Infinity Pharmaceuticals, Inc.
Q1 2017 Earnings Call Transcript

Published: 10 May 2017

[Operator:]

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 the lead operator for today’s call. At this time, all participants are in a listen-only mode. There will be a question-and-answer session to follow. 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.

[Jaren Madden:]

[Technical difficulty] Scientific Officer; 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 factor section of our quarterly report on Form 10-Q for the first quarter of 2017 and in other filings we may make with SEC. These forward-looking statements represent our views as if only 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.

[Adelene Perkins:]

Thanks, Jaren. Good afternoon, everyone, and thanks for joining us on today’s call. We are very pleased with the adv 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. [Technical difficulty] 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 that Jared Madden had read, they are still in impact. So we would appreciate for having you on today’s... [Technical difficulty] Including check point inhibitors. There is also a significant medical need for patients who do respond and then subsequently develop resistance to their immune therapy regimen. 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 are 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 immunoncoloogy approach by reprogramming macrophages within the immunosuppressive tumor microenvironment converting them from a pro-tumor to an anti-tumor phenotype. While many immune therapies that are approved or are in development target T-cells there are few approaches in development target macrophages. And as a first and only selective PI3-kinase gamma inhibitor in the plant we have an opportunity to develop a first in class therapy which by virtue of its distinct effect on macrophages may uniquely compliment and enhance the activity of other therapies. Our preclinical data which Jeff will review momentarily provided 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 therapies 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 four phases or module, first mono therapy dose escalation, second, combination therapy dose escalation, third, monotherapy expansion and fourth, the combination therapy expansion. Dose escalation modules I and II are critical to accessing the safety of IPI-549 and our ongoing as we work to determine optimal doses to evaluate in our expansion module. To expansion modules three and four, we expect to generate clinical data on the activity of IPI-549 in solid tumors including a 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 the IPI-549 was well tolerated as a monotherapy and in combination with Opdivo. The data which Claudio will review in more detail show 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 three key areas this year. First, we’ll complete enrollement in our two dose-escalation module and determine our recommended Phase 2 doses. We anticipate finishing the mono-therapy dose escalation in the first half of the year and a 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 fair review form in the second half of this year. Overall, we are very pleased with the progress we’ve made and are continuing to make with IPS-549 while maintaining strong fiscal discipline. Our experienced team is executing with a great sense of urgency to deliver meaningful data within our current cash runway. Now, Jeff will review the preclinical rationale for studying IPS-549 in solid tumors.

[Jeff Kutok:]

Thanks, Adelene and good afternoon everyone [Technical difficulty] Publications in the general 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 and 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 a transcriptional reprogramming of tumor associated macrophages. This reprogramming shifts macrophages in the tumor microenvironment from the M2, or pro-tumor phenotype, to the M1, or anti-tumor 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 has been a great interest in targeting tumor associated macrophages to augument anti-tumor responses. In terms of preclinical activity we demonstrated dose dependent single agent anti tumor activity in multiple solid tumor models particularly [Indiscernible] that are rich in macrophages reinforcing the mechanism of action of IPI-549. Additionally, in preclinical 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 aggressions when compared to treatment with IPI-549 or the checkpoint inhibitor alone. The combination treatment resulted in long lasting anti tumor immune memory as evidenced by the lack of tumor growth upon re-challenge 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 lead the foundation of our clinical program are, first, PI3K-gamma has a very different biology than other PI3K isoforms. An innovation of the gamma isoform in macrophages affects the critical switch that we program as macrophages from the pro-tumor to the anti tumor 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 [Indiscernible] of this preclinical research and Claudio will now review our clinical program in more detail.

[Claudio Dansky Ullmann:]

