Endocyte, Inc. (NASDAQ:ECYT)
Q2 2016 Results Earnings Conference Call
August 04, 2016 04:30 PM ET
Mike Sherman - President and CEO
Dr. Alison Armour - CMO
Adnan Butt - RBC Capital Markets
Welcome to Endocyte’s Conference Call to Discuss the Company’s Second Quarter 2016 Financial Results and Operations Update.
Participating on the call today will be Mike Sherman, President and CEO; Dr. Alison Armour, Chief Medical Officer; and Dr. Chris Leamon, Vice President of Research and Development. [Operator Instructions].
During this conference call, the company may make predictive statements concerning future events or developments. Actual results may differ materially from those indicated by forward-looking statements. Please refer to Endocyte’s filings with the Securities and Exchange Commission for the discussion of risks and uncertainties impacting those results.
Now, let me turn the call over to Mike Sherman.
Thanks everyone for joining the call. This afternoon’s press release, I think you’ll agree, represents a nice inflection point for the Company. For our development of EC1456 or fully folate-tubulysin, this transition into the expansion phase of the trial and targeted non-small cell lung patients is an important milestone. And for EC1169 or PSMA-tubulysin, even though we’re still dose escalating, the fact that we are in a more targeted patient population from the beginning, has allowed us to see early signs of efficacy, even so far. We’re looking forward to be enabled to disclose more efficacy data on both drugs, later this year.
So, let me start with EC1456, really pleased to move into the portion of the trial that will give us more definitive signals of efficacy in patients we would most likely expect the benefit. Dr. Armour is here to provide some more detailed comments but let me provide a little more context for this stuff.
In moving the twice per week 6 milligram per meter squared schedule forward, we’ll be able to evaluate the schedule with the higher dosing frequency first. With this schedule, we hit the tumor cells four times during the three weeks cycle, providing less time for disease cells to recover or adapt resistance. This schedule also leverages receptor recycling such that we can reload receptors with each dose. While we’re enrolling targeted non-small cell lung cancer patients on the two times a week schedule, our dose escalation work will continue with the more convenient once per week schedule. We’ll enroll at least the first 15 patients on a twice per week schedule before shifting to the ones a week schedule, so we can get a faster and more definitive read on one schedule before moving to the next.
To recall that we’ll be using EC20 to screen patients in the second part and will only select and treat patients in who all the tumors are positive. And tumor positivity is subject to both the intensity of the uptake of the imaging agent compared to the background tissue and the extent to which the majority of each individual lesion shows up as positive.
As we discussed, it’s difficult to get a meaningful efficacy signal in a dose escalation study in which more than a dozen cancer types have been enrolled, some of which are positive and some negative for the folate receptor. That said, we have seen a 45% rate of stable disease as best response across all doses, which provides some hint [ph] to the activity. Also the patients who measured as folate receptor positive in all their disease were twice as likely to have their tumor burden either remain unchanged or decrease as best response compared to all other patients, also another signal at activity even in non-targeted patients.
To recall our focus on non-small cell lung cancer with adenocarcinoma cells is a result of the work we did with our first generation folate targeted drug EC145 or vintafolide. In the TARGET Phase 2 randomized trial of EC145 that was in combination with docetaxel, we observed an advantage versus docetaxel monotherapy in response rates, progression-fee survival and overall survival. So, this is an indication for that another reason. So, we have a lot of promise for EC1456.
Shifting to EC1169, that dose escalation trial’s being conducted in prostate cancer patients from the beginning. So, even without selecting patients with the companion imaging agent, we have an enriched population. As a result, we are predictably seeing activity more consistently and at lower doses. At ASCO, we reported two patients who had PSA responses of greater than 50% reduction. And based on what we’ve seen since that time, I expect the update at ASCO will continue to raise the profile of this drug.
