Infinity Pharmaceuticals, Inc.
Q4 2017 Earnings Call Transcript

Published: 16 Mar 2018

[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 Fourth Quarter and Full Year 2017. My name is James and I will be your 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. Now I'd like to introduce your host for today’s call, Jane Colfin [ph]. Please go ahead.

[Unidentified Company Representative:]

Thank you, James, and good afternoon everyone. Welcome to today’s call to discuss our recent business progress and review of our fourth quarter 2017 and full year financial results. With me here today are Adelene Perkins, Chief Executive Officer; Dr. Claudio Dansky Ullmann, Senior Vice President, Clinical Development; and Larry Bloch, President; Jeff -- Dr. Jeffery Kutok, our Chief Scientific Officer is also here to take questions and we’ll open up the call for Q&A following our remarks. The press release issued this afternoon detailed 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 the full year 2017 and in our 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.

[Adelene Perkins:]

Thanks, Jane. Good afternoon everyone and thank you for joining us. Today, we are pleased to report on our recent progress at Infinity, including advancements we’ve made with IPI-549, our first-in-class oral selective PI3-kinase gamma inhibitor. We at Infinity have a significant opportunity with IPI-549, which represents a novel approach within immuno-oncology and is the only selective PI3-kinase gamma inhibitor in clinical development. The Infinity team and our investigators are advancing the clinical development of IPI-549 with a great sense of urgency to bring this potentially transformative treatment forward for patients. IPI-549 targets and plays a unique role in reprogramming macrophages, from a pro tumor to an anti-tumor function whilst reducing immune suppression and increasing immune activation. We are evaluating IPI-549 both as a monotherapy and in combination with nivolumab a PD-1 immune checkpoint inhibitor in a robust Phase 1/1b clinical study in approximately 200 patients with advanced solid tumors. We're very encouraged by the data for IPI-549 including this clinical data we presented at the Society of Immunotherapy of Cancer or SITC annual meeting in November, which helped to build great momentum for the program and demonstrate IPI-549's potential. First of all, IPI-549 is clinically active having shown single agent activity including an objective response in patient with mesothelioma. This is significant given that aside from checkpoint inhibitors very few if any immuno-oncology agents show objective responses as a monotherapy. Second, IPI-549 has potential as a combination therapy based on demonstrated activity in combination with nivolumab including an objective response in a patient with adrenocortical cancer. Third, IPI-549's activity is on mechanism. We have shown that IPI-549 decreases pro-tumor immune suppression and increases anti-tumor immune activation. This is particularly meaningful given the heavily pretreated and heterogeneous nature of the all-comer solid tumor patient population being treated. Fourth, and importantly, IPI-549 is very well tolerated with no-dose limiting toxicities observed due to monotherapy. IPI-549 is also well tolerated in combination with nivolumab which is particularly important given the expectation that immuno-oncology drugs will be most effective when administered in combination therapy. We are pleased with the rapid progress we are making with the study. The monotherapy and combination dose escalation components of the study and will very quickly after the monotherapy expansion component of the study, building great enthusiasm and momentum for the combination expansion cohorts which are now enrolling. We've expanded the study to include three new combination cohorts of IPI-549 plus Opdivo, and enrollment is now open for all six disease specific combination cohorts with the seventh cohort in patients with high baseline blood levels of myeloid derived suppressor cells or MDSCs that will open for enrollment in the next few weeks. Our combination expansion cohort underway our design to evaluate several distinct hypothesis of IPI-549 in combination with nivolumab, one is IPI-549's ability to overcome resistance to checkpoint blockade which is being tested in three separate cohorts in patients with non-small cell lung cancer, melanoma and squamous cell carcinoma of the head and neck. Another is IPI-549's ability to work for checkpoint inhibitors have limited activity, effectively turning cold tumors hot, which is being tested in patients with triple negative breast cancer who have not been previously exposed to checkpoint inhibitors. In addition, we're seeking to confirm IPI-549's activity in patients with mesothelioma, adrenocortical carcinoma and high baseline blood levels of MDSCs where initial responses with IPI-549 have been observed. We expect to have a flow data throughout 2018 starting in the second quarter when we expect to report data from the monotherapy expansion portion of the study, which importantly will include translational -- clinical and translational data from paired tumor biopsies. The completed combination dose escalation evaluating IPI plus nivolumab, and early data from combination expansion cohort evaluating IPI plus nivolumab in predefined disease specific patient population, though this will be very preliminary data, as we just recently began enrolling this combination expansion cohort. In the second half of 2018, we look forward to providing more mature data from the disease specific combination expansion cohort as well as initial data on the MDSC high combination expansion cohort with clinical and translational data including insights from paired tumor biopsies. To ensure that we deliver on significant opportunity before us with IPI-549, we're continuing to attract great experienced talent to support our efforts. We recently announced that David Beier is joining our Board of Directors. David is a Managing Director of Bay City Capital and spent two decades as part of the senior management teams for Amgen and Genentech. He brings invaluable perspective regarding strategy for entrepreneurial biotechnology firms and the industry in general. In addition Dr. Marie-Louise Fjällskog has been appointed as Vice President of Clinical Development. Dr. Fjällskog has over 25 years of experience in clinical oncology, translational research, and drug development. She joins Infinity from Novartis, where she served as a Clinical Oncology Program Leader, and was the global lead for several immuno-oncology programs, including those targeting CSF-1 and PD-1. We're also happy to announce the promotion of Suresh Mahabhashyam, to Vice President of Safety and Risk Management. Dr. Mahabhashyam has over 20 years of experience in medical practice and epidemiology and has spent the last decade focused on drug development at Infinity, Alexion and Allergan. We've also established a Scientific Advisory Board with several thought leaders in immuno-oncologycology. These include Dr. Dmitry Gabrilovich, a thought leader in myeloid cell biology from the Wistar Institute; Dr. Roy Herbst, a leader in lung cancer treatment and research and Chief of Medical Oncology at Yale Cancer Center; Dr. Stephen Hodi, a leader in the development of immune therapy and the Director of the Center for Immuno-Oncology at Dana-Farber Cancer Center; and Dr. David Munn, a pioneer in T-cell activation IDO research Georgia Cancer Center. Together, we look forward to delivering on the clinical promise of IPI-549, as a potentially first-in-class immuno-oncology drug. We continue to be driven by the magnitude of unmet needs for better treatment options for patients. The more we learn about IPI-549 the more confident we are that it can play an important role in addressing these needs. And now I'll turn the call over to Claudio.

