Infinity Pharmaceuticals Inc (INFI) 2013 Q4 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 fourth quarter and year-end of 2013. My name is Stephanie 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. Kate Murray, Senior Investor Relations Associate at Infinity. Please go ahead.

Thank you Stephanie, and good morning everyone. Welcome to today's call to discuss our recent business progress and review our fourth quarter and year-end 2013 financial results. With me here today are Adelene Perkins, President and Chief Executive Officer; Julian Adams, President of Research and Development; and Larry Bloch, Executive Vice President, Chief Financial Officer, and Chief Business Officer. 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 www.infi.com. Please note that during this call, we may make forward-looking statements about our future expectations and plans, including clinical development milestones, the therapeutic potential of our product candidates, and financial projections. It is possible that our actual results may differ materially from what we project today, due to the considerations described in the Risk Factors section of our 2013 Annual Report on Form 10-K that we filed this morning. 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 any obligation to do so.

Now I'd like to turn the call over to Adelene.

Good morning everyone, and thanks for joining us on today's year-end 2013 call.

Let me start with perspectives on our lead program, IPI-145. In 2013, we developed key data demonstrating that IPI-145 is highly active across a broad range of hemalignancies, and is generally well tolerated. On the basis of this clinical profile, we have two potential registration studies underway -- Dynamo in indolent non-Hodgkin lymphoma, or iNHL, and Duo, in chronic lymphocytic leukemia, or CLL. We're thrilled with the progress of this drug candidate, which we think will be an important medicine to help patients going forward.

Our strategy is to establish IPI-145 as the best available treatment in indolent non-Hodgkin lymphoma based on the strongest monotherapy data yet reported with any targeted drug in this indication. Accordingly, development and approval of IPI-145 in iNHL is our top priority. With good data from our Dynamo trial now underway in refractory iNHL, we expect to seek accelerated approval.

In 2014, we also plan to initiate Dynamo+R, a Phase 3 randomized, placebo-controlled study of IPI-145 in combination with rituximab in patients with relapsed iNHL, which has the potential to serve as a confirmatory study to our Dynamo trial. In moving from the relapsed refractory setting to front line, we also plan to initiate a Phase 2 study of IPI-145 in treatment-naive patients with iNHL, and to initiate at least one additional clinical study of IPI-145 in patients with blood cancer this year.

In CLL, we also remain highly encouraged by our strong monotherapy data, and Duo, our Phase 3 registration-focused study in relapsed refractory CLL, continues to enroll.

For IPI-145 in inflammation, in 2014 we anticipate reporting top line data from our two programs -- Aspira, a Phase 2 study of IPI-145 in patients with moderate to severe rheumatoid arthritis, and our Phase 2a exploratory study in patients with mild allergic asthma. The data from these two studies will guide our next steps for the development of IPI-443, Infinity's second oral PI3 kinase delta-gamma inhibitor. We expect to finish this year with a total of 10 trials of IPI-145, seven of which will be in Phase 2 or Phase 3.

Today we also announced a $100 million debt facility with Deerfield Management, which gives us important financial flexibility as we execute on our strategic plan, ensuring we have multiple avenues to access the resources necessary to expand and accelerate the development of IPI-145.

Recognizing the considerable potential of IPI-145, we've built an exceptionally strong team, and recently promoted Dr. David Roth to Chief Medical Officer. David's depth and breadth of hematology and oncology expertise have proven to be a tremendous asset, and will be critical as we advance IPI-145 through late-stage development and potential registration.

As always, we're laying a strong foundation to become a fully integrated biotechnology company, and have the critically important pillars in place to build the company, including very encouraging clinical activity with IPI-145 providing the basis for potential registration trials now underway, full ownership of worldwide rights to IPI-145 and the opportunity to evaluate value-creating strategic partnerships, a focus on breakthrough science with an extensive translational research effort to identify the most synergistic combinations with IPI-145 going forward, and strong IP protection into 2030.

With that, I'll turn the call over to Julian to walk through each of our development programs.

Thanks. As Adelene mentioned, in the course of our Phase 1 clinical development of IPI-145, we have generated data demonstrating activity with IPI-145 across a broad range of hematologic malignancies. In particular, for relapse refractory iNHL, we've seen a 73% response rate, the highest monotherapy response rate that has ever been observed in this patient population with any targeted drug. In addition, IPI-145 had a 20% complete response rate in this group of patients. In chronic lymphocytic leukemia, or CLL, we have observed a notable response rate of 89%, and a 48% overall response rate as defined by the International Working Group Criteria, or IWCLL criteria, including one complete response.

