ImmunoGen, Inc. (NASDAQ:IMGN)
Analyst and Investor Day
April 12, 2013 8:30 AM ET
Carol Hausner - Head of IR
Dan Junius - CEO
Charlie Morris - CDO
Jim O'Leary - CMO
John Lambert - CSO
Greg Perry - CFO
Marshall Urist - Morgan Stanley
Adnan Butt - RBC Capital Markets
Cory Kasimov - JPMorgan
Matthew Harrison - UBS
Mara Goldstein - Cantor Fitzgerald
Thomas Wei - Jefferies
Boris Peaker - Oppenheimer
Bret Holley - Guggenheim
Good morning and welcome to ImmunoGen's Analyst and Investor Day. We are excited to have you here. I am Carol Hausner Head of IR at ImmunoGen. I want to welcome you today, there is some comments that we always seem to have lousy weather on the day of our Analyst and Investor Day. But we offset that they are having great company; great science.
Our meeting agenda today, we will start with introductory remarks by our CEO Dan Junius who will talk about ImmunoGen and how we are changing the paradigm of the treatment of cancer. We will then have Dr. Charlie Morris who joined us is a most recent member to join our management team, who is our Chief Development Officer and he will talk about development at ImmunoGen. And then Jim O'Leary who is our Chief Medical Officer will talk in more detail about how we are advancing our clinical stage compounds.
We will then have a break that is about 10 minutes and I know that there is a temptation to want to ask questions during this period. I would like to ask everybody just hold their questions till the official Q&A so that they can be webcast. This whole event is being webcast and we do want your very important questions to be webcast.
Dr. John Lambert, our Chief Scientific Officer will talk about IMGN289 which we just unveiled data for at ACR. And then our Chief Financial Officer, Greg Perry will talk about investing to build value. We will then open the floor to questions. We have a lot of time allowed for Q&A, we welcome your questions and then Dan will be back with closing remarks.
As I mentioned, the whole event is being webcast. In the course of this event, we will of course make forward-looking statements and of course there are risks and uncertainties around forward-looking statements so we encourage you to review our SEC filings including our risks factors in them including our latest 10-K.
And on that, I will turn it over to Dan.
Thank you Carol and let me add my welcome this morning. We appreciate everyone taking the time to join us to get an update on ImmunoGen. Well we have other members of management in addition to the speakers’ here this morning. We will introduce them as we get to the Q&A because we want them to participate in that portion of the program.
We also want to introduce, we have three of our Board members who have joined us this morning. I want to both introduce and thank them for joining us; Dr. Joe Villafranca is with us, Dr. Nicole Onetto is with us and Howard Pien is with us as well so again thank you for joining us.
Let me start in talking about maybe somewhat in a high-level fashion talk about changing the paradigm of how cancer is treated and I don’t we are understating that given that the events that have taken place and how this space is evolving. From a company standpoint, we start with a foundation of a very strong technology platform, and it’s probably worth pausing a moment just to give my view of what that technology platform represents because it’s often misconstrued and viewed to be well ImmunoGen’s technology is its linker or its cytotoxic agent. What you really have is I think is an integrated system of a number of elements that compose the platform so it certainly is the linker. We have we think very interesting linker technology that forms the basic task of keeping a cytotoxin attached to the targeting antibody. But it also conveys certain properties on the cytotoxin when it’s released within the cell; the cytotoxin itself is not simply chemotherapy as it’s often referenced but a highly potent purpose developed agent that is used in the context of this whole system. And it also is, is the antibody itself, currently our targeting vehicles is for restricted antibodies and then in the future you may see other vehicles that are used to deliver a payload.
And all of this is supported by a very deep body of knowledge around both the technology itself as well as the biology of a cancer cell that we need to interact with to have this whole system to be effective.
So from a technology platform, I do think it’s a good starting point to talk about where the company is going. We believe this technology platform is certainly best-in-class. We now can talk about demonstrated success with our first approved therapy. And it’s a platform in which we continue to invest and innovate. I referenced our linkers; we have four linkers that are in the clinic today across a number of different compounds. We have additional linkers that we have developed that we test as we are looking at new formulations. I am sure we will be coming up with additional linkers that can convey additional properties to future compounds. Cytotoxins, we are looking at other cytotoxins that may have therapeutic window in some diseases that are current tubulin -based technology can't meet.
So it is a dynamic area where we are continuing to try to evolve the technology. What it’s led to for us is a very robust and expanding platform and one that importantly is addressing or looking to address a variety of unmet medical needs for patients. Today we stand with one approved product. We will talk about that in just a moment. We have three wholly-owned clinical stage programs.
There are seven additional clinical stage programs from our partners and there is a very deep pre-clinical portfolio both for ourselves and from our partners. Out of that, pre-clinical portfolio you will see another compound coming into the clinic at the back half of this year. We will spend some time this morning talking about some of the pre-clinical data that has led to, it’s been involved in building that particular compound.
And the technology has potential, not simply in liquid tumors but in solid tumors as well. We think that is very important being able to extend this technology. All of this, being focused on the promise that it delivers, and that is being able to transform how doctors are able to treat their patients.
The first product now is approved. So, Kadcyla is going commercial. Also in a minute, I will talk about some data that came out yesterday from Roche around the success that they are having with that introduction. You are aware of the data that came out of the AMELIA study, it showed significant improvement in overall survival, better tolerability and that was in a head-to-head study against Tykerb plus Xeloda.
It’s important to appreciate that the population that it served in that particular study was Herceptin failures. These were patients who were no longer responding to a Herceptin-based therapy. And the reason that's important is I think it speaks to the fact that these patients were benefitting from the enhancement of the ADC technology as opposed to any inherent characteristics of the underlying antibody that you would otherwise anticipate.
With Kadcyla it represents the first ADC that’s been approved for a solid tumor indication; that's important because about 90% of all cancers that are diagnosed are solid tumors. In absent surgery, they then tend to be more difficult to treat particularly when they are first diagnosed often in a metastatic state.
And finally what you see is tolerability benefits of this targeted approach using our maytansinoid-based payload. Historically, the treatment for cancer, as you would push to the maximum tolerated dose and you had efficacy but a very significant issue in terms of patient tolerability. I think what we are seeing with the approval of Kadcyla is the ability to have a very effective treatment while allowing continued good quality of life for the patient.
So, we talk about changing the paradigm, how is it that we think we are changing the paradigm. You now have with the approval of Kadcyla a personalized therapy; so it’s a targeted program that provides enhanced efficacy which in the case of Kadcyla with much better tolerability than other alternatives that are available.
I think as these programs evolve what you will see is there are instances where the more effective application is going to be in combination with another therapy but again because of the nature of this targeted therapy that we have today, we can add that on to existing therapy and maintain that tolerability level while providing enhanced efficacy.
So, we look at Kadcyla has now as we no longer have to speak about the promise of our technology that technology has been delivered and that's extremely important. I think this notion of changing the paradigm really was manifest when we came out of ASCO. It’s certainly something that we have believed as we have been developing this technology over a number of years.
But what you heard from oncologists after they saw that Kadcyla data from the AMELIA study at ASCO they immediately extrapolated beyond the treatment of HER2-positive breast cancer and said this offers a new avenue, a new way to treat patients and so much of an oncologist’s time is spent dealing with side effects. The ability to have a therapy that was going to relieve them of that burden and the patient of the burden of having to deal with the side effects they saw as extremely important in how cancer therapy can evolve.
So, when we think about having this technology developing these products it raises a question. How is that ImmunoGen is going to take these forward? What is the opportunity? As we think about the compounds, the pipeline that we’re building we certainly are looking forward and looking at the potential of commercialization in the long run. But in the short run it’s our intent to maintain ownership of these compounds through proof-of-concept.
We think that, that getting to proof-of-concept de-risks the asset. It’s a very important inflection point in terms of value creation and we’ll see that as we go through our development; we’ll understand what the appropriate path is in terms of our ongoing involvement in these compounds. Each time that we’re generating clinical data, it presents our options to us for moving forward. I think those options will be enhanced based on the magnitude of the success as well as our own internal capacity to move these compounds forward, that would be on case-by-case basis.
Now as we think about a portfolio and we have to think in those terms given that we now will have four compounds in the clinic by the back half of this year. We want to be able to look the overall portfolio and be appropriately aggressive but at the same time not be overwhelmed by the scope of what’s involved. So we’ll be on an ongoing basis looking at how we balance that based on the data that’s generated from the portfolio.
An underlying tenet however is that as we look at what we do with these compounds, we want to ensure that we maintain a significant interest in U.S. rights. We think that that’s not a tremendous revelation. We think that the U.S. is a key market. We think that it offers the clearest path to commercialization for ImmunoGen.
At this stage, we have three clinical compounds that we believe are highly differentiated. We think each of them represents an opportunity to service a significant unmet medical need. In the case of the IMGN901 here is a Phase II compound currently in the study for small-cell lung cancer. This is a cancer that you’ll hear more about very aggressive with really no improvement in the treatment paradigm for at least two decades. For IMGN853 that’s in the Phase I study, we think that the principle indication that we will be pursuing here as ovarian cancer, another cancer that has a very poor prognosis on initial diagnosis.
And then finally IMGN529, this is in Phase I for non-Hodgkin’s lymphoma clearly an area where there’re varieties of therapies available for what is a broad disease that gets broken down into a number of subcategories; however, within then there’re many patients groups that today are underserved. So we think that the characteristic of 529 offers the opportunity to begin to address those unmet needs and you’ll hear more about that later.
The newest compound IMGN289 will be coming into clinic later this year. This is a compound that targets EGFR. Preclincally, it has shown very good efficacy in particularly models that are resistant to EGFR inhibition. All of these compounds are ADCs. They incorporate antibodies that we have developed, our linker technology and our payload agent.
So where are we today? Today, we’re investing to aggressively develop this pipeline. In that context however we’re looking to do that in a fashion that allows us to maintain financial discipline, I’ll come back to that in a moment. At the same time that brings the responsibility and the need to manage the organization as we advanced as we become broader as we have need for enhanced functions to address the additional sophistication and complexity that we faced as these compounds move forward.
While Kadcyla is important as a compound to provide us cash it also has now provided further validation of the technology not simply from a clinical standpoint but now also from a regulatory standpoint having passed the hurdle of receiving FDA approval. One of the dimensions that it introduces that we’re conscious and that we’ll be looking to take advantage of this increased awareness among physicians. This year for the first time we’ll have a booth at Askow to provide visibility to the physician community who is becoming actively engaged with the number of studies that we’re involved with today and that we’d anticipate starting in the future.
And all of this is done with the solid cash position today and cash inflows from multiple partners as we see compounds advance and have them generate milestones and ultimately royalties. So the financial discipline dimension; today we’re investing our propriety programs they’re warranted. We do this based on the data that’s generated and with the sense of wanting to bring these to patients as quickly and as prudently as we can. In each case we’re looking to invest earlier. There are certain things that we need to do around CMC preparedness that will enable us to shorten the timelines for each step of the process to get to a registration study to get an ultimate filing.
In that context with our IMGN901 compound as I noted that’s in Phase II study today we had a plan that would allow us to develop data and hopefully trigger an investment decision that will put us along the pathway to registration, sometime later this year. We’ve seen some patients’ data that’s encouraged just to reduce the starting dose and so we have been looking for interim data and the back half of this year from a subset of patients we probably will not see that data now until sometime around the middle of 2014. You’ll hear more about that later from Jim O'Leary.
At the same time the other three compounds IMGN853, 529, and now 289 each; come into the clinic having gone through a set of reviews and hurdles that have been refined based on what we are on our increased understanding of the technology and the learning particularly from Kadcyla. As we put together the first in human studies we did that with an eye towards having these give us as early a look as possible to be able to gain the insight to be able to make incremental investments to move these forward as promptly as possible.
In the case of IMGN853, we have designed the studies and you’ll hear this from Jim O'Leary in a fashion that we may be able to see data coming out of the expansion cohort for 853 that would trigger investment in and potentially a registration pathway.
I mentioned the organization we have the benefit I believe of having a very strong leadership team in place. But with that and with expansion of the organization, expansion of our trails, and additional functional needs; we’ll overtime be adding the organization and bringing in the expertise to meet those needs. I think the addition of Charlie Morris to the team, Charlie now has responsibility for all product development functions, is a good example of how we’ll continue to expand and enhance the organization.
Looking for people with the right skill set and with the conviction that I think Charlie has about the ability of this technology to bring greater therapies forward for patients. We’ve been doing that successfully I think on a less visible scale, now I think that will be happening more visibly and you’ve seen that thus far with bringing Charlie on to the team.
So let me close so we can get to the rest of the program, we’re very pleased with where we’ve progressed. You think about where this company was three or four years ago now having an approved product, having a very attractive pipeline, seeing our partners moving forward is extremely encouraging. We’re beyond, beginning to realize the promise of technology, I would say with the approval of Kadcyla we’re realizing the promise of the technology.
