Charles Butler – Executive Director, Corporate Communications & Investor Relations
Mike Morrissey – President and CEO
Exelixis, Inc. (EXEL) Citi Global Health Care Conference February 28, 2012 10:00 AM ET
Over to Mike, I will just read the FLS quickly; during the course of this presentation we will be making forward-looking statements regarding future events and our future performance of the company. Actual events and results of course could differ materially. We refer you to the documents that Exelixis files from time to time with the Securities and Exchange Commission, specifically the company’s most recent 10-Q filed on February 22, 2011. These documents contain and identify under the heading Risk Factors important factors that could cause actual result to differ materially from those contained in any forward-looking statements including risks related to the potential failure of cabozantinib to demonstrate safety and efficacy in clinical testing, our ability to conduct clinical trials of cabozantinib sufficient to achieve a positive completion, the sufficiency of Exelixis’ capital and other resources and any uncertainty of the FDA review and approval process.
With that I turn it over to Mike.
Again, thank you Charles, good morning everybody. Thanks for joining us today. I will start this morning briefly framing the Exelixis opportunity and then move into some data that we have as a lead compound, cabozantinib and prostate cancer and tumor types. I think the opportunity we have today moving forward in 2012 is really based upon I think a lot of the emerging data that came up early this year and last year around a variety of different tumor indications for cabozantinib. Our focus is of course in prostate cancer, that’s really have certainly the most robust effect today and certainly a very unique clinical profile that we hope to now convert into unique and differentiated commercial activity. That being said, cabo is more than just a prostate cancer compound and it's more than just a prostate cancer bone drug.
Has a variety of different activities that we have seen today, we have seen objective responses in 12 of 13 different tumor types to-date. We have seen broad activity in nodal disease, this will be these bone disease, visceral disease and we built a unique methods of action that we think is driving the activity both in terms of its primary activity on tumors but also in blocking resistance and I think we cannot – last Friday in counter discovery talking about the roles that both met and they just play in terms of simultaneously driving tumor growth but how important it is important to block (inaudible) in terms of really blocking a primary resistance to a variety of different types.
Very interesting papers that came out with one of our collaborators from USF (ph) that came out with one of our collaborators from USF I doubt which I think helps frame the opportunity that cabo has been broadly active in sense of compound but I will challenge right now is to really take this forward now and provide significant clinical differentiate in pivotal trials that will allow us into differentiate commercially and make that franchise as high value as possible.
So how this cabo is different, what have seen today, again our overall adjusted response is being very broad and again talk to 13 different tumor types. We have I think for the first time shown very rapid inconsistent resolution of metastatic bone lesions. This has been a real challenge going back now for almost 20 years to address this compartment, we are going to test these off of the Trial II (ph).
We have very broad activity in the bone, we have seen that today in prostate cancer, renal cell carcinoma, thyroid cancer, melanoma, as well as others. So, really again very good activity here again not just in terms of prostate cancer but broad bone activity across multiple tumor types.
We have been able to shown with some data we had last year in June, last year that this bone scan resolution appears to correlate with various signs of clinical benefit including extension of PFS by six months. Pain reduction, opioid reduction, et cetera, so, very good overall emerging correlations or associations between the ability of cabo to resolve existing metastatic bone lesions and then having that lead to clinical benefit in patients.
And one of the big breakthrough that we made over the last few months is using the prostate cancer opportunity to look to a fill those response in the clinic, again to do this really exhaustibly you want to have a tumor type in the clinic that is highly prevalent and prostate cancer is certainly is that, but has the bio-marker, so you will be able to let you rapidly look at different doses and get a relevant read out quickly.
And certainly with the fact that most prostate cancer patients have bone metastases and most of those patients respond to cabo with resolving bone metastases. We have been able to then rapidly with collaborations with Mass General, Matthew Smith there be able to define what we think are the important lower active doses with much improved tolerability.
I will talk about that in a few minutes but we have always had good insight into being able to maintain a response by lowered in doses and classic introduction format but now looking at lower starting doses, either 60 milligrams or 40 milligrams, provides much better overall tolerability and very good activity as well.
