Agios Pharmaceuticals Inc (AGIO) 2015 Q3 法說會逐字稿

Good morning and welcome to the Agios Third Quarter 2015 Conference Call. At this time, all participants are in a listen-only mode. There will be a question-and-answer session at the end. Please be advised that this call is being recorded at Agios' request.

I would now like to turn the call over to Renee Leck, Senior Manager, Investor and Public Relations of Agios.

Thanks, Christie. Good morning, everyone and welcome to our third quarter call. You can listen to a live webcast with slides or a replay of today's call by going to the Investors and Media section of our website, agios.com.

With me on the call today with prepared remarks are Dr. David Schenkein, our Chief Executive Officer, who will provide an overview of our corporate strategy, vision and progress to-date; Dr. Chris Bowden, our Chief Medical Officer, who will review our recent clinical development updates; and Glenn Goddard, our Senior Vice President of Finance, who will summarize Agios' third quarter 2015 financial results.

Before we begin, I would like to remind you that today's discussion will include statements about the Company's future expectations, plans and prospects that constitute forward-looking statements for the purposes of the Safe Harbor provisions under the Private Securities Litigation Reform Act of 1995.

Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the Risk Factor section of our Annual Report on Form 10-K which is on file with SEC. In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking statements at some point in the future, we specifically disclaim any obligation to do so even if our views change.

With that, I'll turn the call over to David.

Thanks, Renee and good morning, everybody and thanks for joining us today. Today's call will be brief, given that we've recently spent time together at our R&D Day and I encourage those of you who were not able to attend the event to listen to the replay on our website. We'll also be meeting with you this coming Sunday after our presentation at the Triple meeting in Boston.

At the beginning of 2015, we laid out an ambitious set of goals, which included multiple data read-outs and trial initiations across all of our programs in cancer metabolism and rare genetic metabolic disorders. And from where we stand now in November, I'm proud to say that we expect to achieve 100% of those important milestones. Today, Agios is a company with five clinical stage investigational medicines, two of which are moving rapidly towards regulatory approval. These medicines have the potential to help a large number of patients around the world.

Behind this clinical portfolio, we have a robust research pipeline in both cancer and RGDs that continues to expand and deliver novel targets. We're an organization with deep scientific routes that has successfully transitioned into a late-stage development company and beginning to build commercial capabilities. On top of that, we're very proud of our strong culture, which is driven by our passion to help patients and following great science.

As we think about what's possible for patients with our IDH inhibitors, we're deploying a clinical development strategy of speed and breadth to move as quickly as possible with AG-221 and AG-120 in acute myelogenous leukemia and then beyond into multiple indications and cancers.

Chris will go through the details of our clinical trials in both hematological malignancies and solid tumors, but I'd like to focus on our vision for the future, when every patient with an IDH mutant positive cancer in which we've demonstrated clinical benefit will receive one of our inhibitors from the time of their diagnosis throughout their entire illness. And we have a lot of work ahead of us to realize that vision, but that's what we're here to do, patients and their families are waiting and counting on us.

We are extremely proud of our current clinical pipeline, which contains multiple development candidates in both cancer metabolism and RGDs, including AG-519, the most recent addition to our clinical portfolio and our second PKR Activator. As you can see, we're keeping the clinical group busy as they conduct numerous important clinical trials with our five investigational medicines.

On the research side, at R&D Day, Scott Biller, our Chief Scientific Officer, discussed the terrific progress we've made discovering novel cancer metabolism targets as well as potential opportunities in the RGD space that we're moving towards clinical development as quickly as possible. The quality of our research engine is one of Agios' strengths and we remain extremely excited with Wave two and Wave three of our research pipeline.

I'll now turn the call over to Chris so he can review our clinical updates and the specifics of our recent clinical development milestones.

Thanks, David. David has outlined to you the role we hope our IDH inhibitors will one day play in the treatment of IDH mutant positive cancers. The clinical development plan we have in place for acute myelogenous leukemia combines the strategy of speed and breadth to help us achieve this goal. Speed is represented by our single agent expansion cohorts that are up and running for both in AG-221 and AG-120 and designed to provide registration quality efficacy and safety data.

At R&D Day, we announced another significant milestone for this program, the initiation of IDHENTIFY, the Phase 3 international multi-center open-label randomized clinical trial sponsored by Celgene. This study represents the first randomized trial with global potential for AG-221 in AML. It is designed to compare the efficacy and safety of AG-221 versus conventional care regimens in patients 60 years or older with IDH-2 mutant positive AML that is refractory to or relapsed after second or third line therapy. The primary endpoint is overall survival, and some key secondary end points include event-free survival, duration of response and safety.