Beyond iNHL and CLL, we have observed activity in additional patient populations, including those with T-cell malignancies -- with peripheral T-cell lymphoma, or PTCL, we have observed a response rate of 55%. We have also seen activity in patients with advanced aggressive non-Hodgkin lymphoma, including diffuse large B-cell lymphoma, or DLBCL. In preclinical studies, we have observed synergistic activity in combination with ibrutinib, a Bruton tyrosine kinase, or BTK, inhibitor.

With regards to safety, adverse events have been predominantly low-grade or asymptomatic and are manageable, and are consistent with the co-morbidities associated with these diseases. We've also learned through our own experience, and the experience of others developing B-cell receptor inhibitors, how to manage these events so that we can keep patients on drug for an extended period of time to ensure that they may receive the full benefit of treatment. On the basis of the strong activity and tolerability we've seen to date, we're now in potential registration studies in two distinct hemolytic indications -- iNHL and CLL.

Let's drill down a little more on our clinical experience for IPI-145 and why we're so excited about the prospects for this drug. Let me start with the development of IPI-145 in iNHL. At ASH in December, we announced data from the ongoing Phase 1 study that I referred to a minute ago, showing that IPI-145 was clinically active with an overall response rate of 73%, including three complete responses among patients receiving IPI-145 dosed at 25 milligrams or less twice daily.

Responses occurred rapidly. At the first response assessment, or the end of Cycle 2, IPI-145 achieved a 60% response rate. This is very meaningful for both patients and physicians because the quicker patients respond, the faster they feel better and the more likely they are to stay on-study. In addition, 53% of patients remained progression-free for over one year, and durability matters for patients that are used to cycling through many lines of therapy.

The patients in this trial have had a median of four to five prior therapies with advanced disease, so the fact that the patients have been on drug for over a year is significant. There is evidence in other hematologic malignancies of the connection between speed of response and durability of response, and based on our early data, we hope to prove this is the case with IPI-145 as well.

On the strength of these results, we are enrolling our Phase 2 Dynamo study. The trial is expected to enroll approximately 120 patients with indolent lymphoma whose disease is refractory to radio-immunotherapy or to both rituximab and chemotherapy, and who have progressed within six months of receiving their last therapy. We are using IPI-145 at a dose of 25 milligrams twice daily, with a primary endpoint of objective overall response rate, and with good data, expect to see accelerated approval. We have met with the regulatory agencies and have incorporated their feedback to support this clinical strategy.

We also plan to initiate a potential confirmatory trial this year, Dynamo+R, a randomized, double-blind, placebo-controlled 400-patient study of IPI-145 plus rituximab versus placebo plus rituximab. Our development strategy is to start in the monotherapy refractory setting, because we believe that that is the fastest way to get the drug approved and to patients. We are complementing this monotherapy strategy with our Phase 3 combination study, Dynamo+R, designed to expand use in later lines of therapy and enhance overall response rates, including complete responses.

In a disease like indolent non-Hodgkin lymphoma, where so many patients move to second- and third-line therapy, a relapsed refractory setting is very significant. We believe there are approximately 30,000 treatable patients in the population in the G7 countries, which is comparable to the number of patients in the front-line setting, so the relapsed refractory population should give us a very meaningful starting point for expansion into additional populations within iNHL.

We are very encouraged by the strength of our data in refractory patients with indolent lymphoma, and based on these results, we are investigating earlier lines of treatment with relapsed and front-line patients. We plan to initiate a Phase 2 trial in treatment-naive patients later this year. Our vision is to provide effective oral and chemo-free regimens to treat a broad range of patients with iNHL.

Let me now turn to our work in CLL. Based on the strong Phase 1 data reported to date, we are enrolling Duo, a Phase 3 study with IPI-145 in patients with CLL. This randomized, open-label study is designed to evaluate the safety and efficacy of IPI-145 dosed at 25 milligrams twice daily compared to ofatumumab in approximately 300 patients with relapsed or refractory CLL. The primary endpoint of this study is progression-free survival.

At ASH in December, in addition to showing that IPI-145 was highly active in patients with relapsed refractory CLL, we showed that onset of activity was rapid, with the majority of responses occurring in less than two months. We also showed activity in high-risk patients, with 17p deletions of p53 mutations. This is very encouraging, as high-risk patients generally have a poor response to chemotherapy and an even worse prognosis. Of the 12 high-risk patients treated with 25 milligrams or less twice daily evaluable for response, there were six partial responses, five patients with stable disease, and one disease progression in a patient with a previously undiagnosed Richter transformation.

In addition to the encouraging activity seen in the relapsed and refractory setting, we have shown interesting early data in the treatment-naive setting. We saw a reduction of adenopathy in all six treatment-naive patients treated to date. Three of these patients had notable responses, including two patients with p53 mutations.

