Charles Morris - EVP and Chief Development Officer
Jason Kantor - Credit Suisse
ImmunoGen, Inc. (IMGN) Credit Suisse Healthcare Conference November 13, 2013 6:00 PM ET
Jason Kantor - Credit Suisse
Thank you. Good afternoon. Welcome to the late afternoon portion of 2013 Credit Suisse Annual Healthcare Conference. My name is Jason Kantor, I am one of the biotechnology analysts here at Credit Suisse, and it has been my pleasure for many-many years to cover the next company that I am going to introduce, ImmunoGen, really a transforming technology in terms of being able to take cancer antibodies and make them more potent, and I think one of the most exciting drugs in the cancer space out there now, Kadcyla, having come from the technology developed at ImmunoGen.
So it's my pleasure to welcome Charles Morris, who is Chief Development Officer, and sharing this dais is also Carol Hausner. Thank you.
Thank you, Jason, and good afternoon everybody. I want to remind you that this presentation and my remarks will include forward-looking statements, these are subject to risks and uncertainties, so please see our SEC filings, including our 10-K for discussion of these.
What I am going to talk about today at ImmunoGen, talk about progression as a company with the approval of Kadcyla through our partner, Roche and Genentech, talk about our internal pipeline and then talk a little bit as well about our various other partners, as well as position of the company in terms of our cash and cash equivalents.
As Jason pointed out, I think, Kadcyla is proving to be one of the most exciting drugs currently around in development. This uses ImmunoGen's Antibody-Drug Conjugate Technology. We have the composition of matter patent on the linker, and the payload, and this is all combined to Genentech's trastuzumab antibody, which of course is very well known and very successful as Herceptin. And after the initial clinical material manufacturing, there has been a scale-up by ourselves as well.
This is really a very interesting space, antibody drug conjugates. This is really the first one that has been prevalent -- for prevalent indication. It’s the only one currently with full approval, having sharing a [slight little] advantage in a solid tumor.
From our company's perspective, obviously that's very important, because it gives [consolidation] to our technology. It provides us with a revenue stream, and I think it also supports Roche and many of their aims, as they work towards the personalization of medicine, precision medicine, and clearly from everybody's perspective hopefully, it's proving to be a great product.
Kadcyla was approved and launched in the United States in February of this year, and therefore commercialization has begun. We are also beginning to see approvals in other significant markets, notably Japan, Switzerland, Canada, and we are on track in the EU as well, where we now have a positive opinion from the CHMP in September of this year. So based on typical timelines, we will be optimistic that we will be seeing an approval for Kadcyla in Europe in the very near future.
The sales year-to-date have been very encouraging for an initial launch, already at CHF152 million in the US and CHF4 million for the rest of the world, so that's a total of about $168 million, and our royalty revenue is reported one quarter in arrears, from a revenue perspective.
The implication of [presences] for the treatment of HER2 positive metastatic breast cancer in patients who have previously received Herceptin and a taxane, so clearly this is no longer responsive to Herceptin in chemotherapy, and in a comparison to lapatinib and Tykerb, that share an improved survival and benefits, and serve as a tolerability.
So really, delivering on the promise, I think the promise that ADC has always promised to be, which is targeted delivery of a cytotoxic agent to the cancer cell, expressing the target with relatively little impact on the normal cells that do not express target at significant levels.
It is ongoing, but very excited to see the broad and aggressive registration program that Roche and Genentech has put into place. We are seeing approvals now, we'd like it to expand not just geographically but also to different users, and if you think about what the indications have been for Herceptin with indications in combination in the first line treatment of metastatic breast cancer and the adjuvant setting and more recently, in gastric carcinoma, based on the program put in place with Kadcyla, we expect more approvals to be put into place.
So, we already have that indication that we described, following progression on Herceptin and a taxane-based regimen here in the US and elsewhere. First line data to the MARIANNE study is expected in 2049, hopefully with a submission in 2015. New adjuvant study is ongoing, with data expected in 2015. A study in high risk patients with residual cancer, following preoperative chemotherapy and surgery called the KATHERINE study is also ongoing, and is an adjuvant program. In addition, it could expand beyond breast cancer, with the ongoing study in gastric cancer GATSBY second line study, which is expected to be submitted in 2015.
