Charlie Morris - EVP & CDO
Sam Martin - Jefferies & Company
ImmunoGen Inc. (IMGN) Jefferies 2013 Global Healthcare Conference Call November 21, 2013 8:40 AM ET
Sam Martin - Jefferies & Company
Good afternoon and welcome to the Jefferies 2013 Global London Healthcare Conference. It's my pleasure to introduce Charlie Morris, Executive Vice President and Chief Development Officer of ImmunoGen. ImmunoGen is based in United States and develops targeted anti-cancer therapeutics.
With that, I will turn it over to Charlie.
Thank you Sam, and good afternoon everybody. As Sam said, my name is Charlie Morris; I'm responsible primarily for the development of the proprietary pipeline for ImmunoGen. Today's presentation will of course include forward-looking statements and future results may vary.
ImmunoGen today is in an interesting position of having made progress on a number of fronts. I will focus on a number of different aspects. First of all, we'll talk about Kadcyla using our antibody-drug conjugate technology that has been approved now in multiple markets including Europe just yesterday for the treatment of HER2-positive breast cancer. I'll talk about the progress being made with our own proprietary pipeline of ADCs and talk a little about our other partnerships and our current financial position.
So first of all, to start with Kadcyla, Kadcyla previously extensively known as T-DM1, really has been the principal validation to-date of our antibody-drug conjugate technology. This compound includes our linker and payload known as DM1 and the linker is known as SMCC. We are the holders of the composition of matter patents, and we use the same linker and payload technology in a number of other compounds.
This obviously has been the first ADC, which has now been approved for a major solid tumor indication, the only one to have shown survival advantage in the large randomized study. And obviously it gives, as I said, both validation and of course, importantly, royalty revenue as a result to what has been done, and Roche to-date has had a very successful launch in the U.S.
The U.S. approval occurred in February of this year. It has subsequently been approved in a number of markets, as I said, including the final AMA approval just yesterday after the CHMP positive recommendation a couple of months ago, and sales year-to-date have amounted to 152 million Swiss Francs; in the U.S. formally and from elsewhere in the world, giving us a total of approximately $168 million, and we report our royalty one quarter in arrears.
Current indication for the treatment of HER2-positive metastatic breast cancer, which is for patients who had previously progressed on Herceptin and taxane, so at this point, the cancer is obviously unresponsive to the existing Herceptin chemotherapy combination, yet by linking our payload to the trastuzumab antibody, we've been able to provide both a survival advantage and tolerability benefits compared to current standard of care of Tykerb and Xeloda, and we estimate to see the numbers there on the right of the first line and second line population in the U.S.
Roche put into place a pretty aggressive program and obviously that's good news for patients, good news for Roche, good news for us assuming future success. With the number of approvals beginning to happen, and there is a broad development plan, which goes even more expansively, I think you will see (inaudible) that was put in place for Herceptin historically.
So we have the current indication as described, but there are first-line studies ongoing with data expected during 2014 and hopefully a submission in 2015. There are ongoing neoadjuvant studies. There is another study in what we call here residual cancer, which is sort of a population of relatively aggressive disease with residual disease after initial chemotherapy and surgery, as well as a large adjuvant study similar to that which has previously been very successful for Herceptin, and in addition like Herceptin, this is now being pursued in gastric cancer as well with data expected again from that study probably in 2015.
But beyond Kadcyla, of course, we have to apply the technology to a number of similar ADC types of products. I now have a number of these advancing in clinical trials, including a total of four under our own drive. We try to leverage our expertise. We've done very well in developing the antibody component. We've got great expertise on the linker front, and now have a selection of linkers from which to choose, as well as the -- from the maytansinoid perspective, both the DM1 and the DM4 as the payload component. The -- as we look to make these into ADCs, we've tried to find the best combination of those based on a numbers of features obviously looking at which has the most impact in cell lines. We're also trying to apply the link technology to best help with retention of payload in the cell and to ensure the stability of the payload in the blood.
