MacroGenics Inc (MGNX) 2014 Q2 法說會逐字稿

Good afternoon. We will begin the MacroGenics second-quarter conference call in just a moment. (Operator Instructions) At this point, I will turn the call over to James Karrels, Chief Financial Officer of MacroGenics. Your line is now opened.

Thank you, operator. Good afternoon and welcome to MacroGenics's conference call to discuss our second-quarter 2014 financial and operational results. For anyone who has not had a chance to review our results, we issued a press release this afternoon outlining today's announcement, which is available under the investors tab on our website at www.macrogenics.com.

You can also listen to this conference call via webcast on our website and it will be archived there for 30 days, beginning approximately 2 hours after the call is completed.

I would like to remind listeners that we will make forward-looking statements in today's call. Therefore, I would like to also remind you that today's discussion will include statements about the Company's future expectations, plans, and prospects that constitute forward-looking statements for purposes of the Safe Harbor provision under the Private Securities and Litigation Reform Act of 1995.

Actual results may differ materially from those indicated by these forward-looking statements as a result of various important factors, including those discussed in the risk factors section of our annual report on Form 10-K, filed with the SEC on March 20, 2014.

In addition, any forward-looking statements represent our views only as of today and should not be relied upon as representing our views as of any subsequent date. While we may elect to update these forward-looking at some point in the future, we specifically disclaim any obligation to do so, even if our views change.

Now I would like to turn the call over to Dr. Scott Koenig, MacroGenics's President and Chief Executive Officer.

Thank you, Jim. I would like to welcome everyone participating via conference call and webcast today. Thank you all for joining us. We are very pleased that during the second quarter, we continued to accomplish key objectives that we set for MacroGenics to achieve in 2014 and to make contributions in the emerging field of immuno-oncology. This includes advancing our first DART into the clinic and submitting and clearing the IND for our second DART with the FDA.

During the second quarter, we also announced the option agreement we entered into with Takeda Pharmaceutical Company for the development and commercialization of MGD010, a DART molecule for the treatment of autoimmune diseases.

For this call, Jim will give a brief recap of our financial results and then I will review our second-quarter accomplishments in more detail and provide an update on plans for the remainder of 2014. After our prepared remarks, we will open up the call for a question-and-answer session.

With that, I'll hand it over to Jim.

Thanks, Scott. This afternoon, we reported financial results in line with our expectations. Briefly, as we described in our release, MacroGenics had research and development expenses of $17.3 million for the quarter ended June 30, 2014, compared to $11 million for the quarter ended June 30, 2014.

This increase is related to the advancement of programs into later stage clinical trials as well as the addition of new product candidates to our pipeline and is consistent with comments made on our earlier conference calls this year.

We had general and administrative expenses of $4.1 million for the quarter ended June 30, 2014, compared to $1.5 million for the quarter ended June 30, 2013. We recorded total revenues consisting primarily of revenue from collaborative research of $9.2 million for the quarter ended June 30, 2014, compared to $12.3 million for the quarter ended June 30, 2013.

Collaborative research revenue includes the recognition of deferred revenue from payments received in previous periods as well as payments received during the year.

For the quarter ended June 30, 2014, we had a net operating loss of $12.3 million compared to a net operating loss of $0.3 million for the quarter ended June 30, 2013. Our cash and cash equivalents as of June 30, 2014, were $194 million compared to $116.5 million as of December 31, 2013.

Based on these cash balances and our current operating plan, we continue to expect that our current cash and cash equivalents, combined with anticipated nonequity funding from strategic collaborations, will fund the Company's operations into 2017.

With that, I will hand the call back to Scott.

Thanks, Jim. As Jim mentioned, in the second quarter, we extended our track record of advancing our portfolio product candidates, both those fully owned by MacroGenics and those being developed in partnership with our collaborators.

Further, we strengthened our balance sheet with additional payments under our existing corporate partnerships in addition to our recently announced collaboration with Takeda.

As many of you know, every product candidate in our portfolio was designed for a specific therapeutic application, using our proprietary antibody technologies. These technologies include our Fc Optimization platform, which enhances the body's immune system to mediate the killing of cancer cells through antibody-dependent cellular cytotoxicity, or ADCC.

Our dual affinity retargeting, or DART platform, which enables the targeting of multiple antigens or cells by using a single molecule with an antivirite structure and our cancer stem-like cell platform, which provides a unique discovery tool to identify cancer targets shared both by tumor-initiating cells and the differentiated cancer cells derived from them.