We’re seeing good progress with the propriety pipeline. We’re pleased with where we’re with the three compounds in the clinic. We’re very excited about 289. Hopefully we’ll be able to share that excitement with you as you hear about the AACR data later from John Lambert. Our technology portfolio continues to build. We think that there are additional opportunities to make this technology even more robust than it is today and we have a portfolio of partner programs that will further extend the technology. We will hear lot more about those as we come through 2013.
So I look forward to the discussion today. I think thank you again for joining us and let me now turn it over to Charlie.
Thank you, Dan and good morning everybody. As Dan said, my name is Charlie Morris; I came on board in November as a Chief Development Officer. What I would really like to do this morning is talk with you a little bit about what the scope of that role is, how it plans to help in moving the company to much more of a product-focused development organization, developing and delivering new therapies for patients with cancer.
Also, I want to talk a little bit about the philosophy of how we plan to work in the development arena, looking at the common success factors of approved products and then showing that the those applied wisely to our program so that we can get the success that we believe that this portfolio products deserve and also then just to briefly review some of the key development events that we can anticipate over the next 18 months. The details on individual programs will come from Jim O'Leary’s presentation after mine.
So, my responsibility now is for obviously all development related functions and that really comes in as a point where we nominate a product to go forward to IND-enabling studies all the way to regulatory approval and hopefully to cross beyond. So, in terms of functional areas that includes translational R&D which is let Bob Lutz, who is standing at the back of the room. We have Clinical Development led by Jim our Chief Medical Officer, Regulatory Affairs with Theresa Wingrove and Program Management also under Bob’s leadership.
By putting things together in this way, we are able to ready to take cross product and cross functional approach looking at a planning and trying to optimize you so both our human and financial resources addressing many needs, but also we are able to be planning right from the point of entering the clinic all the way through regulatory approval and beyond. And so even in the early stages, thinking for example when it comes to biomarkers not just about have they can applied and how things with our clinical trials where they undoubtedly come but also I have that might define patients for both regulatory labeling and for pricing and reimbursement considerations at a later time.
Of course, as we move products through and get closer to those approvals, we will begin to add in additional functions be the health economics outcomes with research with medical affairs as we continue to expand our knowledge base on the products and gets closer and closer to market.
In terms of what that means if we look at sort of that a standard approach to the development of a drug for a drugable target, those things on the left of the slide, over to slide 18 for those on the webcast, show that primarily from targeted identification through to the nomination of a product that will still reside in John’s group as CSO but from the point where we get that IND nomination and the studies in the toxicology biomarker qualification and so forth, those will now be in the development group.
I think the key thing here to remember is that these things are always iterative and obviously as products moves through early discovery, we have a lot of input from regulatory from the translational groups and from clinical and equally as we move things through the clinic and we learned new things, we need to continue to work with John’s group to ensure that we have the input in understanding that comes from the deep preclinical knowledge that John and his colleagues have generated.
So what qualifies me for this role? Well I have been in this industry now about 18 years. I am a medical oncologist by training. I spent the first 12 years in my pharmaceutical career at AstraZeneca bringing Faslodex through to the market as to global medical lead, initiating the Phase I development to the Iressa. I have spent time in medical affairs with Casodex, Zoladex in prostate cancer and ultimately led all of the post-proof of concept products which most recently and immediately after I left. I lead to the approval of Caprelsa or vandetanib for medullary thyroid carcinoma.
Subsequently, I have spent three years at Cephalon where shortly after I joined, submitted and gained the approvals of Chronic Lymphocytic Leukemia and Non-Hodgkin’s Lymphoma. Mostly recently at Allos with proliferate T-cell lymphoma. So I think it brings a wealth of development experience across all phases of development through commercialization both in the solid tumor side and in extensive experience on hematology side as well.
So as I look at the pipeline, I see what I think is a very exciting and promising success opportunities. And the focus here is got to be to bring better therapies for cancer patients. Looking for not just longer cancer control, enabling cancer patients to lead longer and hopefully better lives, and our approach would be to continue to create, to advance these novel therapeutics and exploiting what now Dan has said, approving technology. And by understanding what the major success factors are, we can begin to apply those to increase our likelihood of success.
As you know, this is an extremely competitive area this is the annual pharma report from 2012 according to this report we’re currently over 900 products of various types and various stage of development for oncology indications. And as you know, the number of approvals seems to be increased a little over the last couple of years’, still remains relativity low.
But if we look at what recent approvals have been and there is some examples here on the left hand side of the slide, slide 22. I think we’ve begin to see some recurring things, not necessarily that apply to all of them. But I think the things from which we can learn and ensure that we’re applying some of these learning, all of these learning’s as we go through our development process.
I think what we see here is extensively validated technology for most of the products. We see a predominance of Tyrosine kinase inhibitors and monoclonal antibodies for example. The developments already following the preclinical findings, taking the drugs into well-defined patient populations, effective use of biomarkers both is for identifying patients and for making some of the key decisions along the way. A lot of these are indicated for what have been unmet medical needs. And I think that’s an area where we have a real opportunity. And we also can think about how people leverage regulatory initiatives such as accelerated approvals and prior to reviews to try and reduce some of the review times, bring the products to market quicker.
I believe that we can apply all of these key factors to our pipeline and we will. The, as you have heard and you are very aware the Kadcyla data but just to remind you here that it really is now the top technology really has been fully validated, not just from a clinical perspective but obviously with the FDA approval from a regulatory point of view as well.
And to my mind, what we see here is our technology delivering on the real promise of personalized medicine. Identifying those patients most likely to respond and treating them with a new product which not only delivered a significant improvement in overall survival compared to on a pervious standard of care but does so with less toxicity than we’ve experienced previously. I think that has to be the type of aim that we have as many of our products as possible as we go forward.
And of course it’s not just Kadcyla. Kadcyla, I think is particularly interesting because it’s the first full approval of an ADC and it’s the first significant improvement that we’ve seen in solid tumor but also we see example such as not for SAR3419 which is a CD19 targeted agent. The Sanofi is developing and showing the initial efficacy in hematologic tumor and non-Hodgkin’s lymphoma and in various subtypes of B-cell disease including aggressive lymphoma such DLBCL and the lymphoma such as follicular lymphoma. So I think that really has had examples of why I see this is as a validated technology, which should really boost our confidence as we move forward with our own pipeline.
I mentioned the importance and now on slide 24, following our preclinical findings and really trying to do what that tells us and to guide us. So here if we say an example of IMGN901 in multiple myeloma as a reminder, multiple myeloma expresses CD56 in approximately 70% of the patients. And we see on the left hand box that we clearly have activity of IMGN901 alone and we also see the activity of lenalidomide and dexamethasone with clearly synergistic activity if we have the three drugs together on the platform that serve us right.
Similarly, this really helped us design what we have done so far in multiple myeloma in the clinic. As a single agent we saw a modest activity in patient who received multiple prior agents, clinical benefits in around 16% stable disease or better in 41%. But when we combined these with Revlimid and Dexamethasone, we're already following very much what the preclinical data suggested. We see that in those patients who had not received prior Revlimid would get 88% clinical benefit rate. But high response rate also in those who would see previous Revlimid of 48%. Interestingly in this study as well I remind you that we saw activity in patients with higher cytogenetics as well as patients with double refractory disease.
I think this is a type of thing which is also a driven what Jim will show you later for 901 in small-cell-lung cancer where based on the preclinical data, we have really pursued very hard the combination approach based on the very strong combination data that we saw pre-clinically rather than just pushing forward on the single agent.
Talked a little also about well-defined patient populations, and Jim again will go into this in some more detail later. But I think it is important that we remind ourselves that, with all of these products we will be identifying those patients according to target receptors. In some cases where the disease is known to highly expressed receptor in all patients, we may not necessarily be screening at this point. But we will tend to collect samples that we can see if there is a correlation between expression and the degree of response but equally then when there is less than 90% to a 100% expression we will screen for those patients from the (inaudible).
Importantly, we’ll be using primarily immunohistochemistry. As you know, this has been a validated approach antibody based therapeutic identifying antigen presence and expression profile. And obviously for those agents where this becomes required to identify those who are most likely to respond. This will be thought about companion diagnostic strategy which we are certainly thinking about and we’re appropriately developing for all of our products as we go forward.
Again, the advantage there of course is what the impact that this can have on our clinical trial size as well as on the availability to enable reimbursement and pricing at the later date. By identifying those are mostly likely to respond, we do not include patients in our studies so they are not going to have the benefit of the treatment that reduces our trial size, it increase our trial speed and it reduces our trial cost.
As I said it also informs the companion diagnostic strategy, this allows us as we go into the regulatory process and the reimbursement and pricing process to be able to advice those responsible that we can identify those patients most likely to benefit and therefore we’re enhancing cost benefit as well as allowing our sales pricing flexibility.
So, I think you see even through our products are primarily in Phase I, Phase II, we have a long term view to the future based on the planning for success as we go forward. Again, you’ll hear a lot more about biomarkers in our clinical trials from Jim but I think it is very important that we use these effectively all across our programs. We’re looking at circulating tumor cells in our 901 and 853 programs to see if there is correlation with response. As well as looking for early pharmacodynamic signals in biopsies pre and post treatment here with the IMGN853 in ovarian non-small-cell on patients as well as looking for earlier markers of response which may help to accelerate some of our programs.
And again I said, one of the key to success seems to have been targeting unmet needs. I think that’s the very much where we are as a company right now in small-cell lung cancer for 901. The treatment paradigm has not changed for 20 to 30 years. We are combining with carboplatin and Etoposide dose, those are the products that I used in the clinic 20 years ago and so there really has not been any significant progress.
In ovarian cancer, for those patients who become resistant to platinum therapy, the overall survival and progression-free survival are very poor. And again in think it’s a very important area where we have an opportunity to improve outcomes and certainly that suggested by the preclinical data for IMGN853. And with 529, although there are many drugs, both approved and in development for B-cell malignancies, there remain many opportunities to reduce toxicity, for improving outcomes for patients who relapse after transplant in the aggressive diseases. And, although we have done very well in endolymph lymphoma, it remains an incurable disease with a need for further treatments for relapsed patients.
We talked a little bit on the first slide as well about our opportunity to leverage regulatory initiatives. What I mean by that is what we see as a number of opportunities that can help us either show some development of FDA review times or can reduce our risk as we move forward into the later stages of our development programs. For example, we have often drug designations for a number of our indications, for example the IMGN901. And we will also keep an eye on our opportunity to perceive things like fast track status; accelerate to approve some priority reviews as on date to become available.
Obviously, we are also very aware and we will seek the opportunities if there are early clinical data for any of our products is exciting enough, we will look to breakthrough status. Obviously this is something which is in the process of being established and I think is somewhat being completely understood at this point. But it is a great opportunity for rapid interaction with FDA as we move forward. And as we think about moving programs in to pivotal studies we will also assess the opportunities and needs for special protocol assessments.
So where it might apply to our programs and this is on slide 30. So, this is obviously pure speculation but for IMGN901, for example, if we see a positive outcomes on the ongoing NORTH study we will probably, that will almost certainly lead us to design and relate Phase III study informed by the design of the Phase II with carbo etoposide plus or minus 901; that we would evaluate the need for a SPA though one could argue with an overall survival endpoints as to primary endpoints of Phase III study, that may not be absolutely necessary. But we do believe that with positive result the BLA would be a candidate for priority review because it’s the first new drug to treat small-cell lung cancer in such a long period of time.
Similarly with 853 has Don eluded, we remain hopeful that we can see exciting activity in our ongoing Phase I study, and the dose expansion cohorts. And if that signal is strong enough we would certainly wish to talk to FDA about pivotal Phase II designs and certainly in that case undertaking special protocol assessment to get that agreement with a view to accelerate the approvals prior to reviews. So I think we have to be aware of the potential for these strategies as we go through. We have to seek those opportunities as they arrive. And we remain cognizant and aware that these may be opportunities that we wish to take full advantage of.
So coming back to slide that I showed earlier, think we can see that throughout our development and the paradigm from discovery all the way through to BLA submission; we really are thinking in terms of those key success factors which have been seeing for many products. John’s group obviously looking to validate the technology, working together with the clinical team, and thinking about the unmet needs that can be targeted and then providing the preclinical findings on which our development programs are to be based.
Jim will talk in a lot more detail about how we are defining our patient populations, how we use our biomarkers, and we will remain very aware and anxious to use the regulatory initiatives which help the company such as our own.
In the near term we have got a number of key milestones coming up over the next one to two years. We will complete the enrolment to the IMGN901 Phase II study or NORTH, with full data being presented from that during 2014. We continue to review the potential next steps in multiple myeloma development.
For 853 we should see the first clinical data during this year with more complete efficacy data in some of the targeted patient populations coming through, hopefully early in 2014.
IMGN529, as you know is also into clinic, B-cell malignancies, and we hope to have first clinical data towards the end of this year. And we will activate the IND for IMGN289 as well as hoping to see first clinical date from that program again during 2014. So I think it’s a very busy time, but it is a comprehensive program with multiple shots on go, and I think real opportunity to success in a very exciting pipeline.