Clearly, a considerable upside here, potential for more indications, longer use obviously in the adjuvant setting than would be expected in the metastatic setting, and a competitive pricing as well, relative to herceptin. So all in all, it makes for an encouraging picture for patients, but also obviously an encouraging picture for ourselves in terms of future potential royalties.
If we now move on to our own pipeline, this is what I am personally, primarily responsible for within ImmunoGen. We have three wholly-owned compounds advancing to the clinic, the force in the clinic is 901, I will talk a little bit about that after the announcements that we make next week and where we will expect to determine next steps in the near future.
We are primarily and in fact, exclusively, an antibody conjugate company, and obviously when we choose our targets and select our candidates, we are really trying to leverage our expertise. To that extent, we look at targets, evaluate those targets, try to understand the unmet medical needs. We have an antibody development expertise, and we are able to select antibodies, really based on a number of features. If the target is well described, and is known to have a role within the cancer, we may well look for anti-cancer activity within the antibody, as well as affecting the payload, in some cases, such as IMGN901 or IMGN853, it is essentially the male man carrying the payload to the cancer cell.
We can convert a number of different conjugate designs, and we do this through an evaluated process during our discovery work, looking at different linkers. We have alternative payloads, throughout (inaudible), options, we have one called DM1, the other is DM4, and we recently described new linkers and new payloads of which we have been working, and that was presented just this past month.
We have preclinical, clinical regulatory capabilities, as well as extensive experience in manufacturing and quality control. This has led to us having four INDs, three of these INDs having occurred in the last 18 months, as we advance programs with what is known as 853 folate receptor, and I will come to these in more detail. 289 and EGFR positive cancers, IMGN529 for B-cell malignancies, and IMGN901 for CD56 expressing tumors, primarily small cell lung cancer.
So, I will talk first of all about 853, this is currently in phase one studies. The rationale here is that the folate receptor alpha, which is the target for the 853 antibody is highly expressed in a range of tumors, not just in a range of tumors, but particularly those where we had development in recent years has not always been particularly successful. So here we see for example, an ability to develop a new agent for ovarian carcinoma. As you know, about 22,000 diagnoses a year, 14,000 deaths in the US alone, and endometrial carcinoma, high expression folate receptors, somewhere where drug development has really been very unsuccessful in the recent past, as well as being expressed in the range of non-small cell lung cancers, most notably in the subset of patients who have no carcinomas, and clearly again, we all know, that's a prevalent cancer.
The activity of a single agent in our models is very compelling in preclinical testing, and this was one of the candidates that we took forward.
By design, we have an antibody here, as they said selected on the basis -- really selected for its payload delivery properties, with the linker engineered to help the [solid] retention, and to overcome the multi-drug resistance that you will frequently see, particularly in ovarian carcinoma, with the DM4 payload.
There is an ongoing Phase-I evaluation, some initial data from this was reported to ASCO earlier this year, currently in the dose finding phase. The initial development was on a three weekly schedule. We went through the initial dose escalation, identified dose limiting toxicities and are preparing to expand into cohorts of patients in the dose expansion phase.
During this phase, we believe that we will be entering into the expansion phase early next year, initially in platinum-resistant ovarian cancer, and in relapsed and refractory endometrial carcinoma, and in parallel to that, we are going to be doing some additional work, looking at an alternate schedule, which will dose patients on day one, 815 of a four-weekly schedule. Here looking to see if we can increase the overall exposure, while not having an excessively high initial (inaudible).
Of the third week, had initial date presented earlier this year. This was patient of a mix of cancer types, different treatment histories, and levels of target expression in dose levels. Here we escalate it until we saw dose emitting toxicity, very standard design for a Phase-I cancer study, and the high dose that we tested here was 7 milligram per kilogram. So first of all, we were very encouraged that we were able to escalate with dose, but we certainly haven't escalated one of our own products too previously. As I said, 7 milligram per kilogram, by comparison it was round about 4.8 milligram per kilogram for Kadcyla.
With the dose emitting toxicity being one of a reversible ocular toxicity with some corneal changes. This has been described with other antibody drug conjugates, including our own, such as SAR3419 which is partnered with Sanofi, has been seen with other technologies. It has even been seen with Abraxane. So it seems to be something which would relate to tubulin agents, and in our hands, as we described on our recent quarterly calls, seems to relate very much to the initial exposure to the drug, and therefore, part of our calculation has been to find ways, whereby given this rather clear cut in correlation between pharmacokinetics in ocular toxicity, to identify means of dosing the drug, which will allow us to avoid the toxicity to a great extent, and while maximizing the opportunity for efficacy.