Through the successful integration of these platforms into our product development efforts, we remain on track to initiate clinical developments of additional product candidates, such that we will have a total of six programs within our proprietary immuno-oncology portfolio by the end of 2015.

Our most advanced product candidate is margetuximab, a monoclonal antibody engineered using our Fc Optimization technology to target a broader range of HER2 expressing tumors than current HER2 therapies. We have now completed the enrollment of three Phase 1 intermittent dosing cohorts that explore dosing every three weeks at doses up to 18 milligrams per kilogram in various tumor types.

Margetuximab continues to exhibit a favorable safety profile and to display evidence of single-agent activity in refractory HER2-positive cancer patients. We have previously indicated plans to initiate pivotal trials and certain indications in patients with cancers with HER2 gene amplification by FISH and with the highest levels of HER2 expression by IHC.

And to that end, our planning is underway for a Phase 3 study in patients with HER2-positive gastroesophageal cancers who have progressed after standard first-line and second-line therapy.

In addition to developing margetuximab in our refractory patient population, we are also looking to expand the potential market for margetuximab therapy to include subpopulations which currently do not receive anti-HER2 therapies. We continue to enroll our Phase 2a study in patients with metastatic breast cancer whose tumors exhibit lower expression of the HER2 protein and lack evidence of HER2 gene amplification by FISH.

As you may recall, this is a two segment study and we will only advance to the second segment if we have a response rate of 10% or better in the first segment. Timing wise, it is taking longer to recruit patients than we had originally anticipated, so we are adding additional clinical sites, which may delay the completion of enrollment beyond 2014.

Our second FC-optimized monoclonal antibody in the clinic is MGA271, which targets V7H3, a member of the V7 family of molecules involved in immune regulation. Given the high level of V7H3 expression on many cell tumor types, we believe that MGA271 has more potential and is currently positioned to be a first-in-class therapeutic agent against this target.

We expect to complete enrollment of the first three dose expansion cohorts of a Phase 1 clinical study of MGA271 by the end of the year. We also plan to initiate additional monotherapy expansion cohorts in the coming months and also plan to initiate additional trials that investigate MGA271 in combination with other therapies for certain tumor types.

Shifting now to our DART technology, our approach provides unique advantages over other methods used to create bi-specific or multi-specific molecules. Further, we believe that this platform may afford considerable flexibility in developing combination immunotherapy approaches for cancer and autoimmune disease.

Accordingly, several large pharmaceutical and biotech companies have recognized the versatility and potential of our DART platform and have partnered with us to utilize this technology. Our first DART molecule to enter the clinic is MGD006, a bi-specific molecule that binds to both CD123 and CD3.

CD123, which is the interleukin-3 receptor alpha chain, is expressed on leukemia and leukemic stem cells, but at very low levels, if at all, on normal hematopoietic stem cells. CD3 is expressed on T cells.

MGD006 is specifically designed to engage these two targets by binding to CD3 on T-cells and activating them to kill CD123-expressing leukemic cells, which we believe is an ideal illustration of the utility of our DART platform.

MGD006 is part of an option-based regional collaboration with Servier. They exercised their option in February 2014 to obtain an exclusive license to develop and commercialize MGD006 in certain territories. MacroGenics retains development and commercialization rights in North America, Japan, Korea, and in India.

During the second quarter of 2014, we dosed the first patient in a Phase 1 clinical trial of MGD006 in patients with acute myeloid leukemia. The initiation of clinical trials for MGD006 was a key corporate objective for MacroGenics this year, but also one that we believe is an important milestone for the DART platform itself.

In May, we were very pleased to announce that we entered into an agreement with Takeda Pharmaceutical Company for the development and commercialization of MGD010, a DART molecule that simultaneously targets CD32B and CD79B, two B-cell surface proteins.

MGD010 is being developed for the treatment of autoimmune diseases. As part of the agreement, we received a $15 million offer on payment. We are also eligible to receive an option exercise fee that, when combined with an early development milestone, would total an additional $18 million.

Assuming successful development and commercialization of MGD010, we could receive up to an additional $468.5 million in milestone payments and double-digit royalties on any global net sales. We have the option to co-promote MGD010 in the United States and may participate in funding late stage development of the program in exchange for a share of North American profits.

