Daniel M. Junius – President and Chief Executive Officer
Matthew Harrison – UBS Securities, LLC
ImmunoGen, Inc. (IMGN) UBS 2012 Global Life Sciences Conference Call September 20, 2012 3:00 PM ET
Matthew Harrison – UBS Securities, LLC
Afternoon everyone. Next up we have ImmunoGen presenting and we have the CEO, Dan Junius.
Daniel M. Junius – President and Chief Executive Officer
Matthew, thank you. And thank you to UBS for inviting ImmunoGen to present at the conference. In my comments, I will make some forward-looking statements. I would point you to ImmunoGen’s filings with the Securities and Exchange Commission for risks associated with investments in ImmunoGen.
In talking about the company, we have a position of leadership and what is becoming a very interesting area of antibody drug conjugates. I think what gets most of the attention these days is T-DM1, which is the most advanced compound in the portfolio. It’s a program being advanced by Roche that’s tracking that of Herceptin, Herceptin being about a $6 billion compound worldwide. It’s being developed across the full spectrum of uses in HER2+ cancer that would include metastatic, as well as earlier stage breast cancer and now also in gastric cancer and we’ll talk more about that in a minute or two.
I think that what’s significant of the data that’s been developed with T-DM1 is that it does hold the potential this technology to be transformational in terms of how ADCs can become therapeutics in cancer treatment over time. That was the theme that we heard from many oncologists at ASCO when the most recent T-DM1 data was presented.
What you have is the benefit of a targeted technology that provides as seen with T-DM1, a higher level of efficacy accompanied by a very good level of tolerability, which is uncharacteristic of most applications in oncology. Beyond what we do with Roche, we have partnerships with Sanofi, Bayer, Amgen, Novartis and Lilly. Out of those partnerships, as well as work that we’re doing ourselves, you are seeing an expanding pipeline that’s moving forward in the clinic. We now have 10 clinical stage TAP compounds, three of those wholly-owned by ImmunoGen, as well as numerous earlier stage compounds both our own as well as partners.
In building this, people often think of the technology and focus on the cytotoxin and the linker, but I would also remind people about ImmunoGen expertise and antibodies. We have deep expertise in developing panel antibodies against a variety of targets. I would point to one of the compounds in the clinic with Sanofi is a naked antibody targeting CD38. CD38 becoming an interesting target for non-Hodgkin’s lymphoma and it’s a very good data having and generated around CD38 although we haven’t entered the Sanofi data. But that antibody expertise is very important.
And lastly from a financial standpoint, the company is in very good shape having raised money just in July to add to the $161 million we had on our balance sheet as of the end of our fiscal year in June. So we’re now in a position to very comfortably advance the compounds that we wholly own to proof-of-concept.
Let me talk a little bit more about T-DM1 also known as Trastuzumab emtansine. What you have here is the technology that ImmunoGen has brought forward and that would be around a cell killing agent I note a very potent cell killing agent, the method of linking that cell killing agent to the antibody and actually at the source, the idea of using this technology in combination with Trastuzumab. We approached Genentech with the concept going back into the late 90s.
Genentech, we’re working with their Trastuzumab antibody, and unmodified the same antibody that’s marketed today as Herceptin and we think that the data that’s incorporated in the various studies with T-DM1 demonstrate the transformative potential of our technology.
The most recent data was disclosed at the ASCO Conference back in June, it was featured in a plenary session and it was around a study referred to as the EMILIA study, it was looking at T-DM1 as monotherapy compared to the current therapy for post-Herceptin treatment in metastatic patients that being Tykerb plus Xeloda.
And what that data showed was a meaningful improvement in progression-free survival taking it from 6.4 months in the control arm of Tykerb plus Xeloda to 9.6 months or 50% improvement in progression-free survival, and while the overall survival data was not yet mature, the indication from some of the data suggested a dramatic improvement in survival for patients that had been on study for at least a year, there was a 7.7 percentage point, not 7.7%, but 7.7 percentage point improvement in survival and for patients evaluable after two years almost an 18 percentage point improvement.
We now know post ASCO that that overall survival benefit is statistically significant and we expect to see the data at ESMO in just over a week from now.
Beyond the efficacy, I mean the efficacy is certainly, is extremely important, what you’re finding and what was disclosed at ASCO is a meaningful benefit of tolerability or improvement in tolerability versus the current standard of care. I mean from a starting point it was disclosed that virtually all patients received the full dose of T-DM1 over their course of therapy 99.9% versus lower levels for Tykerb plus Xeloda. At Xeloda it was just over 77% of the projected dose having been received and Grade III or greater adverse events were meaningfully lower with T-DM1 just over 40% versus 57% in the control ARM.