In that dose escalation phase, efficacy and activity have been seen. This is still the data that was described at ASCO earlier this year, but obviously we were encouraged to see initial evidence of activity in ovarian and endometrial carcinomas, each of which we had always thought would be potential targets for the drug. We see here patient with a CA-125 response, having had multiple bylines of therapy with ovarian carcinoma, at the dose as low as 3.3 milligram per kilogram. PR, which at that point was unconfirmed after four cycles of therapy, 5 milligram per kilogram, and another patient who had a PR, which at the time of ASCO was unconfirmed, would have three prior therapies and was platinum resistant, and who had an initial dose of 7 milligram per kilogram.
So we seem to be seeing activities encouraging the low doses. What we believe is that by retolling our dosing calculation to a moderate extent, we can get a very nice, tight control over the exposure, to be able to manage -- to offer patients the opportunity for efficacy, while avoiding the major -- the only one toxicity that we have seen to any significant extent, which has been the ocular toxicity.
Now, we are also very pleased to be able to announce last week, that our next candidate, IMGN289 has begun clinical testing, and the first patient just being dosed. This is a project which targets the EGFR, and I think there is some interesting parallel here, between this particular candidate and the TDM with Kadcyla that we talked around, that's the Roche-Genentech product. EGFR like is a member of the same company of receptors as HER2, as I am sure many of you are aware, and it's widely expressed and the structure here is an active antibody with the SMC, T-DM1 link of payload combination that we also have seen in T-DM1.
We think there are multiple opportunities here for areas where EGFR is highly expressed, including squamous cell carcinomas of the lung, head and neck cancers, as well as areas where resistance is developed through EGFR inhibition in other settings as well. And the combination obviously of active antibody and payload, gives us a double opportunity for cell kill. The antibody is also selected on the basis that it appears to avoid skin toxicity, despite the fact that it is highly active and has comparable efficacy to Erbitux preclinically, and as we mentioned, [singling] from payload.
This is a summary of the preclinical data, working from left to right; you see activity here -- there is activity for naked antibody comparables for that of Erbitux in an EGFR dependent at no carcinoma model, but once the payload has been added to the antibodies, much more marked cell kill, relative to either naked antibody alone. In the middle you see in EGFR, independent squamous cell carcinomas -- squamous cell carcinomas often expressing very high levels of the target, where there is no activity of either Erbitux or our naked antibody to 898, but if we look at IMGN289 with the attached payload, we clearly see significant activity.
Then if we think about some of the clinical realities, a situation such as TDI resistance and T79 mutations, again in the model on the right, you will see that there is activity in patients with 289, which is not seen either with antibodies, or with a small molecule such as Tarceva.
So as we mentioned Phase-I testing has begun. This will go for a typical dose finding phase on a weekly dosing schedule. We will then go into an expansion phase, looking at EGFR resistance in lung cancer. Squamous cell carcinomas at the lung; squamous cell carcinomas at the head and neck, as well as the range of other types of EGFR positive tumors.
On the hematologic malignancy side, we are developing IMGN529 of CD37 positive malignancies which tend to be very similar to those which expressed CD20. One of the key features of this particular molecule is unlike other ADCs and development for B-cell malignancies, we again have an active antibody, as well as the payload being carried by that antibody, and you will see in the preclinical model demonstrated here, not only is the antibody somewhat more active than rituximab, but once the payload is added, we see a considerably greater activity in this particular cell line model.
So it's a very similar design. Once again, as to Kadcyla, using the SMCC-DM-1 construct, Phase-I testing is underway. We have seen effects, both from a safety and efficacy point of view with lower than expected doses, and we are managing our way through those at the moment, but believe that we have means to be able to continue to escalate the doses, so that we can begin to take full benefit from the efficacy that has been seen at the lower than expected dosing levels.
Finally, we have to discuss 901. 901 had been our lead product, it's targeted CD56, which is target found on small cell lung cancers and other (inaudible), as well as in about 70% of patients with multiple myeloma. And it's previous early development, we have seen evaluation in almost 200 patients in monotherapy, with a level of activity, and without some (inaudible) tolerability other than some neurotoxicity. And I have done previous combination studies with revlimid and dexamethasone in multiple myeloma.