In our CLL trial, IPI-145 was generally well-tolerated, with a safety profile consistent with the co-morbidities generally seen in patients with advanced hematologic malignancies. The majority of side effects were low-grade or asymptomatic and manageable, and consistent with the most common side effects seen in patients with relapsed refractory CLL.

Further underscoring the broad potential of IPI-145, we also recently announced preliminary data from our Phase 1 trial in patients with relapsed refractory cutaneous and peripheral T-cell lymphoma, a very difficult to treat hematologic malignancy with few available treatment options. At the sixth annual T-Cell Lymphoma Forum in January, last month, we presented data showing that IPI-145 is generally well-tolerated and clinically active in patients with T-cell lymphoma, with an overall response rate of 38%, including one complete response and nine partial responses amongst 26 patients evaluable for response.

We saw the highest response rate in patients with peripheral T-cell lymphoma, or PTCL. Among 11 patients with PTCL evaluable for activity, treatment with IPI-145 led to one complete response and five partial responses for an overall response rate of 55%. These are heavily pretreated patients who have exhausted all treatment options. These data helped further our understanding of the clinical potential of IPI-145 in additional indications and will guide our future development plans.

We believe that IPI-145, and our PI3 kinase program, also have the potential in inflammation, where we have focused our initial efforts on rheumatoid arthritis and asthma, and have Phase 2 trials underway. In rheumatoid arthritis, we are conducting Aspira, a robust, double-blind, placebo-controlled Phase 2 study which is enrolling 300 patients. We are evaluating doses of IPI-145 which are considerably lower than the doses we're evaluating in oncology.

In the Aspira trial, our doses are 0.5, 1, and 5 milligrams twice daily of IPI-145 plus methotrexate versus placebo plus methotrexate. The treatment period is 12 weeks in duration with a primary endpoint of ACR 20 response rate, which is defined as the proportion of people who have achieved at least 20% of reduction in a composite score of symptoms and inflammation. We will be reporting top line data on this study in the second half of this year.

Also on the inflammation side, we are conducting an exploratory Phase 2a randomized, double-blind, placebo-controlled, crossover study of IPI-145 in patients with mild allergic asthma. We will announce top line data on that trial later this year.

Lastly, we have built a portfolio of additional delta-gamma PI3 kinase inhibitors, and have identified a second promising molecule, IPI-443, that will provide important strategic optionality in optimizing the PI3 kinase delta-gamma franchise in oncology and inflammation. We plan to confirm our development strategy for IPI-443 later this year after we collect data from the ongoing inflammation trials.

As I've described, IPI-145 has compelling activity in a broad range of indications, and so we are excited to continue to advance and expand into development into 10 trials by year-end. Importantly, we believe IPI-145 has the potential to become the best oral therapy to treat indolent non-Hodgkin's lymphoma, so that is our top priority. We are exploring its potential in the relapsed refractory settings, and will be moving into earlier lines of therapy with treatment-naive, indolent non-Hodgkin's lymphoma patients. We are also actively enrolling in our Phase 3 trial in CLL. In addition, with data readouts from both our trials in inflammation indications, this will be a pivotal year for our IPI-145 development program.

With that, let me turn you over to Larry Bloch for the financials.

Thanks Julian.

As Adelene mentioned earlier, we're in a strong financial position to execute on our strategic development plan with approximately $215 million at the beginning of 2014, and the $100 million debt facility we announced today, which provides important flexibility as it allows us to access these funds over the next 12 months without any obligation to do so. Deerfield is a top shareholder, knows our programs and team well, and has been a long-time supporter of Infinity.

Turning to our financial results briefly, as of December 31, 2013, we had total cash, cash equivalents, and available for sale securities of $214.5 million, compared to $326.6 million at the end of 2012, and $250.9 million at the end of the third quarter of last year.

R&D expense for the full year 2013 was $99.8 million, compared to $118.6 million for 2012. The decrease in R&D expense in 2013 compared to 2012 was primarily due to the conclusion of our Hsp90 and Hedgehog pathway programs, along with decreased milestone payments to Millennium Takeda for IPI-145 and IPI-44. It was, partially offset by higher clinical development expenses for IPI-145.

G&A expense was approximately $27.9 million for both the full year 2013 and 2012.

Net loss for the full year 2013 was $126.8 million, or a basic and diluted loss per common share of $2.64, compared to $54 million or basic and diluted loss per common share of $1.70 for 2012.

