Infinity Pharmaceuticals, Inc.
Q4 2018 Earnings Call Transcript

Published: 14 Mar 2019

[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 Full Year 2018. My name is Candice, and I'll 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 would like to introduce your host for today's call, Jayne Kauffman. Please go ahead.

[Jayne Kauffman:]

Thank you, Candice, and good morning, everyone. Welcome to today's call to discuss our recent business progress and review our full year 2018 financial results. With me here today are Adelene Perkins, Chief Executive Officer; Larry Bloch, President; Dr. Sam Agresta, Chief Medical Officer; and Dr. Jeff Kutok, our Chief Scientific Officer. We will open up the call for Q&A following our remarks. The press release issued this morning 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 the full year 2018 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 make updates to 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.

[Adelene Perkins:]

Thanks, Jayne, and thank you to everyone for joining us. We're excited to review the progress we made during 2018 and highlight several recent developments that significantly advanced the value creation strategy we outlined at the beginning of the year. Value creation at Infinity will be driven by compelling clinical data with IPI-549 in areas of significant unmet patient need and access to the resources necessary to generate this data. MARIO-3, the study we announced this morning with Roche/Genentech is a very important milestone in enabling the generation of this data while accessing key resources. We're thrilled to be adding a clinical collaboration with another top tier oncology company in leveraging IPI-549’s unique mechanism of action in reprogramming macrophages to enhance outcomes for patients with triple negative breast cancer or TNBC and renal cell cancer or RCC. A core component of our clinical strategy is to move IPI-549 into early lines of therapy with novel combination. In MARIO-3 we are adding IPI-549 to a newly approved and emerging standard-of-care in the frontline setting. Last week, the FDA granted accelerated approval for the combination of Tecentriq, Roche's PD-L1 inhibitor and the chemotherapy Abraxane or nab-paclitaxel in treating front-line PD-L1 positive triple negative breast cancer patients. The approval was based on results of the IMpassion130 study, and this combination is the first immuno-oncology regimen to be approved in TNBC, is widely accepted to become a new standard-of-care. Immediately on the heels of this approval, we are very pleased to be adding IPI-549 to Tecentriq and Abraxane which could lead to a truly transformative therapy for front-line patients with TNBC. We're also enthusiastic about the potential for mechanistic synergy and combining IPI-549, Tecentriq and the VEGF inhibitor Avastin in front-line patients with renal cell carcinoma. There's an equally significant unmet need for RCC patients and an equally compelling mechanistic rationale for the combination. Jeff will describe the mechanistic and preclinical rationale for both these triple combination front-line therapies in more detail. After which Sam will describe the design and objective of the MARIO-3 clinical study, which we expect to initiate in the third quarter of this year. The data that will be generated in the front-line with MARIO-3 complements the data that will be generated in the second-line with MARIO-275. MARIO-275 being conducted in collaboration with BMS is a randomized Phase 2 study evaluating IPI-549 and Opdivo or nivolumab in immuno-oncology naïve patients with urothelial cancer. MARIO-275 integrates findings from two studies

[Jeffery Kutok:]

Thanks, Adelene. As an important part of our development of IPI-549 as a first and best-in-class drug candidate, we remain committed to optimizing our understanding of the biology of IPI-549 both as a monotherapy and in combination with immune checkpoint inhibitors as well as other agents. Our preclinical work and the in-depth analysis of translational data from our existing MARIO-1 study has contributed to the initiation of new trials, including the previously announced MARIO-275 in collaboration with BMS and today's announcement of MARIO-3 in collaboration with Roche/Genentech. We’ve spoken in detail about the effect of IPI-549 on reducing MDSC levels, which provided a rationale to combine with Opdivo in urothelial cancer, given the association of shorter survival with high baseline MDSC levels demonstrated in CheckMate 275 at last year's AACR Meeting. In addition, preclinical data recently presented by Arcus Bioscience at a Keystone Symposia Meeting focused on mechanisms of immune-based therapy in cancer, showed that IPI-549 synergized with their adenosine receptor inhibitor AB928 in settings with high levels of adenosine. We're therefore excited to see the clinical effects of IPI-549 combined with AB928 and chemotherapy in relapsed/refractory triple negative breast cancer, a collaborative study with Arcus that is expected to start in the second half of 2019. I addition, we have other preclinical collaborations ongoing in various tumor models to support the combination of IPI-549 with other mechanisms of immune-suppression or immune activation and to establish the best targets for further development and expansion. Lastly, I'd like to focus on the mechanistic rationale for pursuing the triple combinations of IPI-549 with the checkpoint inhibitor in either chemotherapy or in anti-angiogenic in front-line TNBC and renal cell cancer as part of our new clinical collaboration MARIO-3 with Roche/Genentech. First, with respect to the combination of IPI-549 and the checkpoint inhibitor Tecentriq, we published extensive preclinical data in multiple cancer models that IPI-549 reprograms macrophages from a pro-tumor immune suppressive function to an anti-tumor immune activating function and in both augment the activity of checkpoint inhibitor therapies, as well as recover the activity of a checkpoint inhibitor resisted model. Second, with respect to combining IPI-549 with chemotherapy or anti-angiogenics I well described in the literature that tumor-associated immune suppressive and pro-growth M2 macrophages accumulate in tumors after chemotherapy or anti-angiogenics. And therefore, contribute to tumor re-growth and revascularization after these treatments. Targeting these newly recruited macrophages of IPI-549 could therefore reverse the effects. To that end we've previously presented that murine tumors treated with IPI-549 after chemotherapy, showed inhibition of tumor re-growth compared to no therapy. And we have internal data that the combination of anti-angiogenic with IPI-549 shows enhanced inhibition of tumor growth. These data provide a clear rationale for treating with IPI-549 and Tecentriq in combination with either Abraxane or Avastin to target the tumor and the tumor microenvironment. I will now turn it over to Sam, who will discuss more on the clinical relevance of these combination studies.