[Dr. Claudio Dansky Ullmann:]

Thanks, Adelene. This afternoon, I will provide updates on the progress we've made in our clinical study of IPI-549. 2018 will be an important year for the program. The trial has generated a lot of positive momentum which has further accelerated in the past few months as combination expansion cohorts began enrolling. IPI-549 is the only selective PI3-kinase gamma inhibitor in the clinic and represents a novel approach within the field of immune-oncology, targeting macrophages in the immune-suppressive tumor microenvironment. This field continues to emerge as a compelling approach to reduce immune suppression. As we've discussed previously, our rationale for our multifaceted Phase 1/1b clinical study was based on the mechanism that targeting PI3-kinase gamma with IPI-549, reprograms tumor associated macrophages from an M2 or pro-tumor to an M1 or anti-tumor function. In addition, for clinical data demonstrated that IPI-549 overcomes resistance to checkpoint inhibition and enhances activity of checkpoint inhibitors, which was the basis for our checkpoint combinational therapy strategies. The data from monotherapy dose escalation portion of the trial serves as an underpinning for the entire study, and we are encouraged by the favorable results that represented at SITC showing the IPI-549 was well tolerated and clinical active dose once daily. Among 18 patients evaluable productivity, there was a 44% clinical benefit rate, defined as patients who had relied on treatment for at least 16 weeks including one partial response in a patient with advanced peritoneal mesothelioma who has remained on treatment for over one year. Among 19 patients evaluable for safety, nose dose-limiting toxicities were identified and a maximum tolerated dose was not reach. The majority of side effects reported were Grade 1 or Grade 2, and there were no treatment related serious adverse events of deaths. The pharmacokinetic and pharmacodynamics properties of IPI-549 appear favorable with near complete and sustaining inhibition of PI3K-gamma are doses at or above 20 milligrams QD, supporting once daily dosing of IPI-549. Based on these findings, IPI-549 dose of 60 milligrams QD was selected as the dose for the monotherapy expansion cohort. At SITC for the first time, we also reported early translational data from peripheral blood samples of patients in the monotherapy dose escalation. Here the data show that IPI-549 treatment across multiple tumor types on dose levels resulted in reduced immune suppression with reinvigoration or proliferation of exhausted CD8 positive T-cells and increased immune stimulation, with upregulation of interferon-gamma responsive factors. Additionally, initial translational data show that clinical benefit was associated with increased numbers of immune-activated monocytes suggesting a biologic correlate can be identified in patients who remain on treatment longer. The monotherapy expansion portion of the trial is now fully enrolled and we have completed the combination does escalation portion. We will be reporting data on these in the second quarter of 2018. Six disease specific combination expansion cohorts are open for enrollment at the recommended Phase 2 dose of 40 milligrams once daily of IPI-549 plus nivolumab at 240 milligrams every two weeks in patients with non-small cell lung cancer melanoma, triple negative breast cancer, head and neck cancer, mesothelioma and adrenocortical carcinoma. The cohort of patients with high baseline blood levels of myeloid derived suppressor cells will be open for enrollment in the next few weeks. We look forward to sharing more matured data throughout this year that will be crucial to the development of this first-in-class product candidate. Now, Larry will review our financial results for the quarter.