In addition to our progress with MGD006 and MGD010, I would like to update you on MGD007, a DART molecule that recognizes both the glycoprotein A33 antigen, or GPA33, and CD3. GPA33 is expressed on over 95% of primary metastatic human colorectal cancers, including cancer stem cells, which are thought to be responsible for tumor recurrence and metastasis. The primary mechanism of action of MGD007 is its ability to redirect T-cells via their CD3 component to kill GPA33-expressing colon cancer cells.

Just a few weeks ago, we also announced that our IND application was cleared by the FDA and we are now planning to initiate a Phase 1 study trial for MGD007 in patients with colorectal cancer later this year. The clearance of our IND also triggered a milestone payment of $5 million from Servier.

I hope that this overview provides everyone with an understanding of the clinical, preclinical, and business development opportunities that MacroGenics's antibody technology platforms have generated and the significant activity arising from those opportunities.

With that, I would like to conclude my formal remarks and open up the call for questions. Operator?

(Operator Instructions) Michael Schmidt, Leerink.

Could you just comment on margetuximab, regarding the Phase 2a study in breast cancer? Why does it take so long to enroll the study?

Thank you very much for the question. I appreciate that, Michael. So when we set out to enroll for this study, we relied on published literature in terms of looking at the incidence of this expression pattern in patients with breast cancer.

These, as you know, are typically patients who are deemed HER2 negative. The literature had clearly documented that when looking at any patient with any degree of IHC positivity, we would -- we're expecting that two-thirds or more of those patients would have expression of HER2 at the 2 plus level without gene amplification.

When we actually did our analysis -- and in fact, we've screened over 100 patients. The rate of 2-plus expression was lower than previously reported. And so therefore, we underestimated the time in terms of recruiting this particular population.

We in fact found approximately two-thirds of the patients were more at the 1-plus level rather than at the 2-plus level. And this, we think, was probably the main reason that this hasn't enrolled as quickly as before.

Having said that, we have a number of patients ready to go on study. As you know, one of the requirements for treatments with margetuximab in this population is the requirement that these progress on other previous therapies. And so until that happens, we can't -- the patients can't be enrolled in this trial.

We have a large number of patients who are ready to go for this study, but they have to progress on current treatment. So rather than prolong this and keep the number of sites we currently have, we made a decision that we would like to complete this study and we made a decision to seek out additional centers that could also participate in the study. And that, we believe, is the main reason here. Nothing more than that.

Yes. Okay. And on MGA271, when do you think you will be able to present first clinical data on that program?

So Michael, as we've discussed before, as you know quite well, we are in this Phase 1b expansion cohort in three distinct populations -- 15 patients with melanoma, 15 patients with prostate cancer, and then 15 patients with a combination of other tumors expressing V7H3, of which no more than five would be ever a given tumor type.

The expectations, as we indicated today, is that we will complete enrollment of those three segments this year. And of course, we don't know how long those patients will continue on the therapy and we're hoping that they will stay on therapy quite long. And as a result, we can't have precision specifically about when we will present that data.

We've also indicated that we want to start additional monotherapy cohorts beyond that of melanoma, prostate, etc., and we have a number of monotherapy studies being planned. As I have previously indicated, one of the things that precluded us from doing more studies in a larger population earlier is that we had manufactured material at our site and did not have sufficient drug ready to be able to go to a larger number of cohorts.

Now we have that drug available. We expect to start these additional monotherapies in the next couple months. We also had a plan to combine MGA271 with other therapies and those studies are expected to start in very early in 2015.

So what I would best guide you at this point is stay tuned. We expect the enrollment of the melanoma, prostate, and third cohort done by December. We will have a better idea in terms of how many patients will be still on therapy and we can give you a little bit better guidance about describing that data with those cohorts plus additional cohorts that we plan to start this year and early next year.

Okay. And on MGD007, I guess it would be the first bi-specific antibody from your portfolio that will target a solid tumor as opposed to a hematological indication. And I was wondering whether there are special considerations on that topic or whether you would expect a similar -- whether there is no difference, really, whether -- scientifically, whether you will target a solid versus a liquid with a bi-specific antibody.

So from a strategic standpoint, we will get this platform being uniformly able to target both hematological liquid tumors as well as solid tumors. And so you should expect, in addition to the ones we described, future trials will include both types -- tumor types or tumor types that fall in both categories.