So overall I think we are truly focused on successfully delivering better therapies to cancer patients. We will work together both internally and with our external partners, investigators and opinion leaders to continue to validate our approach in our technology to ensure that we are organized to identify and apply the success factors as effectively as we can to bring candidates or agents forward for patients. We have multiple differentiated product candidates and we have to look primarily pursuing highly unmet medical needs which gives us great opportunity to leverage both in the oncology community as well as with regulators and we are ready and prepared to add the skills that we will need, and the functions that we will need to advance those programs to ensure success both from a development regulatory and ultimately commercial perspective.
So at this point I would like to hand over to Jim, who is going to go through the details of some of our clinical-stage compounds. Thank you.
Good morning everyone. This morning I have the pleasure of walking you through our approach to advancing our clinical-stage compounds through development. The content of my presentation will really follow the same format for each of our product candidates in development. I will introduce you to the product candidate or the immunoconjugates, tell you a little bit about our thinking in terms of rationale for developing these product candidates in specific tumor indications; share with you some clinical features, designs of the studies that we are executing in the clinic; and then finally a round up with a summary of where we are in the clinic in terms of making progress with the development of these compounds.
As you have heard IMGN901 which is also known as Lorvotuzumab Mertansine is our most advanced compound in the clinic. It targets CD56 which is also known as neural cell adhesion molecule and this target of expression is highly expressed on a number of various neuroendocrine tumors, small-cell lung cancer, Merkel cell carcinoma, some subcategories of ovarian cancer. So it’s a product that could have a broad applicability across many tumors.
So why are we pursuing development in small-cell lung cancer? As you have heard from Charlie and from Dan, small-cell lung cancer truly represents an unmet medical need. Progress has not been made in the past two to three decades, for frontline treatment of these patients. When patients are diagnosed with the disease, there prognosis is very grim. First line patients have a life expectancy that’s measured in months, anywhere from nine to twelve months and they tend to recover very quickly after being treated for their first line or first time that they are diagnosed; progression-free survival is on the order to five to five and a half months.
One of the obstacles for agents that have tried to developing combination, try to be developing combination with etoposide/carboplatin, is the fact that etoposide/carboplatin is associated with a high rate of myelosuppressive effects. And a lot of compounds have been applauded by this because when they combine with the etoposide/carboplatin you often see exacerbation or synergy in terms of the myelosuppressive side-effect profile.
So if success is to be made in the treatment of patients with small-cell lung cancer, it really will probably have to come from improving frontline therapy. And that’s one of the reasons why we are choosing to combine 901 with the standard-of-care for frontline treatment of small-cell lung cancer. As I said earlier, once patients recur their life expectancy is measured in weeks not even a month, that’s how dire the prognosis is. So any attempt to improve the frontline regimen and extend the durability of response in the frontline again is really where we will make inroads to success in the treatment of this deadly disease.
So, why the rationale for developing 901? You heard earlier that small-cell lung cancer is characterized by very high expression of CD56. We have also seen single-agent activity with IMGN901 in patients who have received multiple lines of prior therapy and the patients who are deemed to platinum refractory as well as platinum sensitive to frontline platinum-based regimen. We have seen maybe not a high degree of partial responses, but we have seen a number of patients, who our lung cancer experts consider clinically relevant durations of stable disease, and this really provided the impetus to go forward and explore the 901 in combination with etoposide/carboplatin. We also saw evidence of activity in a related tumor; Merkel cell carcinoma is a rare carcinoma that is a small-cell carcinoma of the skin. It is treated similarly to small-cell lung cancer with etoposide/carboplatin, and it has the same clinical cause. Initially a high objective response rate which is then followed by a very short period of disease pre-interval patients again recur quite quickly. In this tumor, we have seen evidence of single-agent activity with IMGN901 as well. We saw durable complete responses in several patients and also durable stable disease and patients where the progression free survival is on the order of only one to two months.
We also thought based on the single-agent toxicity profile of 901, we saw very little clinically significant myelosuppressive effect, so we thought that was a competitive advantage with that we will be able to combine 901 with Etoposide Carboplatin and not exacerbate the myelosuppression that is observed with the standard regimen. Part of the single-agent profile of IMGN901 we also observed a high degree of low grade peripheral neuropathy on the order of about 30%.
Based on the occurrence of this low grade peripheral neuropathy we choose to partner 901 with Carboplatin instead of a cisplatin-based regimen, because as you may know Carboplatin is associated with a lower degree of neurotoxicity. And finally touching back to something that Charlie mentioned, pre-clinically he demonstrated for you how activity with IMGN901 in combination with Rev/Dex showed great pre-clinical synergistic activity in xenograft models and this translated to success in the clinic.
If we advance to slide 39, you will see evidence of the same type of pre-clinical synergy in a xenograft tumor model of resistant non-small-cell lung cancer. You can see the green line representing the combination of Etoposide Carbo in 901, where there was complete regression of tumors in the animals, and tumors had, the animals had tumor-free progression lasting the duration of the experiment. So again, quite compelling pre-clinical activity in a resistant pre-clinical tumor model.
The study 007 was designed as a Phase I, II study design. And of course the goal of the Phase I dose escalation portion of the trial was to identify the proper dose 901 to take forward into subsequent trials. Because this was a Phase I trial and we were looking to expedite getting to that recommended Phase II dose of 901, we allowed patients with any type of solid tumor for which a treatment with Etoposide Carboplatin was deemed an appropriate treatment regimen to participate in that study. During this study we identified a dose of 901 at 112 milligrams per meter squared as the recommended Phase II dose when combined with standard doses of Carboplatin Etoposide.
This slide just highlights some of the adverse events that were noted during the conduct of the Phase I portion of study 007. And as you can see on the left hand side of the slide as expected peripheral neuropathy was really the most common treatment-related adverse event. This was anticipated as I mentioned earlier based on the single-agent profile of IMGN901 where we saw a high degree of grade 1, grade 2 peripheral sensory neuropathy. And as expected based on the established toxicity profile for etoposide/carboplatin we also saw that most common grade 3, 4 event center sensory cytopenias, thrombocytopenia, Anemia, Leukopenia, as well as lymphopenia. And this again was expected based on established profile of etoposide/carboplatin in the clinic.
Slide 42 shows a waterfall plot. And I would like to spend little time on this because it tells several stories I think. Globally, if you look at it and you concentrate on the right hand side of the slide, you see tumors that normally express CD56. And in these tumors we saw evidence of objective responses taking place. If you look at the left hand side of the slide, you see tumors that typically do not express CD56, though there are tumors that are highlighted in red and as would be expected, lack of CD56 predictive for lack of response to treatment with 901.
Maybe digging a little bit deeper in to the detail you can see we accrued a number of patients with small-cell lung cancer. And among those patients with small-cell lung cancer we had objective responses. But perhaps the most compelling evidence of activity was the fact that we saw two partial responses in patients who were deemed platinum refractory to their first line platinum-based treatment regimen and this is very rare to see objective responses in patients who are refractory to a prior platinum-based regimen. And this kind of activity is really what gets investigators excited and makes them want to participate in trials such as the NORTH trial.
As mentioned earlier, in a related tumor Merkel cell carcinoma we also saw evidence of objective responses again supporting the fact that evidence in a similar tumor should potentially support the potential to see activity in small-cell lung cancer. I would just like to highlight two patients who were treated during the dose finding portion of the study 007. The first set of radiographs shows the patient who was truly platinum refractory to their first-line platinum-based regimen. This is a patient who progressed through their first-line platinum-based therapy. They never developed an objective response. This patient was subsequently treated within about a month or two of coming off their first-line treatment regimen with IMGN901 administered dose of 90 milligrams in combination with etoposide/carboplatin and as you can see this patient had quite a dramatic reduction in the size of the metastatic tumor burned in to the liver.
Since the patient population for the Phase II portion of this trial is restricted to those patients with chemotherapy naïve small-cell lung cancer. I thought it was also instructive to show an example of another patient treated during this Phase I portion who had never received prior treatment for small-cell lung cancer. This was the patient’s first treatment with a platinum-based regimen. And you can see here also that this patient had quite a large extent of tumor burned metastatic to the liver and also had a dramatic response in decrease in the size of the tumor lesions in the liver. This patient was also treated with IMG901 at a dose of 90 mg/m2.
Shifting focus a little bit, I just like tell you, a little bit about our thought process in designing the Phase II study, also known as the NORTH Trial. This trial was designed to recruit only those patients with small-cell lung cancer that was chemotherapy naïve. Patients must have had extensive stage small-cell lung cancer and not received prior treatment. Patients were randomized in a two to one fashioned treatment with standard therapy plus 901 versus standard therapy alone. And in those patients in the 901, who were responding to the treatment, they had the option to continue treatment with IMGN901 alone.
This is not a truly randomized comparative study. The study is not power to show a statistically meaningful difference between the two treatment arms, but this is typical of Phase II studies at this stage of development. The study was really designed as a signal generating Phase II study to provide information to inform a pivotal program.
So the update on the Phase II studies, portion of study 0007, we established a data monitoring committee to work with us to monitor the safety of patients during the conduct of the trial. And prior to initiating the trial, we set up specified time points to reflect inflection points in database, at which point the DMC would need to review the data. The DMC has comprised of some of the world’s leading experts in lung cancer and we were preparing for our most recent DMC meeting which occurred in late March.
So, in preparation for that meeting, we did a thorough review of any clinical patient’s data that we had available to us as of early March. And upon performing that review we noted that some of the patients in the Phase I, in the first stage of Phase II were experiencing a higher degree obviously than we had anticipated. We identified the signal, we came up with the treatment paradigm and more formalized guidelines for dose reductions for IMGN901 at the first occurrence of any low grade peripheral sensory neuropathy.
We discussed this treatment algorithm with the DMC. They fully concurred with our approach, they also recommended that reconsider reducing the starting dose of 901 from the dose of 112 mg to 90 mg/m2. And the whole intent of this two-pronged approach reducing the starting dose and also enforcing what formal dose reduction guidelines for 901 is really to minimize the chance for a seeing a high grade neurotoxicity, while also maximizing potential period of time that patients can stay on study, except they can derive maximal benefit and efficacy from treatment with the triple drug regimen.
So at present we are amending the protocol to enact with these changes. We are formalizing the dose modification guidelines for reduction of IMGN901, again at the first sign of low grade peripheral neuropathy. We are also reducing the starting dose upon recommendation of the DMC to 90 mg/m2.
Let’s recall the two patients that I highlighted who had dramatic resolution or decrease in this, I should say, regression of that tumor lesions during the Phase I portion of the trial. Both of these patients were treated at a dose of 90 mg/m2.
So, while the implications of these changes to the protocol and these findings on the execution of the study, I think now we can say we know that a dose of IMGN901 at 112 mg/m2 is not a dose that we would take forward in any potential Phase III total registration trial.
We need to gain additional experience with IMGN901 at this dose and with patients treated according to these dose modification guidelines and we will do that throughout the execution of the latter half of the study.
As Dan mentioned, we probably will not be releasing results until we have fully recruit the study and have had an adequate period of follow-up to assess the impact of safety and efficacy in the full lead of recruited study and based on that decisions for pivotal planning will be differed.
So if I just take a minute here to pause, I think I can summarize this by saying what we saw is really part and parcel of the Phase II development and this was the response of the DMC members and the investigators participating in the trial. We started out at the starting dose that we thought was the right starting dose, we identified a finding that needed to be addressed which we addressed through dose modification and dose reduction of 901. We investigate; we discuss this finding with investigators and with the DMC. And as I said, their attitude really was that this is just part of Phase II development and I think this is underscored by the fact that recruitment to the trial has continued to maintain a high pace of recruitment. Our investigators remain committed to seeing the trial through to completion and had not been discouraged by this finding.
As Charlie mentioned, a big part of our strategy right now is developing biomarkers that can serve as early indicators of tumor response and correlate with efficacy outcomes such as tumor regression, objective responses and prolonged progression for the survival.
CD56 is highly expressed on small-cell lung cancer tissue and one aspect that we will look at in a retrospective fashion is to measure CD56 expression and try to correlate that with clinical efficacy. And because CD56 is so highly expressed on the tissue, we would really be looking to see if only moderate differences in levels of expression have an impact on clinical outcome.
Soluble CD56 is CD56 that is shed from the tumor and circulates in the blood of patients. During the conduct of the trial, we will be measuring levels of soluble CD56 through blood samples from patients. And again the goal here is to see whether or not changes in levels of soluble CD56 in the plasma of patients are an early indication of those patients who will drive clinical benefit from treatment with the therapy.
Circulating tumor cells are another hot topic in small-cell lung cancer research today and part of the reason for that is that patients with small-cell lung cancer had the highest levels of circulating tumor cells in their blood. So it really lends itself to ease the measurement of circulating tumor cells in patients with small-cell lung cancer.