So we talk about that in a few minutes but these lower, more tolerated doses provide certainly an opportunity for a variety of other earlier lines of therapy as well as different combination approaches in prostate cancer and other tumor types.
So, here is a broad view of cabo’s activity across multiple tumor types, again we have done a variety of different Phase II trials, and most notably our randomized discontinuation trial looking at nine different tumor types. We have seen again broad activity on the top five or six (inaudible) from the RTD trial where we have seen broad tumor shrinkage and good progression-free survival and a variant cancer melanoma, HCC, others to give you a real sense of the breadth and depth of activity with cabo across multiple different tumor types. Certainly prostate cancer has been our main focus over the last 18 months or so but I think it's clear that we have seen this activity now in a broad set of patients; we have evaluated cabo in more than 1500 patient’s to-date, 1200 or so outside of CRPC.
So, our database here is certainly growing very, very rapidly to understand the depth and breadth of activity that we have with cabo in these different tumor types.
The most advanced is medullary thyroid cancer or MTC, this is a tumor type that we found to be sensitive to cabo early in its Phase I development. We did about a 35 patients MTC expansion cohort in Phase I, about 90% of those patients show tumor shrinkage, our RECIST confirm response rate was around 30%, we ran a pivotal trial in MTC that read out at the end of last year.
Saw very promising top-line data, has a ratio of 0.28, so very strong support of activity for cabo in this regard looking at progression-free survival. That was an approximate three-fold enhancement for PFS in the cabo arm over the control placebo arm that went to 7.2 months of extension to PFS.
So, very strong signal in this tumor type, we plan to file for this indication as our first filing for cabozantinib. We had a in the DA meeting in December and initiated a role of filling of plants to have that completed in the first half of 2012 and then move that forward.
So and that’s a main priority for us going forward. As we speak today, I am certainly would hopefully be our first approval sometime end of ’12, early ’13 if all goes as planned. Now again a broad activity of cabo something that we are looking in very closely, we have had the opportunity to present a number of different updates over the last three or so months at the end of ’11 and early ’12 looking at different tumor types from the RTD trial as well as other tumor types.
This slide is control of the letter falls from those four different two indications that we studied to-date including hepatoma, liver cancer, renal cell carcinoma, metastatic breast cancer and differentiated thyroid cancer.
And I think what constructed here again is this is a lot of data but I will make a couple of high level summaries here. First you can see in these waterfalls which look at the best tumor response for our patients in those trials. Most of these patients have their bar going down which means they had these patients had tumor shrinkage and their best response, the inflection point is near the left if you will, so majority of these patients feel tumor shrinkage.
As you can also see, we see relatively good activity and consistent activity in those early stage patients and late stage patients, the most noticeably being the RCC patient population in the top right hand corner where you can see patients who had one line of therapy in blue or two to four or more than four in yellow or purple, yellow or orange. All had good tumor shrinkage, our response right here was close to 30%, our median PFS and relatively small population so we supply here was around 14.5 months.
So, real strong signal in a very late stage, highly refractory population. Similar level of activity in DTC below that all those patients had tumor shrinkage, our objective response right here was close to 50%, so again very strong level of activity. So really reinforcing the idea of that cabo was to do in addition of (inaudible) has very strong any tumor activity both in early and late life of therapy.
We have in terms of the next data update, we will have, we have submitted nine different abstracts to the ASCO Annual Meeting that will take place in June, here back on what’s accepted in the mid-March time frame so that would then help us frame how then we will present the next level of data in terms of this maturing data sets coming out in this summer.
So, we have got prostate cancer was our (inaudible) do in a few minutes, we are going to work, planning to work with CTEP at the NCI to help expand our experience and our knowledge of cabo and these other tumor types shortly. We signed a CRADA with CTEP and the NCI to be able to broadly really investigate the actions of cabo across the variety of different tumor types. We have received a variety of proposals from different investigators that we are evaluating right now.
