, there's also clearly a need for the PD-L1 low patients for which checkpoint inhibitors have not been approved.

Our initial MARIO-3 data suggest that the up-regulation of PD-L1 with eganelisib treatment could improve the effectiveness of checkpoint inhibitors in triple-negative breast cancer, regardless of baseline PD-L1 status, such that we see multiple path forward as a maturing data will be instrumental in prioritizing the focus of future clinical development.

In particular, we will assess whether the addition of eganelisib provides a greater benefit to PD-L1 low patients, PD-L1 high patients or all patients, regardless of the PD-L1 status in designing follow-on registration focused studies.

In Q1, we presented data from MARIO-275, our randomized, placebo-controlled Phase II study evaluating the efficacy and safety of eganelisib in combination with Opdivo in second-line platinum refractory IO naive patients with urothelial cancer. The results presented at ASCO GU showed the combination of eganelisib with Opdivo improved the overall response rate, the disease control rate and the progression-free survival versus second-line standard of care Opdivo monotherapy in all patients, regardless of PD-L1 expression levels.

However, the greatest benefit over Opdivo monotherapy was observed in the PD-L1 low patients, bringing the ORR and DCR to equal levels or above the response and disease control rates seen in the PD-L1 high patients by BMS in the approval study for Opdivo monotherapy. The study was called CheckMate-275.

We were also encouraged by the PFS hazard ratio of 0.54, such that patients who received combination treatment were 46% less likely to progress relative to patients on the Opdivo plus placebo arm, an indication of significant patient benefit.

We believe these results demonstrate that eganelisib has a potential to raise the level of benefit in PD-L1 low patients to a level equivalent that observed with the standard care IO therapy in PD-L1 high patients as well as increasing the benefit for PD-L1 high patients.

Based on these results, we are in the planning stages of a registration trial, and we look forward to providing details of our progress in bladder cancer based on our interactions with regulatory authorities and in the context of the recent ODAC meeting, at which accelerated approvals for Keytruda and Tecentriq in frontline bladder cancer were reviewed.

Leveraging the strong data from MARIO-275 and the initial feedback from the FDA, we expect to provide an update on eganelisib in PD-L1 low bladder cancer patients on July 27.

Lastly, moving to our renal cell cohort in MARIO-3. Our guidance remains unchanged, and we expect to report data in the first half of 2022 from our ongoing fully enrolled proof of concept, novel triple combination of eganelisib, Tecentriq and Avastin in frontline renal cell carcinoma.

2021 is going to be a transformative year for Infinity. The key data readouts, the emerging clarity on our regulatory path forward and some indication of the potential commercial opportunity in combination treatments, our results to date have shown consistent and broad activity of eganelisib across diverse settings, indications and regimens, which we view as highly encouraging.

With our strong execution and growing data foundation, we are now poised to advance eganelisib in what we believe are opportunities for success in metastatic urothelial cancer, triple-negative breast cancer patients. Given eganelisib's unique mechanism of action and consistent signs of activity across trials, we also see tremendous opportunity to extend beyond those initial indications, potentially, in PD-L1 low patients, regardless of tumor type, who represent a majority of patients and who are underserved by current therapies.

Before I turn the call over to Larry, I would especially like to thank our patients, investigators, collaborators at BMS, Roche/Genentech and Arcus, as well as the team at Infinity, whose continued dedication has enabled our progress.

With that, I turn the call over to Larry.

Thank you, Brian. Following our February 2021 public offering in which we raised $92 million of gross proceeds, at March 31, 2021, Infinity had total cash, cash equivalents and available for sale securities of $106.8 million compared to $34.1 million at December 31, 2020.

Research and development expense for the first quarter of 2021 was $8.2 million compared to $7.3 million for the same period in 2020. This increase is primarily related to clinical and development expenses to support continued development of eganelisib.

General and administrative expenses for the first quarter of 2021 was $3.6 million compared to $3.2 million for the same period in 2020, and this increase in G&A expense was primarily due to an increase in stock compensation.

Turning to net loss. For the first quarter of 2020, this was $11.6 million or basic and diluted loss per common share of $0.15 compared to a net loss of $10.9 million or basic and diluted loss per common share of $0.19 for the same period in 2020.