We also know that patients with high levels of circulating tumor cells at baseline are those patients that usually have the worse prognosis in this disease.
So as part of our biomarker strategy, we will be assessing circulating tumor cells both pre-treatment and at specified time points while the patient is on study to see if changes in the number of circulating tumor cells again will act as a harbinger for those patients who will go on to achieve clinical response in terms of tumor regression and prolonged progression free survival.
We also know that CD56 is expressed on the circulating tumor cells with patients with small-cell lung cancer. So, in addition to measuring changes in the level of circulating tumor cells, we will also look to see if levels of CD56 expression on circulating tumor cells also change and to see if this correlates with clinical efficacy. And then finally we would like to correlate the expression of CD56 on circulating tumor cells with the expression of CD56 on the tumor specimen obtained at baseline from the patients participating in the study.
And the goal here is to be able to select the patients that we think are most likely to derive benefit from treatment with 901 in our future studies. So, by a simple blood test, we might identify those patients with high expression of CD56 on circulating tumor cells and enrich our patient population in future studies towards those patients who have this high level of CD56 expression.
Also as mentioned, the patients with high CD56 expression on circulating tumor cells are those that usually do the worse. If it’s possible for us to demonstrate a magnitude of therapeutic benefit in these patients, that is quite impressive. This could have ramifications on pivotal trial design i.e. we would need fewer patients to demonstrate that magnitude of clinical benefit from treatment with 901.
At this point, I would like to shift focus to our most recent product candidate to enter the clinic IMGN853 which entered the clinic in July of this past year. IMGN853 is an antibody that targets folate receptor alpha. The unique characteristic about of this ADC is that the linker that is used to conjugate the folate targeting antibody to DM4, the cytotoxic payload is a linker that was engineered to resist multidrug resistance, the cellular export pumps that pump cytotoxic chemotherapy out of the cells and thereby the patients are resistance to treatment.
Folate receptor alpha is markedly up regulated in states of high folate demand, typically during neonatal development but also during tumor genesis. And the cell function of this folate receptor alpha is provide the cell better rapidly undergoing DNA/RNA synthesis and proliferation with the folate levels that they need to continue the high rate of proliferation.
Slide 52, shows those tumors that are known to have high folate receptor alpha expression. So various stages of ovarian cancer express and various subtypes of ovarian cancer have difference levels of folate receptor alpha expression. Endometrial cancer has high levels of folate receptor alpha expression and within the category of non-small-cell lung cancer adenocarcinoma has high expression on the order of 70% for any degree of expression and 60% for those patients who have 2+ heterogeneous or higher expressions.
Bronchoalveolar carcinoma is another category of non-small-cell lung cancer that is also noted to have high expression of folate receptor alpha. And finally renal cell cancer is also having high expression of folate receptor alpha. And the levels of folate receptor alpha on these tumor indications are guiding us in our early clinical development of IMGN853 in the clinic at this point in time.
So, right now we are recruiting patients to our First-in-Human trial with 853 and we’re recruiting patients to the dose escalation phase of this trial. Consistent with what I said earlier, there are number of tumors that are known to have high folate receptor alpha expression. Patients who present for participation in the trial with those types of tumors are not required to have pre-study conformation in folate receptor alpha on expression.
Those patients with tumors that are not highly associated with folate receptor alpha expression must submit tumor biopsies prior to being enrolled in the study so that we can confirm that they are expressing folate receptor alpha before participating in the Phase I dose escalation portion of the study. The recommended Phase II dose or the maximum tolerated dose of 853 is established in the dose escalation portion of the study. We will embark on the dose expansion cohort and the study is designed to have three specific dose expansion cohorts, each dose expansion cohort is uniquely designed to provide valuable information.
If we focus on the first dose expansion cohort, this will concentrate on those patients with platinum resistant ovarian cancer. What we’re looking for here is a signal of clinical activity. And when I say clinical activity I mean efficacy that is demonstrated through routine resist response criteria. Patients who have objective responses, partial responses or complete responses and as far the strong signal activity in this expansion cohort will help us plan for pivotal studies in the near future or other forms of rapid registration strategies.
This cohort of ovarian cancer patients will be restricted in that they will only be allowed to have received three prior treatment regimens. So again enhancing the patient population making it more homogenous so that if we do see a strong signal of activity we’re looking at this signal of activity in homogenous group of patients.
The other two cohorts have a little bit of a different focus. The next two cohorts are designed to provide biomarker information and to look at clinical evidence of activity as kind of secondary endpoint or a byproduct of participating in the study but the true focus here is really on biomarker evaluation of response and identifying early pharmacodynamic signals that may serve as surrogates for response later on during treatment for those patients who develop objective responses or prolonged progression-free survival.
The relapsed refractory ovarian cohort is a little bit different from the ovarian cohort that I just described also in that these patients are allowed to receive unlimited number of prior therapies. They can be categorized as platinum relapsed or platinum sensitive or platinum resistant, so they are not as strongly a homogenous group as that first expansion cohort is ovarian cancer patients.
And what we’re looking for here is patients will have to provide pre and post treatment tumor biopsies in order to participate in this cohort. We will be looking at the various biomarkers that are highlighted on the slide. We will be looking at folate receptor alpha levels on tumor specimens both pre and post treatment to see how these correlate with evidence of clinical activity.
We will be looking at the impact on tumor cell proliferation to understand if a decrease in tumor cell proliferation noted by Ki-67 analysis or tends those patients who will go onto have objective tumor regression and prolonged progression-free survival. And as mentioned, the unique characteristic of this product candidate is its linker which was structurally engineered to resist proton MDR resistance through P-glycoprotein. So we will be performing IHC staining on these patients to see how 853 behaves in patients with multidrug resistant protein.
Focusing now on the cohort of patients with relapsed refractory non-small-cell lung cancer, again a broad population of patients, those who have relapse disease, refractory disease and have unlimited number of prior therapies; the focus here again is to asses biomarker response and look at clinical evidence of activity as a secondary endpoint.
Non small-cell lung cancer is a tumor type that is not easily amenable to serial biopsy acquisition. Therefore we favored a noninvasive approach to understanding whether or not 853 was affecting impact on clinical biomarkers response, so what would PET measures is the uptake of radio labeled thymidine into rapidly dividing proliferating tumor cells and clinical studies have proven that those patients have early decrease in the uptake of thymidine as assessed through PET scan.
Patients that typically go on to achieve either objective response or prolonged progression-free survival, so again we’re using FLT to look at the change in the number of proliferating cells to understand if this can be an early pharmacodynamic marker of biologic activity that will indicate those patients who are most likely to respond to treatment.
Some centers that are participating in our trial do not have ready access to FLT and PET scan technology. And for those centers we allow patients to come on if patients agree to undergo pre and post treatment tumor biopsy. For these patients we would look at the same biomarkers that I described for the ovarian cancer cohort of patients.
And then finally, in the vein similar to the discussion of circulating tumor cells for the small-cell lung cancer patient in the NORTH trial. We will also look at circulating tumor cells across all three cohorts of patients in the 853 First-in-Human trial. And again we will be looking at similar mechanisms of action looking for a change in number of circulating tumor cells to see if that correlates with biomarkers of clinical activity.
We will be looking at the expression of fully receptor α in circulating tumor cells. Correlating that with expression on the tumor specimens from the patients and also seeing if all of those factors and measures correlate or provide again pharmacodynamic biomarkers of activity that will identify those patients who are most likely to derive clinical benefit from treatment with 853.
So, where are we in terms of progress in the clinic with this clinical candidate development program? We are currently recruiting patients to the First-in-Human study and we are specifically recruiting patients to Dose-Escalation phases of this study. We have not yet identified the maximum tolerated dose but believe we are approaching ranges of doses that should be therapeutically active.
We will be presenting the preliminary data from the Dose-Escalation Phase as opposed to submitted for ASCO and we will also be reporting on preliminary signs of activity during this stage of the development. And as discussed, it's really the cohort of patients in that first ovarian expansion cohort that will have very relevant clinical impact for us in terms of identifying a strong signal of clinical activity that may allow us to consider and discuss and plan for a pivotal testing with this immunoconjugate.
IMGN529 is another product development candidate in development. And IMGN529 is comprised of a CD37 targeting antibody that is bound with the same linker and the same cytotoxic commodity that is used in Kadcyla. CD37 is highly expressed on non-Hodgkin’s lymphoma with patterns of expression similar to that for CD20. It’s also expressed on chronic lymphocytic leukemia. So various avenues for development for this compound.
And 529 is unique in its anti-cancer activity and it invokes several mechanisms of action and perhaps this is best displayed on the insert on the right hand side of slide 67 which shows preclinical In Vitro activity of the naked antibody CD37 comparable to that seen with Rituximab in a human lymphoma cell line. At the cytotoxic payload two the naked antibody and you further enhance the activity of this immunoconjugate in this human lymphoma cell line.
So why pursue an avenue of development for this immunoconjugate in non-Hodgkin’s lymphoma? We recognized that this is a crowded arena with many competitors and other agents in development but keep in mind that non-Hodgkin’s lymphoma really represents the largest hematologic malignancy with an annual incidents of about 140,000 cases across the U.S. and Europe. And among the various sub-types of non-Hodgkin’s lymphoma, B-cell lymphomas are the most common representing up to 85%. So we are talking about a very large population of patients where we believe there are still opportunities to probe fast to market, fast to patient strategies for compounds that differentiate themselves from the competitors. So to just give you a taste of some of the areas that we could concentrate in to bring clinical benefit from 529 to patients. Non-Hodgkin’s lymphoma is typically disease of an elderly population, but the elderly really can't tolerate the toxic consequences of the existing therapies for this disease. So, bringing a new therapeutic invention to the clinic for elderly patients would really be a huge success. There are also other populations within non-Hodgkin’s lymphoma that still represent areas of unmet medical need.
So, patients who relapse from their frontline therapy but are not candidates for stem cell transplant or other forms of transplant. As you can see on the slide, this represents a sizable population of patients within, range anywhere from 50% to 70%. Also, patients who relapse after having received prior transplant therapy; if this is an indication where there are no approved therapies.
And then looking to the future, despite the success that Rituximab has made, as I said earlier there are still many areas of unmet medical need within non-Hodgkin’s lymphoma. And looking to the future again one of the frontline patient populations that is not served well by Rituximab are those patients with diffused large B-cell lymphoma. So the patients receive an induction treatment regimen but there are no therapies approved for maintenance in their setting after they have received their induction treatment regimen.
On the flipside of that, follicular lymphoma patients are treated with Rituxan combined with standard induction therapy but then followed by Rituxan maintenance. So they are really served well by Rituxan. So any inroads to success to develop a maintenance strategy and diffuse large B-cell lymphoma would really be a huge success.
So, again it’s a crowded area there are many compounds in development but we still believe there are quick to market opportunities, fast to patient strategies that are out there for our compounds that differentiate themselves from the competitors. So in the clinic we are currently recruiting patients to the First-in-Human trial specifically to the dose escalation phase of the trial. And patients with the typical sub-categories of non-Hodgkin’s lymphoma are eligible to participate in the trial.
Once the MTD is identified during the dose escalation phase; again in a fashion similar to the 853 study that I outlined before you. We will embark on enrollment of patients to various expansion cohorts. At this point in time, we are not quite sure of what patient populations we will explore, we have an idea but we would really like to be guided by any early efficacy signals that are seen during the dose escalation phase of the First-in-Human trial with IMGN529.
So, in closing I hope I left you with a sense of what each of our product development candidates have in terms of the attributes and characteristics that make them amendable to exploration in specific tumor indications. And many of these specific tumor indications can tap into areas of high unmet medical need.
Picking up on a theme from Charlie's presentation, we are trying to advance the concept of personalized medicine. And we are doing this through two approaches, first by patient selection to participate in the trial. We are selecting those patients who have relevant expression of the antigen that is matched with the product development in candidate. We are doing this by a proven method, immunohistochemical assessment of tumor specimens. But we are also complementing this with our biomarkers strategies, again looking for those indications of early response that will correlate with clinical efficacy in those patients who drive benefit from treatment with the product candidate.
Also I have introduced you to some features of our clinical program that are designed to help us make decisions at an earlier stage of development and enable us to exploit the possibility to develop these agents according to more rapid pads of regulation, get us into registration trials in a faster time period. And we continue to bring innovation to the clinic by broadening our portfolio of clinical staged compounds. And as you heard earlier, we are very excited to introduce our latest immunoconjugate into the clinic in the second half of this year when we expect to dose our first patients with IMGN289.
So at this point, I believe we are going to have a break, and after the break Dr. John Lambert our Chief Scientific Officer will come back and describe for you the science and the pre-clinical development of IMGN289.
Unidentified Company Representative
Thanks Jim. Yes, we are going to go to a break. Again, I’d like to just remind you (audio gap) 10 minute break and I’d like to ask you to hold your question till the end so that we can have them in the webcast. Thank you.
Unidentified Company Representative
Good morning. We are coming to the end of our break.
