TRACON Pharmaceuticals Inc (TCON) 2015 Q4 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the TRACON Pharmaceuticals Fourth Quarter 2015 Earnings Conference Call.

At this time, all callers are on a listen-only mode. After the speakers' prepared remarks, we will conduct a question-and-answer session and instructions will be given at that time.

During today's call, we will be making certain forward-looking statements including statements regarding expected timing of clinical trials and results, regulatory activities, future expenses, and cash runway and our developmental plans and strategy. These statements are subject to various risks that are described in our filings made with the Securities and Exchange Commission including our annual report on Form 10-K for the year ended December 31, 2014, subsequent quarterly report on Form 10-Q and our current reports on Form 8-K. You are cautioned not to place under reliance on these forward-looking statements, and we disclaim any obligations to such statements.

Now, I would like to turn the call over to Dr. Charles Theuer, President and CEO of TRACON Pharmaceuticals. Dr. Theuer?

Good afternoon and thank you for joining us today for TRACON's Fourth Quarter and Year-End 2015 Financial Results and Business Update Conference Call. I will begin with an update on our pipeline and recent activities. Following that, our Chief Financial Officer, Patricia Bitar, will review our fourth quarter and year-end financial results. Finally, we will conclude by taking questions from call participants.

The strong momentum across our entire pipeline continued into the fourth quarter of 2015 and early first quarter of 2016. We presented positive data on TRC105, our Phase II endoglin antibody, and announced initiation of Phase II development for a small molecule product candidate, TRC102. In addition, in January, we announced orphan drug designation by the FDA for TRC105 and soft tissue sarcoma, an indication that includes angiosarcoma where we expect to initiate a pivotal Phase III trial this year.

Let's begin with a detailed update on TRC105. While our product candidates have broad potential, TRACON has initially focused on orphan drug indications in order to potentially provide more rapid paths to approval and commercialization. Importantly, we have seen encouraging signals in patients with both angiosarcoma and choriocarcinoma, and we intend to initiate global studies in both these indication in 2016 that may be registration enabling. Phase II trials in mid-sized market indications are ongoing as well, and data are expected in 2016 that could enable further Phase III development in 2017. We also expect to initiate enrollment in certain Phase I/II trials in large market indications in 2016 in order to maximize the commercial potential of the TRC105 oncology franchise.

In November, Dr. Steven Attia of the Mayo Clinic reported positive clinical trial results for TRC105 combination therapy in soft tissue sarcoma at the Connective Tissue Oncology Society or CTOS 2015 Annual Meeting. The presentation reviewed the Phase I portion of the Phase I/II study of TRC105 in combination with Votrient in patients with advanced soft tissue sarcomas including angiosarcoma.

A total of five patients with angiosarcoma, a sarcoma subtype known to express high levels of endoglin; have been evaluated for response in the Phase I/II study. All of five patients have radiographic tumor reductions, and median progression-free survival, or PFS, for the subgroup is at least 9.3 months. Notably, two patients demonstrated ongoing durable complete responses by RECIST and remain on study for 45 and 75 weeks at this time. In comparison, no complete responses were reported in the 246 patients treated with Votrient in its pivotal Phase III PALETTE trial.

Given the high express of endoglin in nearly every case of angiosarcoma and the activities [seen] to date in angiosarcoma patients, we intend to initiate a global Phase III trial. The trial will compare the combination of Votrient and TRC105 to Votrient alone in angiosarcoma patients. Following protocol-related discussions, we expect to have with the FDA in the first half of 2016.

Enrollment of the initial 63 planned patients was completed in the Phase II portion of the study, which was designed to evaluate the combination of TRC105 and Votrient. Top line data indicates that median PFS of 3.9 months was similar to the PFS expected for Votrient alone, a subdata from the Votrient Phase III PALETTE trial in soft tissue sarcoma. Importantly, our study was prospectively designed to stratify the primary endpoint of PFS by tumor histology and tumor endoglin expression, including an undifferentiated pleomorphic sarcoma where we have seen a durable complete response ongoing at 51 weeks of treatment.