[Larry Bloch:]

Thanks, Claudio. 2017 was the year of important progress for Infinity and IPI-549. Strong financial discipline has enabled us to extend our cash runway from the first quarter 2019 into the third quarter 2019 thereby ensuring that we have the key resource in place to execute our development plans for IPI-549. As of December 31, 2017 we had total cash, cash equivalents and available-for-sale securities of 57.6 million, compared to 92.1 million at December 31, 2016. Revenue for the year was $6 million, all of which related to the milestone payment from Verastem. Revenue for 2016 was 18.7 million related to Infinity's previous collaboration agreement with AbbVie. R&D expense for 2017 was $20.8 million, compared to 119.6 million for 2016. The decrease in R&D expense was largely related to the 2016 restructuring activities and the out-licensing of duvelisib, duvelisib to Verastem. General and administrative expense was $21.6 million for 2017, this compares to 42.2 million in 2016. The decrease in G&A expense was primarily due to 2016 restructuring activities. Net loss for 2017 was $41.8 million or a basic and diluted loss per common share of $0.83, compared to a net loss of 30.1 million, or a basic and diluted loss per common share of $0.61 for 2016. Our updated 2018 financial guidance is as follows

[Operator:]

Thank you. [Operator Instructions] Our first question comes from Katherine Xu with William Blair. Your line is now open.

[Katherine Xu:]

I just got a quick question. In the patients who are MDSC high, what are the other biomarkers that are correlating to that phenotype? For example PDL status or idol status, anything you can comment?

[Adelene Perkins:]

I'm going to turn that over to Jeff Kutok, who is our Chief Scientific Officer and who lead the discovery of IPI-549, as we said in the prepared remarks, we're very excited about the MDSC high cohorts which will be opening soon and Jeff can get into the details behind your question of other associated biomarkers.

[Dr. Jeffery Kutok:]

Hi Katherine, it's Jeff. So if I understand your question correctly, are you asking about other markers on the myeloid derived suppressor cells or other associated biomarkers that may be associated with that cohort of patients?

[Katherine Xu:]

Yes, so let's say PDL-1 other tumor cells in those patients for MDSC high. I don't know whether those are looked at.

[Dr. Jeffery Kutok:]

As I've stated that you know we're working on -- working through and that we're hoping to present on future meetings.

[Operator:]

Thank you. Our next question comes from Anupam Verma with JP Morgan. Your line is now open.

[Eric Joseph:]

It's Eric in for Anupam. Thanks for taking the question and congrats on the progress. Just looking ahead to the 2Q data readouts here based on what you're seeing in terms of patient recruitment and the combination expansion cohort, cohorts rather with nivolumab. Is there particular histology or set of histologies you have us focused on ahead of data? Any color you can kind of provide around indication in patient numbers will be helpful?

[Adelene Perkins:]

Sure, so the combination expansion cohorts which we just begun enrolling are in six defined diseases and so that is in the non-small cell, melanoma, head and neck, adrenocortical and mesothelioma and triple negative breast cancer. So those are the six disease types and for each of those there are different hypotheses being tested with respect to prior exposure to PD1. Beyond that, it's because they just opened it's really too early to say what will be presented, we can say is that the data will be early in the second quarter what will be our complete data set is from the combination dose escalation at which we determine our recommended Phase 2 dose. And Claudio, anything you could add.