Unidentified Company Representative
Welcome back everybody. For those of you on the webcast, I am on slide 62 and I am through to actually describe the data on our newest compound IMGN289 that is moved from our discovery research into development. In my presentation now I will show you some of the data that was presented just two days ago at ACR and generated a lot of excitement there.
So this compound targets EGF receptor, so why we would consider this is a target for an ADC? Well EGF receptors strongly over-expressed on several occurrences with high unmet need. In particular, squamous cell carcinoma of the head and neck and on the large percentage on the non-small-cell lung cancer. EGF receptor is validated as a target for therapeutic intervention. The anti-EGF receptor antibodies B toxin, Vectibix that inhibit EGFR function and there are the Tyrosine kinase inhibitors, Tarceva, Iressa that inhibit the signaling through the EGF receptor.
However, cancer often becomes resistant to agents that were solely by targeting EGFR signaling function and so there is a need for new EGFR targeted therapies that have a second mechanism of action and that’s could be provided by an ADC.
Slide 64 shows you the expression of EGFR on squamous cell carcinoma of the head and neck. Virtually all cases over-expressed EGFR and in this example of 84 cases examined within ImmunoGen’s laboratories by a calibrated Immunohistochemistry technique, 82 of 84 cases were positive EGFR receptor and more than 90% of them actually expressed high levels. The blue bars of moderate to high expression are from about to quarter million to a million or more than a million receptors per cell to this target.
Slide 65 shows you expression EGFR on non-small-cell lung cancer. Now, the several subtypes of non-small-cell lung cancer, the largest subtype adenocarcinoma represents about 40% of non-small-cell lung cancers and in adenocarcinoma some 25% to perhaps 30% of them have over expressed the EGFR.
Squamous cell carcinomas represent 25% to 30% of lung cancer and for them about two-thirds of them have overexpressed the EGFR and large cell carcinoma which represents 10% to 15% is similar to squamous in its expression of EGFR receptor. In the two panels on the right, it just you an example of an adenocarcinoma or a squamous cell carcinoma with the brown staining showing the strong staining for EGF receptor.
Now thinking of targeting EGF receptor which is one of the ErbB family receptors, I think it’s instructive to also look at what HER2 has taught us about targeting ErbB family. HER2 is Erb2 and EGF receptor is ErbB1. So these ErbB targets and both overexpressed on several cancers that are solid tumors and what Kadcyla has now shown is our technology clearly works for solid tumors.
Both of these targets are widely expressed at low levels on healthy tissue as well as being over-expressed on the certain tumor tissues. And I think what Kadcyla has shown is that the TAP compound to a target with this profile can have excellent efficacy and tolerability so Kadcyla is well tolerated despite the normal HER2 levels that are quite spread. And both of these ErbB targets can function as a driver oncoproteins in certain solid tumors.
And that what Kadcyla also demonstrated is that for such a target, the use of an active antibody that has its own intrinsic activity, in a TAP compound, can achieve a TAP compound that has multiple methods of cell killing. So our criteria for an EGFR targeting ADC, actually, the first criteria, criteria apply to any new ADC that now develop and were applied to 853 and 529 during their pre-clinical development. So we have these criteria that we would apply to IMGN289 what we look for broadly speaking is anti-tumor activity in relevant models that are at least equal that have Kadcyla in its breast cancer models that have been well published.
Furthermore, the toxicity of the ADC should be less or equal to that of Kadcyla not exceed that of Kadcyla in relevant models to be able to judge the potential for toxicity in humans. But for the targeting EGF receptor itself, our initial criteria specifically for EGFR whereas the antibody components should cause less skin toxicity than the existing EGFR antibodies.
And of course the full ADC in the end should provide superior efficacy to the antibody with favorable tolerability. So, on slide 68, I talked about the selection of the antibody component for the EGFR targeting ADC. So we made and screened many-many anti-EGFR antibodies and what we were looking for was that the impact on skin cells regardless of EGFR expression, we were looking for antibodies with no impact on the growth of human keratinocytes. We also wanted to look for an antibody with strong binding affinity for both human and monkey EGFR to be able to assess the toxicity in relevant animal models in due course. And we identified several promising candidates. But in our screen we identified a novel class of antibodies and the lead antibody was termed J2898A, which is a partial antagonist of EGFR signaling, and it exhibits low skin toxicity but also pronounced inhibition of the growth of EGFR expressing tumor cells.
So the impact of this antibody that is a partial antagonist is shown in the panel on the right of this slide 68 which shows you the impact on the growth of human keratinocytes exposed to antibodies, 10 microns new antibody. So Erbitux and Vectibix as you can see that these antagonistic antibodies to EGFR inhibit the growth of keratinocytes by some 60% to 80%. From our own screen an antibody that I will term K as you will if you like the super Erbitux, we identify the antibody that had very strong antagonistic activity and it clearly inhibited the cell growth of keratinocytes. Also in our screen was the M antibody which is an antibody that finds EGFR receptor but has no inhibitory function whatsoever, so it doesn’t interfere with EGFR signaling and it has no effect on skin keratinocytes. But the J antibody, the partial antagonist, actually also had no effect on skin keratinocytes.
But on slide 69, we show you data to say that the antibody component of 289, the J2898A antibody actually was as effective as Erbitux at inhibiting the growth of cancer cell lines. In vitro I show you an example of a Squamous cell carcinoma of the head and neck cell line. And also a non-small-cell lung cancer cell line. So in green is Erbitux and in red is the antibody component of 289 and you can see they have equivalent activity. And I just show you one example of a EGFR dependent cell line it’s actually a Squamous, a model of a Squamous cell line growing as a xenograft in SCID mice where again the in red the antibody component of 289 shows equivalent activity at Erbitux in green and this is a single dose of 5 mg/kg in this experiment. So with this antibody it represents a new class of antibody and this antibody with its own anti-cancer activity but with reduced impact on skin cells was then combined with the payload DM1 attached by the SMCC linker which is the design in Kadcyla. And so what we want to do is add the potent anti-cancer activity of the DM1 and it’s an activity that we expect to be unrelated to any EGFR signaling function and resistance.
So on slide 71, I show you that IMGN289 is in fact highly active in Vitro on cancer cell line. So this is a panel of three cell lines. They are all non-small-cell lung cancer cell lines. And in the left panel is a cell line that is dependent on signaling through EGFR for its growth. And as expected in the black and the green lines, the naked antibodies, the green line is Erbitux and the black line is the antibody component 289, have some inhibition of cell growth. But in red arming the antibody with the payload produces very significant cell killing. In the middle is an EGFR independent cell line. In this case as you might expect the antibodies that inhibit EGFR function have no effect. This cell grows independently of EGFR signaling and yet it is still sensitive to the payload delivered via the EGFR antibody as shown in the red curve. And on the right and perhaps most exciting is a cell line that expresses EGFR receptor that has become resistant to tyrosine kinase inhibitors. And it is in fact also resistant as you can see to any inhibition of signaling via the naked antibodies as you would expect. Again, the cell line now grows independently of signaling through EGFR and is resistant to tyrosine kinase inhibition. And yet the antibody can clearly deliver the toxic component of DM1 and kill the cells as shown by the red lines.
And so in summary, you could say that with 289 is an antibody that has superior activity on cell lines where the antibody works. It actually works on cell lines where the antibody doesn’t work and more importantly it works on cells that have become resistant to inhibition to tyrosine kinase inhibition and these all three of these represent development opportunities, especially the latter in clinical development. So slide 72 shows that 289 is also highly active In Vivo models. In the last panel is EGFR dependent cell line, it’s actually a model of a Squamous head neck cancer and because it’s EGFR dependent the naked antibody has a very good clinical, a very good effect at inhibiting tumor in this cell model it’s a single dose of 5 mg/kg shown in the black. And yet arming the antibody with DM1 increases the activity and you can see the red line approached zero at about 25 days. So there are clear responses from this single dose administration of 289.
In the right is a model of a squamous carcinoma but this time a non-small-cell lung cancer cell line that is EGFR independent. And as you would expect as shown in the black line the naked antibody has no effect, the cells grow independently of any inhibition of EGFR signaling. But arming the antibody with the payload as in 289 is shown by the red curve you now have tumor regressions and a very good effect from a single dose administration that 10 mg/kg in this model.
So slide 73 makes the point that IMGN289 is highly active against EGFR dependent non-small cell lung cancer cell lines. The left panel is a vitro experiment where the naked antibodies in the black and the green have some effect but IMGN289 really has a much greater effect at killing the cells. And in the right panel is the in vivo experiment, the red curve shows you what a single dose of 5 milligrams per kilogram antibody does in this EGFR dependent non-small cell lung cancer model. But adding the payload to the antibody gives you the curve in black with a very substantial anti-tumor activity. Again, this is a single dose study.
IMGN289 is highly active against EGFR independent non-small-cell lung cancer. On the left the red curve shows you the 289 can effectively kill these cells while the antibodies have no effect as expected. And in the right it shows you the IMGN289 can really eradicate the tumor. Again, the antibody has no effect in this EGFR independent model.
And on slide 75, shows the activity of IMGN289 against non-small-cell lung cancer cell line, but they are resistant to the effect of tyrosine kinase inhibition. So this is a set of three cell lines with a kind gift of doctors Mitsudomi and Suda in Nagoya in Japan. And in the left hand panel is the parental cell line. It’s a HCC827 cell line. And this cell line, the EGFR receptor contains the deletion that renders the receptor sensitive to the effects of Tarceva. And you can see that Tarceva which inhibits EGFR receptor, the naked antibodies B-Tox and the antibody component of IMGN289 and IMGN289 itself all inhibit the cell line, the growth of this cell line very effectively.
In the middle panel, shows you, it’s the same cell line but actually it’s been further engineered to overexpress MET, and overexpressing MET is well known mechanism by which cells become resistant to the effects of TKIs. Because essentially they can now bypass signal link through the EGFR receptor, and you can see that the effect of Tarceva is reduced by about a thousand fold on these cell lines and the antibodies that inhibit EGFR receptor actually have not effect to the highest concentration tested. Yet IMGN289 can still very effectively kill these cells. Indeed in the particular experiment IMGN289 is far, far more active at killing this cell line than the parental cell line.
The panel on the right shows you the cell line that was instead of MET amplification, it was engineered to actually have an additional deletion, genetic modification in the EGFR receptor that also renders the cells insensitive to Tarceva and this is a modification that is found in patient, it was first found in patients. Again, the Tarceva is now a thousand fold less active at killing cells than on the parental cell line. The naked antibodies are inactive as expected. But IMGN289 still kills this cell line extremely effectively.
So this certainly offers a good opportunity for development of this agent since lung cancers that are treated with TKIs, the appearance of resistance, it does appear to be inevitable but this agent 289 looks like it would be an effective agent as attacking these cancers.
Finally just to underscore that IMGN289 is highly active against squamous carcinoma with head and neck, on the left panel is an in vitro experiment showing the killing of 289, actually in blue in this case, killing the cells. And on the right panel is the in vivo experiment, a model of squamous carcinoma with head and neck. In the purple line, is the effect of a single dose of (inaudible) of the naked antibody, and you can see which has a good effect, this is a cell line whose growth does depend on the EGFR signaling, but 289 with the DM1 payload has an additional killing power.
So I would like to return to actually mention the skin toxicity of EGFR targeted therapies. There are two mechanisms of toxicity that are thought to apply. That when one targets and inhibits EGFR, you can have direct type of induction of cell death by apoptosis, but EGFR inhibition also modulates cytokine production resulting in chronic inflammation and cell death and inflammatory responses together thought to underline the chronic dermatologic toxicity of EGFR targeting therapies.
So on slide 78, I want to discuss the impact of 289 on human keratinocytes. So first considering the induction of inflammatory cytokines that in the presence of TNF that induces the skin keratinocytes to produce in the context of antagonistic EGFR antibodies, actually increases the production of inflammatory cytokines. And indicated in the blue dot is the production of CCL5 and CXCL10 in the two different panels in yellow and red, that incubating the cells with TNF and antagonistic EGFR antibody, in this case it was Erbitux, greatly increases the production of these inflammatory cytokines.
The M- antibody, the second column across is an antibody that binds EGFR, has no effect on EGFR signaling, no effect increasing or amplifying the production of inflammatory cytokines in the presence of TNF. So that actually represents the background level of inflammatory cytokine production, and you can see that the IMGN289, the one indicated by the orange dots and or its naked antibody has hardly any effect on the production of CXCL10 and has a much lower effect at producing CCL5 than Erbitux. They are close to the background levels.
IMGN289 is also less cytotoxic than Erbitux on skin keratinocytes. In this experiment skin cells were exposed for five days to about a nanomol of either the naked antibodies or the ADC, and you can see that Vectibix and Erbitux depress, reduce the surviving fraction by some 40% to 80% whereas the antibody component of 289 and 289 itself despite being armed by maytansinoid actually has little effect on the surviving fraction of skin keratinocyte.