Importantly last week though, we had to announce that the Phase-II trial had been stopped. This was in combination with Etoposide and Carboplatin in small cell lung cancer. Historically, a very difficult development here in a difficult combination of drugs to combine with. But the VMC, on the basis of combination of safety findings and the unlikelihood that the study was likely to prove positive, made the recommendation that we should stop that study.
We don't have all of the explanation for that at the moment. Clearly, we are working with our investigators, dabbling on with the data, and hopefully able to provide greater clarity on the cause of these findings during the course of next year.
So finally, just want to say a little bit about the company and where we are in terms of other aspects. As you may know, we have seven partnerships in total, including the one we have described with Roche-Genentech. Many of these moving forward into clinic. Five licenses have been taken by partners this year, including the announcement of a license taken by Novartis just this week. We have seen recent data at meetings such as the MCIA-ACR meetings just this past month, and we will see further data on a number of these at ASH next month.
So in terms of the cash position that's described on the slide, and the key thing is, remembering that we have a fiscal year that runs from June to June, we anticipate that cash position at the end of June 2013 is that we will have around $119 million to $123 million. This is a solid financial position, with revenues coming in obviously from the various partnerships and from the partnership around Kadcyla.
Finally, just talk a little bit about the news flow over the next year or so. From our own in-house or proprietary compounds, we expect to see the expansion -- into the expansion phase of the 853 Phase-I study in the first quarter of next year and to be presenting data around some of the -- specific data in the middle of the year. For 529, we would also expect that expansion phase to start in 2014, and to be presenting our first clinical data.
289, as you are aware, has only just begun clinical testing, but we would hope to be able to present some clinical data at some point in 2014, and we will continue to review what the recent finding from 901, so that we can describe the conclusions of that assessment by the middle of 2014. We also recently described the profile of a new linker or a new payload technology that we refer to as IGM, at the recent MCIA-ACR in Boston and we will give some more information on that in the second half of 2014.
On the partner side, we expect to see approval for Kadcyla in the very near future. Continue to see growth in the sales, both in the US and the rest of world, as well as the very important MARIANNE results in the second half of 2014. From the ASH abstract, you may have seen that we have clinical data for SAR3419 from Sanofi, as well as one naked antibody that is partnered also with Sanofi, for which the first clinical data, against the CD38 targeted drug for myeloma will also be attached. And BTO62 with Biotest will also have its first combination data with revlimid and dexamethasone at the ASH meeting, again in myleoma.
Our partners also would anticipate clinical data from one, and probably more compounds at both AACR and ASCO, and we also anticipate to hear about new INDs and preclinical data from some of our partners as well. So I think overall, we are looking at a very exciting time, as we heard at the beginning, I think a technology that has the potential to be formative and with a sort of an exciting range of both proprietary pipeline and partner compounds, and I thank you for your attention today.
Jason Kantor - Credit Suisse
Thanks for the presentation. Just two quick questions on the payloads? You have a couple of different payloads and a couple of different linkers that you use, and now you are sort of finding, in some cases, you need toxicities with those. And I am just wondering, is there a way to -- is there a reason not to use the same toxin and payload that's in Kadcyla in every one of your programs at this point, given that it's certainly clinically and regulatorily validated? Is there something that -- it doesn't provide that the others you think are providing?
Thanks Jason. I think SMC T-DM1 has clearly been shown as a good lead. We are using that in a couple of our own compounds and it is also involved in license (inaudible). In a couple of settings, the choice has really been made around looking at various combinations, what appears to be that best combination of linker and payload. So I think we may see somewhat different toxicities in each case, but remembering that as we go, these -- if you look at our own pipeline, primarily in Phase-I, the aim of the Phase-I study is to discover what that dose emitting toxicity is, then dial back the dose. I think if we take 853 for example, treatments we dialed back and we get into that range, we know that those ocular findings have been the dose emitting toxicity, that not being high level of adverse effects, certainly not great (inaudible) beyond that, and therefore I think the will likely have a very sort of healthy looking side effect profile, once we move that forward.
I don't think its going to be a one size fits all. I think the current approach is there. But clearly, [it's going] to be thinking -- could this be better than the SMC T-DM1, I think is always going to be a fair question.
Jason Kantor - Credit Suisse
[No question and answer session for the scheduled event].
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