When you look at the top adverse events, upgrades were a greater comparing the two. The top two adverse events for Tykerb plus Xeloda were diarrhea and hand-foot syndrome at the 15% and above levels for both, 20% in terms of diarrhea for T-DM1 much lower thrombocytopenia was under 13% and then increased liver enzymes of just below 5%.
The nature of the toxicity and the required engagement of the physician in treating the patient and dealing with the patient side effect is very important. It was noted by the presenter at ASCO that managing some of these side effects of the control ARM takes a lot of physician time, as well as being a significant burden on the patient.
There’s data beyond the EMILIA data and that is looking at T-DM1. In first-line use there is a Phase II study that’s been disclosed actually at the last two as most comparing T-DM1 versus the current standard of care for first-line metastatic treatment. And what that showed again was about a 50% improvement in progression-free survival with T-DM1 as monotherapy versus Herceptin plus taxane. So again, an opportunity to provide a high-level of benefit to patients while taking taxane and its associated toxicities out of the therapy.
Again that’s demonstrated by the incidents on Grade III or greater adverse events in this study, which you saw was 46% Grade III or greater adverse events for T-DM1 verses almost 90% for the control ARM. So, barely half of the Grade III or greater adverse events.
In addition, what were shown is a very low level of alopecia so hair loss in the T-DM1 ARM was in extremely low level about two-thirds of the patients in the taxane and Herceptin ARM showed significant hair loss.
So what this is led to, it supports a very broad development program that’s underway with Roche. In the metastatic setting what you have is BLA submission in the U.S. for T-DM1 for patients after having received treatment of Herceptin plus a taxane. So clearly this would include second-line or latter metastatic patients, there is also the opportunity that this could address patients who have been diagnosed in for first-line metastatic who may have received Herceptin in the adjuvant setting. We’ll see what are the regulators view that and there is a pending application, we haven’t been informed whether that’s been submitted in Europe at this point in time, but it was to be imminent at the time they submitted in the U.S.
You also have, we’ll have a filing in first-line that’s a Phase III study that they call MARIANNE. The enrollment of that study is complete. The guidance is that they would expect to submit in 2014, and then there is a later stage patient although, while enrolling we’re not sure that will lead to any particular submission.
In early stage HER2+ breast cancer at ASCO, we understood that there is a strategy from Roche to essentially address the full spectrum of early stage breast cancer, so that would be neoadjuvant, adjuvant as well as patients with residual invasive disease after surgery. Those studies will start across the course of 2013; the earliest to have data readout in 2015; some of the largest studies will be looking at data in 2018.
And lastly, we are now getting some insight into the strategy around gastric cancer. There is a Phase II, III study underway looking at HER2+ gastric cancer patients, who have relapsed from first-line therapy. As we said the study has started, the Phase III is expected to be completed by 2015.
I’m not going to go through the entire chart of all but it’s taking place around T-DM1 as you can see from this timeline, it will be a very active three years, it has been to-date, but now that you have marketing submissions, we would expect to see approval either very late this year or early in 2013 and in the U.S., sometime later in Europe, submission in Japan and then succeeding submissions and data coming out across the various studies for first-line therapy for adjuvant therapy et cetera, so a very active environment.
As I noted at the outset, I think what you have is that this type of data demonstrates the transformation of potential of T-DM1. You’re seeing it against a prevalent tumor type, so with T-DM1 in particular I think that oncologist viewed that particular type of cancer to have reached, for the bar tool have been set very high. You had a targeted therapy with Herceptin that have shown dramatic improvement for that patient population.
With T-DM1, you’ve gone against a very high bar and moved it even higher and going into a solid tumor type as oppose to liquid tumors. What you’re seeing on the chart is, with another compound that was developed by ImmunoGen SAR3419, which is being developed by Sanofi-Aventis in non-Hodgkin’s lymphoma. You are seeing activity across a variety of tumor types in later stage patients. A significant level of objective responses and very good tolerability again demonstrating both aspects of what you would look for in a targeted therapy.
At the same time tolerability as I noted, tolerability is very good, grade toxicity are generally Grade I or II. They will vary somewhat based on the target and the compound. One thing that you don’t see that allows these compounds to be effective and to be dosed in combination is a lack of any meaningful bone marrow suppression. So very encouraging in terms of what we are seeing with T-DM1 and the implications for this technology on a broader basis.
As we transition from T-DM1 and talk about the rest of the portfolio, are very active from the second half of this year through 2013. The green boxes there would identify activity with ImmunoGen proprietary compounds, the blue with partners and just some highlights. We’ve had data out just within the last week or two around our most advanced proprietary compound we’ll talk about that in first-line small cell lung cancer.
