Infinity Pharmaceuticals Inc (INFI) 2012 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 first-quarter 2012 financial results. My name is Mary, 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.

At this time I would like to introduce your host for today's call, Ms. Jaren Madden, Director of Investor Relations and Corporate Communications at Infinity. Please go ahead.

Thank you Mary, and good afternoon everyone. Welcome to today's call to discuss our recent business progress and review our first-quarter 2012 financial results. With me here today are Adelene Perkins, President and Chief Executive Officer; Julian Adams. President of R&D; and Gerald Quirk, Vice President of Corporate Affairs. Following our remarks, we will open up the call for Q&A.

The press release issued earlier today details our results and is available on our website at infinity.com. Please note that during this call, we may make forward-looking statements about our future expectations and plans, including clinical development milestones and financial projections. It is possible that our actual results may differ materially from what we project today, due to the factors risk described in the Risk Factor Section of the Form 10-Q for the first quarter of 2012 that we filed this afternoon.

While these forward-looking statements represent our views as of today, they should not be relied upon in the future as representing our then current view. We may update the statements in the future, but are not taking on an obligation to do so. With that, I'd like to turn the call over to Adelene.

Thanks, Jaren, and welcome everyone. Thank you for joining us on the call today. We continued to make important advances across our pipeline during the past few months. With six clinical trials underway across our three programs, we believe we have one of the broadest and most exciting pipelines of any clinical stage biotech company.

Each of our development programs is in multiple clinical trials designed to address diseases with significant unmet needs. With data anticipated from four of our six trials in the second half of this year, and read-outs from the remaining two trials expected by the end of 2013, we have several value inflection points over the next 6 to 18 months.

We believe that the success in any one of the indications we are pursuing provides both a path to registration and a foundation on which we can build the Company. We began the year with considerable financial strength to advance our business.

Our current cash and investments, combined with our strategic alliance with Purdue and Mundipharma, provide us with significant funding to support our Hedgehog, PI3 kinase, and early discovery programs through 2013. Looking ahead, positive data from our existing trials will be the most important driver of our future success.

Good data will ensure access to minimally dilutive capital in 2014 and beyond, and enable us to progress our programs to approval and launch. We have all the key elements in place, programs that we are executing thoughtfully and strategically on the basis of compelling scientific rationale, a strong financial foundation, and an experienced team.

With full US commercial rights to all of our oncology and inflammation programs, and potential for substantial royalties on sales outside of the US, we are well on our way to becoming a sustainable, fully integrated biotech company. With that, I'll turn the call over to Julian to provide a review of our program.

Thanks. As Adelene mentioned, we currently have six clinical trials underway; two in each of our three development programs. Saridegib, or IPI-926, our oral molecule targeting the Hedgehog pathway by inhibiting smoothened; retaspimycin hydrochloride, or IPI-504, our novel Hsp90 inhibitor, and lastly IPI-145, our potent oral inhibitor of PI3 kinase delta and gamma.

Let me begin with our Hedgehog program. Malignant activation of the Hedgehog pathway occurs in a broad range of cancers through multiple mechanisms, including signaling directly to tumor cells, signaling to tumor progenitor cells, and finally signaling to the tumor microenvironment.

We are pursuing a development strategy with saridegib aimed at ultimately exploring all three biological mechanisms. Currently we are evaluating saridegib in Phase 2 trials on chondrosarcoma and myelofibrosis. In chondrosarcoma it is believed that there is [adochrine] signaling of the Hedgehog pathway within the tumor cell, and inhibiting this pathway can suppress tumor growth.

As chondrosarcomas are largely resistant to chemotherapy and radiation, the standard therapeutic strategy is surgery. Patients with advanced, inoperable disease have no currently approved treatment options. We are excited to about developing saridegib in this indication, as we have the potential to change the treatment paradigm.