On the financial front, there was really only one item of any variance from our last several quarters and that was the reflection of the compensation expense related to Ron Ellis severance. As noted in the release, most of that was non-cash equity related, representing an extension of vesting period and an extension of the time allowed to exercise those options before they expire. While on that topic, I’d like to maybe just take a minute and reflect on the transition with Ron, it’s going extremely well. As you would expect, based on the fact that we worked so closely together over the last 10 years, the handoff was straight forward. Although we have been indebted to Ron for what he has done for the Company and for me personally, he frankly brought us to a great place, the talented organization, a strong platform, a deep pipeline and a sound development plan. Now, it’s really my role and this team’s role to execute on that plan.
Speaking of plans, we updated our guidance for yearend cash, increasing that expected balance to $130 million or higher at yearend. And as implied, cash spend for 2016 of approximately $40 million; that gives us good flexibility for the next phase of development.
Before we turn over to your questions, let me hand it off to Alison, who can provide little more detail and color on the clinical activity and plans there.
Dr. Alison Armour
Great, thanks Mike. So, I’d first like to talk about EC1456, because as Mike said, we are now moving into the next stage of development, the Phase 1b cohort expansion part of the trial, which as he mentioned is in folate positive non-small cell lung cancer patients.
And actually, we were already in the process of considering moving into targeted patients without establishing MTD because we are really seeing quite minimal toxicity. But I can confirm that we will move forward fit with the 6 milligrams, twice weekly regimen.
So, we -- as initial 6 milligrams per meter squared cohort was very clean and very good safety profile, so when we moved up to 7.5 milligrams per meter squared twice a week, patient started to have side effects as we have seen before fatigue, GI disturbance. [Indiscernible] and I knew that patients in the Phase 1 trial facing [ph] are often extremely ill and they have multiple health problems, there was just a problem, getting patients to totally sustained dosing. But it was non-specific that they had to find fatigue. And one of the patients in fact got back by 6 milligrams per meter squared, and she remains on the study and is still doing well. So while there was no protocol defined DLT, we didn’t really feel that the 7.5 milligrams per meter squared would really be a dose that would be sustainable in the clinic. So, as I said, we decided to take 6 milligrams forward. And in the mean, while we were experiencing this, we were also testing the 15.5 milligram per meter squared dosing once a week.
So presently, we give once weekly dosing, two weeks on and one week off. But we were seeing the same type of side effects, a higher grade of side effects of fatigue and GI disturbance that qualified for DLTs. So, what we have done is back then we’ve expanded that cohort to 12.5 milligrams per meter squared, and we expected to clear that safe dose by the end of the month. So, it’s likely not a coincidence that we were seeing this maximum dose emerge around same total weekly dose as it appears that toxicity with this molecules, of the total molecules maybe [indiscernible] related.
These molecules actually have tremendous potential flexibility in dosing. So, while we will continue to put the twice weekly regiment in the Phase 1b part of the trial, we are going to take time to see if we can actually drop the rest week from the once weekly regimen. As I said, at the moment, it’s given two weeks on and one week off. If we can deliver treatment once a week, every week more dose can be delivered per cycle. So, you can see that we are aiming to confirm what’s most important with these molecules is that the total dose per cycle is given a maximum single dose, it is really important to keep pressure on the tumor with multiple dosing.
So, let’s go back to the part 1b that we’re about to go into the twice weekly schedule. We will be looking for efficacy in lung cancer patients who are fully positive, people who’ve been exposed to platinum doublet and very likely PD-L1 inhibitor. So response rate in that setting of 20% in the first 15 patients would suddenly be justification for further development. If we see a response rate of more than 20% with the monotherapy treatment in this setting, I think that that indicate that we would look for more accelerated regulatory path forward.
But let’s switch gears everyone to 1169 and its companion diagnostic, the imaging agent 652. So, this trial continues to recruit very well. We’re currently dosing at 8.5 milligrams per day two weeks on and one week off. The safety profile looks extremely good so far. We are seeing the same moving toxicity as we saw the 1456, the only fatigue GI side effects, but to date there have no drug-related serious adverse events and no dose limiting toxicities.
