Infinity Pharmaceuticals Inc (INFI) 2017 Q1 法說會逐字稿

Ladies and gentlemen, thank you for standing by. Welcome to the Infinity Pharmaceuticals conference call to discuss the company's financial results for the first quarter of 2017. My name is Bruce, and I'll be your lead operator for today's call. (Operator Instructions) Please be advised that this call is being recorded at Infinity's request. At this time, I would like to introduce your host for today's call, Ms. Jaren Madden, Senior Director of Investor Relations and Corporate Communications at Infinity. Please go ahead.

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Scientific Officer; Dr. Claudio Dansky Ullmann, Senior Vice President, Clinical Development; Dr. Joe Pearlberg, the medical lead for our IPI-549 program; and Larry Bloch, President. Following our remarks, we'll open up the call for Q&A. The press release issued earlier today 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 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 quarterly report on Form 10-Q for the first quarter of 2017 and in other filings we may 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.

And now I'd like to turn the call over to Adelene.

Thanks, Jaren. Good afternoon, everyone, and thank you for joining us on today's call. We are very pleased with the advancements we've made with IPI-549, our oral selective PI3-kinase-gamma inhibitor. Today, we'll discuss our progress with the Phase I clinical study of IPI-549 in patients with advanced solid tumors and also review our first quarter 2017 financials.

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Pardon me, Ms. Jaren?

Yes.

You may begin.

Okay. This is Adelene Perkins from Infinity Pharmaceuticals. We are very sorry about the technical difficulties. But we will begin right at the beginning of our prepared remarks again and remind you that the forward-looking statements that Jaren Madden had read are still in effect. So we're appreciative of having you on

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Including checkpoint inhibitors. There is also a significant medical need for patients who do respond and then subsequently develop resistance to their immunotherapy regimens. Given our preclinical data demonstrating that IPI-549 can overcome resistance to checkpoint blockade, coupled with the clinical data recently presented at the AACR Annual Meeting, we're encouraged about the potential of IPI-549 to address these medical needs.

Another reason we are enthusiastic about our IPI-549 is based on our published preclinical research which demonstrates that selectively targeting PI3-kinase-gamma represents a novel immuno-oncology approach by reprogramming macrophages within the immunosuppressive tumor microenvironment, converting them from a pro-tumor to an antitumor phenotype. While many immunotherapies that are approved or in development target T-cells, very few approaches in development target macrophages. And as the first and only selective PI3-kinase-gamma inhibitor in the clinic, we have an opportunity to develop a first-in-class therapy, which, by virtue of its distinct effect on macrophages, may uniquely complement and enhance the activity of other therapies.

Our preclinical data, which Jeff will review momentarily, provide a compelling rationale for our Phase I study and underscores the potential for IPI-549 to serve as a cornerstone in a broad range of combination therapy for the treatment of solid tumors. Our ongoing Phase I trial is evaluating IPI-549 alone and with Opdivo, a PD-1 immune checkpoint inhibitor, in patients with a broad range of advanced types of cancer. The study includes 4 phases or modules: first, monotherapy dose escalation; second, combination therapy dose escalation; third, monotherapy expansion; and fourth, a combination therapy expansion. Dose escalation modules 1 and 2 are critical to assessing the safety of IPI-549 and are ongoing as we work to determine the optimal doses to evaluate in our expansion modules. Through expansion modules 3 and 4, we expect to generate clinical data on the activity of IPI-549 in solid tumors, including in non-small cell lung cancer, melanoma and head and neck cancer. We are pleased with the dose escalation data recently presented at AACR, which demonstrated that IPI-549 was well tolerated as a monotherapy and in combination with Opdivo. The data, which Claudio will review in more detail, shows that there were no dose limiting toxicities or serious drug-related side effects, and no side effects led to treatment discontinuation.

As we look ahead, we expect to make progress in the following 3 key areas this year: First, we'll complete enrollment in our 2 dose-escalation modules and determine our recommended Phase II doses. We anticipate finishing the monotherapy dose escalation in the first half of the year and the combination module in the second half of the year. Second, we'll begin enrolling patients in our expansion modules in the second half of 2017. And third, we'll report additional data in a peer review form in the second half of this year.

Overall, we're very pleased with the progress we've made and are continuing to make with IPI-549 while maintaining strong fiscal discipline. Our experienced team is executing with a great sense of urgency to deliver meaningful data within our current test runway.

Now Jeff will review the preclinical rationale for studying IPI-549 in solid tumors.

Thanks, Adelene, and

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publications in the journal, Nature, late last year. We worked with collaborators at the University of California San Diego and Memorial Sloan-Kettering to explore the importance of targeting PI3K-gamma in cancer. In contrast to the other major PI3K isoforms, PI3K-gamma is highly expressed in tumor-associated macrophages and plays an important role in the pro-tumor function of these cells. We discovered that blockade of PI3K-gamma signaling by treatment with IPI-549 results in the transcriptional reprogramming of tumor-associated macrophages. This reprogramming shifts macrophages in the tumor micro-environment from the M2 or pro-tumor phenotype to the M1 or antitumor phenotype, increasing the number of T-cells that can attack the tumor and increasing the production of pro-inflammatory molecules. This was an important finding because there's been a great interest in targeting tumor-associated macrophages to augment antitumor immune responses. In terms of preclinical activity, we've demonstrated dose-dependent single-agent antitumor activity in multiple solid tumor models, particularly those that are rich in macrophages, reinforcing the mechanism of action of IPI-549.