For AG-120, we plan to initiate a registration-enabling Phase 3 study in AML patients in the first half of 2016. In addition, I'm excited to talk about two Phase 1 combination trials with AG-221 and AG-120 in newly diagnosed AML patients. Our goal in the frontline setting is to develop combination data for any newly diagnosed IDH mutant-positive AML patients, including those individuals that can handle intensive chemotherapy and those that cannot based on their morbidities, age and physical status. For newly diagnosed AML patients eligible for intensive chemotherapy, a Phase 1b combination study of our IDH inhibitors with standard induction and consolidation chemotherapy. This is planned to start by the end of 2015.

For newly diagnosed AML patients not eligible for intensive chemotherapy, a Phase 1/2 combination study of either IDH inhibitor with VIDAZA is planned for the first quarter of 2016. This study has a Phase 1 component to determine the safety of the combinations, followed by a Phase 2 randomized component evaluating the safety and clinical activity of each IDH, VIDAZA combination versus single agent VIDAZA using a primary endpoint of overall response rate. Myelodysplastic syndrome is also an emerging area of therapeutic focus for IDH inhibitors, particularly high risk MDS patients who have very limited options and poor outcomes. We're working with our partner Celgene on a development plan in this indication, and we'll update you as these plans progress.

Also at the end of the year, we'll be presenting new data from our lead cancer metabolism and RGD programs in seven abstracts at the annual ASH meeting in Orlando in December. The abstracts from our ongoing AG-221 and AG-120 trials in advanced heme malignancies, which will be available today and the clinical profile around our IDH inhibitors and provide further confidence on our clinical development strategies. Our presentations at the meeting itself will also include longer follow-up data and additional patients since the submission of today's abstract.

We are also pleased that three abstracts from our PK pyruvate kinase deficiency program, including new PK pharmacodynamics data from AG-348 and updated findings from the natural history study being conducted by Boston Children's Hospital will be presented.

Turning to the AG-120 Phase 1 study in solid tumors. We will be presenting the first dose escalation data from this study on Sunday at the AACR-NCI-EORTC Triple meeting in Boston. The purpose of this study is to evaluate the safety, pharmacokinetics, pharmacodynamics and clinical activity of AG-120 in patients with a broad set of advanced solid tumors that harbor an IDH1 mutation.

As we've mentioned previously, glioma, chondrosarcoma and intrahepatic cholangiocarcinoma and three solid tumors that carry a high prevalence of the IDH mutation and are extremely difficult to treat. We look forward to sharing our data and discussing next steps for this program at our IR event on Sunday at 1:00 PM Eastern Time, which will also be webcast.

We are also studying AG-221 in a Phase 1/2 trial in IDH2 mutant positive advanced solid tumors and angioimmunoblastic T-cell lymphoma. This study is continuing to enroll patients.

And finally, from our cancer metabolism portfolio, AG-881 is a small molecule, brain penetrant IDH inhibitor, and the third program from our portfolio of IDH inhibitors. We are currently studying AG-881 in two Phase 1 open label dose escalation and expansion studies. The first in advanced IDH mutant positive solid tumors, and the second in patients with advanced IDH mutant positive hematologic malignancies who's cancer has progressed on a prior IDH inhibitor therapy. AG-881 represents a potential second generation molecule that we believe will expand our opportunities for clinical development across the spectrum of IDH1 and IDH2 mutant positive tumors as a pan-inhibitor. A brain penetrant molecule may be especially important for glioma patients with earlier presentations of the disease and glioma patients is represented in our Phase 1 solid tumor trials.

Now turning to our PKR activators AG-348 and AG-519. We are evaluating AG-348 in DRIVE PK, a Phase 2 trial and the in adult transfusion-independent patients with Pyruvate Kinase Deficiency. DRIVE PK is a global open-label multi-center randomized study that includes two arms with 25 patients each receiving 50 milligrams or 300 milligrams twice daily for at least six months. Aside from safety and tolerability, we will evaluate the pharmacokinetics and pharmacodynamics of AG-348 to confirm activation of the PKR pathway.

Hematologic indicators of clinical activity, including hemoglobin levels will also be measured. We opened the study in June and are pleased with enrollment in our operational progress to date. We will keep you updated.