We are conducting the first ever double-blind randomized placebo-controlled trial in chondrosarcoma. In this rigorously designed Phase 2 trial, we are enrolling patients who have histologically confirmed, conventional chondrosarcoma, and [centrally] reviewed radiographic progression within the past six months. We believe these strict inclusion criteria should ensure a homogenous patient population and enable us to clearly interpret the data.

The primary end point is progression-free survival, as defined by the [sis] criteria and determined by blinded radiology review. We are on track to complete enrollment of approximately [140] patients at about 50 sites globally in the second half of 2012. We anticipate reporting data in the first half of 2013.

If the data are compelling, we plan to approach the FDA and the European Medicines Agency to discuss our next steps, including the possible submission of an NDA based on the Phase 2 data. Positive data would also embolden us to initiate clinical development in additional sarcomas. At this time, pre-clinical explorations of potential indications is ongoing.

Let me now turn to myelofibrosis, a malignancy characterized by an abnormal hematopoietic stem cells, leading to pathogenic fibrosis. We are evaluating saridegib in exploratory open label Phase 2 trial, designed to test the hypothesis that inhibiting the Hedgehog pathway could improve the underlying fibrosis associated with this disease.

The primary end point is a response rate according to the International Working Group criteria. As we stated in our last call, the first evaluable cohort of 12 patients has been enrolled. If we see sufficient activity in this group, we will further expand the trial for a total of 35 patients.

We anticipate presenting data from this study at a medical meeting in the second half of this year. JAK2 inhibitors have been shown to relieve symptoms associated with myelofibrosis, and so we may explore saridegib in combination with roxolitinib. We also believe that positive data from our myelofibrosis trial could serve as a foundation to explore saridegib in other diseases characterized by fibrosis. Beyond these two trials, we believe that saridegib has tremendous potential across a broad range of malignancies.

Last month we presented new pre-clinical data at a mini symposium session at the AACR national meeting, demonstrating that the anti-tumor activity of saridegib in models of residual disease in which malignant cells remain present after primary treatment. These data show that the ability of saridegib to delay tumor recurrence is time-dependent, emphasizing the importance of administrating saridegib immediately after tumor masses have been optimally debugged by surgery, chemotherapy, or radiation.

These data provide a strong rationale for the development of saridegib in residual disease settings, including ovarian cancer and small cell lung cancer, and also provide insight to the design of potential future clinical trials. Overall, we remain very enthusiastic about the potential of saridegib, and look forward to updating you on future development and progress.

Turning now to our Hsp90 program, let me first take a step back and provide our perspective on Hsp90 as a therapeutic product. Hsp90 is a molecular chaperone that is often exploited by cancer cells to support oncogenic client proteins and buffers cellular stresses induced by malignancy. Cancer cells are more dependent on Hsp90 than normal cells, and are therefore more susceptible to Hsp90 inhibition, making Hsp90 an ideal target in oncology.

In non-small cell lung cancer specifically, the tumors of smokers have higher mutation loads, and may therefore have an increased dependent on Hsp90. Because Hsp90 plays a key role in diverse oncogenic pathways critical to tumor growth and survival, an addition of this target may provide a novel approach to treating cancer.

Our Hsp90 inhibitor, retaspimycin hydrochloride, is a naturally derived product that preserves the activity of its predecessor in the ansamycin class with Hsp90 inhibitors by overcoming the prohibitive formulation issues and toxicities associated with early ansamycin.

Unlocking the potential of Hsp90 inhibition requires finding an optimal therapeutic index that maximizes activity and minimizes toxicity. We believe that we have achieved that, an optimal therapeutic index, and we're testing this hypothesis in two lung cancer trials in patient subpopulations with limited treatment options.

The first trial is a Phase 2 study comparing retaspimycin with docetaxel to docetaxel plus placebo in approximately 200 second- or third-line non-small cell lung cancer patients who are heavy smokers and who are naive to docetaxel treatment. This is a rigorously designed trial. It is double-blinded, randomized, and placebo-controlled, with a primary end point of overall survival. Other end points include progression-free survival and overall response rate.