We -- our preclinical data, our toxicology data, our studies pre-clinically have all shown a very potent activity of this molecule. And as I have spoken previously, based on both the pharmacodynamic, pharmacokinetics, as well as the activity profile, we expect, depending on the tumor type and obviously depending on the specific molecule designed and the targeted antigen, the dosing range for this molecule could be in the range of nanograms per kilogram to micrograms per kilogram. So again, very low dose is required, both in solid tumors as well as liquid tumors.

Of course, we have established what we believe is a very wide window of therapeutic responses that would give a very favorable safety profile, but obviously until we dose patients, we will not have a confirmation of that observation.

I should also note that the MGD007 will be our first DART molecule which will have the Fc domain incorporated in the bi-specific part of the molecule, which will allow us to give less frequent dosing of this molecule. And so again, this will be the first chance to explore some of the pharmacokinetics around Fc in a situation where we are targeting a solid tumor.

Yes. Did you expect differences in T-cell infiltration rates to affect the -- across different tumor types to affect the effectiveness of MGD007 or any other bi-specific antibody?

That's an excellent question. As we've begun to really understand the importance of immune-oncological approaches, particularly T-cell dependent approaches, we look back in terms of the historical responses in patients who haven't received such therapy.

And as you know, there's been some publications that have shown that patients with particular tumor types -- and a perfect example here is in colorectal cancer, that individuals, irrespective of the stage of disease, those patients who have tumors with larger numbers of infiltrating T-cells clinically had better responses.

They tend to have a longer lived and irrespective of, actually, the stage. And so I would not be surprised that in particular, histological types that have a higher infiltration of T-cells, these patients may respond better.

Having said that, the extraordinary activity of these molecules on this platform to essentially recruit any cell -- any T-cell that is circulating in the body -- and obviously that will traverse also into tissues -- could potentially be recruited.

And so some of the subset of these cells may also be actually antigen specific, so in addition to expanding populations that do not have cognate recognition of the particular target, you may actually be able to actually sensitize more antigen specific T-cells. We have not shown that.

This is obviously an objective of future studies, both preclinically and clinically. But if we were able to achieve that, that would be obviously a very good opportunity for a long-lived response in these patients.

Steve Byrne, Bank of America.

Yes, I'd like to continue down that same path that Michael brought up and that is do you have any evidence that when the CD3 is one of the binding domains, that you can effectively trigger the T-cells to be cytotoxic, even if you have the checkpoint inhibitors are up-regulated, either on the tumor or on the T-cell? Do you have evidence that it will still work?

The answer is -- thank you very much, Steve. That's a terrific question. And so the answer is absolutely yes. In fact, particularly for MGD007, we have the advantage here that there are small amounts of GPA33 expressed on normal mucosal tissue.

And as a result, if you put the extreme of dosing of this molecule, we have been able to number one, show that we can activate T-cells. And actually, they will be recruited to those areas of the normal mucosa and actually kill those parts of mucosa.

Of course, we have established quite nicely in our preclinical studies, a very nice, broad safety window in which we can get antitumor responses in the absence of responses in normal tissue, so we have objective, in-life evidence that we can do that in monkeys.

We have objective evidence also in reconstituted mice, so if you take immunodeficient mice and reconstitute it with human T-cells and you let a tumor grow subcutaneously, intradermally, and you then at a second site give your bi-specific molecule, we have now a number of cases where we see a beautiful recruitment of the T-cells, specifically into the tumor site, and destroying those tumors. That was obviously the basis for going ahead with a lot of these molecules.

With regard to the question about immune checkpoints, that was a question we addressed quite directly. And so when dosing monkeys with constant infusions over many, many weeks, over a month of dosing of these animals, where we can actually detect up-regulation of the markers of particular immune checkpoints.

When you take out those T-cells and look for cytotoxic activity against a target ex-vivo, and you actually compare it to T-cells that are naive and had not been exposed to the DART molecule, there was exact equivalent amount of effector cell killing -- T-cell killing of those targets.

One should be aware that if one looks at the hierarchy of the inhibitory responses that T-cells will demonstrate, loss of cytotoxic function is virtually the last thing to go. And so despite the fact that many of these T-cells may have up-regulation of specific checkpoint markers, they tend, almost in all cases, to be very effective killers. And therefore, we think that our technology would serve the treatment of cancers very well in this setting.

And can you comment on what kind of combination studies you are considering with MGA271? Is it more along the lines of other targeted drugs or the various immunotherapy drugs?

That's an excellent question, Steve. And so as you know -- as we've spoken before, we're sort of looking as a much broader question. It's obviously people gravitate and say, well, which immune checkpoint do you want to add to MGA271?

