Ron Squarer - CEO
Matt Lowe - JPMorgan
Array BioPharma, Inc (ARRY) JPMorgan Healthcare Conference January 14, 2014 7:00 PM ET
Matt Lowe - JPMorgan
Hi there, I’m Matt Lowe of the JPMorgan biotech team. Our next company to present is Array BioPharma. There will be a breakout afterwards in the Olympic Room down the corridor. To present today will be the CEO Ron Squarer, so I’ll hand over to Ron.
Thank you and good afternoon everyone. Very pleased to be here today to provide an update on our progress over the last year. So this time last year at this meeting we were talking about the possibility for pivotal trial starts across our program. And now one year later we’re pleased to have visibility to a full seven pivotal or Phase 3 programs across three of our assets. So it really has been a tremendous year of progress not just in generating data but actually moving forward into the trials that are going to make a difference.
I’m going to be making some forward-looking statements and forecasts, so I do encourage everyone to take a look at our 10-K and other regulatory filings for a full disclosure of risk associated with those statements.
So as I mentioned seven pivotal or Phase 3 trials across our portfolio and I think the one that we’re perhaps most excited about is the announcement that we made recently of our intention to start a Phase 3 trial for our wholly-owned multiple myeloma program Filanesib formerly 520 that should begin and we continue to be on-track for it to begin mid this year. We’ve actually already started a complementary Phase 2 program I’ll discuss the layout of those trials with you in a little bit.
At ASH we were also -- where it’s a few weeks ago very pleased to present new data on our myelodysplastic syndrome program pointed to our pronounced effect in a endpoint which we believe is an important regulatory endpoint.
The MEKs continue to move well and there are six pivotal trials in the mix there, three with AstraZeneca and three with Novartis that’s with selumetinib and MEK 162. We also had some good news few months ago, on an asthma program. This is a oral CRTh2 antagonist where we met the primary endpoint and could be one of the first new asthma, oral asthma drugs to be introduced in about 15 years since Singular came to market and before that lost patent it was doing about $5.5 billion.
We also had some new collaborations, always an exciting part of our portfolio is the science that our discovery teams generate and partner with other companies, specifically we have a highly selective oral HER2 program that we partnered with Oncothyreon although we do maintain global commercial rights and very good economics and they’ve initiated already a number of studies which I’ll discuss.
We also announced a new collaboration with Celgene for undisclosed technology and formed a company called Loxo that has a PAM tracker, a very exciting new mechanism that’s been getting a lot of attention lately and I’ll say that Loxo has been racing to the clinic at a very impressive pace, so looking forward to hearing more from them in that program overtime.
So as I said Filanesib our wholly-owned multiple myeloma program that we plan to take into registration trials starting mid this year. Myeloma is a very large and unfortunately hematologic disease and significant unmet need unfortunately most patients do ultimately progress and die and in our studies, even in our studies we’ve seen patients who typically will see six, seven, eight, even 10 and 11 lines of therapy.
There’s been some important new introductions in the field namely a new proteasome inhibitor Kyprolis and a new IMiD in Pomalyst, new versions of the dominant mechanisms that have been used to treat myeloma both with very strong peak sales, Kyprolis driving the $10.5 billion sale to Amgen and I think yesterday Celgene announced the renewed peak sales estimate for Pomalyst about $1.5 billion, so not only a lot of unmet need but that is translating into substantial financial value for companies in the area.
What we’re most excited about is that we’re a unique mechanism, we’re not an IMiD, we’re not a proteasome inhibitor and we seem to be effective whether you’ve failed an IMiD or proteasome inhibitor and we seem to be somewhat agnostic to how many times you failed and which agents you have failed on.