We expect to report these important data at a major cancer meeting in the first half of 2016. If we find that tumor endoglin expression correlates with PFS, it may allow for tumor endoglin expression to be used a biomarker for enrollment into a separate Phase III trial that would include general soft tissue sarcoma patients.

We have seen a durable complete response following treatment with a combination of TRC105 and a VEGF inhibitor and a second tumor type that highly expresses endoglin as well. In September 2015, Dr. Neil Horowitz of the Dana-Farber Cancer Institute, reported a durable complete response in the first phase with choriocarcinoma treated with TRC105. The patient had refractory and metastatic choriocarcinoma and was treated with TRC105 and Avastin to a single-patient protocol. She developed a complete response at month four of treatment that is ongoing at this time, which is month 12 following trial enrollment. Subsequently, a second patient also with refractory and unresectable metastatic choriocarcinoma was treated with TRC105 and Avastin but did not respond to treatment.

The assessment of tumor endoglin expression may inform as to the disparate outcomes in these two patients. We intend to initiate a global Phase II trial with response rate at the primary endpoint in patients with choriocarcinoma and less aggressive forms of gestational trophoblastic neoplasia or GTN in the first half of 2016. We have also applied for orphan drug designation in GTN.

Patient enrollment in three other TRC105-related Phase II trials, two randomized and one open label, remains ongoing. We believe positive data from the two randomized trials would allow us to proceed with further Phase III developments. In each of these ongoing trials, TRC105 is being dosed with a combination of with an approved VEGF inhibitor and data from both randomized trials are expected in late 2016.

The first is the TRACON-sponsored Phase II randomized TRAXAR trial in patient with clear cell renal cell cancer. This study compares treatment with TRC105 and Inlyta to treatment with Inlyta alone in patients who have received one prior VEGF inhibitor. Encouraging updated data from the Phase Ib portion of the study of TRC105 and Inlyta was presented by Dr. Toni Choueiri of the Dana-Farber Cancer Institute at the Kidney Cancer Association Meeting in November. Notably, median PFS in clear cell renal cell cancer patients treated with TRC105 and Inlyta was doubled than expected with Inlyta dose as a single agent.

The second trial is the NCI-sponsored Phase II randomized trial of TRC105 and Avastin in glioblastoma that has completed enrollment and data are expected in late 2016. In hepatocellular cancer, we've initiated a multi-center Phase I/II trial with a primary endpoint of overall response rate. The goal of this study is to reproduce the robust 40% response rate reported by the NCI at ASCO 2015 in 10 patients treated at recommended safety doses of TRC105 with Nexavar for comparison. This is setting with the expected partial response rate of single agent Nexavar has historically been 2%. We believe that corroboration of the robust response rate reported by the NCI would justify the initiation of a Phase III trial comparing the combination of TRC105 and Nexavar to Nexavar alone in hepatocellular cancer.

During the fourth quarter, we also initiated a Phase I trial of TRC105 in combination with Avastin and chemotherapy for the first-line treatment of patients with lung cancer and a Phase I/II trial in patients with breast cancer. We expect patient enrollment in both trials commence in the first half of this year.

Beyond oncology, we believe there is significant opportunity for endoglin antibodies to improve treatment options for patients with wet AMD. VEGF inhibitor drugs, such as Eylea and Lucentis, are the current standards of treatments in wet AMD, and we believe they represented backbone therapy that could be complemented by our endoglin antibody.

The market opportunity here is significant as the annual sales of VEGF inhibitors for ophthalmic indications have reached $7 billion. We have partnered global rights to develop our endoglin antibody in eye disease including wet AMD with Santen. Santen is recruiting patients into a Phase I trial of DE-122, which is the ophthalmic formulation of TRC105 to assess the safety, tolerability, immunogenicity, and bioactivity of DE-122 for refractory wet AMD.

Turning now to our second product candidate, TRC102. TRC102 is a noble small molecule inhibitor of the DNA-based excision repair pathway. Activation of this pathway created resistance to alkylating and antimetabolite chemotherapeutics. And in addition, this pathway could lead to improve patient outcomes. We reported positive clinical data combining TRC102 with Fludara at ASH in 2014 and with Temodar at AACR and ASCO in 2015.