As the enrollment grows extremely well, it probably speaks to the enthusiasm we’re seeing around this drug, and that’s driven largely by the two lead investigators, Mike Morris from MSK and Dan Petrylak from Yale. You know these two physicians are absolute leaders in the field of prostate cancer and we’ve been lucky enough to have them to support us and designing our path forward.
For the next stage of the study, we plan to look at prostate cancer, metastatic -- castration resistant prostate cancer with the primary endpoint of radiological progression-free survival. We’ve been encouraged to look in two types of patients, not just patients who have been exposed to taxane but also encourage to look at patients who haven’t been exposed taxane and are likely to be chemotherapy naïve. The radiological progression-fee survival is obviously a key element of the new guidelines in the Prostate Cancer Working Group guidance that recently published and it’s a relatively robust endpoint for Phase 1 study. We are very keen to have this endpoint because we have seen that PSA drops don’t often reliably translate into longer term efficacy and later studies. We will of course be looking at other endpoints for example PSA drop, the overall survival, the control of pain in the study, and exploratory endpoints that are actually taking [ph] tumors out.
Next update in the study is both of these trials are open plan. We plan to give you updates as we go. The next stage update should be ESMO in October and of course the 17th World Lung Cancer Conference in December in Vienna maybe a good opportunity to present to you with an update on our work on 1456 and non-small cell lung cancer.
Now, would you like me to turn it back to the operator to questions?
Yes, I think we are ready for questions. Thank you.
[Operator Instructions] And our next first question comes from the line of Kennen MacKay of Credit Suisse. Your line is now open.
Hi, this is Zovy [ph] on for Kennen. My first question is how do you see ImmunoGen being required to run a full Phase 3 trial for their ADC and folate receptor positive ovarian cancer impacting dual development strategy in this indication and when might we see some ovarian data and what insights might you look for specifically in order to just guide on path forward? Thank you.
I’ll there take the first cut at that. There were multiple parts. So, Alison, help if I miss one of those. First of all, I guess I am too surprised by the development path they have gone down, the Phase 3 trial that they have proposed seems to mirror the Phase 3 trial we executed with our first generation drug EC145. So, our dialog with the FDA kind of led it the same place. Of course PFS endpoint was one that would be subject to review the data as the FDA told us. So, I’m not aware to what their conversations were like. So, I think the design of that trial is not surprising.
Our work in ovarian cancer largely depends on what we see in this next phase of the trial. If we see activity of the agent in lung cancer, I think it encouraged us to expand that into other indications. Ovarian cancer, triple negative breast cancer, endometrial cancer are among the prime targets we have for secondary indication. It could also trigger activity -- or work with combinations that could be meaningful in the ovarian space. So, our focus first is on single indication that we’ve demonstrated with our first generation, produced some very positive results, one that will allow us to really validate the schedule, the importance of the schedule, so that when we get to an opportunity to expand other indications, we know we are taking the right schedule forward. And we have a learned a little bit more too about the selection of patients using our imaging agent.
Dr. Alison Armour
I don’t think there is anything to add. I think what we have being doing so far as is selected patients who were keen to get into targeted population. And then, we can assign our monotherapy singles but as Mike said, we are ultimately also a combination therapy. So, we look at what they are doing with interest, but we have good forward with lung at the moment.
Thank you. And another question, what gives you confidence in the EC1456 like what squared meter dose, and what were the dose limiting toxicities are with the dose here? And I am also wondering how this relates to the efficacious dose that we saw in animals?
Dr. Alison Armour
Okay, I didn’t hear all of that question, so if I don’t answer, please let me know. I think you asked what were dose limiting toxicities of 15.5-milligram? One was, both of -- two patients with DLT, they both had fever, one had profound fatigue with that and the other patient had nausea and vomiting despite being premedicated. So, they fulfilled the criteria. I am very confident that with both the regimens, the weekly regimen and the twice weekly regimen, they are within the predicted efficacious range that was predicted from our preclinical work. So, I didn’t have any concerns with moving forward. I am very interested to see now what we do in the targeted population.