At last month's R&D Day, we also announced the selection of our second PKR activator, AG-519. AG-519 is a potent, highly selective and orally bioavailable PKR activator for the potential treatment of people with Pyruvate Kinase deficiency that has no activity against the aromatase enzyme. We have a Phase 1 study in healthy volunteers planned for the first quarter of 2016, that will be an integrated single ascending dose and multiple ascending dose trial. As part of good drug development, this program provides clinical development optionality for our PK activator portfolio and potential opportunities in other hemolytic anemias where PK activation maybe an effective treatment option.

Our Phase 1 healthy volunteer study of AG-519 will be happening in parallel with DRIVE PK or AG-348 and clinical data from both of these trials will determine the late-stage development path.

As we discussed at R&D Day, our understanding of Pyruvate Kinase deficiency is still evolving. However, a picture of disease severity is emerging with a clinical spectrum can range from mild to life-limiting. Our programs, if successful, would be the first to correct the underlying cause of the disease. We and our partners at Boston Children's Hospital are continuing to study Pyruvate Kinase deficiency with an ongoing natural history study.

Initial data presented at EHA in June presented a range of severity for the disorder and identified unifying characteristics such as iron overload, which are common in all age groups regardless of transfusion history.

Looking back over the progress we've made in our cancer metabolism and RGD programs this year, we've made great strides across the board and look forward to updating you at the Triple meeting and ASH.

And with that I will turn the call over to Glenn.

Thanks, Chris. Agios is in a very strong financial position today, and is well capitalized as we advance multiple programs in the late-stage clinical development and expand our research pipeline. As David noted, we're on track to achieve all of our corporate goals and milestones for 2015. With five clinical stage medicines advancing, approximately $408 million in cash, and a great partnership with Celgene, we believe we are in a solid position to build a sustainable multi-product biopharmaceutical company.

Now moving on to the financial results for the third quarter. Our cash, cash equivalents and marketable securities as of September 30, 2015 were $408 million compared to $467 million as of December 31, 2014. The decrease was driven by cash expenditures for operating activities of approximately $101 million, which was offset by $54.8 million of funding from Celgene.

The $54.8 million of funding from Celgene was comprised of the following items; a $20 million extension fee related to the final year, the discovery phase of our 2010 collaboration agreement, $10 million from the signing of our new worldwide development and profit share collaboration for AG-881 and finally, $24.8 million related to IDH development cost reimbursements.

Our total revenue was $5.5 million for the third quarter of 2015 compared to $33.9 million in the third quarter of 2014. During the third quarter of 2014, the Company reported a significant increase in revenue related to the application of new accounting guidance for a July 2014 amendment to our collaboration agreement with Celgene. At the date of this material amendment, the Company recognized a total of $25.9 million in revenue.

Research and development expenses were $36 million in the third quarter of 2015 compared to $25.5 million in the third quarter of 2014. The increase was largely due to increased investments in our three lead investigational medicines as they advance into late stage clinical development along with early development cost for both AG-881 and AG-519.

General and administration expenses were approximately $9.9 million for the third quarter of 2015 compared to $5.2 million for the third quarter of 2014. The increase was largely related to increased headcount -- personnel related expenses and other professional expenses to grow our growing operations.

Today, we are also reiterating our previous guidance that we expect to end 2015 with more than $350 million of cash, cash equivalents and marketable securities, expect this cash position give us runway through late 2017.

Our year-end guidance does not include program-specific milestones that we may be eligible to receive under our collaboration with Celgene. As a reminder, we are eligible to receive up to $120 million of milestone payments for both AG-221 and AG-120 with the initial milestone of $25 million for program being triggered by the first patient dosed in a Phase 3 study.

And with that, I'll turn the call back over to David.

Thanks, Glenn. Our team prides itself on the challenge of making medicines that are truly meaningful, ones that are capable of re-writing the textbook on the diseases they address. The Agios of 2015 has made rapid and exciting progress towards this goal in the seven years since our inception, creating five novel investigational medicines that have the potential to impact patients' lives in a profound way.

By keeping patients at the center of what we do and focusing on four simple principles that support that ideal, we think will increase the likelihood that we'll make important medicines. Vision, science, culture and finally, execution, we're here to make medicines patients are waiting for and to do that, we need to execute and we need to execute flawlessly.

I want to thank you for your time today and as always, we want to thank all the patients, their caregivers, the nurses and doctors who participated in our clinical trials and of course, all of our employees and shareholders for their continued support.

And with that, we can now go to questions. Operator?

Thank you. (Operator Instructions) Seamus Fernandez, Leerink Partners.

This is actually Mark in for Seamus today. I had two questions for you. Number one, can you give us a sense of where you are with enrolment of your 125-patient Phase 1 expansion cohort for AG-221 and AG-120 and how we should think about timing there in terms of completion of enrolment and the potential submission for accelerated approval based on these data?