We expect to have another compound in the clinic in mid-2013 and have additional data across all three of our proprietary compounds in the back-half of 2013. At the same time, we should be hearing more about SAR3419 from Sanofi, from the three Phase II studies that they have underway. We should here be hearing about the other five partner compounds that currently are in Phase I testing. And our expectation is that we may see as many as two of our partner compounds beyond T-DM1 and our registration studies over the course of 2013.
So let me talk now about IMGN901. As I mentioned this is our most advanced compound, it’s for small cell lung cancer. Although, the target is expressed on a variety of cancers, you can see from the chart that would include ovarian cancer, certain neuroendocrine cancers, multiple myeloma and some NK lymphomas.
Our development focus right now is in first-line small cell lung cancer. The target itself CD56 has no known function in the course of cancer development. So that makes it ideal for an ADC, since you are not looking at an antibody or a small molecule to block a function of the receptor or take some other action, you are using it simply as a targeting vehicle and it has the characteristics both in terms of expression, internalization, et cetera that make it very conducive to an ADC.
Why small cell lung cancer, certainly there is an unmet need in this area. If you look at the nature of the disease it’s very prevalent, very aggressive disease, median overall survivals less than a year, progression free survival for first-line patients with extensive disease is five to six months.
We have tested 901 as monotherapy in a variety of CD56 positive tumors, which would include small cell lung cancer and small cell carcinomas in small-cell lung cancer itself. We saw about a 25% clinical benefit rate in second-line in liver patients and this is significant because once small-cell lung cancer patients relapse from first-line treatment. It’s very difficult to arrest the progress of the disease. We also had good experience in a related disease, MCC stands for Merkel cell carcinoma here across 21 patients we saw three very durable complete responses. Merkel cell carcinoma shares many biologic characteristics with small-cell lung cancer. So beyond the clinical data that we’ve seen in earlier studies, we also had conducted preclinical studies in various mouse models and looking at small-cell lung cancer, what we saw was the opportunity for 901 to be synergistic with existing therapies for small cell lung cancer.
In terms of first-line, we went first-line for a couple of reasons. First, it’s where you have the most of the patients and it was also where we saw the greatest opportunity to arrest the progress of the disease. As I mentioned well, there is good response to first-line therapy, it doesn’t have the durability that you would like. So we think there is the opportunity to at least maintain the response rate, but to extend the durability. We also thought given the characteristics of the targeted therapy we could add this on to existing first-line therapy without impacting tolerability. And I’ll share the data with you in a moment that suggests that that appears to be the case.
So we have a study underway, it’s a Phase I, II study. We’re through the Phase I portion and we presented the Phase I portion in Chicago a couple weeks ago at a Thoracic Symposium and we are now on the Phase II. And again I’ll emphasize the Phase I was not looking at our target patient population. We were taking any patients who would receive an etoposide/carboplatin therapy for their existing condition. We then added 901 to get our Phase II dose. And so we’re now recruiting to the Phase II portion of the study, this is being conducted in four countries the U.S., Spain, Canada and the UK. It is a randomized study, so we’re randomizing  patients to the experimental ARM of etoposide/carboplatin plus 901 for every one patient that goes into the comparator ARM.
It’s designed as a Simon two-stage study. So we’ll have a subcohort of patients that we’ll be able to monitor and evaluate the efficacy that we’re seeing at an early stage that will inform us around certain steps that we may want to take it in earlier time to compress the time to allow us to get to a pivotal study.
The data that we reported in Chicago focused as I said it was principally to be a safety study to understand what the dosing would be in the Phase II portion. It was not our NORTH patient population, it was any patient who would receive etoposide/carbo and what we found was the best that we could have hoped for. We were able to dose 901 at the same dosing level that we’ve been able to use with 901 in our monotherapy studies. So once we continued to dose keeping the existing etoposide/carbo at their current dosing and once we got to the full dose of 901, we didn’t go any far there, because we figured that was all that was our highest expectation of the study.
But while it was designed as a safety study, we also had some insight into efficacy with this patient population and again emphasizing not to target patient population at the Phase II. What we saw across this broad range of patients, 33 patients in total 30 of whom were evaluable because those are the 30 that expressed CD56. There was some level of disease control in almost three quarters of those patients.
We also were able to call out the small-cell lung cancer patients in the study and that data again a very small end, but encouraging. In that, of the 13 small-cell lung cancer patients, 10 of them had previously received a platinum-based regimen. And among those 10, four of them had a partial response. And again as a subset of the 10, seven of those 10 were platinum resistant or refractory and we’re able to generate an objective response in two out of those seven. So encouragingly we were able to get that type of activity in what is again a very difficult patient population.
Beyond 901, we have two very much earlier stage compounds, the first being IMGN853 that’s also is wholly owned. The target here is the folate receptor alpha or the folate receptor 1 that is over expressed on a variety of non-small cell lung cancers, as well as certain ovarian cancers. You can see the incidents there for adenocarcinoma non-small lung cancer there is about a 90,000 patient incidence in the U.S. every year, and for epithelial ovarian cancer an incidence of 19,000.