First, 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 a data we presented at the AACR Annual Meeting last month. The objective of this study is to determine the safety, recommended Phase 2 dose, and activity of IPI-549 given orally once daily as monotherapy and combination with Opdivo in approximately 135 patients with advanced solid tumors. As Adelene mentioned, the study includes four distinct phases or modules. The first two modules are dose escalations and the third and fourth modules represent expansion phases of the study. Module one is evaluating the safety, durability, pharmacokinetics and pharmacodynamic profile of IPI-549 as monotherapy. We have completed patient enrollment in five cohorts evaluating doses ranging from 10 milligrams to 40 milligrams. We are now enrolling patients in a cohort to evaluate the 60 milligram dose. We expect to complete enrolment in this module and determine a recommended single agent Phase 2 dose in the first half of this year. Based on our monotherapy PK and PD data which showed significant suppression of PI3-kinase-gamma of 20 milligram, we initiated more then two. The role of this module is to demonstrate that IPI-549 and Opdivo can be safely combined and to establish the recommended Phase 2 dose for this combination. Currently Module two includes two 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 a third and fourth modules of our study. Module three is design to asses the monotherapy activity of IPI-549 in a greater number of patients with a variety of advanced solid tumors. Module four will evaluate the activity of IPI-549 in combination of 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 the initial resistance or who initially responded but subsequently develop resistance to checkpoint therapy. This feature of module four is a direct test of whether IPI-549 can overcome checkpoint resistance as demonstrated in our clinical research values in nature. Additionally, first clinical research will be critical to helping us better understand how IPI-549 work in patients and will inform our future studies. To that end, we have mandatory pre-treatment and on-treatment biopsies in all expansion cohorts so that we can better understand effect of IPI-549 on tumors, the tumor characteristics of patients who respond and biomarker response of resistance. We anticipate starting module three and four in the second half of the year. In April we reported that at from our tumor rule in a poster session at AACR Annual Meeting.. This data were from a March 20, 2017 data cutoff. Monotherapy data from 2015 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 effect led to treatment discontinuation or dose reduction. The PK and PD properties of IPI-549 appear favourable with near complete and sustained inhibition of PI3K-gamma at doses at or above 20 milligram which supports ones daily dosing. Additionally, preliminary from six evaluable patients demonstrated that 20 milligram of IPI-549 in combination with Opdivo was well tolerated. No dose Opdivo limiting toxicities or serious drug related side effects occur and no side effect led to treatment discontinuation. Furthermore, the combination did not result a new or unexpected side effects relating to the non-monotherapy safety profile of each treatment. The PK profile of the Opdivo IPI-549 in combination with Opdivo appeared favourable as suggested that Opdivo does not affect the PK properties of IPI-549. Overall the data we reported give us cohorts in the profile of IPI-549. Demonstrating a favourable tolerability profile for monotherapy and combined with Opdivo is a significant milestone for the program and will enable us to more formally stress the activity of IPI-549 in our expansion models. We are please 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 financials results for the quarter.

[Larry Bloch:]

Thank you, Claudio. The Infinity team is a very enthusiasm about IPI-549, which had the attributes of the type of medicine and it seek to advance. With the novel mechanism action and thoughtful clinical strategy to demonstrate the potential impact of this unique mechanism action addressing significant medical needs. And in resolving our fiscal discipline, we are in strong position to complete all four modules of our clinical study within our current cash runway extend into the first quarter of 2019. At March 31st, 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 of 2017 included $5.2 million of payments related to our 2016 restructuring activities. If we did not report any revenue during the first quarter 2017, revenue for the first quarter 2016 was $9.3 million, all 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 the company's 2016 restructuring activities. General and administrative expense was $6.4 million for the first 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 a basic and diluted loss per common share of $0.21, compared to a net loss of $40.7 million, or a basic and diluted loss per common share of $0.82, for the same period last year. Our 2017 financial guidance that we provided in January remains unchanged. We expect 2017 net loss to range from $40 million to $50 million and we expect in 2017 the cash invested balance ranging from $40 to $50 million. Based on its current operational plans, which exclude additional funding or business development activities. We anticipate our existing cash and cash equivalents at March 31, 2017 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 four modules who are ongoing Phase 1 study of IPI-549. Overall we’re very pleased what achieved in so far this year and expect continue progress throughout 2017. Look forward to keep you update on Infinity as we see to bring considerable benefit to patients. And now we’re happy to take your questions.

[Operator:]

[Operator Instructions] At this time, I’m showing no questions. Pardon me our first question comes Katherine Xu from William Blair. Your line is now open.

[Unidentified Analyst:]

Hi, this is Adriane [ph] for Katherine and thanks for taking my question. In the past you’d mentioned that you’ve seen meaningful suppression of PI3-kinase that 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 other doses?

[Adelene Perkins:]

So thank you, Adriane. That is data that we get presented AACR and perhaps Claudio can address the different doses.

[Claudio Dansky Ullmann:]

Yes. The common is that we are very pleased to see already of 20 milligrams based on our essay formation, 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 sustain innovation of our demo 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 innovation that we are looking at lease to think that that will have clear translation into what we called that IPI-549 is doing in suppressing the target. I don’t know if Jeff Kutok, our CSO would want to comment on that.

[Jeff Kutok:]

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

[Unidentified Analyst:]

And what are you are for your recommended Phase 2?

[Claudio Dansky Ullmann:]

So, we’re looking honestly to the totally 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 integral package if you want and based on that we will decide. Right now as we mentioned we’re enrolling or certainly enrolling to 60 milligram cohort and then we will look at that data once we have all the patient enrolled and we’ll decide based on this parameters, how high we want to go, obviously it will depend if we see DLP story, we see that we have well within an optimal biological dose that we think can move forward. That would be the general assessment very standard on its own.

[Unidentified Analyst:]

And do you see going higher than 34 the combo dosing?

[Claudio Dansky Ullmann:]

Can you repeat that, sorry.

[Unidentified Analyst:]

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

[Claudio Dansky Ullmann:]

Well, it’s a possibility, but we’ll have see, we presented data, they share 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 out or if we want go out to 40 milligrams in combination.

[Unidentified Analyst:]

Great. Thank you.

[Operator:]

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

[Adelene Perkins:]

Thanks, Bruce. We’re excited about the opportunity we have with IPI-549 and our team is working hard to rapidly advance to our Phase 1 study. We look forward to providing additional updates on Infinity throughout the year and hope you’ll all have a good evening and thank you for joining us on today’s call. And I apologize again for the technical disruption at the beginning of the call. Thank you.

[Operator:]

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.