We are also evaluating the relationship between survival and a predictive biomarker identified by our in-house molecular pathology group using data our Phase 1B study. We are on track to complete enrollment in the second half of 2012, with final data anticipated in the second half of 2013. Data from this study will inform our Phase 3 plans, including specific patient sub-populations and trial size.

Our second trial of retaspimycin hydrochloride is an exploratory single-on Phase 1B2 trial, in a combination with an mTOR inhibitor, everolimus, in non-small cell lung cancer with tumors activating KRAS mutations.

We are currently in the Phase 1B dose finding portion of the trial, and expect to report top line data from this phase in the second half of 2012. Following the Phase 1B portion, we will evaluate safety and activity in a cohort of 12 patients. If we see sufficient activity, we will enroll an additional 32 patients. The end point of the Phase 2 portion of the trial is overall response rate. Since neither agent is expected to elicit a response on its own, positive data from this trial could lead directly to a Phase 3 registration trial.

Lastly, I will briefly review IPI-145. Our PI3K program is unique because IPI-145 is the only delta gamma inhibitor in clinical development. PI3K delta and gamma play key roles in immune functions. As such PI3K's delta gamma inhibitor has therapeutic potential in hematologic malignancies, as well as inflammation and autoimmune diseases. We are pursuing a parallel development path with IPI-145.

Our Phase 1 open label dose escalation study evaluating safety, activity, and pharmacokinetics of IPI-145 in patients with advanced hematologic malignancies is ongoing. We expect to present data from this trial at a medical meeting in the second half of this year. Once the dose escalation portion of our trial is complete, we plan to expand the trial in specific key malignancies to further assess the safety and clinical activity of 145.

We think about three broad areas of potential development within the hematologic space. The first is in hemamalignancies already validated with a delta-specific inhibitor, which is chronic lymphocytic leukemia, non-Hodgkins lymphoma, and mantle cell lymphoma. The second is in indications in which a delta-specific inhibitor has shown sub-optimal or no activity, such as diffuse large b cell lymphoma, AML, and multiple myeloma. Third, we may consider indications that have not yet been tested by an delta-specific inhibitor.

As we announced on our last call, we successfully completed a Phase 1 double-blind, randomized, placebo-controlled trial of IPI-145 in healthy volunteers. We were pleased with the tolerability, pharmacokinetic, and pharmacodynamic profile observed in this trial, and plan to present these data at a medical meeting in the second half of 2012.

This trial supports Phase 2 development inflammation, and we anticipate announcing the specific indication in the second half of 2012 when the study begins. With that, I will turn over the call to Gerald, to review our financial results.

Thanks Julian. As Adelene touched on earlier in the call, our solid financial strength enables the continued advancement of our clinical programs toward key milestones. Our strategic alliance with Mundipharma provides funding for R&D expenses of up to $110 million for 2012, and $147.5 million for 2013.

Our current cash and investments, together with the committed R&D funding, provide us with cash runway to 2014 under our current operating plan. With that, I'll review our top-line financial results for the first quarter of 2012. Total revenues for the quarter were $25.2 million, compared to $27.2 million for the same period of 2011.

In the first quarter of 2012, revenue was comprised of $24.2 million for reimbursed R&D services and $1 million from the amortization of deferred revenue associated with the grant of rights and licenses under our strategic alliance with Mundipharma. This compares to $26.2 million and $1 million, respectively, for the same period last year.

Our R&D expense for the quarter was $28.6 million, compared to $24.3 million for the same period in 2011. The increase in R&D expense for the first quarter of 2012 compared to the same period of 2011 was related primarily to advancing the clinical development in all three of our ongoing programs.

G&A expense for the quarter was $6.8 million, compared to $4.9 million for the same period 2011. The increase in G&A expense for the first quarter of this year compared to the same period of last was related primarily to increases in early commercial development and patent expenses, as well as increased head count to support our advancing development programs.