Particularly excited about our single-agent activity, especially when using our patient selection marker, it selects for the majority of patients 75%-80%, near 25% response rate in heavily pre-treated patients and look forward to utilizing that in our program going forward, perhaps the most important news of the year is that we have in fact combined with both Velcade and Kyprolis at the maximum planned doses for both drugs and actually didn’t even got to MTD, stopped at maximum planned dose and have been very pleased with the combinability profile, so Filanesib in fact has little to know non-hematologic toxicity, the primary effect is in on hematopoietic cells and we find that patients are very well managed with supportive measures, and so even a neutropenia tends to be asymptomatic. And so essentially the profile of this drug is asymptomatic to patients, which is very exciting.
We also showed data at ASH showing powerful scientific rationale for synergy with IMiDs and in this case Pomalyst, it’s AML data but it is quite exciting, and could inspire additional work with IMiDs in the future. So we were able to update our single-agent study at ASH here again pointing to this near 25% response rate in heavily pre-treated patients and also with good durability especially compared to time to progression on their prior therapy.
And I think what’s important here is just to reaffirm that we are moving forward with AAG. We think it’s going to be an important marker. We’re using a commercially available test and we’re going to be validating it for use in myeloma. I think also in this dataset what we found interesting, as did investigators, is that there is data that suggest robust activity when patients are actually resistant to IMiDs and proteasome inhibitors and specifically in this trial patients who had seen prior Pomalyst and/or Kyprolis and/or a oral Velcade in fact had a 31% response rate and we think this supports the hypothesis that this drug is going to be very important in patients that have failed IMiDs and proteasome inhibitors or when used in combination with them.
There was a lot of data that we presented at ASH, I’m going to try and summarize them. For Kyprolis I’ll just note the patients heavily pre-treated a 100% Velcade refractor intolerant, 80% Rev refractor intolerant and a full 30% had actually seen prior Filanesib or Kyprolis and this is a Filanesib/Kyprolis combination study. First of all the overall response rate at 37% we kind of compare that to what you might expect with Kyprolis alone of about 16% so we’re quite excited about that high clinical effect, clinical benefit rate as well.
Turning to Velcade, 100% pretreated with Velcade and Rev, 42% Velcade refractory, 68% Rev refractory. And here you see a 42% response rate overall. But most and compelling is in those patients that were formally refractory to Velcade we saw a 30% response rate, a very high also clinical benefit rate. And the tolerability profile, the same as I described earlier typically asymptomatic and little to know non-hematologic effect. So this inspired us to move forward to the Phase 3 registration trial which we’ve announced and we’ll post and provide more details on in the near future.
Perhaps I’ll pause and just explain why carfilzomib because the Velcade data looks great too. And there is a number of reasons; first is, in the patients we would study with Kyprolis, these would be after Velcade they’re going to have a shorter PFS in the control arm leading to a smaller study and a faster study; second, is that there is a window of opportunity in Europe where Kyprolis is really only available through clinical trials for us to recruit the European arm of the study very quickly; and finally, there is very little combination work with novel agents going on Kyprolis and we think that that will further support recruitment.
And ultimately this should be support both a U. S. and EMA filing. There is couple of supportive trials, one is a single-agent trial. And this will hit some important regulatory requirements also helps us to formally validate AAG as a selection marker in single-agent. But it also in our opinion will provide robust evidence for single-agent use now this could be part of a filing in the future that we would hope would lead to labeling in this population.
There is already, starting in November, we started in November a 75 patient randomized trial with Kyprolis. And this study is really designed to confirm the combinability, it’s not gating for the Phase 3 but it gives us an opportunity to once again confirm what we’ve already seen. This allows us to actually validate AAG for the first time in a combination setting, does certainly support some regulatory requirements but very importantly allows us to publish first ORR then PFS and support recruitment and frankly provide additional data and the insight on how the program is going to the investment community, so rough timing.
Phase 3 at the top-mid next year, Phase 2 with a similar design ongoing already and then the single-agent trial to begin just before the Phase 3, so robust program. But we think it’s actually quite efficient in terms of the time and the cost it will take to get to market.