We have now been able to conduct extensive preclinical and increasingly clinical and regulatory work in-house and have extensive abilities in terms of manufacturing and quality control.
So the list of the various products is there on the right. I will focus on any 853, which targets the folate receptor, 289 targeting EGFR, 529 for B-cell malignancies; and give you an update on 901, which has recently had some data come through, that's from a randomized Phase II study.
So for the folate receptor, we're using IMGN853. Folate receptor is highly expressed in a broad range of tumors, most notably, in where we think the initial development is likely to be, in ovarian cancer and in endometrial cancer which is also seen in a subset of patients without no carcinomas of the lung and in some patients with renal carcinoma as well. We saw very compelling single-agent activity in our preclinical testing, and this is an antibody which has been selected purely for its payload delivery properties.
If we think about the Kadcyla structure where you have the active trastuzumab antibody, in this case there is not inherent activity of the antibody; the antibody’s delivery vehicle bringing the payload to itself. This uses the DM4 payload and an engineered antibody, particularly engineered to deal with multidrug resistance, which is a common feature in ovarian cancer patients.
We're currently in a dose finding study. This has been seen as an escalation of the dose beyond the maximum tolerated doses presented at ASCO this year where we saw the dose-emitting toxicities were identified as a form of ocular toxicity associated with vision. We subsequently found that to be very well correlated with some of the pharmacokinetics undertaking a number of approaches to ensuring that we're able to dose to effective doses while avoiding any ocular findings to the greatest of extents including different method of calculating the dose using patient’s adjusted ideal bodyweight rather than their total body weight, and we will be looking in parallel as well as the current three weekly schedule; we will also be looking at a weekly schedule days 1, 8, 15, after the four-week cycle.
We will in the New Year probably be moving into our expanded cohorts in both ovarian and endometrial carcinomas initially on the three week schedule, while in parallel doing additional work on the second schedule. And once we have settled on the ideal schedule, we will add cohorts for the first schedule in adenocarcinomas of the lung as well as in a more refractory group of patients with ovarian carcinoma.
Early findings in this product were presented at ASCO this year. This is from a mix of tumor types and treatment histories. As we said, the highest dose that we tested went as high as 7 milligram per kilogram. That's certainly only highest that we've tested with any of our proprietary products, and the dose-limiting toxicity with the reversible ocular toxicity, which has actually been described with a number of ADCs seems to be a feature relating to tubulin agents.
Encouragingly, last time we had the interesting initial evidence of activity, that is described here including patients with ovarian carcinomas and endometrial carcinomas, patients here with a long-term stable disease and a confirmed CA-125 response, another patient with endometrial carcinoma with a partial response after four cycles, and another patient with ovarian carcinoma with a PR after two cycles. And so, with those encouraging data and obviously continuing to see interesting activity as we go forward, we're quite encouraged by the initial activity for this particular product.
We recently announced that we've also advanced into clinical testing, IMGN289. This is targeted against the epidermal growth factor receptor, which is obviously a well-explored, well-validated therapeutic target having been the target to small molecules such as erlotinib and gefitinib, as well as for monoclonal antibodies such as cetuximab and panitumumab. As you know, highly expressed in a broad range of tumors and it is particularly highly expressed, although not necessarily a key oncogenic driver in squamous cell carcinoma of the lung and in head and neck cancers as well as being expressed in a broad range of epithelial tumors.
In addition to those targets, it's obviously those patients whose disease is currently treated with either monoclonal antibodies or with tyrosine kinase inhibitors, which got an initial preclinical evidence of activity in patients who have already progressed after those types of therapies.
So the profile here, we've screened a large group of antibodies, particularly targeting trying to find something that reduced activity in terms of skin toxicity, initially looking merely to find a carrier antibody to carry the payload, we were actually fortunate for identifying antibody which had not only seemed to have a reduced liability for skin toxicity but also similar activity at least in our preclinical models to that seen with cetuximab, and I will show you some data on that in a moment. And obviously that would make for a very compelling offering if we're able to provide not only an active antibody but an active antibody with reduced toxicity and carrying the payload it becomes sort of a well structured ADC with high potential.