And we are also looking at that pathway, but we're not looking at this quite narrowly. We are looking at the opportunity now to complement both in terms of alternative targets. Other biological molecules, their cell types and mechanisms, and even in some cases, small molecules that may have chemotherapeutic effects.

And so, again, we have mapped out a strategy in multiple different tumor types where a combination of these different therapeutics, we believe, would work quite nicely with MGA271 and that's what we would like to test in 2015.

And on the margetuximab study that's in the metastatic breast, do you think that you could have efficacy, even with the HER2 1-plus non-amplified tumors?

That's the purpose of the study. And so just to give you a little bit more granularity of the -- some changes we have made here is that in addition to 2-plus patients, we are also utilizing -- it's beyond IHC, the [HER mark] test, which will identify the highest level expressing 1-plus patients in the population.

So we will include patients that are both 1-plus positive and 2-plus positive in this study and that will be part of the plan going forward.

Stephen Willey, Stifel.

On the MGA271 expansion cohort studies, these are all open label, correct?

Correct.

So I guess the next logical question would be just given some of the preparations that are being made to expand into additional tumor types and to initiate some of these combinatorial studies, is it safe to say at this point that there's some encouraging signs of activity?

Don't want to comment on specific activity profiles. Again, I believe that it's just too early to discuss. As we described in the original 26 patients on the dose escalation phase, we had -- 10 of those patients had evidence of a stable disease during that treatment.

Didn't have a full PR or CR in those cases, but these were the old criteria that had been used for, obviously, chemotherapeutic intervention and treating patients with cancer. We are going to begin adopting the more current immune criteria for treating these patients. And so we like to have a broader database to be able to prepare and present to give the best look at the activity of this molecule.

Okay. And then just with respect to the combinatorial strategy, are some of the things that you are considering, will they require you to form many -- any additional collaborations? I guess, specifically stuff that's a nonexclusive for drugs that are not yet available?

At this point, we have no specific plans of -- or need to establish a particular collaboration to prepare combinations of drugs that we want to take into the clinic. Having said that, you can imagine a number of the companies that are engaged in this space have expressed interest to work with us on this molecule.

And again, we will make some decisions going forward if that is the best pathway forward. But at this point, we have not planned to establish a specific collaboration to look at combinations in molecules.

Okay. And then I guess just with respect to the guidance to having six oncology-focused compounds in development by the end of next year, I guess my elementary math skills get me to four now and presumably the next -- the next two are going to be programs that are DARTs?

Correct.

Okay. And then maybe just one quick housekeeping question for Jim. How should we think about the amortization of the Takeda upfront? Does that going to the licensing option fee?

Hi, Steve. Yes, some of it does. I don't have the exact amortization period at my fingertips, but a portion of it will be amortized going forward.

Okay. Thank you.

Christopher Marai, Oppenheimer.

Just with respect to MGD006, I know in the literature it had been highlighted that there had been some potential bone marrow toxicity problems with prior CD123 targeted T-cell therapy. I'm wondering if you had seen this in any of your preclinical models and -- or if that finding was just an artifact of the model used in the study? Thanks.

Thanks, Chris. Excellent question. If I recall the study that you're describing, I think that one was with one of the cars, if I'm not mistaken.

Right.

Okay. Yes, no, we haven't seen any issues with data. And obviously, we did very extensive testing in primates, which have a similar distribution pattern on hematologic cell types, and so that turned out not to be a problem.

We haven't seen it in the mouse model systems, which obviously, there's less cross-reactivity. But it's certainly not in the monkeys, so it may have been peculiar to the cars, but obviously, this is something we will monitor going forward.

Okay, great. And then when do you think we're going to first see data for MGD006?

That's the question that I would love to be able to answer. As you know, we've guided people that the FDA -- and I'm sure the European regulatory agencies -- are very cognizant of the potential side effect profiles of certain immuno-oncology drugs.

And as a result, the guidance is to go slow at first. And essentially, these are single patient dosing on sort of a monthly basis to go to the next dose, so it's going to be slow. And we are hoping to be able to give you a better guidance sort of in the middle of next year, both on MGD006 and MGD007 in terms of timing.

Great. And then just lastly, the next DARTs that you're going to bring into the clinic here, are those also going to include your Fc domain? And then how does that impact manufacturing relative to MGD006? Thanks.