Alison mentioned this earlier but we were at a point where probably a couple of months ago, we were considering because we were in the targeted efficacy window, based on what the preclinical models would predict that we might just go ahead and start the second part or the expansion phase in targeted patients, so we could get on with it. And in a way, pleased to see that simultaneously we found with both schedules frankly that it looks like there is 15 milligrams per meter squared weekly dose, however you divided it, seems to be a threshold that is difficult to pass. So, our confidence that we -- and it hit the sweet spot, and both safety and efficacy I think confirms giving us the confidence to move ahead with the biweekly schedule in targeted patients. And yet we still want to, while we’re focused on enrolling, I’ll repeat the comments that Alison made, this notion that we are enrolling patients in the expansion phase just on the one schedule, the biweekly schedule allows us to get that enrolled quickly. And while we’re doing that, not competing for patients, we will continue to work to see if we can drop the rest week with the week once to week schedule. So, it’s about the time we confirm that we can do that, we will then be able to put that into targeted patients as well.
So, it’s a I would say relative to our development of EC145, higher confidence that we’ve got the right dose, higher confidence that we’re going to be able to bring the right schedule forward where we had really only tried to one primary schedule in the studies leading up to our Phase -- or both our ovarian and lungs trials.
Thank you very much. I was also wondering if you can provide us just any update on leveraging the small molecule drug conjugate CAR T combo data, we’ve got AACR to move forward and -- to move forward a program and also have you had any partnership discussions with any cellular therapeutic players in the space?
Yes, I mentioned on our last call that we were keen to have dialogue -- follow-up dialogue with companies that actually approached us after, I believe it was an AACR presentation. So, yes, we have engaged with those parties. The strategy really is to take what we have our expertise in the small molecules, adaptor molecules and recognize that working with a company that has expertise on the CAR T side of the equation is going to accelerate that development. And so that’s really our strategy, but too early to report beyond that.
Okay, thank you very much. One final question, do you have any update or guidance regarding in EC1456 checkpoint inhibitor combo trial?
Nothing other than that is one of the options and a potential attractive path, depending on what we see in this expansion phase. I’ll remind everyone that -- and this is quite literally the most compelling combination data we’ve seen with any of our drugs has been the combination of EC1456 with the a PD-1 inhibitor. And I don’t know if Chris wants to expand on that but the biology of that combination makes a lot of sense. I know that some are compelled by taking single agent drugs that make low levels of activity and there is still a rational that combining them with the PD-1 inhibitor makes sense. I’d much rather bring forward a drug that has activity on its own and explore that combination. So, what we see in this expansion phase, we’ll guide that work.
Thank you. And our next question comes from the line of Adnan Butt of RBC Capital Markets.
Thanks for the question. And Mike, congrats on the new responsibilities. Could you tell us how many patients were treated at the 6-mg per meter squared dose? That’s the one you are taking to the expansion cohort, correct?
Dr. Alison Armour
Yes. I think that there were four patients that were in that cohort. Traditionally, if we get a DLT, we have to drop down and expand to 6, but we really didn’t get a DLT at 7.5 that was the pragmatic clinical decision. There was a patient at that point because we had decided no longer to put to 7.5, so we let her joined the study at 6 milligrams per meter squared. So, there is four patients, they have all progressed through the trial with no safety concerns. So, we are happy.
Okay. And then the rationale behind picking non-small cell lung cancer, was that based on your prior experience or did you see some differentiated activity there? And then, why not try more expansion cohorts beyond just non-small cell lung cancer at this stage?