[Dr. Claudio Dansky Ullmann:]

Just to further clarify, if I understood also part of your question, that all the cohorts are currently open, who're getting from investigators, we're not focusing in a particular tumor type in terms of accelerating the enrollment or generating data. If patients are coming with the different indications are being enrolled in the different sites, so we will have to see as we have more enrollment in a few years down the road, you know which ones are doing more or getting more patients. But right now we're open for all of them.

[Eric Joseph:]

I guess maybe with the dose escalation combination portion fully accrued. Can you just remind us of the number of patients or at least the number of sort of dose levels that you were evaluating here and just maybe how you might be thinking about the mix of tumor indications there?

[Adelene Perkins:]

Sure, so I'll lead that off and then turn it to Claudio to amplify, so we tested three different dose levels, we were working with the approved dose level for nivolumab at 240 mg once every two weeks and we did three dose levels of IPI-549 as oral once daily, that was at 20 mg, 30 mg and 40 mg and selected the 40 mg once daily as our go-forward dose for the combination expansion cohort. Well, the total of 31 patients that they were in the combination dose escalation.

[Operator:]

Thank you. Our next question comes from Mike King with JMP Securities. Your line is now open.

[Mike King:]

Along similar lines, I am just wondering if you could tell us in the Phase 1/b I assume -- I am assuming that's where you've the MDSC high patients or is that also in the Phase 2 combination?

[Adelene Perkins:]

No, that's in the Phase 1/1b portion, that's one of our seven expansion cohorts.

[Mike King:]

And so would it roughly be one seventh of the 200 that you expect to enroll? Or is it too early to say precisely what that number would look like?

[Adelene Perkins:]

No, no we know -- for each of our seven expansion cohorts I can tell you that the enrollment number is still -- it will be 20 patients each for non small cell lung cancer melanoma and head and neck cancer, it will be 29 patients in triple negative breast cancer, it will be 10 patients in mesothelioma and adrenocortical, and 20 patients with high MDSC levels and as we've mentioned, the cohort for patients who have high MDSC will be opening soon, so we won't have data on that cohort in the second quarter, we’ll data on that in the second half of the year.

[Mike King:]

So, further to that cohort, can you tell us if -- are you going to be doing, any kind of immunophenotyping in other words looking for the portion of M1 versus M2, pre and post treatment with IPI?

[Adelene Perkins:]

So, I'll turn that to Jeff to address.

[Dr. Jeffery Kutok:]

Yes, so we're continuing to do a full complement of translational studies in all of these cohorts including immunophenotyping in the patients in the expansion combination cohorts where -- and the monotherapy expansion cohort where we are obtaining per and on treatment biopsies to evaluate changes in the tumor microenvironment.

[Mike King:]

Any imaging stage included in that?

[Dr. Jeffery Kutok:]

No.

[Mike King:]

And then just in the combination on -- do you suspect you will be getting a -- I assume you'll be getting patients who have responded and relapsed, patients who have never mounted to response? Do you have any idea sort of your ideal breakdown between those two cohorts to really get a clear signal out of the combination without nivo?

[Dr. Claudio Dansky Ullmann:]

At this point, we really don’t know. We discussed it a lot. We’ll see as enrollment grows and what type of patients flow into the cohorts. We’ll see how that turns out.

[Adelene Perkins:]

And that's for the three cohorts in long along melanoma and head and neck where that’s an inclusion criteria is that patients will either have developed resistance or have de novo resistance to a checkpoint inhibitor. The other cohorts like in triple negative breast cancer we're going to checkpoint inhibitor naïve patient population.

[Dr. Claudio Dansky Ullmann:]

Yes, so in other words we're being agnostic.

[Mike King:]

Sorry, couldn't hear that last?

[Dr. Claudio Dansky Ullmann:]

That's for mesothelioma and adrenocortical carcinoma were being agnostic so patients that have been exposed or not previously to point -- could be enrolled for those two cohorts.

[Mike King:]

But [indiscernible] that's sort of purely not checkpoint naive.