This is a very efficient way for us to be able to focus our internal activities on prostate cancer while we have to been with the NCI to help us explore the wide variety of different tumor types that are available. This is a very financially attractive way to go as well; we spend a very small amount of money for trial here and then can really gain a large body of information from these trials as we move forward
Again we have received a variety of different proposals from investigators, only few of those now we have already prioritized two, one of the single agent study in bladder cancer which has again very strong biology implicating both VEGF and MET as well as a first combination study of cabozantinib with Taxotere in CRP.
So, again the whole focus here is to be able to do a variety of different new trials, either signal searching phase, ones are randomized Phase IIs to help us prioritize then what goes next in terms of pivotal trials as we again try to build value with cabo for both patients and shareholders.
Okay, so now let’s move to prostate cancer, as many of you know prostate cancer is very important and unique type of cancer and many with advance metastatic disease. Prostate cancer is unique and that building metastasis are the pre-dominant form of metastatic disease in this tumor type. These metastatic lesions are often off the osteoblastic in nature meaning that the cell type that produces new bone is hyper activated and you perform new mechanically compromised bone that is very likely to fracture or cause pain or lead to spinal cord compression and I think as it has been said by KOLs with advance prostate cancer often die an awful death and their morbidity and ultimate mortality is really defined by their bone disease.
So, really important medical need, I think prostate cancer is certainly is the most prominent here but many other tumor types also have the involvement bone. What’s been said over the years is that when they become resistant to deprivation therapy and then become metastatic. Their average survival is between 18 and 24 months. So relatively short time course for survival, what’s being shown is that bone pain a higher alkaline phosphatase, ALP which is a biomarker to osteoblastic activity as well as lower hemoglobin all associate with shorter survival time.
What’s interesting for us is that cabo will cures the impact those three individual parameters; individually in such a way that we think we can actually have an impact on not only pain both can respond but also potential on survival.
So, we talk about that some more in few minutes, again from a commercial point of view, this is certainly a very important area, certainly being a lot of success here over the last several years. It is becoming increasingly crowded and evolving landscape with different therapies they are post-chemo potentially pre-chemo as well.
I think our goal here is to take the unique clinical profile with cabo and again convert that into commercial differentiation, cabo is unique in this regards not only for providing enhanced progression-free survival and we have seen that now in several tumor types and MTC being one but also from the RTD and of course we had in ASCO and CRPC but also in reducing pain very rapidly in reducing or discontinuing narcotics again using the ability for a bone scan response to almost predict activity. So we have variety of different unique features with cabozantinib that we hope to then further allude it and validate in pivotal trials but to ultimately build commercial differentiation.
We are not going to be first in the area of prostate cancer with cabozantinib and that would be second or third the variety of pivotal trials for competing compounds for going or ongoing but first we found first (inaudible) about a year and half ago but we think we are different and ultimately could be better relatively to how these disease progresses and how it impacts patients clinically stage and ultimately their ability to advance with disease. Okay in terms of what’s happening here, we have seen with a variety of clinical biomarker work very strong signal of activity across the three different cell types that draw the development and the maintenance of metastatic bone lesions.
I think cabo is unique in that regard; it's the first compound that shows activity against osteoblasts, osteoblasts and tumor cells, certainly other compounds purpose and single individual cell types here. Cabo is the first that shows simultaneous activity at then regulating these three different cell types so very I think attractive way to rationalize this happening and this is all based upon clinical data that we have been able to generate to-date over the last 18 months.
So very clear activity on certainly in tumor cells, looking at tumor shrinkage in both a variety of different tissues as well as looking at the metastatic bone lesions resolve. So, very clear activity in terms of how cabo is working from a clinical point of view at the cellular level in these different patients.
So we have articulated a very I think very broad pivotal trial program to again establish clinical differentiation that can lead to commercial differentiation in the prostate cancer setting, throughout on our overall survival called COMET-1 formerly known as a 307 trial to look at extending rest in patients who progressed and either on docetaxel and abiraterone or Medivation 3100, we are finalizing the details here and planning to start these trial in the first half of 2012.