Adnan, I’ll take a crack at that first, Alison. So, there are multiple reasons why non-small cell lung cancer makes sense to start, not the least of which I think dates back to the rationale for doing the Phase 2 trial that we did with our first generation EC145 agent where the level of presence and consistency of the folate receptor in that disease was compelling. The data that we saw in terms of the sensitivity of that disease to the warhead that we are delivering including what we saw in PDX models, we see an amazing consistency and the activity of EC1456 in multiple lung models and then capped that off with the data that we saw in the TARGET trial.
In ovarian cancer, I think it is still a very interesting indication for folate receptor targeting. ImmunoGen’s work there is I think great evidence of that. Our work is there particularly in the Phase 2 and even in the Phase 3 where our combination with PLD performed exactly as we predicted it would. It was a control arm on question. However, a little bit more heterogeneity, if not in the level of receptor presence, defiantly had heterogeneity in the sensitivity of those -- of that disease from patient to patient. And we saw a little bit of that in some tumor models including PX models where we would see some resistance. EC1456 got over a lot of that but we still saw some heterogeneity. So, there is still some more to learn about patient selection there. We will follow one with lung cancer. We think that’s the right place to be. So, it’s an opportunity to certainly be a leader in folate receptor therapy in lung cancer as well, the rationale if we go in there first. I think we then expand beyond that. But, we want to see -- we should see activity in this indication, if there is promise in other indications. So, we want to confirm that and confirm the right schedule on the process.
Dr. Alison Armour
Thanks. Adnan, I think you also asked we have seen any activity so far. There’s been very small [ph] lung cancer patients in the Phase 1 unselected population that we have been dose escalating in. It’s not uncommon, not for the lung cancer patients that survive multiple lengths of therapy to reach the Phase 1 setting. So, we only have three patients to-date; they’ve had variable [ph] status; they are not in adenocarcinoma. And of course you can’t rely on what you see because you don’t know if you have an efficacy dose or not. So, I think we are very much in line on our previous experience and the TARGET trial showed proof of concept for me that this is something that could work in lung cancer.
And we had reported this quite a while ago. One of the first few cohorts on 1456, we had a non-small cell lung cancer patient albeit not an adenocarcinoma one, very low dose, and had a reduction in some of their tumor diameter between 20% and 30%. It wasn’t quite a bona fide PR [ph] but they also stayed on drugs for some time. So, I think it was more than -- it was 18 cycles. So, when we look back at what we’ve seen and sort of comforting that among the best results that we’d seen on that dose escalation was in a lung cancer patient, yet another reason that we’re optimistic about that indication.
If I can kindly get one follow-up please on -- could you expand a bit on the design of the expansion stage? Is it going to be just one study; is it going to -- and I heard you mention certain response creates, were those the kinds of hurdles that you are looking for in this particular expansion phase that you are starting now?
First, of all. I think the precedent was set at six or seven questions. So, by all means, you can ask another one.
No, no, [multiple speakers].
Dr. Alison Armour
I think there are verticals [ph] associated with and the tremendous flexible with these molecules and we are starting with the twice week regimen. We are going to recruit 15 patients and then send back and see if we get a response. So, if we get a very good response, you could have less number of options, you can know accelerate and go quickly forward, thinking that that’s a reasonable regimens taken to the clinic. But if we see thee is pure response, then we’d certainly go back, [ph] we can look at the alternative and give regimens giving a every week or even four times a week. If we switch something in between, we will use all of the information that we have, [indiscernible] biomarkers at that stage, responses, the duration of t hem, and so it’s very much. I think what’s important at this point is that once we start [ph] with patients, other regimens will be ready to go to monotherapy. If we think we can really achieve even a step change in efficacy with a different regimen, we have got the ability to even try that at that point. And of course we’ve also given Mike the flexibility of when we do want to get combination mark or other indication.
Yes. I think important thing is we want to really nail down the schedule here. And the only way you can do that is by focusing on one indication and then you can proliferate that chosen schedule, if one rises to be dominant to the other; that’s a schedule you take to the other indication. So, an important point to note.