We do get questions about where does this fit. And we think we have a very compelling positioning here so Filanesib across the top with both the single-agent approach and a combination with Kyprolis, and here are some things to note; first, we are really the only agent that is, novel agent, that’s combining with Kyprolis in a pivotal trial; secondly, we’re rare amongst novel agents for a single-agent activity; and typically, not always, but typically you do see at least an additive effect when you combine two active agents. The other point is we’re the only product that has a selection marker and we think that’s going to be quite important. So we’re going to focus on the relapsed/refractory population.
We think there is compelling reasons to consider Velcade a combination for the future especially for Europe where Velcade will likely remain an important agent when it’s off patent. And I spoke to the synergy we have seen in animal models that would encourage us to do an IMiD or Pomalyst study as well, so a lot of opportunity out there and a lot of unmet need amongst these patients.
So, I am going to touch on 614, this is our second wholly-owned hematology program. It’s in MDS which is one of the largest hematologic disorders and we have been focusing here on low-risk/int-1 HMA patients. And in fact this is our second formulation, we had another formulation that needed some improvement.
And so the results we were able to show a few weeks ago at our ASH are with our new formulation. And once again for the second time we have seen a pronounced effect in taking patients who are dependent on transfusion for platelet disease and making them independent and this is a hard regulatory endpoint. In this data, we were able to show 44% of those patients had a transfusion, a reduction in transfusion and 31% became transfusion independent. I would expect that for folks to become spontaneously independent to be quite rare and this is one of the worst prognostic factors for the disease. So we think it’s quite an important endpoint, no approved therapies for these patients once they failed an HMA.
We are letting this data mature, we just finish recruiting trial into next year, talking to regulators essentially proposing a protocol and hope to have more communication about our intentions with this program around mid this year so just a few months away. I will point out that there are no other agents being investigated at this time for platelet disease. There are some that have some red blood cell effect and so we feel quite comfortable that this is an important agent for which there is really not even a treatment option on the horizon.
We do have a pronounced effect on neutrophil counts, but at the end of the day the harder endpoint is going to be infection, you need a randomized trial to determine that. We do benefit red blood cells as well but we think the prominent effect is really in platelets.
Turning to the MEK inhibitors and I think AZ is maybe presenting now or just did. We are very pleased with selumetinib that AZ and Pascal view this as one of the most important programs they don’t have a lot in the late stage, continue to discuss it as a billion plus opportunity. And they have a very robust program in non-small cell lung cancer study is already enrolling. And this is in second line KRAS about 25% of lung cancer, but we are particularly excited about what we believe is a franchise in lung that they are building, going to first line and potentially even to unselected patients.
There is a UVO study that’s been posted, we expect it to initiate very soon. The posting points to a July 2015 data read and so we see the possibility of revenue from selumetinib to Array in 2016. Thyroid program enrolling well and there is 46 additional, there is 46 trials in total running, 30 Phase 2s and so at ASCO we would expect some more data to emerge on the drug.
Just pointing to some of the exciting trials that we are seeing out there, a number of new combinations that AZ is running with other cytotoxics that are common in first line lung cancer, this would be paclotaxel, carboplatin, pemetrexed, cisplatin and gemcitabine. And so we do see them building a robust franchise in lung cancer and they are certainly are well ahead of anyone else in terms of this approach.
Novartis, great economics there, high double-digit royalties with AZ, double-digit royalties and we are excited that they are running a trial in NRAS mutant melanoma about 20% of melanoma, Novartis still calling it a 2015 filing, so we would expect revenue potentially even earlier than UVO for selumetinib but it’s going to be close a large commercial opportunity in BRAF mutant melanoma, about 40% of melanoma large trial. They believe they have not just the best-in-class MEK in MEK162 but the best-in-class RAF inhibitor LGX818. So, the data at ASCO was impressive and especially in terms of tolerability but certainly also in terms of efficacy.