And finally we evaluated 289 in cynomolgous monkeys in toxicology studies, and we find that it is well tolerated and the toxicity profile is similar to that reported to Kadcyla.
So to summarize the preclinical findings, 289, it combines the antibody EGFR-inhibition activity with a separate and a potent DM1 cytotoxic activity. And to underline the antibody component is a novel antibody that inhibits tumor cell growth, like Erbitux that has little effect on the growth of skin keratinocytes. 289 is highly active against EGFR-overexpressing tumors, regardless of whether they depend on that overexpression to cell growth or not.
IMGN289 exhibits less cytotoxicity towards skin keratinocytes. It’s less cytotoxic than Erbitux and Vectibix, and it has little or no effect on the production of chemokine and cytokines again unlike Erbitux or Vectibix. And most importantly 289 is well tolerated in toxicology studies with a profile similar to that published for Kadcyla. And so we think that IMGN289 represents a very promising new therapy for EGFR-overexpressing solid tumors.
And my final slide on slide 80 just to say that IMGN289 we are on track for filing IND in mid this year and to begin clinical testing in the latter half of the year. The clinical trial via dose escalation phase to establish MTD within several dose expansion phase is being considered. One obvious one would be to look at EGFR-resistant non-small-cell lung cancer. Another group would be look at squamous cell non-small-cell lung cancer. Another group clearly would be the squamous cell carcinoma of the head and neck and the fourth group might be any other type of tumors that overexpressed EGFR to certainly triple negative breast cancer. A descent proportion of them overexpressed EGFR and a variety of other tumor types where there is some proportion of EGFR overexpressed.
So, we’re very excited in our discovery research that this come to have develop this compound and we enthusiastically hand it over to the development group. With that I’ll handover to Greg Perry.
Thank you, John. So, I’m Greg Perry, CFO, and I’m very happy to be standing here today and assure you that ImmunoGen is in a very strong position. As you've heard today we have three soon to be four compounds in the clinic, each of these position to generate data, news flow, and potential partner interest throughout this year and the coming years. In our first and most famous partnered program Kadcyla was recently approved and launched with 18 million Swiss francs with just over one month worth of sales, it certainly is up an impressive start. And we think this will be one of the first potential markets with many more to come and many more indications to come for that exciting drug.
And also we’re looking forward to the first royalty check that we’ll get to cash in this current quarter and as you know will be reporting royalties one quarter in arrears from when Roche reported their sales. Our partner programs are also important source of strength for ImmunoGen. We have seven other partner programs in the clinic with more expected from the Novartis and Lily. These all will be in a position to generate data, news flow, milestone payments and eventually hopefully expected royalties.
And we believe, the next program to go into pivotal testing using ImmunoGen technology will occur in 2013 and as a reminder we finished up 12/31/12 with 211 million in cash and no debt.
So from that strong starting point, we believe we have multiple paths of value creation for ImmunoGen shareholders. The biggest and most important lever we believe is our wholly owned proprietary pipeline. As Dan mentioned, we planned to move these programs through proof-of-concept, and then we’ll allow the data as well as the profile of the drug candidate as well as the profile of the indication to define next steps.
So will we invest and continue to hold 100% of the program or what we partner to mitigate commercialization risk, development risk as well as to mitigate some of the burn. And with the portfolio of four programs we certainly could be confronted with multiple successes which will drive a number of choices for the leadership team, but all of those choices will be made in the framework of optimizing shareholder value.
We recognize that we have a very important asset in the Kadcyla royalty stream. We believe that’s an asset that is continuing to grow in value. If you think about the development of Kadcyla, it basically has outperformed every step of the way in its history. We believe it has the potential to outperform again in terms of launch ramp and peak sales. We’re also aware that we have the ability to monetize that royalty and we have no plans to do so at the current time.
So how are we deploying our capital? Well we’re investing in the production of double drug product as we expand the number of clinical trials and as we expand the number of patients that are available to receive our drug product in these clinical trials. We’re also investing in the development of pivotal processes and pivotal material so that again we can advance our product programs to registration trials with the special focus on 901 and 853. We’re also investing to build out and solidify our CMO network.
Now, the second big area that we’re deploying capital and it is building our organization. We’re certainly investing in our people and adding personnel in development as well as in operations and quality to support higher product levels and also the support of a number of important projects as we develop these pivotal processes including a number of tech transfers. And there will be a bit knock on effect as we add them support staff to support this larger team.
We’re in a very solid financial position relisting our financials from 12/31/2012. We had reported for our first fiscal year half about $50 million in net loss and a cash balance of about 211 million. And on that call, we had provided guidance of a net loss of between $70 million and $74 million and a cash and marketable securities number of $172 million to $176 million. We continue to feel very good about the cash number but I’ll echo the comment I made on that second quarter call that the net loss can certainly be influenced by the timing of partners taking certain licenses.
And as you recall, when we entered into these multi-target agreements and we get those upfront payments that gets hung up in the balance sheet in terms of deferred revenue, and then we they take license a big chunk of that comes down as it recognizes revenue. So we’re monitoring couple of those timings as we close out the year here.
Now looking forward on the financials, one thing is we certainly have four very exciting programs and so spending levels are going to increase as we support those programs and move them to important inflexion points through the clinical development cycle. But one of the things that we do believe also is that the net cash utilized in supporting those programs will be mitigated by the advent of the Kadcyla royalty and also other revenues. For instance we expect to see a pretty healthy step-up in milestone payments as our patterns continue to make progress with our technology in the clinic.
And just as a quick note, we currently have no plans to provide guidance on Kadcyla sales or Kadcyla royalties because as a matter of fact we really don’t have any special insights there anymore than say you would. But one thought we had was to provide some summary of ImmunoGen analyst estimates for key financial metrics associated with ImmunoGen and then feed that back to the sell-side analyst so that they can have some sense of where they their forecast are relative to their peers.
And certainly we believe that continued pipeline success will result in higher share prices which will enable us to continue to finance this strategy. Business development has been a critical part of the value creation story at ImmunoGen for some time and Peter Williams and his team just did a fabulous job of monetizing the technology platform brining in some substantial upfronts associated with the multi-target deals with Lily and Novartis and in fact setting a commercial benchmark for ADC technology.
But just as ImmunoGen’s focus is changing to a focus on proprietary pipeline; Peter and his team are changing their focus as well. So they’re going to be focused much more on a technology scouting initiative to maintain our ADC leadership position as well as applying the learning that our company has developed about what makes an ideal ADC target in looking and working with some of the folks out there that are doing some very innovative things in identifying a novel oncology targets.
And we are also be doing a lot of work preparing for a potential partnering discussion, again working to optimize the value of each of these assets. And as I mentioned, multi-propriety pipelines successes will certainly drive choices and his team works very hard in terms of curving the leadership team to make the right choices.
Our pipeline as well as our partner pipeline is going to deliver strong news flow in 2013. As you heard 289 is expected to have the IND file mid-2013 and then begin clinical testing in the back half of 2013. We’d expect to show our first clinical data for 485 in June at ASCO and in 901 we are anticipating completing enrollment in the Phase II trial in the back half of ‘13 and providing an update on the safety data in the fourth quarter of 2013.
And then also for 529, we are anticipating the first data for 529 to be in the fourth quarter of ‘13. On the partner side of course we are all excited about watching the ramp of catzilla (ph) and then the expected approval in Europe in the second half of 2013. And we have seven other partner programs in the clinic in which all or mostly all will be presenting data.
And as I mentioned, we also anticipate the next program to enter pivotal testing with ImmunoGen technology will occur in 2013. So, we believe we have a clear path to value creation by investing in CMC in an organization that move our programs forward by supporting partner programs to enhance value and gain excess to those milestones and eventually royalties by leveraging business development to maintain our leadership position in the ADC technology while mitigating risk and optimizing the value of our programs and by maintaining a solid financial position. Thank you.
Thanks Greg. I could have the rest of our officers come up to the front for the Q&A we are now going to the Q&A. And the people who will be joining us up here is Bob Lutz arriving first who is our VP Transitional Research, Theresa Wingrove who is the VP Regulatory, Godfrey Amphlett who is VP Process and Analytical Development and then Peter Williams Business Development, VP Business Development.
Good and if we could raise your hand and then I will have Sarah Cue from the IR Department of ImmunoGen will come with the microphone. And please identify yourself.
Marshall Urist - Morgan Stanley
Hey good morning. Marshall Urist from Morgan Stanley thanks for doing the event today. So, a couple of questions for me. First just on 853, wanted to get a better sense the early patient mix through the dose escalation in terms of what should be our expectation on the early activity, are physicians going to enroll ovarian or lung as you get to these higher dosage and should we be able to see something early? Thanks.
Yes, I quite don't know how much to answer because as you know we like to hold some of that information for out of respect for our investigators who are participating in the trial. We will be presenting that at ASCO. But I can say we have probably a solid mix predominantly in ovarian focus and major patienr recruitment to-date.
Marshall Urist - Morgan Stanley
[Inaudible] to get a little bit more information on the neuropathy signal. So could you give a better sense of how early is it happening and can you give us a sense of what the discontinuation rate was early on? And I guess you are thinking in lowering the dose, why is that, why it’s going to that level, the sort of the right dose to manage that?
So, in terms of time to onset, it’s quite common to see onset within cycle one or cycle two, of the low grade peripheral neuropathy. And then over the course of the time, this can transform into a higher grade of peripheral neuropathy. In terms of discontinuations it’s on the low side, I can't give you the exact number. And I forgot the third part of your question.
Marshall Urist - Morgan Stanley
Knowing the lower dose.
Knowing the lower dose, yes, so we went back, we looked at the Phase I data and we saw that lower dose maintains the efficacy. I pointed out to you the two patients who had dramatic response in the metastatic tumor liver burden. And but we did not see a high incidence, actually we did not see any incidence of grade three peripheral neuropathy at that dose when we went back and didi a retrospective analysis of the database.
Marshall Urist - Morgan Stanley
Why is it you are seeing now when you didn't see it in the monotherapy or the run in?
So in the run in, we did try to identify to make sure that the recommended Phase, the MTD was the recommended Phase II dose that we should take forward. And among a cohort of 12 patients that was expanded to confirm that recommended Phase II dose. Two of those patients did have grade three peripheral neuropathy at a later time of onset. Charlie I don’t know if you would like to add anything?
The only I would say so I think the main difference from earlier on is that we have got now got longer durations of exposure obviously as the trial has developed. We have got less heavily pre-treated patients who have perhaps been able to stay on longer than the mixed collection of patients that we saw in the stage one. And ultimately this is; I think it’s not uncommon in a Phase II study, and I think we have identified it we have acted upon it and I think a combination of reduced dose and pretty rigorous sort of dose interruption and dose management schedule holds a lot of promise for being able to maintain good dose intensity of both top side and obviously 901.
Adnan Butt - RBC Capital Markets
Thanks it’s Adnan from RBC; first on 901; for the 90 mg per meter square dose, is that the lowest dose for the company has seen activity and in terms of a dosing down; how low do you think you can dose down and still see activity? Start with that please.
So, actually activity has been noted at doses as low as 36 milligrams per meter squared. So, I referenced the Merkel cell patients who had complete response, one of those patients was dosed with single agent IMGN901 at a dose of 36 milligrams per meter squared. That patient had an objective, complete response and remained progression free for five years, so it was really quite a durable impressive complete response. We've also seen in our multiple myeloma studies stable disease and minor responses that start to occur at doses as low as 40 milligrams per meter squared. So, we do have evidence of activity at the lower doses.
Adnan Butt - RBC Capital Markets
And in terms of how low you think you can go when you will dose reduce?
So, the protocol is designed to allow dose reductions of IMGN901 as low as 30. Do I think we going to need to go there? I severely doubt it. I think to-date, the lowest dose reductions that have mandated or been necessary have been no lower than 60 milligrams per meter squared.
Adnan Butt - RBC Capital Markets
And in terms of the status, the 59 patients have already been enrolled and do you still think that 120 patients is the right trial size to get a signal?
So all of this has been happening really recently and we are still getting our heads around how to proceed forward but that is part of the discussion that we are having with statisticians to understand if we need to add additional patients to the study. I think our thinking is to preserve the integrity of the original statistical design. We would analyze the projected 80 patients who will be treated with IMGN901, Etoposide and Carboplatin as planned but perhaps we would look at additional patients to get a better sense of safety and efficacy at the reduced dose of 90 milligrams in combination with Etoposide Carboplatin.
Cory Kasimov - JPMorgan
Cory Kasimov of JPMorgan, a couple of questions on 901 and then one on 289. So on 901 first, when you made the decision to amend the protocol, was there an efficacy look taken on the existing data?
Absently, too early, the data is too immature. we have no idea what the efficacy will look like and that was one of the things that the data monitoring committee readily acknowledged upfront that they would not even, hazard a guess as to what the efficacy looks like, it’s just too early.
Cory Kasimov - JPMorgan
Okay. And then how many patients worth of data do you have at that 90 mg dose?