The reason for the avoidance of skin toxicity, we believe, it's because it's a partial antagonist. Generally speaking, I think if you were going to be trying to develop a naked antibody against EGFR, you would look for the most potent antagonist you could find. Our key demand here was that we should have a lower liability, skin toxicity, and therefore this antibody was identified and seems to have a different impact on keratinocytes as well as a different impact on cytokines, which release and seems to be associated with EGFR skin rash. And the overall structure then is very similar to Kadcyla, an active antibody, and the SMCC linker and the DM1 payload.
And so here we see examples of the in vitro activity. On the left, you see an example of a non small cell lung cancer adenocarcinoma. This one, we know to be a dependent on EGFR signaling because we see inhibition of growth when we add the green line, which is cetuximab and also the naked antibody component of 289, which is the black line on here. Whether that same antibody component with it and it has to link from payload attached, this killing scene on the red line which is clearly much more dramatic than that seen at the other interventions.
In the middle, we see squamous cell carcinoma. Squamous cell carcinomas, many of you will know, has been a difficult target for the EGFR targeting agents despite the high level of expression, here both for our naked antibodies as well as for cetuximab, you do not see activity as a single agent. Once again because you're carrying the payload, you do have the cytotoxic effect and, therefore, some marked activity when you have the 289 ADC in place.
And finally as on the right, using a slightly different paradigm here, we’ve looked at a series of types of resistance to tyrosine kinase inhibitor. The example here is a T790M mutation, where again having become resistant to treatment with erlotinib Tarceva, which is the blue line on here. We still are able to demonstrate activity because obviously there is still expression of the target, and therefore there is still the ability for the ADC to bind, and so the -- for the effects of cytotoxin to take place. And therefore, you see examples of activity in these resistant models.
And that really sets us up to where we're taking this in terms of the Phase I dose exploration. We're currently, as you know, and we just started clinical dosing, in the dose finding phase when we've identified a dose to take forward, we will then move into an expansion phase and really based on the type of the ADC we will look at non-small cell lung cancers she have already been exposed to EGFR therapies and become resistant.
We will look specifically at the subset of patients with squamous cell carcinoma. We will look at the lungs -- we will also look at patients with squamous cell carcinoma of the head and neck, again something that's just been treated well with cetuximab as well as a subset of other types of EGFR over expressing tumors.
Moving away from solid tumors in the hematologic space we have IMGN529. This target is a lesser known marker called CD37. CD37 tends to appear on same types of B-cells as CD20. And even here, again we have a similar structure, an active antibody with multiple means by which to kill cells by itself with also the SMCC DM1 linker and payload attached.
So if we look at the example graph here on the right hand side of the slide you'll see that the antibody load has somewhat better activity that Rituxan in this particular model. But once you add the payload to that antibody you clearly have a much greater level of activity always in a preclinical setting. So based on these preclinical data we have moved into Phase I testing starting at relatively low doses. We have already disclosed that we have seen some effects which should fulfill the criteria for dose-limiting toxicity at relatively low doses although these are primarily laboratory findings. And so what we believe we understand the likely mechanisms for this and that we will be able to give patients prophylactic management to avoid this and, therefore, be able to escalate the doses further. Interestingly though, we have even at the similar low doses seen this level of efficacy and activity consistent with the mechanism of the drug.
So we're actually quite encouraged and hopeful that we can continue to dose escalate as one would suspect that being at low doses any activity right now would be most likely antibody-driven and obviously we want to escalate to ensure that we get to doses where we also see the benefit of adding the payload to the antibody.
IMGN901 is actually have been our furthest advanced therapy. This has been in Phase II development for small cell lung cancer. This targets CD56 which is a common indicator of tissues of neural origin. It's seen in small cell lung cancers in the broad range of neuroendocrine tumors. And based on our preclinical data and the initial clinical data we had advances into randomized Phase II study in small cell lung cancer in combination with standard doses of Carboplatin and Etoposide.