In January, we provided financial guidance for 2014 which remains unchanged, with the exception of an extension of our cash runway. We expect operating expenses for 2014 to range from $170 million to $180 million. We expect net loss for 2014 to also range from $170 million to $180 million, and we expect that our current cash investments, together with the $100 million availability under our debt facility, will provide a cash runway into the second half of 2015.

With that, we'll open the call for Q&A.

Thank you. (Operator instructions).

Our first question comes from Cory Kasimov with JP Morgan. Your line is open.

Hi guys, this is Whitney on for Cory this morning. First question, on the additional clinical trial for IPI-145 in hemalignancies, should we be thinking about that as sort of a part of the iNHL/CLL sort of development program, or not part of that, say T-cell or something else?

No, I think you've got it right. It should be considered as part of the iNHL program.

Okay, and then in terms of the asthma data and the additional cohort that you're enrolling, have you given any data in terms of what that additional cohort is, whether it's a different dose or different patients, or something to that effect?

No, we haven't guided to what that cohort will be. We're waiting to complete the trial to give the top line data.

In second half?

In the second half, that's correct.

Great, okay. Thanks for taking the questions.

Our next question comes from Joel Sendek with Stifel. Your line is open.

Hi, thanks. Just a couple questions about Duo. I'm wondering if you could give us some -— I know it's early, but some idea how enrolment has been so far, and if you don't mind, if you can give me what your expectation is for the control arm, the alpha arm as far as PFS?

Yes, thank you for the question. So we are enrolling Duo. It has begun and it's enrolling. We have anticipated that Duo will be a challenge to enroll in the United States because we've anticipated the approval of ibrutinib, and that has of course occurred.

Nevertheless, we are engaged with key academic sites that are very committed to this trial because they're doing a lot of qualitative science in these patient populations. The majority of the trial, we expect, will be enrolled in Western Europe as well as Poland and Hungary. We've taken this into account when designing the trial and accounting for the randomization to ofatumumab.

And your expectation for the control arm PFS?

You can look up the expected PFS for ofatumumab, but we're not guiding on the statistical assumptions in the trial.

Okay, thanks.

The next question comes from Jason Kantor with Credit Suisse. Your line is open.

Thanks. I guess a clinical question and a financial question. On the inflammation side, is it your intention that if positive, to move forward with IPI-145 in inflammation, or did I understand you correctly that you're looking to position your other compound potentially in inflamm, just to separate the two in terms of dosing and pricing and such?

Thanks, Jason. It's an important question. One of the reasons that we have both IPI-145 and IPI-443 is so that it gives us the flexibility to figure out the optimal positioning of both of these molecules in oncology and inflammation, and so it will depend in large part on what dose we choose to go forward with in inflammation. We've declared our dose in oncology as 25 milligrams twice daily.

We need to look at what dose makes sense in inflammation and make sure that those are compatible from an ultimate commercial positioning, and if they are compatible we could take IPI-145 together in both, and if we believe that the portfolio will be optimized by directing IPI-145 to hem and IPI-443 to inflammation, we have that flexibility.

Okay, and then in terms of the new debt facility, did you in fact draw on that upon signing it? I know you can draw it in $25 million increments. Is that all available or did you draw some already?

Thanks Jason, appreciate your question. No, we have not drawn any on the facility, so we still have the full $100 million real option to pull down at our discretion.

Okay. What would likely trigger you doing that or not doing that?

So the real optionality is the value. So the two major things that we're focused on currently is the execution on our current and additional trials to prosecute IPI-145 towards registration, and then we also want to be in a strong financial position as we enter into potential strategic collaboration discussions.

And would you announce it or would you just wait until the quarter to disclose it if you do draw on it?

I think we'd probably just wait for the quarter. We don't think it's a fundamental change in our financial position.

All right, thank you.

Thanks Jason.

Our next question comes from Matthew Andrews with Wells Fargo. Your line is open.

Yes, good morning. Thanks for taking the questions. Two for me. First of all, can you provide us a status update on the Phase 1/2 combination study with Dr. Flynn? And did any of these data help inform on your Phase 3 Dynamo+R combination study you'll start this year? And then second of all, how much more efficacy and safety data do you need to see from the Phase 1/2 PTCL/CTL/CTCL study before you make a decision on investing in a pivotal program there? Thank you.

So for the first question, the study with Dr. Flynn as an investigator-sponsored study, so we are not the sponsors of that study, and therefore the status of that trial is left to the investigator as to when he will report data. We've enrolled a substantial number of patients, though, to enable the combination with Rituxan and Rituxan/bendamustine, so it was a very important study for us to enable Dynamo+R. And with the safety that has been shared with us, we feel confident in the Dynamo+R trial design.