We recruited total of 59 patients.
Cory Kasimov - JPMorgan
At 90, yeah.
From phase I portion I believe we had six patients at 90, 12 patients at 112.
Cory Kasimov - JPMorgan
Okay. And then on 289, do you have any data on that candidate's potential impact on emerging mutations to existing EGFR therapies?
So, pre-clinically I showed you data that said the 289 was active in two settings with a well-known to be settings were that conferred resistance to targeting EGFR receptors. So, one is (inaudible) over expression and certainly 289 seems to able to kill cells that are resistant to other EGFR targeting therapies by (inaudible) over expression and in every case that we’ve so far where we have cell lines on models that are resistant to the effect Tyrosine kinase inhibition and that includes those cell lines where that was actually induced by growing the cells for a long time with low levels that Tyrosine kinase innovation.
It would appear that delivering the maytansinoid payload will still kill those cells very well and so the mechanism of the ADC which is to bind and deliver maytansinoid is clearly independent to EGFR signaling defects. So, I would be optimistic that that would play out in the clinic. That certainly would be the intention to assess that in the clinical trial.
Thank you. My first question is on 901 also maybe, can you pin down or can I pin you down more in when we'll get the data in 2014 and what the historical benchmarks are that we should compare to once we have the data and then I have partnering question after that.
I think as Dan mentioned, we expect full recruitment of the trial with sufficient follow up to assess efficacy and safety in mid-2014. In terms of benchmarks, as I mentioned during my presentation, the trial is designed to show an improvement in progression free survival and historical control data to estimate progression free survivals on the order of five to five and a half months.
So, on the partnering side, first as it relates 289, I’m wondering if you’ve attempted to or if you talked to Lily about that you obviously have a relation with Lily with respect to Erbitux, or is the approach here to retain rights to this and come up with a better approach that would compete, what’s your thinking in that respect?
I don’t know if the mic was on, so I will repeat it, the question was, with respect to 289 had we spoken to Lily given their involvement with Erbitux and what our plans be? I think that goes back to the broad position that we conveyed that we would look to take each of our pipeline compounds on our own through the proof of concept and I don’t know that we would from a starting point see anyone having a preferred position as a potential partner, I think that will be manifest by what we see with the individual compound, what we see developed with the overall pipeline.
Matthew Harrison - UBS
Thanks Matthew Harrison, UBS. Two things, first on 853, I noticed in your presentation you talked about potentially moving right into a pivotal phase Interleukin. I think that contrasts with what endocyte is doing it looks like there are running a full phase III. Maybe you can just talk about what the potential regulatory differences are in your two programs? And then on 289, is there any thoughts on just testing the naked antibody against (inaudible) to see what the efficacy is in patient. Thanks.
Yes. I mean in terms of 853 as we noted at the time it’s a somewhat speculative thing of course we are in a dose escalation portion of phase I. I think we’re very much aware of the (inaudible) development and of course had little in terms of response during their initial dose escalation. So, things are already got to be data driven and what we will escalate you know, we’ve got compiling activity from the preclinical information as a single agent.
We’re optimistic that we can see that by selecting the right patients as we go forward. And if the opportunity arises as results of what we see in dose expansion then we would certainly consider talking to FDA by going forward on an accelerated approval route. But at this point, that’s already damn speculation I would say.
The short answer is that is no, we wouldn’t plan on doing a clinical trial comparing with the naked antibody that we’ve developed against it.
(Inaudible) from Roth Capital. Two questions here. First let`s start with 901. Besides lowering the doses, is any other sort of options do you account on play in terms of dosing times, how does may have an impact?
So, in terms of responding to the appearance of (inaudible) optic part of that treatment algorithm, that has been formalized, in addition to allowing for dose reductions at the first onset of peripheral neuropathy. At higher grades of peripheral neuropathy we recommend that the dose be delayed while Carboplatin Etoposide be maintained on its regular schedule of administration. After dose delay, once the peripheral neuropathy results to grade I or lower, at that point in time IMGN901 would be administered at a reduced dose.
Okay. And another question is one of other partnering compound, as they are 3419, is there any updates on that? Are they going to presenting at the (inaudible) and other conferences? Thanks.
Yes. I think a standard response that we have when we’re talking about partner compounds is that the discloser of information by partners is controlled by them. We know that 3419 is in development in three different phase II studies. We have some awareness of what’s taking place with 3419 but we’ll just have to wait for Sanofi to have further disclosure on the compound.
Mara Goldstein - Cantor Fitzgerald
Mara Goldstein, Cantor Fitzgerald. Just two questions. The first on 853 and the indication not a strong response, so you’re able to benchmark for us what you would consider an appropriate response to go on to acceleration in that trial to a larger registration trial? And then on 901, do you have any information on the neuropathy and the total cumulative dose as opposed to the starting dose?
I can answer the second question first. As I said, we’re just wrapping our heads around what’s been going on and looking at the data in more detail to understand things. So we will be looking at that to see if there is any relationship.
In terms of the 853, as you can imagine we are discussing with multiple key opinion leaders in the ovarian field and in gynecologic oncology, what that efficacy criteria would have to look like. We are kind of also looking at what GLG uses for their clinical efficacy hurdles when they are developing compounds in their 170 series, or I can't remember the name of the other series that they evaluate for ovarian cancer.
And I would say, based on historical single controlled arm activity, for accepting (ph) line platinum resistant ovarian cancer, the response rates are notoriously low, anywhere from 7% to about 15%. So I think when you are talking about an objective response rate on the order of 25% or higher, that would provide a measure of comfort to start considering going forward with a pivotal registration strategy.
(Inaudible). I work with John Soni at William Blair. I had a couple of questions. One of them on 901. The multiple myeloma data in December looked really good and also with Merkel cell, do you guys have any future plans with that? And also, one thing that Seattle has shown recently with (inaudible) that they were able to get responses in tumors with very, very low levels of antigen. Have you also seen that with some of your ADCs in situations where you can't detect the antigen, but have a really good response to it?
I will take the 901 question. In terms of 901, I think the key driver I think at the moment has got to be the small-cell lung cancer study. We’ve invested significant amount in that, it’s ongoing. I think obviously when we turn the card on those data the next year that will have a significant impact.
There are certainly things coming on board, I think we do need to continue to explore the best potential combinations in multiple myeloma. It isn’t straightforward because of the so many new entrants into that market and almost constantly shifting paradigm of how patients are currently being treated. So in the sense we saw small-cell lung cancer is just a little bit simpler, as a route forward, but yes, we will continue to watch out and I think if we do continue to push forward on small-cell lung cancer, then we can expect to be looking quite hard at myeloma as well.
Merkel cell, again is something that which we have certainly asked the team to look again at where the data are and we are looking at whether they are routes forward with that at the moment. The challenge I think with Merkel cell is it’s such a rare disease, that I think for it to stand alone is a path forward. So 901 could be quite difficult. But I think again with the outcomes of the North study, if that would support this going forward into a phase III, and those going forward obviously with confidence, then I think understanding whether Merkel cell could get us out there a little bit sooner, and give us that opportunity to start building out at commercial floor so earlier would certainly be something that would be up for discussion at that point. But I think we need the phase II data from small-cell first. The (inaudible) question.
Yes, I am searching by memory banks of data to, see if I can remember, if we have had patients with low expression of CD56, who had gone on to achieve objective response. I think, I can't answer that, but I think the answer is that, most of the tumor indications that we have been evaluating for efficacy with IMGN901 are tumor indications that have high expression of CD56, mostly on the order or 3+ heterogeneous, 3+ homogenous. So for example in Merkel cell, almost every patient that we evaluated had 3+ homogeneous expression of CD56 and the same would hold true for the small-cell lung cancer patients. Off the top of my head I cannot remember if we had patients with low expression that had good evidence of clinical activity.
Dan, do you have any input on that?
I could make a more general comment. I am not familiar with the details of what Seattle report and I wouldn’t know if there deep details there, but just a general comment would be that lymphoma cells, generally, you can kill them with ADCs at much lower antigens per cell level than those solid tumors and I can say that from just consideration of our own experience in developing the compound that Sanofi has it in the SAR349, cell lines with 20,000 antigens per cell can be very well killed by that agent. Solid tumors, you need to be probably 10 fold higher in antigen levels to have really good killing. So it could well be that (inaudible) lymphomas for the most part, it may be that in the range of sensitivity, you can go from huge expression to quite low and still actually have sensitive killing.
And I am sorry, at the risk of having too many people answer one question. I don’t think it should be a priority for us right now. I think we should follow the principles that I laid in the beginning which is to say, we believe that we need to see the target, we should be looking for the patients with the highest level of target and proving the concept of what we’re trying to do. I think once you have got a drug through to the market, you can start asking some of those other questions. But I think at this stage we risk diluting out efficacy by exploring the wrong patients. So let’s go for the high expressive now and the rest of that can fall into place later.
Thomas Wei - Jefferies
Thomas Wei from Jefferies. I had a series of 901 follow up question. I know you aren’t willing to share the actual number of discontinuations but can you talk how patients developed grade III peripheral neuropathy in that 59 patient first cohort here?
Yes, so that was the number I gave during my presentation. We saw a grade III peripheral neuropathy in 30% of those patients, what’s about, what’s the map there.
Thomas Wei - Jefferies
And for the 90 mg dose, you have six patients worth of data on, how many developed grade I or II peripheral neuropathy?
So I have to correct my number. The trial was designed with two dose escalation because we were looking at IMGN901 in combination with carboplatin and had an AUC of six for the first part of the study and I believe we treated six patients at a dose of 90 in that part of the study. And I agree we have treated additional three patients at 90 mg/m2 in combination with carboplatin and AUC of five. So I’d say we probably have at least nine patients worth of data from the combination with the etoposide carboplatin at a dose of 90 mg/m2. And I’m sorry, the second part.
Thomas Wei - Jefferies
And how many developed grade I or II peripheral neuropathy at 90?
Let’s see if I can remember that. So among the patients at 90 mg, none developed grade III peripheral neurotoxicity. I can't remember that number, who developed grade I and grade II, I’m sorry.
Thomas Wei - Jefferies
In the revived protocol, it sounds like, are your dose reducing patients if they develop grade I peripheral neuropathy or does it need to be grade II?
Where dose reducing patients, if they develop grade change greater than grade I in intensity. So for example the protocol allows patients to come on, who have a baseline peripheral neuropathy of grade I. So in those patients we would need to see that their peripheral neuropathy goes to grade II, at which point we would dose reduce them.
Thomas Wei - Jefferies
And if they did not have peripheral neuropathy at study entry, then if they develop grade I, they would be dose reduced?
Thomas Wei - Jefferies
And so it might actually be a relatively significant proportion in patients in the trial who end up needing a dose reduction?
It could represent a significant number of patients, but the thing to keep in mind is that if these patients cannot stay on treatment because of the development of peripheral neuropathy, this is the right approach to take to extend their duration of time on study and receiving active study drug, thereby improving their chances to demonstrate efficacy.
Thomas Wei - Jefferies
And for the patients so far that you have had in the 59 patient cohort to start, was the peripheral neuropathy something that developed during the first six cycles in combination with Etoposide Carboplatin or was it during the maintenance phase?
It was usually onset of peripheral neuropathy, not direct peripheral neuropathy. Typical pattern was that patients would develop a low grade peripheral neuropathy that progressed to a higher grade by about cycle four, cycle five.
Boris Peaker - Oppenheimer
Boris Peaker from Oppenheimer. Not to beat a dead horse here but on the peripheral neuropathy, again on 901, I’m just curious what the feedback was from physician and when you say the committee decided to reduce or allow dose reduction, it included dose reduction protocol, was this based on the physician saying that we have a lot of neuropathy and then that’s a concern or how does that actually play out in practice?
So actually none of these cases of peripheral neurotoxicity qualified to be serious adverse events. They were just grade III events that investigators did not qualify as serious adverse event. And part of the explanation for that is that the assessment of peripheral neuropathy is really quite subjective, both by the patient and by the physician. What I consider a grade 1 peripheral neuropathy, you may consider grade 2. So it’s really a difficult assessment to understand what the true grade of peripheral neuropathy is. But part of the in depth database review was triggered by two investigators who had patients who characterized the grade III peripheral neuropathy in their patients as a serious adverse event.
I’m just trying to understand for the first 59 patients that you will have data form, if you have 30% who developed peripheral neuropathy in the 901 part, I’m trying to understand how impaired that data might be. What actually happened, if patients didn’t discontinue or if there is a very low rate of discontinuation, might that data still worth robust or were people, I guess help me understand a little bit how interpretable that data is really going to be?
I think to a certain extent we are going to have to wait and see until we get to that 59 patient analysis and that is in many ways why we sort of said we shouldn’t be expecting go/no go decisions off of that particular date sector. So obviously the 112 is not now the starting dose. Having seen a level of peripheral neuropathy which is similar to above that for what you may see for other marketed products. You think things like botex (ph), maybe things like oxaliplatin.