Prior to going into the study we'd dosed to pay at least -- I'm sorry, not at least, approximately 200 patients as a single agent where it's been generally well treatment and we haven't seen evidence of the excess rates of infectious diseases that was -- sorry, infectious adverse events that was recently reported in the current combination study. So in the recent study based on the recommendation of the data monitory committee well that study is now being discontinued because they did not feel that we were likely to see the benefits that had been projected at the start of the study. And honestly we are working hard to understand the findings and to determine the next steps, if any, for this particular product.
So talk a little bit about Kadcyla and where that is in terms of the royalty, talk a little bit about the pipeline, but in addition to that we, even though the company is also supported by having a good cash position as well as many partners with things in development. So I think if you look at this particular slide, you'll see a number of large companies with significant presence in the oncology space such as Amgen, Bayer, Sanofi, Lilly, Novartis; gotten deals with a total of seven partners if we include the Roche and Genentech. And we expect to hear information about a large number of these products over the coming one to two years.
In terms of our cash position, we've previously disclosed that working on financial year which ends at the end of June, so at the end of our financial year '14 so June 30 of next year, we anticipate being in the range of $119 million to $123 million. So a good cash position for us at this particular point.
So in terms of likely events over the coming year or so, on the left we see those for the proprietary pipeline. For 853, we expect to disclose our initial data for what we call disease specific data, so likely ovarian carcinoma, possibly endometrial carcinoma around the middle of 2014 from the dose escalation, initial inflammation from the dose expansion phase of the ongoing Phase I study.
For 529, again, we saw malignancies. We would expect to be presenting first data during June, 2014, again likely mid 2014 as well. 289 has only just begun clinical testing, as we have said. So I think it may be little late in the year but we -- there is potential for first clinical data to be presented in 2014. And obviously, as we continue our review of the outcomes of the study for 901, we will disclose more completely that information during mid '14 as well.
We also recently disclosed the profile of a new payload that we referred to as IGNs and we will complete -- further disclose the profile of that particular payload as we move through 2014 as well.
On the right you see forth coming events on -- for our partnered compounds. Kadcyla, I said the news was just yesterday that we have now have approval in the EU and we expect of course to continue to see growth in sales with our quarterly reporting, as well as having first-line data from the MARIANNE study in the second half of 2014.
At ASH, the ASH abstract book is already available. There are two oral presentations included among the three, which is listed on here for SAR 3419 with Sanofi, which is a CD19 targeting antibody drug conjugate in B-cell malignancies with data coming there in lymphomas.
650984 is not an ADCC, it's a naked antibody which we are developing or Sanofi is developing following our work on that particular compound targeting CD38 in myeloma, with again with data expected at -- well coming forward at ASH. And BT062 is Biotest, we'll also have data myeloma at ASH. We expect from an at least one or more of our other partners to be disclosing data at both AACR and ASCO during 2014. We're also hopeful to hear of INDs and first preclinical data from at least one or more as our partnered compounds.
So I think overall, as I said, we're working in the targeted anticancer space specifically with antibody drug conjugates, very encouraged by the validation of the technology that comes from Kadcyla and, therefore, there are now extensive approvals going on worldwide and are hopeful that that gives us a strong position from which to develop our own proprietary pipeline. Thank you for your attention.
Sam Martin - Jefferies & Company
Obviously we have the existing deal in place with Novartis having options for a number of licenses. So that was just moving forward on that prior agreement. But obviously we're encouraged that Novartis have now taken three licenses this year and other partners have taken two as well, so this calendar year that’s been five. So again, I think we're encouraged as such major players in the space are obviously feeling comfortable enough with what we're seeing preclinical that they want to move to next stage. So that’s been good news and but I don’t think there is anymore to comment beyond that at this point.
Sam Martin - Jefferies & Company
Well, if there's no more questions I'll say thank you and obviously if anybody who happened to have any questions I'll be just straight down in the front. Thank you.
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