This again is an ADC, we think that the design here is unique and that here we’re using the antibody as the targeting vehicle, there is another compound that we’re aware of in the clinic that also targets the folate receptor that uses dietary folate as the targeting vehicle. We think there is an advantage to using an antibody, because the antibody targets a different epitope on the receptor than dietary folate. So we’re not competing with dietary folate to access the receptor.
At the same time, this is the first time we brought into the clinic a particular linker that’s been designed to counteract multidrug resistance. So the preclinical data here was extremely strong, we begun dosing patients. We’re anxious to see the data that we generate. And the expectations we’ll be able to get to a therapeutic dose relatively quickly since we have a protocol design that allows us to look at single patient cohorts until we get to a certain level and then have to expand into the traditional three-patient cohort. So this is underway and preceding very well.
Once we achieve the maximum-tolerated dose, we already have a design in place we’ll begin enrolling a disease specific population in three individual cohorts, two of them focusing on ovarian cancer, the third focusing on non-small cell lung cancer. And in addition to looking at those individual patient populations, what we’ll also be doing in a couple of these studies is looking to see if we can identify some biomarkers that will let us further stratify the patient population for further studies.
While we’re going through at an early stage with this particular trial, we’re investing on a separate path on some of the work that needs to be done to support a pivotal study, so that if we see that the quality of data that would support further development that our CMC activity is aligned and will allow us to compress again the time to a pivotal study.
Our third proprietary compound we refer to as IMGN529, we think this is a unique compound for B-cell malignancies. B-cell malignancies is crowded space there, some very effective therapies in place today for early staged disease, but we think that both the target CD37, as well as again our conjugate design give us some distinction here. This particular target is found on most non-Hodgkin’s lymphoma, as well as chronic lymphocytic leukemia. And the design is interesting, because what it does is it takes an antibody that has shown activity pre-clinically that appears to be as active if not more active than Rituxan and on top of which we’ve added our ADC technology.
So while we acknowledge that non-Hodgkin’s lymphoma space is quite crowded. We are bringing forward something we think that is highly differentiated and once we get through our early stage dosing and get therapeutic levels, we’re excited to see what the potential is here. So the Phase I here is underway. And again hopefully, we’ll have data to be able to report on this as we get to the back half of 2013.
I mentioned at the outset, our financial position, the guidance that we provided when we released our year end results was were that by the year end of fiscal ’13 and we expected to have about a $160 million in cash. That would reflect cash – I’m sorry about a $170 million to a $176 million in terms of ending cash balance. That would reflect cash usage of about $80 million over the course of this year that would be above prior years, but prior years were supported by a number of partnership deals.
In 2010, we did a multi-target deal with Novartis. In fiscal 2011 sorry fiscal 2012, we did a multi-target deal with Lilly. As we provide our guidance for fiscal ’13, we’re not anticipating or certainly not forecasting that type of an infusion, but there continues to be significant interest in the technology. So we’ll see what evolves.
In terms of events for upcoming over the next several quarters getting back to T-DM1, the survival data as I noted from EMILIA should be available very shortly at ESMO, we should hear very soon as well about the status of a filing with the FDA that meaning the submission having been accepted, as well as understanding the PDUFA status. That should lead to approval. In the first half of ‘13, we would expect with sales to follow. We would also expect to see – get our first look at the first-line metastatic breast cancer data sometime over the course of 2013.
For early breast cancer, the three registration studies that I referenced earlier should initiate over the course of the year and the gastric Phase II, III study was slated to begin enrolling patients in the third quarter of this year. So that may well be underway at this point.
For the other partner compounds in the clinic, we may see Sanofi data for SAR3419 possibly later this year, if not certainly over the course of 2013. And then with the other compounds and testing with our partners, we would expect to see HER data certainly not later than the second half of the year.
For our own products, we submitted an abstract expect to have data on the Phase I multiple myeloma study that’s been conducted dosing 901 in combination with Revlimid and dexamethasone at ASH and then have our initial data from the NORTH study sometime in the back half of 2013. The same would hold true for our other two proprietary compounds, and then our next compound in the clinic, we would have preclinical data probably at AACR and that’s the current plan, with the IND being submitted in the middle of the year.
So we think that we’ve progressed very well. The initial, the Roche program is tracking very well to follow-on to Herceptin in a variety of different indications. I mentioned earlier, we think this demonstrates, while the transformational potential of our technology. We have a very strong and growing pipeline both growing and advancing into later clinical status. And then a very strong balance sheet to support development of these compounds.
So, thank you for your attention. I believe we’re in the Carnegie breakout room downstairs and look forward to answering your questions there. Thank you.
[No Q&A for this event]