Net loss for the quarter was $10.7 million, or a basic and diluted loss per common share of $0.40, compared to $2.3 million, or a basic and diluted loss per common share of $0.09 for the same period in 2011. At the end of the first quarter, we had cash, cash equivalents, and available for sale securities of a $104.9 million, compared to a $115.9 million at December 31, 2011.

In summary, the business is strong, and we look forward to advancing all six clinical trials towards key inflection points. With that, let me now turn the call over to Mary for questions.

Certainly.

(Operator Instructions)

[Carter Gould], Rodmand & Renshaw

Stepping in for Mike today. Two questions. First one is, we were wondering if you're looking into IDH1 and 2 mutations in your Phase II chondro trial? And the second question is, if there's any plan or intentions in doing a study of retaspimycin in Braf positive melanoma, given the pre-clinical activity of HSP90 inhibitors that's come out recently?

Two excellent questions. We have tissue collection from all patients entering the study. This will be archival tissue, for the most part, and we do plan to look at a variety of biomarkers, including a IDH1 and IDH2.

Carter, with respect to second question. We have a long list of additional indications that we'd like to pursue with retaspimycin hydrochloride based on the strength of pre-clinical data and client proteins of HSP90, and we have not yet disclosed how we have prioritized those, but you'll hear more as we go forward.

Mani Mohindru, Thinkequity.

I was really looking forward to the second half of this year for all the data releases. But maybe couple of quick questions on two of your programs. One, the myelofibrosis program with the saridegib. As I see it. I am, I think, aware of one other competitor who's doing, who's pursuing a similar indication with their Hedgehog pathway inhibitor. Any insight that you can get from that program, and if I'm not wrong, that program was initiated earlier than your's. So, just wanted to get a quick read from you in terms of opinion leader feedback, or what's going on with that trial to sort of get a sense of where we could see your compound fitting in myelofibrosis?

Well, we are aware that there are competitors, one of which is pursuing key malignancies and has reported a single response in myelofibrosis, including reduction in fibrosis. Of course, that's anecdotal. It was part of a Phase I dose escalation study. So, we will not try to over-interpret what was reported at a scientific meeting, namely ASH last year, but we continue to pursue and are encouraged that on its own merits, saridegib is worthy of investigation in this disease.

You had just mentioned that you probably would want to see it in combination with the JAK inhibitors. Is there a particular rationale for that, or just because that takes care of one part of the disease? Do have any pre-clinical evidence, or is it based more on, because there's a therapy out there, so it makes sense to combine, especially if you're not -- if the pathways are not really overlapping?

Yes. Mechanistically, the pathways are complimentary. Ruxolitinib is an approved standard of care in this disease, and provides rapid symptomatic relief, and it stands to reason that this is something we want to get ahead of on this, get ahead of the curve on the optimal treatments for this disease. As I mentioned, ruxolitinib, though approved, has no affect on fibrosis. It was not a disease-modifying agent, it simply deals with symptomatic relief of the splenomegaly. So we think that the two complementary agents can provide some enhanced benefits to patients, and a more durable outcome.

That's very helpful. One quick question on IP-145 and hem malignancies. Have you reached the maximum tolerated dose in the trial yet?

We have not talked about the dose regimens in either the normal volunteer studies, nor the heme malignancies [inaudible]. We are still in dose escalation, and so that continues, and I think we will be reporting on that in the second half of this year. We anticipate reaching the NTD and confirming that NTD, and reporting on that in the second half of this year at a medical meeting.

Thank you.

(Operator Instructions)

Well, thank you everyone for joining us on the call today, and we look forward to providing you with further updates on our six ongoing trials throughout the rest of the year. Thanks again.

Ladies and gentlemen, thank you for your participation in today's conference. This does conclude the program, and you may all disconnect at this time.