There is an ovarian trial enrolling well both in the U.S. and Europe which could be an important part of the story but many additional trials running with important combinations, three different PI3Ks being combined with MEK162, a CDK a protein kinase, see in a new trial recently started combining with panitumumab in pancreas and colorectal. These are the two diseases dominated by KRAS mutant drivers that probably singulation isn’t the answer for it but a combination with MEK and another agent could have an important benefit. So, we are looking forward to that data and hopefully updates at ASCO from Novartis.
So, I’ve talked about some exciting new deals, I am just going to touch on 380, a highly selective oral HER2. We believe this drug can have important utility both in control of metastatic disease but potentially and this is probably the first data that will emerge may have benefit in brain metastasis. And for those who follow, breast cancer it is in fact brain metastasis that is the sort of last frontier that proteins can’t typically help with. And the small molecules that have been developed have not had much benefit.
So we have evidence from animal models that we crossed the blood-brain barrier well and that there is an active metabolite that’s as active as the parent compound that not only assists with raising concentrations of active molecule in the brain, but we find that the active or theorize that the active metabolite might actually even accumulate. So there is a study already ongoing and are recruiting well at c; all patients with brain metastasis open label.
So, you know ASCO is coming up but San Antonio would be a little bit later, this would be a huge benefit to patients suffering from breast cancer with those metastases. And if it is positive that’s great. But even if not, the control of metastatic disease with a drug that’s highly selective, very well tolerated and could be used chronically, we think is extremely important and looking forward to moving forward.
So in addition to the Dana-Farber study on clinicaltrials.gov you will find two additional combination studies, one with T-DM1, the other with Herceptin, trastuzumab. And we look forward to those studies enrolling in the near future and sharing data with you in the future. As I mentioned we do control commercial rights here globally although we do have a profit share with our partner Oncothyreon who is funding these studies that you see at the bottom of the page.
So just to review what we have to look forward to after an exciting year as I mentioned, now we have visibility to seven pivotal programs. So quite a different outlook from where we were just this time last year. And so starting with Filanesib; EHA is coming up. We don’t expect to have much more information by then than we just shared at ASH a few weeks ago. But with this Phase 2 randomized trial that we are running 75 patients, by the end of the year or certainly by the time abstracts are published for ASH, we would like to present some new data that we think could be compelling and may support recruitment of our Phase 3 which should be well up and running by then.
With MDS and 614 as I described, we are going to let the data mature, we’re planning to talk to regulators about a protocol focused on transfusion-dependent platelet disease in MDS. With the MEK inhibitors these studies are all enrolling or announced. UVO is the only one that is posted and is about to start enrolling, all the rest are enrolling. And at ASCO we look forward to hearing updates from both Novartis and AstraZeneca, we are not in a position to describe what those are, look forward to Astra and Novartis sharing that insight.
And then with asthma what I would say is, you might have noted on our first slide, at the end of our last quarter we had about $125 million in cash and with our current run rate it gives us a pretty good runway. But we would like to see a deal on this asthma program ARRY-502, talking to a number of companies, it is a primary care indication. And so it’s not a quick process, but we will certainly be providing updates on how it’s going overtime and I would say by mid next year we should have a good feel for how that is going.
There is a meeting coming up in the very near future. This is Quad AI, which is the appropriate place for us to discuss a little bit more about ARRY-502. We did note that it had a marker and in a predefined analysis of the upper median which represents about a quarter of overall asthma. We did see a nearly 7% increase in FEV1. At that time we didn’t reveal what the biomarker was, only a list of the biomarkers we’d examined. And we think at Quad AI we would be able to share a little bit more detail. And our primary investigator Sally Wenzel will be sharing information, but could be an important source of revenue and eventually a value for the Company. But as I said, primary care as you know is a challenging field no doubt.
And so I am again very pleased with the progress, look forward in to keeping people informed, but really ultimately look forward to moving towards commercializing our first wholly-owned hematology/oncology program. It’s a large and important business segment and we think it well complements the value that our partners are generating through selumetinib and MEK-162. So looking forward to continued progress as we move forward.
So with that I am going to wrap up and we are going to re-convene in Olympic Room and we will take questions there. Thank you very much.
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