Additionally, in pre-clinical models, treatment with IPI-549 in combination with the checkpoint inhibitor showed greater tumor growth inhibition and improved survival rates, including a greater number of complete tumor regressions when compared to treatment with IPI-549 or the checkpoint inhibitor alone. The combination treatment resulted in long-lasting antitumor immune memory as evidenced by the lack of tumor regrowth upon rechallenge with the same tumor in the absence of any further treatment.

While the synergy between IPI-549 and checkpoint inhibitors was encouraging, resistance to checkpoint blockade therapy represents another challenge. Our preclinical data demonstrated that increased pro-tumor M2 macrophages are associated with resistance to checkpoint inhibitor therapy. And treatment with IPI-549 in combination with checkpoint inhibitors can overcome this resistance through its effect on macrophages. The key preclinical findings which laid the foundation of our clinical program are first: PI3K-gamma has a very different biology than other PI3K isoforms. And inhibition of the gamma isoform in macrophages affects a critical switch that reprograms macrophages from the pro-tumor to the antitumor phenotype. Second, we've demonstrated the activity of IPI-549 in multiple preclinical models of cancer. And third, we've shown that IPI-549 can enhance the activity of checkpoint inhibitors as well as overcome resistance to checkpoint inhibitors in cancer models. Importantly, our ongoing Phase I study is a faithful recapitulation of this preclinical research, and Claudio will now review our clinical program in more detail.

Thanks, Jeff. I'm really pleased with our progress with IPI-549 in the clinic. This afternoon, I will review the design of our ongoing Phase I study and summarize the data we presented at the AACR Annual Meeting last month. The objective of this study is to determine the safety, recommended Phase II dose and activity of IPI-549 given orally, once daily as a monotherapy and in combination with Opdivo in approximately 135 patients with advanced solid tumors.

As Adelene mentioned, the study includes 4 distinct phases or modules. The first 2 modules are dose escalations, and the third and fourth modules represent the expansion phases of the study. Module one is evaluating the safety, tolerability, pharmacokinetics and pharmacodynamics of IPI-549 as a monotherapy. We have completed patient enrollment in 5 cohorts, evaluating doses ranging from 10 milligrams to 40 milligrams. We are now enrolling patients in the cohort to evaluate the 60-milligram dose. We expect to complete enrollment in this module on determining a recommended single agent Phase II dose in the first half of this year.

Based on our monotherapy PK and PD data, which showed significant suppression of PI3-kinase-gamma at 20 milligrams, we initiated module 2. The goal of this module is to demonstrate that IPI-549 and Opdivo can be safely combined and to establish the recommended Phase II dose for this combination. Currently, module 2 includes 2 cohorts evaluating IPI-549 at 20 milligrams and 30 milligrams combined with the standard regimen of Opdivo. We expect to complete this module in the second half of the year.

Our expansion cohorts represent the third and fourth modules of our study. Module 3 is designed to assist the monotherapy activity of IPI-549 in a greater number of patients with a variety of advanced solid tumors. Module 4 will evaluate the activity of IPI-549 in combination with Opdivo in patients with specific types of cancer, including non-small cell lung cancer, melanoma and squamous cell carcinoma of the head and neck. Importantly, enrollment to the disease-specific cohorts is reserved for patients who have demonstrated initial resistance or who initially responded but subsequently developed resistance to checkpoint therapy. This feature of module 4 is a direct test of whether IPI-549 can overcome checkpoint resistance as demonstrated in our clinical research published in Nature.

Additionally, transitional research will be critical to helping us better understand how IPI-549 works in patients and will inform our future studies. To that end, we have mandatory pretreatment and on-treatment biopsies in all expansion cohorts so that we can better understand the effects of IPI-549 on tumors to tumor characteristics of patients who respond and biomarkers of response and resistance. We anticipate starting modules 3 and 4 in the second half of the year.

In April, we reported data from our first 2 modules in a poster session at the AACR Annual Meeting. These data were from a March 20, 2017, data cutoff. Monotherapy data from 15 evaluable patients treated with doses of IPI-549 ranging from 10 milligrams to 40 milligrams demonstrated that IPI-549 was well tolerated. No dose limiting toxicities or serious drug-related side effects occurred, and no side effects led to treatment discontinuation or dose reduction. The PK and PD properties of IPI-549 appear favorable, with near-complete and sustained inhibition of PI3-kinase-gamma at doses at or above 20 milligram, which supports once daily dosing.

Additionally, preliminary data from 6 evaluable patients demonstrated that 20 milligrams of IPI-549 in combination with Opdivo was well tolerated. No dose limiting toxicities or serious drug-related side effects occurred, and no side effects led to treatment discontinuation. Furthermore, the combination did not result in new or unexpected side effects relative to the non-monotherapy safety profile of each treatment. The PK profile of IPI-549 in combination with Opdivo appear favorable and suggested that Opdivo does not affect the PK properties of IPI-549.