We have a pain palliation trial that was initiated in December of 2011 and the same population looking to improve pain, reduce narcotics as well as tracking by bone scan response in patients in the same population that was initiated. We expect to have most of our sites up in the first half of 2011. The rationale here again as I mentioned before, pretty straight forward looking at cabo to be able to continue to improve the median PFS that we have seen in the RTD trial.
It has a good impact on median while reducing pain and then CTC. So all factors that then correlate now with a lower level of overall survival. We have some data in November and the EORTC Meeting. It was focused on a non-randomized extension cohort, we were able to amend the RTD protocol to look at a new set of patients pushed Taxotere that had moderate assisted (ph) to your pain on the brief pain inventory field or the BPL field had a pain scale of four or more. The series of snapshot of the first 29 patients looking at their best pain reduction in the waterfall.
You can see that the vast majority of these patients all had pain reduction as their best response about half of these patients had a pain reduction that was about 30% or more which is a cut for an objective pain response and what’s interesting is to notice that these pain reduction happened very quickly, often we saw pain reduction after three weeks of dosing at the first time point that we looked for the pain response.
So a very rapid onset of action which is certainly given from a patient point of view, again as half of the patients had a durable pain response at week six and around week 12, about 60% of patients had a decrease in their narcotics and maybe most importantly about 25% of patients actually discontinued their narcotics completely. Which is a very unique finding, there is very little sure on the ability other compounds in this space to actually lead to a discontinuation of narcotics.
We have talked to a lot of KOLs and they have confirmed this is a relatively rare event with other kinds of compound. So again, really speaking to the potential activity of cabo in the space and looking at resolving metastatic bone disease by targeting both the tumor and the key bone (inaudible) causing them to become less active and then leaving to a decrease in pain.
So very good level of encouraging early activity and one that we hope to continue to reinforce and understand with the pivotal trial plan that we talked about few months ago. So, I will wrap up briefly with this slide, again we are company focused on cabozantinib, we have focused all of our activities here for the last 18 months or so. We have completely restructured the company around cabo stopped the vast majority of other activities both in discovery and development so we can focus, have our complete focus beyond cabo in building value for patients.
Shareholders, I have this slide to remind that we have a number of other important compounds in the hands of very capable and expert partners in big pharma and big biotech pursuing a variety of other indications. Most notably is our MET inhibitor that’s been developed by Genentech Prous XL-508 (ph) looking at different combinations either with Zelboraf, melanoma or their tyrosine kinase inhibitors GDC 941.
We have our own PI3K inhibitors with Sanofi, XL-147 and 765 in a variety of Phase II trials. We have a second generation dual MET and VEGF inhibitor, for XL-880 with GSK also in a variety of Phase II trials and then our hedge-hog antagonist XL-139 moving forward BMS.
So, these are compounds that are advancing with other pharma and biotech partners. We are not involving that development, we are not paying any of the development cost but we certainly have an opportunity to sharing the upside in terms of both milestones and potential growth.
So exciting data coming out of this hopefully in the near term, but I think it reinforces the value proposition for the company and for Exelixis certainly we are focused on cabo but have a lot of other irons in fire with other compounds that we even moving forward with other partners.
So with that I will end, just remind you that again we are focused on cabo. It's our certainly very compounded, very unique clinical profile which provides an opportunity or very strong clinical and commercial differentiation that’s the key message for today. The positive data from our MCC pivotal trial call exam, I think really underscores the promising any tumor activity that we have seen to-date with.
The compound certainly, lots more is going on and just in QC but certainly that’s certainly the first potential filing we have. The pivotal trial plan in prostate cancer has been certainly strengthen by our regulatory discussions and is ongoing as we speak. Lots of news flow this year, again expect to have a strong presence at ASCO and beyond in terms of new data and prostate cancer other tumor types and again we are in a pretty good spot financially, had a small fund raising a few weeks ago which has given us more flexibility and more optionality to monetize cabo and other aspects as we believe is best for the company, for shareholder.
So, I will stop there and look forward to taking the questions in the break outs. Thank you.
[No presentation session for this event]
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