And the second question I had is, at this point have you seen any issues with enrolment in your AG-120 and AG-881 solid tumor trials in that they might be competing for the same patient pool? I understand that some of the IDH mutant solid tumor indications are actually quite rare, and at what point would you consider modifying eligibility criteria to avoid competition for the same patients between these programs there?

Yes, thanks for your question. I'll take the first one and then ask Chris Bowden to take the second one on the AG-120, AG-881. So with respect to enrolment, I think as you may know from our typical guidance that we don't give out details around the enrolment. What I can tell you is that we're really pleased with enrolment to-date, everything remains on track and sites have done just a terrific job across the country and our ex-US sites as well. So everything there is on track in enrolling.

We, as you know, feel that this is a very important set of patients that we're enrolling both for AG-221 and AG-120. And we think that data will be important for patients, for physicians and potentially for regulators, but I want to make it clear, we certainly have not given out any guidance on what the regulatory landscape looks like or whether that will be used to file for accelerated approval. We're excited to generate that data as quickly as possible and then share that with the appropriate audiences.

Let me turn it over to Chris for the second question.

Yes, it's Chris Bowden here. The question about a potential competition between AG-120 and AG-881. The trials are enrolling well, we're not seeing problems with that and in fact we put a fair amount of thought into setting studies up in AG-881, so that would pause -- reduce the possibility that would be a problem. We'll continue to look at it, but if you think specifically about AG-881 and hematologic malignancies, as I stated previously, those patients have to come on to AG-881 on the hematologic cohort (inaudible) hematologic Phase 1, they have to have progressed after an IDH inhibitor.

Eric Schmidt, Cowen & Company.

Just a quick housekeeping one for Glenn and I apologize if I missed this. But did you mention the size of the milestone payments you might be getting from Celgene for initiation of these pivotal trials?

Yes. So that will be -- so Phase 3 milestone will be $25 million for each program.

And are there any other milestones you're expecting, say as we look over the next 12 months?

You know we're not specifically guiding on the timing of milestones, but if you think -- so the -- think of the milestones really in the three pieces, the first piece is, as we're initiating these later stage clinical trials, then there is this -- so that's $25 million per program under the 2010 agreement. And then there is a second wave of milestones up to $70 million worth of milestones and those will be upon regulatory and -- those are really regulatory and approval milestones. And then the final milestone in that cascade of $120 million is $25 million milestone based on a commercial -- hitting a commercial number. So that's kind of the way to think about it, Eric.

Goldman Sachs, Terence Flynn.

Hi, this is Sameer on for Terence. We had a question on the AG-348. We know that enrollments recently began the Phase 2 DRIVE PK trial, but is it possible for you to report interim data from this trial next year, and if so, what's the trigger?

Yes. We've not given out any guidance yet on when to expect to see data. And as you know, our policy is that we wait to see when there is an aggregate amount of data that make sense to bring to a medical conference or medical venue, and we've not given out any guidance to that yet, but we will give you guidance in advance when that's ready. DRIVE PK is going great, enrolling fine, on track and we look forward to be able to share that data at some point in the future.

Anupam Rama, JPMorgan.

Just a quick one AG-881. David, I know you qualitatively talked about similar 2HG declines in potency to IDH1 and IDH2 for AG-881 relative to AG-221 and AG-120. Just wondering when we might get a formal preclinical presentation at a medical meeting or a publication to try to better understand that molecule?

Yes. Thanks, Anupam. So there are two aspects of AG-881 program where -- when we think the timing is right, we'll bring out to the medical venues conferences. One of them will obviously be the first clinical data and we haven't given out any guidance, again as Chris mentioned enrolment is doing really well and is on track for AG-881. So at some point, when there's an aggregate amount of data, we'll bring that out and at some point we'll bring out some pre-clinical data as well, at the appropriate venue showing event. As you mentioned though, we are very pleased with AG-881 because it is equally potent against both IDH1 and IDH2 and as potent as the lead molecules, AG-221 and AG-120. But it is on the radar screen and we'll try and get out there as soon as we can.

Thank you and that concludes our Q&A session for today. I would now like to turn the call back over to Mr. David Schenkein for any further remarks.

Thanks. Again I just want to thank everybody for all your support and those of you who are attending the Triple meeting this weekend, we hope to see you at our event, which as you know, is at 12:30 at the Hilton Back Bay, and if not, it will be on our webcast. So enjoy the rest today and thanks for all your support.

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