[Samuel Agresta:]

Thanks, Jeff. 2019 will be a really exciting year of execution for us at Infinity as we continue to broaden the development of IPI-549 and expand its therapeutic potential by

[Lawrence Bloch:]

Thank you, Sam. As you heard from Adelene, Jeff and Sam, we're really proud with the progress we've made in 2018 and are absolutely focused on and committed to continue to build on this progress in the year ahead. Early this week we were pleased to receive $20 million in net proceeds from HealthCare Royalty Partners for the monetization of COPIKTRA or duvelisib royalties which we announced last week. These funds combined with our consistent fiscal discipline ensures that we will have the key resources in place to execute on the expanded IPI-549 development plan that we announced today. As of December 31, 2018, we had total cash, cash equivalents and available for sale securities of $58.6 million, compared to $57.6 million at December 31, 2017. We recorded $22.1 million in revenue during 2018, related to the amount from Verastem for the approval by the FDA of duvelisib. This compared to $6 million at this time last year, which was related to the amounts received from Verastem for the successful completion of the duvelisib DUO study. Revenue reported for 2018 does not reflect the recent duvelisib royalty monetization would HealthCare Royalty Partners. R&D expense for 2018 was $19.8 million, compared to $20.8 million for the same period in 2017. General and administrative expense was $14.2 million for 2018, compared to $21.6 million for same period in 2017. And the decrease in general and administrative expense was primarily due to reduction in bonus and stock compensation. Net loss for 2018 was $11.3 million, or a basic and diluted loss per common share of $0.20, compared to a net loss of $41.8 million, or a basic and diluted loss per common share of $0.83 for the same period in 2017. We expect 2019 net loss to range from $30 million to $40 million and we expect to end 2019 with a cash and 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 that our existing cash, cash equivalents and available-for-sale securities will provide cash runway well into second half of 2020. This cash runway includes potential $2 million milestone payment from PellePharm, the private company upon initiation of a Phase 3 study for the hedgehog inhibitor program, which we licensed to them in 2013. And I’d like to finish by reviewing our key 2018 accomplishments, recent developments, as well as our plan for 2019. In 2018, we delivered on our key objectives for the year, which included reporting positive data from the monotherapy expansion in combination with dose escalation portions of our MARIO-1 study and reporting positive data updated from the combination expansion portion of the trial. We did this while also expanding our melanoma and triple negative breast cancer combination cohorts and announcing our clinical collaboration with Bristol-Myers Squibb, Arcus and now the Roche/Genentech collaboration. In addition of MARIO-3 study in collaboration with Roche/Genentech, the Arcus collaboration and the MARIO-275 study in collaboration with BMS to the ongoing MARIO-1 study in collaboration with BMS, Infinity will be evaluating IPI-549 in the anti-PD-1 refractory, the IO naïve and the front-line settings in the total of over 500 patients, while also ensuring a cash runway well into the second half of 2020 and retaining all clinical control and commercial rights of IPI-549. We look forward to updating you on our continuing progress during the course of this year. At this time, we can open the call for questions. Operator?

[Operator:]

[Operator Instructions]. And our first question comes from Katherine Xu, William Blair. Your line is now open.

[Katherine Xu:]

So can you remind us the MARIO-1 in your TNBC patients, any follow-up and details on that? And also, did you see -- were they PD-L1 positive or negative? And also for RCC, I was just wondering the choice of Tecentriq and Avastin because the front-line space is getting quite crowded with the most recently KEYNOTE-426’s success. So the choice there is, is because it's just a convenient with the supply agreement of Tecentriq with Roche or other rationale? And the other question is, have you found from MARIO-1a sort of the rare cancer to go forward so that -- of course right now you're targeting quite major indication from rare cancer to go forward, so that it would take less time and less resources and to get approvals some kind of low hanging fruit, have you been able to identify such special indication? Thank you.