Overall, the data we reported give us confidence in the profile of IPI-549. Demonstrating a favorable tolerability profile, both as a monotherapy and in combination with Opdivo, is a significant milestone for the program and will enable us to more formally test the activity of IPI-549 in our expansion modules. We are pleased with the progress we are making, and we look forward to providing an update in the second half of 2017.

Now Larry will review our financial results for the quarter.

Thank you, Claudio. The Infinity team is very enthusiastic about IPI-549, which had the attributes of the types of medicine Infinity seeks to advance, with a novel mechanism of action and a thoughtful clinical strategy to demonstrate the potential impact of this unique mechanism of action addressing significant medical needs.

And as a result of our fiscal discipline, we are in a strong position to complete all 4 modules of our clinical study within our current cash runway, which extends until the first quarter of 2019.

At March 31, 2017, we had total cash, cash equivalents and available-for-sale securities of $75.4 million compared to $92.1 million at December 31, 2016. Cash used for operating activities during the first quarter 2017 included $5.2 million of payments related to our 2016 restructuring activities.

Infinity did not record any revenue during the first quarter of 2017. Revenue for the first quarter 2016 was $9.3 million, all of which related to the previous AbbVie collaboration for duvelisib.

R&D expense for the quarter was $4 million compared to $39.2 million for the same period last year. The decrease in R&D expense was primarily related to a decrease in clinical development expenses for duvelisib in addition to Infinity's 2016 restructuring activities.

General and administrative expense was $6.4 million for the quarter compared to $10.8 million for the same period last year. The decrease in G&A expense was also primarily related to 2016 restructuring activities.

Net loss for the first quarter of 2017 was $10.5 million or basic and diluted loss per common share of $0.21 compared to net loss of $40.7 million or basic and diluted loss per common share of $0.82 for the same period last year.

Our 2017 financial guidance we revised in January remains unchanged. We expect 2017 net loss to range from $40 million to $50 million, and we expect to end 2017 with a cash investment balance ranging from $40 million to $50 million. Based on our current operating plans, which exclude additional funding or business development activities, we anticipate our existing cash and cash equivalents at March 31, 2017, to provide cash runway into the first quarter of 2019.

As I mentioned earlier, our cash runway allows us the time to generate safety and activity data from all 4 modules of our ongoing Phase I study of IPI-549.

Overall, we are very pleased with our achievements so far this year and expect continued progress throughout 2017. We look forward to keep you updated on Infinity as we seek to bring considerable benefit to patients.

And now we're happy to take your questions.

(Operator Instructions) And at this time, I'm showing no questions. Pardon me, our first question comes from Katherine Xu from William Blair.

This is Audrey on for Katherine. In the past, you had mentioned that you had seen meaningful suppression of PI3-kinase at 20 mgs and higher. I was wondering if you had any more color on the differences that you've seen so far between 20 and 40 and the other doses you've been using?

So thank you, Audrey. That is stated that we did present at AACR, and perhaps Claudio can address the different doses.

Yes. The comment is that we were very pleased to see already at 20 milligrams based on our assay formation and gamma suppression that we were in that effective already, effective suppressive concentration. As we move up in the dose, obviously, we see that there is some room for more sustained inhibition of our gamma target as we move up in the dosing. And that's what we see, it's very incremental. But the good thing is that all above the target of the percent inhibition that we are looking at least to think that that will have clear translation into what we hope that IPI-549 is doing in suppressing the target. I don't know if Jeff Kutok, our CSO, would want to comment on that something else.

No, I think, Claudio, that definitely summarizes it.

And what are you looking for, for your recommended Phase II dose?

So we're looking obviously to the totality of the data. So not only how the PK and PD performance characteristics are and, obviously, the safety, and we will look at all the data, the internal package, if you want. And based on that, we'll decide. Right now, as we mentioned, we're in the enrolling or start enrolling the 60-milligram cohorts, and then we will look at that data once we have all the patients enrolled, and we'll decide based on these parameters how we want to grow. Obviously, it will depend if we see DLTs or we see that we have -- we're already within an optimal biological dose that we think can move forward. That would be the general assessment. Very standard on its own.

And do you see going higher than 30 for the combo dosing?

Can your repeat that, sorry?

Do you foresee possibly going higher than 30 milligrams in combination with Opdivo?

Well, it's a possibility, but we'll have to see. We presented the data at AACR on the 20 milligrams. And we're right now evaluating the 30 milligrams cohort. And again, looking at the totality of the data, we'll decide if we can go up or if we want to go up to 40 milligrams in combination.

And 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, Bruce. We're excited about the opportunity we have with IPI-549, and our team is working hard to rapidly advance our Phase I study. We look forward to providing additional updates on Infinity throughout the year and hope you all have a good evening. And thank you for joining us on today's call, and apologize again for the technical disruption at the beginning of the call. Thank you.

Ladies and gentlemen, thank you for your participation in today's conference, and this does conclude the program. You may all disconnect. Everyone, have a great day.