Infinity's 2021 financial guidance following our February 2021 public offering is as follows and remains unchanged. Infinity expects net loss for 2021 to range between $40 million and $50 million. And at the end of 2021, we expect to have year-end cash, cash equivalents, available for sales securities balance ranging from between $70 million and $80 million.

We really appreciate your continued support as we move forward with the development of eganelisib and are very much looking forward to sharing with you our progress with development of eganelisib at our upcoming July 27 update webcast.

At this time, we are going to open the call for questions. Operator?

(Operator Instructions) Your first question comes from the line of Robyn Karnauskas from Truist.

So two quick ones. So July 27, can you set the standard for how many -- what kind of update will we get for sure? Maybe there's some ambiguity about how much information you'll actually clean from the FDA or about your trial design. So how much for show will we get around trial design that FDA will back? And how much will we not?

And the second question would be around your data and strategy. Do you think at that time you may be in a position to give us some clarity around strategic view of your data in your plan? And how are you thinking about what the best strategic vision would be for your company?

Thanks, Robyn. Appreciate the question. So on July 27, what we are confident that we will be sharing, because it's within our control and we know what patients we have enrolled, is an update on the TNBC data, and we're going to have data on at least twice as many patients as we had at San Antonio Breast in December.

On bladder cancer, what we're committing to share is an update on our current outlook for the future development of eganelisib, but that's going to depend on a couple of different variables that are a little bit outside of our control. One is what decisions the FDA will make on the accelerated approvals for Keytruda and Tecentriq and the frontline based on the recent ODAC as well as the status of our current interactions with the FDA. So we'll provide the most recent outlook based on where we're at, but it will depend on those 2 variables.

And with respect to what the data will mean for our strategy going forward, that really depends on the quality of the data. So we are really looking forward to having data on twice as many TNBC patients. There will be, as we presented at San Antonio, because PD-L1 low patients are about 60% to 70% of the patient population as they were in bladder cancers as well, we will have more data on the PD-L1 low patients.

So we'll have both response rates as well as some durability, particularly on the patients who are already -- or the 20 patients who are already enrolled at San Antonio in December. And so depending on what that data looks like, as Brian said, the data will determine are we going to concentrate our efforts going forward on the PD-L1 low patients, on the PD-L1 high patients or on all patients. The data that will have greatest visibility into -- in July is the TNBC PD-L1 low patients.

And as a follow-up, I mean, what are your strategics interest in? I think they'd probably be bigger, more focused on the broader opportunity. I'm sure they're watching everything. Do you have a sense of their one key thing they're focused on from -- if you're going to go after the broader opportunity and do a partnership?

So obviously, everyone who's developing cancer drugs are looking for better treatment, and that's certainly true in both bladder cancer and breast cancer.

With respect to what any specific strategic potential partners are looking for, and their strategies and intentions, it's probably better to speak with them directly because we're not going to comment on the status of ongoing discussions.

Next question comes from the line of Ted Tenthoff from Piper Sandler.

Great. Looking forward to the event on July 27. I wanted to ask, I know you're also evaluating eganelisib in renal cell carcinoma. Should we be expecting an update from that cohort as well? And is that something we could also get update on July 27?

Thanks, Ted. No. Our guidance remains unchanged for renal cell that we will be providing an update on that in the first half of 2022.

2022. Okay. Great. Awesome. Great. Yes. Go ahead, sorry.

Yes. So the July 27 update will be primarily focused on the TNBC with a substantial number of additional patients and the current status of our future development in bladder.

Next question comes from the line of Anupam Rama from JPMorgan.

This is Tessa on the call today for Anupam. So for the MARIO-3 update in triple-negative breast cancer in July, you noted kind of the size of patients we should be -- we should see there. But can you provide a bit more granular on how you think about what a win scenario would be for you guys for that update? And then a second question would just be, when you give us the update on the pivotal study in urothelial cancer in July as well, will you have the FDA minutes in hand?

Sure. So Brian, why don't you start with our thinking about the outlook for data in TNBC? And then I can follow up on the FDA interaction.

So I think what we do have is we do have , for the PD-L1 positive and the total group, there's very clear benchmarks for what the combination of Tecentriq and Abraxane does. For the PD-L1 low group, there's clarity on the PFS and the OS, but there's not much guaranty on response rate, and they've sort of given a range.

So in terms of what I'll be looking at is about 15% above of what you think the control group performs and, more important, the duration of response and the totality of the data in terms of PFS, durability, all the other pieces.