[Adelene Perkins:]

Okay so Katherine, why don't we go through each of your three questions? First on the triple negative breast cancer. As you know in MARIO-1 one of the explicit purposes was to look for patients that would not be expected to respond to nivolumab alone. So we had the both three cohorts of patients in who had immediately progressed on a checkpoint inhibitor and then the triple negative relapsed/refractory because those patients typically don't respond to Opdivo alone. So we presented at SITC, activity, and I'll let Sam elaborate more on that. But what we were very encouraged by is seeing activity there where you wouldn't expect it with Opdivo and that was as a foundation in our discussions with Roche/Genentech that got them enthused to do this collaboration. Sam, you want to elaborate?

[Samuel Agresta:]

Sure. This is Sam. What we presented at SITC was early data in the cohorts, and I'll remind you that you that we did see a nice near partial remission in a very late-line triple negative breast cancer patient. Remember that data was caught in October of 2018, so we'll continue to look at that cohort, that cohort will continue to mature. And in conversations with Roche/Genentech, we certainly shared the information that we have presented and more to outline the way path forward.

[Adelene Perkins:]

And then on your earlier question with respect to renal cell cancer, Jeff described the rationale for combining with a VEGF inhibitor. And then we worked closely with the team at Roche/Genentech to determine what are the best settings to evaluate that combination and there remains a significant need for better treatment for patients with renal cell cancer. And so part of our clinical development is to leverage findings we have out of MARIO-1 but also to expand it. And so given the strong mechanistic rationale for combining with Tecentriq and Avastin and 549, we together decided that renal cell was a good place to test that hypothesis where there remains a significant need.

[Samuel Agresta:]

Yes, and this is a Sam. Again one of the key assets of 549 is the safety profile. So as we think about the changing paradigm and standard-of-cares in renal cell cancer, in this case, it makes preclinical sense and it makes clinical sense given the safety profile of drug and the activity to be able to combine in front-line patients. So we look forward to starting that Phase 2 study.

[Adelene Perkins:]

And then your third question was about rare cancers and whether we could pave a path to an approval. And I'm going to turn this over to Sam, but I'll remind you one of the reasons we were so excited to have Sam join the effort is, he has a pretty extraordinary track record in working very closely with the FDA and when he was Agios got both IDHiFA and TIBSOVO approved on single arm Phase 1 data. So Sam is all about any trial can be approved if you're really showing a significant benefit in a well designed study and a well designed patient population. And he has certainly brought that perspective to our development of 549. And Sam?

[Samuel Agresta:]

So this is Sam and I -- again I think rare versus opportunity for patients are probably the same. So what I would consider the opportunity in -- for MARIO-1 is the unmet need -- the opportunity to allow for retreatment with checkpoint inhibitors in late-line cancers. That could be in several different indications. The FDA has precedents where they've given labels to checkpoint inhibitors that are agnostic of histologic indications. So TNBC high cohort, the cohorts where we mandate an immediate prior checkpoint inhibitor resistance, are opportunities for us to help patients very quickly. So we’re looking forward to see that data maturing.

[Operator:]

And your next question comes from Anupam Rama of JP Morgan. Your line is now open.

[Tessa Romero:]

Hi. This is Tessa on for Anupam this morning. Thank you for taking my questions and congrats on all the progress. So looking forward to next data from the program -- from the MARIO-1 program, how should we be thinking about next medical meetings you might think about targeting for some more of this expansion data and kind of the scope of a potential update we could see maybe in 2019? And then maybe on the MARIO-3 trial announced this morning. What are the gating factors to getting this trial started in the third quarter? I'm curious how you are thinking about timeline for enrollment, potential synergies with other trials? Thanks so much, guys.

[Adelene Perkins:]

Thanks, Tessa. So MARIO-1 as we mentioned in the prepared remarks is continuing to mature. And any updates on data from next will be driven by the relevance to our existing studies MARIO-3, MARIO-275 or to the extent that they inform a new study that we want to initiate. And so we'll continue to monitor that data and to the extent that it applies to our going forward development we are reporting the data. In many ways MARIO-1 has already delivered what we hoped and it showed that IPI-549 is very well tolerated, is active. And it was a key to driving based on the triple negative activity we saw with MARIO-3 collaboration, as well as based on the MDSC results, the CheckMate 275. With respect to any updates on MARIO-3, as well as our other study, we'll provide more granular guidance on the timing for enrollment in data, once we have more information on the enrollment kinetics as those studies are initiated later this year. And the team -- there's really nothing that’s gating to us going. The team is forging ahead working with our CRO selecting sites and are very aggressive and optimistic about our ability to get that up and going in the third quarter.

[Lawrence Bloch:]

Right after this call, we are going to cut loose Sam to go and kick-off meeting for the trial today. So we're absolutely focused on execution.

[Operator:]

Thank you. [Operator Instructions]. And I'm showing no further questions at this time. I’d like to turn the conference back over to Adelene Perkins for closing remarks.

[Adelene Perkins:]

Thank you. And thank you everyone for joining us this morning. We're very excited about the opportunity we have with IPI-549 and we look forward to updating you on our progress throughout the year. So have a good day, everyone. And thank you for joining us.

[Operator:]

Ladies and gentlemen, thank you for participating in today's conference. This does conclude the program. And you may all disconnect. Everyone, have a great day.