The second question relates to our future plans in T-cell lymphoma. We're still aggregating data there, still patients on study, and we're still discussing internally and with key opinion leaders about what the next steps should be, and when we come to such a decision, we will let you know, of course.

Okay, thank you.

Our next question comes from Ian Somaiya with Nomura. Your line is open.

Hi, this is Do Kim in for Ian. I was hoping that you could maybe provide some more details on the backup compound, IPI-443, maybe on how close you are to bringing it to clinic. And relative to IPI-145, how does it compare in inhibiting the delta and gamma isomers?

Thank you for your question. IPI-443 is very similar to IPI-145 --- I mean, chemically distinct. It's got a separate intellectual property, but I mean it's similar in terms of it is also a delta-gamma inhibitor. It has very similar potency for the delta isoform, and it is about threefold more potent for gamma.

Other than that, we have completed some of the preclinical -- well, we've completed preclinical studies to enable Phase 1 investigation, and so are very pleased with the general performance of IPI-443. It provides us the option to move that molecule into inflammation should we decide to do so once we've analyzed all the data from our inflammation studies.

And as a follow-up, since IPI-443 is three times more potent on gamma, do you think gamma could be more important in autoimmune indications?

Yes, I think there's some very interesting literature data and our own in-house data that suggest an enhanced role for gamma in certain autoimmune conditions.

Great, thank you.

(Operator Instructions). Our next question comes from Navdeep Singh with Goldman Sachs. Your line is open.

Hi, this is Lisa in for Navdeep. Thanks for taking the question. If you apply those same response criteria the FDA applied on Imbruvica on its label, which was using different follow-up times, what would you calculate the response rate to be with IPI-145 in relapse refractory CLL?

We're not in a position to recalculate our data. We don't have the exact methodology that the FDA employed, and I don't think given the numbers of patients that we have and the general heterogeneity of a Phase 1 population, I don't think it is a meaningful comparison. We can compare our Phase 1 data to their Phase 1 data, which is a similar population, but I don't think it's instructive to do the comparisons the way you have just described.

Okay, thanks. And then a follow-up --- can you just walk us through the decision of entering into the $100 million debt facility versus a partnership? Are you still receiving interest from pharma companies on potential partnerships?

Yes, so we're certainly receiving, and continue to receive, interest from partnerships, potential partners. IPI-145 is a wholly-owned Phase 3 asset with strong activity, as you've just described with Julian, that's comparable in many indications to some drugs that have been approved or have obtained PDUFA dates, and so because there's a very scarce number of drugs with that kind of profile, and in terms of your question regarding the financing, it's not an either/or, it's an and. We really want to be in a strong position financially to execute on the ongoing clinical trials that Julian described, as well as additional trials that we've committed through our guidance to start this year, and also to be in a strong position to select the best partnership to move forward with IPI-145 going forward.

Okay, thanks. Last question --- for Duo, what was your rationale for proceeding with monotherapy comparison? Any reason why you didn't take the same approach as Gilead, which is evaluating idelalisib plus or minus Rituxan? Thanks so much.

Yes, it's a great question. First of all, we think that our activity is superior to the Gilead profile, and we think that the most efficient and fastest path to full approval was this randomized study comparing with the standard of care, ofatumumab. We discussed that with both the FDA and EMA, harmonized our trial design and endpoints, and we feel that this is the most efficient and quickest way towards an approval.

Thanks again. Congrats on the progress.

Thank you.

Our final question comes from Katherine Xu with William Blair. Your line is open.

Hi, this is actually John in for Katherine. Just a couple of quick questions. First on the debt facility -- my understanding is the $25 million increments can happen theoretically today and tomorrow. There is no set time frame like one a quarter or anything like that. Is that true?

Exactly. The full discretion is with Infinity over the term of the loan drawdown, which is across the next 12 months.

Okay, great. And then the next question is clinically related. In terms of the T-cell opportunity, it seems very attractive. I know that there's a little bit of confusion because all the data is not sorted out at this point. But is there a possibility, given the delta-gamma relationship in the affinity for gamma, the potency related to gamma, that IPI-443 may be a candidate in T-cell and maybe as you're waiting this out, or how does this all shake out?

So I think if we are to proceed with further T-cell trials, it would be with IPI-145.

Okay, great.

We have confidence that we are substantially inhibiting the gamma isoform in those patients.

Great. Thanks for taking the call.

There are no further questions. I will now turn the call back over to Management for closing remarks.

Thank you all for joining us today, and we'll look forward to updating you through the remainder of this year. Have a good day.

Thank you ladies and gentlemen. That does conclude today's conference. You may all disconnect and have a wonderful day.