[Dr. Claudio Dansky Ullmann:]

Yes, [indiscernible] is the only one purely checkpoint naive, correct.

[Mike King:]

Sorry, I believe I cut you off.

[Adelene Perkins:]

No, we're just going to say we have the three that are in patients who have developed resistance. We have the one in patients who are naïve and then we have the other three that checkpoint inhibitors, not part of the hypothesis. So, that’s not been an inclusion criteria.

[Operator:]

Thank you. [Operator instructions] Our next question comes from Jim Birchenough with Wells Fargo Securities. Your line is now open.

[Yanan Zhu:]

Thanks for taking the question. This is Yen dialing in for Jim. So first question curious about, what are the typical tumor types, that's associated with high MDSC? And whether you are focusing on your enrollment in that high MDSC cohort in those tumor types?

[Adelene Perkins:]

Thanks Yen. I’ll start that off and then turn it over to Jeff. We're going to learn a lot about MDSC levels in patients as we use that as a screening mechanism. So we've looked with a collaborator. We're working with metrics in this test and they have shared that in general patients meet the criteria for high MDSC in about 30% to 50% of the patients. But Jeff, can discuss this in more detail.

[Dr. Jeffery Kutok:]

Yes, I think with respect to this cohort, the exciting thing is we're being agnostic to tumor type and we're focusing on patients who have high circulating MDSC levels of cancer. So, you see a range of MDSC levels in patients with cancer that seems to increase with stage of disease. And, so we're hoping that this biomarker will identify patient population that sensitive to IPI-549 plus nivolumab and that sensitivity will translate across multiple different tumor types.

[Adelene Perkins:]

The other thing that I would highlight is that to ensure that we're not -- the MDSC high cohort is not competing with the enrollment for other disease specific patients who qualified for the six disease specific cohorts will not be eligible for the MDSC cohort. But we will go back and do a retrospective analysis on the MDSC levels of the patients in those six disease specific cohort. So we'll have both the retrospective on all of the patients in the combination expansion, but the pre-screening in the MDSC targeted cohort.

[Yanan Zhu:]

Got it, that’s very helpful. And also could you talk about, if there's any correlation between MDSC and tumor associated to the macrophages and also perhaps with less effect does 549 have specifically a MDSC cells?

[Dr. Jeffery Kutok:]

Yes. So, yet the tumor-associated macrophages, the M2, immunosuppressive macrophages are highly related functionally to the circulating myeloid derive suppressor cell. They have a very similar ability to inhibit T-cell activation and proliferation. We've shown pre-clinically in our studies, published in Nature in 2016 that IPI-549 can overcome the suppressive effect of MDSCs that we generated in culture from human blood on the ability to -- T-cells to proliferate, so 549 can overcome the suppressive effects of MDSCs in vitro. So, we're optimistic that we’ll see similar effects on MDSCs that we would on tumor associated macrophages with IPI-549.

[Adelene Perkins:]

We're also interested in this cohort because there's been published data that in patients with high level of MDSCs, they don’t respond it well to checkpoint inhibition which makes sense given the immuno-suppresive nature of those MDSCs, and so that's where we hope that we can reverse that trend by adding 549.

[Yanan Zhu:]

And also in your translational works, that's you have done for the dose escalation arms as well as for the monotherapy dose expansion arms. Have you got a chance to look at MDSC levels and also the effect of 549 on those markers?

[Adelene Perkins:]

So, what we need to public today is that in some of our clinical responses in our Phase 1/b trials, these patients have had high baseline levels -- blood levels of MDSCs. And we're looking forward to providing a more complete picture on the MDSCs and associated other clinical and translational data in our upcoming presentation.

[Adelene Perkins:]

And the data that Jeff was referring to, it was included in our SITC Presentation in November where we showed -- Dr. Holmes in his presentation showed that there was -- that patients who had responded had high MDSC level.

[Operator:]

Thank you. [Operator Instructions] At this time, I am showing no further questions. So, I'd like to turn the call back to Adelene for closing remarks.

[Adelene Perkins:]

Thank you very much, James. We're excited about the opportunity we have with IPI-549, and we look forward to updating you all throughout 2018. Have a good day everyone and thank you for joining today's call.

[Operator:]

Thank you. Ladies and gentlemen that does conclude today's conference. Thank you very much for your participation. You may now disconnect. Have a wonderful day.