Another thing, I think we may have mentioned this in the past, there is -- in addition to the -- I think there will be additional learning around the patient selection. We’ve really refined our imaging rules for who qualifies. I think those are -- refined is probably the word relative to what we use in the PROCEED and TARGET trials previously. But we think that will enhance the likelihood of success.
The other thing we’re going to do is sort of a separate study where we are going to look at in ovarian cancer patients that have prior to their debulking surgery, we would dose them with EC1456 and then evaluate the tissue from that they removed during surgery. It’s going to help us answer a lot of questions, and physicians will -- I’ve been interested in this data for some time, but will be able to track not only, is our imaging agent confirm the targeting of or the presence of the receptors that we see in our imaging, are we able to confirm that with the tissue samples, number one. Are we in fact targeting the way we believe we are targeting. We have already confirmation of that obviously with activity and win with our imaging agent. Some measure of how much drug we are delivering to the cell and even maybe some early evidence of antitumor activity. So, it will be a nice proof-of-concept. I guess I’ll add to that. Not only are you targeting the cell, are you delivering the drug inside -- or the payload inside the cell and is it being fully released or do you still have intact conjugate inside the cell, a lot of data that will I think support our both knowledge and the mechanism of the drug and inform our path forward on future developments. I think it will be data that will be important, not only to physicians, to us but also to investors kind of confirming the activity beyond just what we’re seeing in efficacy just another endpoint to follow.
Okay, I’ll get back in line. Thanks.
I think you maybe the last one in queue. So, if you have another one, please go ahead.
Let me ask a bit about 1169 events; actually I’ll combine the two. So, what exactly do you expect to present at ESMO then? I mean, are we - what should be the focus there for us?
So, I would say for 1456, the update at ESMO will be really a follow-on to the dose escalation work. That will be too early for us to have much in a way of data on the first lung patients that we would have enroll in the expansion cohort. For 1169, I see that differently because frankly the patients that we’ve been enrolling the last -- from the beginning but in particular the last couple of cohorts are -- look, while maybe more advanced than what we would see in the expansion phase there, they are in effect targeted patients. So, our ability to report, and the importance of paying attention to the efficacy data there will be more meaningful. So, I answered that those efficacy data we’ve seen since ASCO that we’ll update there. I don’t want to leave the impression however that these patients are exactly what we would enroll in the expansion phase for the prostate cancer, not the least of which is the issued that we are not haven’t selected any patients or we haven’t excluded any patients based on the imaging agents. And in fact there are some patients that we’ve enrolled. While every patient has shown some level of PSA activity, there have been some based on the rules that we define that we would have excluded in the expansion phase, not many but some. And so that will further refine and increase our confidence in seeing activity in the expansion phase. But nonetheless, -- we’re in that mode now where both in prostate cancer because -- for the 1169, because we’re in prostate cancer and most of the patients are targeted anyway and because we are now in lung cancer and we’ll select them with our imaging agent, virtually every patient we enroll from here, the efficacy we see is going to be meaningful.
And Mike, when do you expect to provide an update on at least on for the 1456 expansion phase, since you’re starting [Multiple Speakers].
Yes, the first opportunity I think will be at that lung cancer conference in December.
Thank you. And I’m showing no further questions at this time. I would now like to turn the call over to Mr. Mike Sherman for closing remarks.
Yes, thanks again everyone for joining the call. Obviously, we’re excited here at Endocyte, really for the reasons I just highlighted. We’re now in a place where every patient is going to be more in line in terms of the actual efficacy of these agents and as a result, the data that will flow from the studies from here will be more meaningful, and really looking forward to providing updates on that data in the conferences ahead and weeks and months ahead. So, with that thanks again. And have a good evening.
Ladies and gentlemen, thank you for participating in today’s conference. This concludes today’s program. You may all disconnect. Everyone, have a great day.
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