So I think it would be nice to have a specific number. But if you had a response rate of 75% with a duration of 4 months, it's not really meaningful. So I think you really have to look at the totality of it. And the nice thing in June is we'll have patients on drug for at least a year. We'll be able to get an early feel in terms of those 3 sort of separate questions, the response rate, the durability of response and how the whole group performed and, then lastly, how the 2 subsets, the PD-L1 positive and PD-L1 negative perform.

But I think the absolute numbers that's arranged for the -- well, PD-L1 high, we know. So 59 plus about 15 percentage, so you're now in the high numbers. For the PD-L1 low, the numbers are a little bit all over the map, anywhere from 40% to 50%. So we could -- you could make an argument around that, but it's really the totality of the data.

And then on your second question, Tessa, about our plans in bladder cancer. If we have completed our discussions with the FDA, and we finalized the trial design, and we know exactly what that's going to look like, we would share that.

If we haven't yet finalized the discussions and we don't have the final design, what we'll do is give you an update on when we think we'll have that and what the expected timing for that would be.

Next question comes from the line of Nick Abbott of Wells Fargo.

Just going back to the TNBC study, I think a clinical trial -- the trial originally was going enroll around 90 patients, but I know the expansion cohort have triggered early by the encouraging data. So, first, I mean, are you still expecting to enroll around 90 patients in the study?

So the way -- so plan is to have, Nick, at least 30 PD-L1 low patients and 30 PD-L1 high patients. So at a minimum, 60 patients with total study, but I think it's really going to depend a little bit on the data and how it enrolls. We're enrolling currently -- for every 2 PD-L1 lows, we're enrolling 1 PD-L1 high, so we might be a little bit shy of one and a little bit more rich than the other.

Okay. And then just going back, Adelene, your comment on at least twice the number of patients from San Antonio. Is that in reference to the 13 efficacy eligible patients or the 20 total patients?

Both.

I'm sorry. That's both. Okay.

Yes.

So the San Antonio number is going to be at least 40, of which at least 2/3 of those will be efficacy eligible. Is that the way to think about it?

Correct.

Okay. Perfect. And then just last one for me. I know that you're supporting an IIT with Ezra Cohen standard UCSD in neoadjuvant head and neck setting. Do you have any updates on when we might be able to expect some data from that?

So Brian, do you want to talk a little bit about that study?

I mean, that study, we -- a little bit -- it's a little bit dependent on the investigator, but the more data we can get to you, as soon as we get that data available, we'll get it out to everybody.

It has a lot of translational work built in, so it's not so much getting the patients on. It's much more getting all the translational work done. But we don't have a firm time line from Ezra as of yet. But obviously, as soon as we get them available, we'll send it to you. We'll get it out there.

(Operator Instructions) Next question, we have the line from Soumit Roy from Jones Trading.

I don't know if you guys ever touched upon the uncomfortable discrepancy between IMpassion130 and 131. Curiously, you would show us some more depth details in the data, July 27, maybe co-mutational status of these patients' BRCA or more biopsy data and steroid usage, that kind of details. And the second question is, would you consider redesigning initiation trial in terms of IMpassion132, like Tecentriq -- chemo combo rather than Abraxane?

So I think the first question, we'd like to share with you as much data as we can. That would be the goal. In terms of the translational data, as I mentioned, the same thing with the Ezra study is obviously the translational data sometimes lags behind. So we will have much less translational data to share with you.

In terms of other comorbid indications, I think if the sample sizes are big enough and the groups are big enough, definitely, we'll share with you. That will really depend on how big the different groups are. And we are aware of some of the potential biases that crept into the data for the different studies with Tecentriq in breast. So hopefully, we can review that. It will be in an uncontrolled setting, so a little bit more difficult to interpret.

In terms of our drug with just a chemo combination, we've thought about it quite a lot. It makes mechanistic sense based on some of the preclinical models, but we really have to evaluate the total program. And as you said, the data is really good. We could easily introduce an arm into a study. But right now, it's not forefront of our plans, but a very good and common thought that we have within our group.

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, Mel. We're very excited to be advancing a tremendous and near-term opportunity for eganelisib in PD-L1 low patients and look forward to meaningful MARIO-3 triple-negative breast cancer data update at our corporate update on July 27, for which details will be forthcoming.

So thank you very much for your continued support and for joining today's call. Have a nice evening.

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