There is certainly a clear sense that we needed to act to manage that, to prevent the potential for dose interruptions, which could lead to not just reduced amounts of 901 obviously but could also lead to reduced amounts of the standard chemo therapy as well.
When the dates come through, obviously we will look at it and we will make an interpretation, but I think we feel that in order to be able to make the critical decision for the next stage, we really need to have some of the data with that new starting dose of 90, in order to really be able to trigger confidently investment in the Phase III manufacturing in particular.
Maybe a different way to ask it is if a patient was not discontinued, is the issue that they had their dose interrupted and they didn’t get all six cycles and/or maybe on the top of that Carboplatin was reduced?
So it played out in various scenarios. Some patients had their dose interrupted while they maintain treatment with Etoposide Carboplatin, other patients had their dose discontinued, other patients continued to be treated through low grade neuropathy with the addition of medications that helped to reduce the pain associated with the peripheral neuropathy with gabapentin or with Lyrica and it’s really difficult to get our hands around this right now.
As I have mentioned earlier, this is something that was discovered recently with a database that’s not quite mature with follow-up of resolution of neuropathy in these patients that is not quite mature. So we still need to gather a lot more information from our sites in terms of how patients fared with the development of peripheral neuropathy and we will be better able to answer these type of questions once we have a more mature database to analyze.
This meeting with the DMC was comprised of the 59 patients that were treated in stage 1 but we really only had follow-up data on a proportion of those patients. We did not have follow-up data on all 59 patients and that’s just a reflection of database lag that you see with any study in the clinic.
Bret Holley - Guggenheim
Yes, Bret Holley with Guggenheim. I have a question about the safety update at ASH and the nature of the data you might be presumably at ASH you said like 13. And with the protocol revision for 901 going down to 90 as the starting dose, I’m wondering if you saw the development of the high grade neuropathy in cycle 4 or 5, how many patients are we really going to get with the lower dose later on this year?
You kept mentioning ASH and I quite didn’t get the question.
Bret Holley - Guggenheim
Sorry, so you said there could be a safety update on your slide later on this year with the new starting dose of 901 at 90?
We are planning to submit an abstract to our conference. We have identified which process it would be a solid two month conference obviously.
Bret Holley - Guggenheim
Sorry just confused my conferences. Late 2013 you are going to give this update, right? The protocol revision is now presumably the number of patients that you have with a new starting dose. There are cycles of therapy you are not going to be varied (ph), that’s the question sorry.
No I think you are right. Obviously the type of conference that we would look at in a world (inaudible) lung cancer for example is in October. We can submit the abstract and we will have about six months of recruitment and follow-up on the earliest patients coming into the study and patients are coming on at a fair rate at the moment. So I think that although it will be sure follow-up, I think we will have enough information to give us reasonable confidence about how well it’s going both with the new dose and with the new interventions for managing the dose and keeping patients on study.
Bret Holley - Guggenheim
So, just to clarify, the higher grade neuropathy happens cycle 4 or 5 with the 112 starting dose?
Correct. Its onset was, in most circumstances at a later time point and it usually progressed from a lower grade early on in cycle 1 or cycle 2. So we really feel that the intervention to dose modify, dose reduced or delay IMGN901 really should have an impactful effect on the durability for the time that patients can be treated on study.
Bret Holley - Guggenheim
Quick question, once they are done with the six cycles, they go on to the maintenance 901. Of the patients that you saw that had peripheral neuropathy, finished their six cycles, went on to maintenance, did the peripheral neuropathy go back down?
So the database is really immature and we don’t have enough data to answer that question. We do know that the patients have gone to single agent treatment with IMGN901 but again the database was just too immature to draw a conclusion like that.
Bret Holley - Guggenheim
Just to switch to 853, were you defining the patients by their level of expression of folate alpha and where you sub segmenting marked as to whether they were very high expressers, medium expressers or low expressers and then with, I guess you are using IHC to kind of determine the expression. So just wondering how sensitive that assay is to really get that level of folate expression.
So I can answer the first question. If your question was how we were using this in the phase I study design, as I mentioned during my presentation, for the phase I dose escalation portion of the trial, patients with tumors that are known to have high expression folate receptor do not have to submit tissue specimens in events of enrollment for confirmation of folate receptor alpha expression.
Those patients who have tumors that are not known to have high expression folate receptor alpha must submit the tissue so that we can analyze it for folate receptor alpha expression. During the dose escalation portion of the trial the threshold is lower. We require that the patients have at least 1+ heterogeneous expression or higher.
When we embark on the dose expansion cohorts, again trying to get a more homogenous patient population, we will mandate that patients submit tumor specimens prior to enrolment into the dose expansion cohorts and they must have a higher level of expression at that point in time. Right now we are talking about a level of 2+ heterogeneous or higher expression of folate receptor alpha on that tumor in order for them to participate in the dose expansion cohorts. In terms of the IHC assay, I would turn to John or Bob.
Could you repeat the question?
Bret Holley - Guggenheim
I just asked how sensitive with IHC assay in terms of being able to kind of fully characterize the level of expression of folate alpha on the tumor cells.
So, we developed an IHC assay using our new calibrated IHC approach where we developed the full dynamic range that characterizes a large data set of patient samples that we can go from known antigen levels from negative so zero expressions up to some range in the 1 million to 2 million receptors for antibody and then we set the sensitivity of the assay so that we can see a large differentiation across the patient samples for that.
So for example with our 2+ set from our assay, that prediction of about 50,000 to a 100,000 receptors per cell and then 3+ is somewhere in the 1 million to 2 million receptors per cell So it’s a very well expressed antigen. We made sure we build our assay that we can fully describe the level of expression on the patient’s samples.
Marshall Urist - Morgan Stanley
Just I apologize one more 901 question and then I have a total of seven questions. So first, is the 901, are you definitively not going to make any comment on efficacy with this first, when you talk about this safety findings later this year? So it seems like you have to all of these questions, you know with a decent amount at least from the first 59 patients of response data and follow up from there. So are we going to see anything in that later this year on efficacy?
I think that’s a discussion that I guess we would have to have at executive management at the time that we see the efficacy data from that stage one cohort of patient, Dan I don’t know if you want to make a comment?
No, I think that’s right to me. It’s a little bit hard to say given the dynamic that we have now. I think we want to look and see if we can gain any insight around the efficacy but it’s just so early, we don’t have enough data to be able to take a look at. I think with the change the focus is going to be have we been able to address safety with this particular change and I think that will be the primary focus whether we would present at a conference and in that context then is there anything meaningful we can provide around efficacy but it’s just too early to say.
Marshall Urist - Morgan Stanley
Okay great thanks and just I have a question maybe just for Dan or for Greg. So Greg you mentioned royalty monetization in your slide. So, curious where your thoughts are on that. Obviously you have a lot of the proprietary pipeline coming together. That’s going to be expensive to develop. It’s obviously a favorable market for royalty monetization. So how would you think about that in the company’s plans versus continuing to use equity to fund the company?
Marshall, it’s a great question. So we’re thinking about evaluate but as I mentioned we don’t really have any plans to do anything immediately. In primary drivers, we don’t really have a need for additional capital immediately. But I think we’ve looked at it pretty classically in terms of looking at cost to capital and so you have evaluate all of our options whether it would be equity or a convert or potentially monetizing the royalty in the framework of relative cost to capital.
And then may be some sequencing that plays into that as well but I think at the end of the day, it will really depend upon how the data kind of drives some of these choices because we will have to see what the demands are for capital, what the options are as I mentioned business development, options to mitigate burn going forward but that’s hardly the framework we would use.
All right. I hope there’s one more room for the 901 question, which is that the data release of this, second half of this year in terms of safety, what kind of contacts am I thinking about right now in terms of just compared to two doses or more comprehensive details? What should we sort of generally think about that?
I mean I think the key question is going to have be one of, have we, since data monitoring committee and since certain investigators considered the rate of grade III that we were saying too high. I think what we have hope to do is provide some color. It will be relatively early a little bit at least some color to the notion that we look like we are able to both reduce the rate of grade III toxicity whilst being able to deliver to carboplatin and the Etoposide and 901 consistently to patients.
So I think we will have some sense of in terms of the number of dose reductions that will have been required. I think we will have some sense of the dose intensity that, I think it plays back some of the questions they were asking earlier. I think we feel very confident that the dose levels that we are dealing with are those therapeutic range. I think being able to show that we can maintain patients in that therapeutic range with the dose adjustment is going to be very important.
Certainly, I think John would echo that the pharmacokinetics would certainly suggest that the 1975 mg/m2 levels would be those associated with pharmacokinetically provide levels that were associated with efficacy in the pre-clinical models. So I think if we can provide some comfort that the dosing adjustments are maintaining the levels that we would have targeted, that would be a good thing.
Alice? I think this is going to be our last question.
Just, it’s a very simple one. So in the dose reduction algorithm now, so if you would develop grade I or one grade higher peripheral neuropathy, what exactly has your dose dropped to? Is it 75 or is it 60?
75 would be the first step.
And then the second step is 60?
If you remain at grade I, you would remain at 75. If you have a worsening of peripheral neuropathy beyond that, the next step now would be 60.
And with that 60 you got a dose holiday as well?
For grade I, no. Fir grade II and higher, way after recovery to grade I before retreating with 901. And that was two questions.
And now I’m going to turn it over to Dan for closing remarks.
Thank you Carol and thank you again everyone for joining us, for your interest, for your questions. I think that’s a very useful exercise. Let me just close by coming back to maybe where I started. I think that we have a very important and what is now a validated technology that’s providing a great survival benefit to patients with good tolerability advantages in a meaningful solid tumor indication. So we are very proud of the fact that this technology has improved the quality of life for patients with a very difficult disease and this represents the first ADC to gain full FDA approval.
Beyond that our scientists are applying this technology to build a pipeline of very high potential wholly owned compounds. We are excited about the pipeline. It represents I think a major step forward in personalized therapy, with the ultimate objective of providing better solutions to patients. And if we’re able to do that and provider better solutions to patients, I’m sure that our shareholders will be well rewarded. For each of the compounds we have in the clinic and 289 coming into the clinic, as we noted earlier they are targeting a significant unmet medical need.
From a strategy standpoint, we do intend to retain these compounds through proof-of-concept. We think we have the will and resolve to do that and that will present us multiple options of how we build the portfolio, how we finance the portfolio post proof-of-concept. There will be issues, certainly we’ll have addressed from an organization standpoint, but they’ll be defined by the portfolio evolution, by the bandwidth that we need to support that and how we choose the finance that; but we think as noted in the Q&A there are a number of different ways to get at that.
We’re building the organization. I think we’ve been successful there. I’m very proud of the organizations that have in place. Some of that is currently coming in a most accelerated basis in development where we’re seeing expanded activity. We’ve identified functionality that we need to bring to that group and beyond that we’ll add scale to support our multiple advancing programs.
But out of all that we think that we are very well positioned to deliver successful therapies. So we’ve got industry leading technology, a very solid product portfolio, a good team in place and we’re doing that against a very good balance sheet to allow us to be able to move these compounds forward. At the same time beyond our propriety, our partners are doing a good job of advancing their compounds and we’ll look forward to the data that’s delivered over the course of this year.
So again I thank you for joining us. It was a productive morning. We look forward to continuing to update you on the progress of ImmunoGen and the Company’s portfolio. Thank you.
Copyright policy: All transcripts on this site are the copyright of Seeking Alpha. However, we view them as an important resource for bloggers and journalists, and are excited to contribute to the democratization of financial information on the Internet. (Until now investors have had to pay thousands of dollars in subscription fees for transcripts.) So our reproduction policy is as follows: You may quote up to 400 words of any transcript on the condition that you attribute the transcript to Seeking Alpha and either link to the original transcript or to www.SeekingAlpha.com. All other use is prohibited.
THE INFORMATION CONTAINED HERE IS A TEXTUAL REPRESENTATION OF THE APPLICABLE COMPANY'S CONFERENCE CALL, CONFERENCE PRESENTATION OR OTHER AUDIO PRESENTATION, AND WHILE EFFORTS ARE MADE TO PROVIDE AN ACCURATE TRANSCRIPTION, THERE MAY BE MATERIAL ERRORS, OMISSIONS, OR INACCURACIES IN THE REPORTING OF THE SUBSTANCE OF THE AUDIO PRESENTATIONS. IN NO WAY DOES SEEKING ALPHA ASSUME ANY RESPONSIBILITY FOR ANY INVESTMENT OR OTHER DECISIONS MADE BASED UPON THE INFORMATION PROVIDED ON THIS WEB SITE OR IN ANY TRANSCRIPT. USERS ARE ADVISED TO REVIEW THE APPLICABLE COMPANY'S AUDIO PRESENTATION ITSELF AND THE APPLICABLE COMPANY'S SEC FILINGS BEFORE MAKING ANY INVESTMENT OR OTHER DECISIONS.
If you have any additional questions about our online transcripts, please contact us at: email@example.com. Thank you!