So -- thanks for that question. Yes, both DARTs that we intend to bring into the clinic will contain the Fc domain. We -- in fact, our -- have and are continuing to plan to manufacture those lots for those new product opportunities for the clinical trials next year, so that will be done in-house.

As you recall, part of the proceeds for the follow-on offering earlier this year were to expand our production facility in MacroGenics. So we are in the engineering phase -- planning phase of that. We will start to turn over the site for the larger tanks.

So we will be actually be able to produce at 1000 liters scale and we expect this will increase our productivity two- to threefold shortly thereafter.

All right, thank you.

David Nierengarten, Wedbush.

Since everybody asked questions on all the DARTs, I will go back to margetuximab. I actually -- when you talk about continuing to see responses, could you -- is the response rate similar to what we've already seen or could you give us any more detail on any responses seen in the dose cohorts that you've treated?

Thanks, David. As we indicated, we finished these intermittent dosing regimens, which were -- patients were receiving every three weeks either 10 milligrams per kilogram, 15 milligrams per kilogram, or 18 milligrams per kilogram. And -- on a weekly basis -- on a Q3 weekly basis.

And we are very, very encouraged. There are a lot of patients still on therapy. I know we have at least one of the patients who is in the 10 milligrams per kilogram dose is now still on therapy -- over 15 months of therapy -- and is doing exceptionally well.

I asked the folks to take a look at this data closely and to get a better sense of are we seeing even a better response in this intermittent cohort than the earlier patients. And I think it's just too early to come to that conclusion.

There's obviously different mixtures of tumor types. And so it's just too early to give you that, but it's extremely encouraging. Extremely encouraging.

Great, thanks.

(Operator Instructions) Debjit Chattopadhyay, ROTH Capital Partners.

Firstly on margetuximab, as you planned for the MAGENTA trial, given the responses that you are seeing with the intermittent dosing, up to -- it would be 18 milligrams per kilogram cohort, would you reconsider the dosing for -- in the gastrocancer setting?

And also, does it have any implications for the lower HER2-expressing breast cancer patients? Could you go higher with an intermittent dosing in the Phase 2b trials -- Phase 2a trial?

Debjit, those are great questions. And you know, this is a topic of conversation ongoing right now, giving the very favorable pharmacokinetics and responses we're seeing in intermittent dosing population.

And so we are having conversations now with the principal investigators and others who are planning to participate in the study. We haven't made a decision about that, but that's certainly a topic under discussion.

With regard to the lower HER2 expressing -- again, we want to get at least this first cohort done on the 6 milligrams per kilogram weekly, but that would be certainly a additional topic of conversation that we need to address once we have a fuller analysis of the current Phase 1 study, when that's complete. So that is something we might go back to if we don't -- if this provides an opportunity to increase the response rate.

Then on the DART platform and the T-cell infiltration question, is there a biomarker that you can look at to maybe prospectively identify patients or it's going to be drawn down through the tumor samples that you collected to kind of predict if these patients with higher T-cell responses or T-cell infiltration would respond better?

That's something that we are not going to do prospectively in the Phase 1 study. We will obviously capture that data. One of the key questions will be to understand both the profile of cells at the time of diagnosis as well as the profile of particular T-cells and other inflammatory cells that we'll be infiltrating into the tumors.

And for current trials and for future trials, we expect to obtain biopsy specimens to be able to begin to analyze that. We will also obviously -- we're certainly obviously monitoring circulating T-cells as well to look at changes of activation markers. And so we will gather that information and hope that will give us some better guidance in terms of a preferred population that will -- might best response.

And one last question. In terms of memory that you could potentially creating, have you seen any impact on re-challenge models in your mouse models?

We haven't done any re-challenge models. Obviously, again, as you know, these models that we've been focused on are using xenograft models in immunodeficient animals and they -- those aren't usually the best models for re-challenging.

Obviously, the circulating T-cells really have finite periods of time when they last. Some of the re-challenge models are best tested in these mouse [enginaic] systems, but certainly, it's something that we could consider in future studies.

Thank you so much and congratulations.

Thank you. This concludes the question-and-answer session. I will now turn the call back to Dr. Koenig for closing comments.

I would just like to thank everyone again for joining us and let you know that we look forward to updating you on each of the programs that we discussed today as we continue to make progress in 2014. Thanks again. Bye.

Ladies and gentlemen, thank you for participating in today's conference. This does conclude today's program. You may all disconnect. Everyone have a wonderful day.