The NCI is currently enrolling a dual-arm Phase I/II trial consisting of Phase II cohort of TRC102 with Alimta in patients with mesothelioma and a Phase I cohort of TRC102 with Alimta and cisplatin in patients with solid tumors. Ultimately, we expect a total of 58 patients to enroll in this trial. In addition, a Phase II trial of TRC102 with Temodar in 66 patients with glioblastoma was recently initiated, and we expect the Phase I trial of TRC102 in combination with chemotherapy and radiation therapy in patient with lung cancer to begin in the first half of 2015.

As you can see, we remain very active on the clinical development front, and we look forward to a highly productive 2016, which will include a number of key pipeline-related milestones. We continue to achieve progress in a cost-effective manner through the TRACON clinical operations team that manages the metric trials without a significant cost or complexity associated with outsourcing to a CRO. In addition, our collaboration with the NCI allowed us to be even more active on the clinical development front with both of our clinical [stage] assets than we would be on our own.

We also continue to conduct pre-clinical studies on the use of endoglin antibodies to treat fibrosis. Pre-clinical data indicate that endoglin is a key driver of fibrosis and antibodies to endoglin have inhibited or reversed cardiac and liver fibrosis in pre-clinical models. We have designated a separate endoglin antibody, TRC205, specifically for fibrosis development, and we expect to report pre-clinical data in fibrosis at a scientific conference this year.

Our financial position remains strong. We continue to anticipate that our current cash resources will be sufficient to complete five ongoing Phase II studies of TRC105 to support manufacturing activities that once are required for regulatory approval, to initiate Phase III clinical development, to initiate additional trials of TRC105 and other large market oncology indications, and to pursue additional programs addressing important unmet medical needs including the development of endoglin antibodies for fibrosis.

Beyond our internal pipeline, we also continue to evaluate product candidates to potentially then license and intend to be opportunistic in this regard. Ideal candidates would leverage the cost effective internal clinical operation capacity at our company.

At this time, I will turn the call over to Patricia Bitar, our Chief Financial Officer, who will provide an update on our financials.

Thank you, Charles, and good afternoon, everyone. TRACON reported collaboration revenue of $1.4 million with the quarter ended December 31, 2015, and $7.9 million for the year ended December 31, 2015, compared to $1 million and $3.6 million with the comparable period to 2014. The increases were results of the Santen agreement, which we filed in March 2014 and a $3 million milestone that was triggered by Santen's filing of an IND in wet AMD in June 2015.

Total operating expenses were $12.2 million within quarter ended December 31, 2015, and $31.4 million for the year ended December 31, 2015, compared to $3.3 million and $9.8 million for the comparable period to 2014. These increases reflect higher expenses in both R&D and G&A.

Research and development expenses were $10.6 million for the quarter ended December 31, 2015, and $25.7 million for the year-ended December 31, 2015, compared with $2.6 million and $7.7 million with the comparable period of 2014. These increases were primarily the result in increased manufacturing and clinical study related expenses for TRC105 and higher personnel cost resulting from increased headcount.

General and administrative expenses were $1.7 million for the quarter ended December 31, 2015, and $5.7 million for the year ended December 31, 2015, compared to $700,000 and $2.1 million with the comparable period to 2014. These increases were primarily attributable to higher personnel cost resulting from increased headcount and increased costs associated with becoming and operating as a public company.

Our net loss was $11 million for the quarter ended December 31, 2015, and $24.4 million for the year ended December 31, 2015, compared to $2.5 million and $6.8 million with a comparable periods to 2014.

Turning to the balance sheet of December 31, 2015, our cash and cash equivalents in short-term investment totaled $52.2 million compared to $57.7 million in September 30, 2015. We expect our capital resources to be sufficient to fund our currently planned operations for at least the next 12 months. As you may have seen, we filed a Form S-3 registration statement and established an ATM facility on February 1st, the first date upon which we were eligible for shelf registration. While we do not have immediate plans to raise capital, we believe this was a sweetest step in providing financial flexibility to TRACON, and it will allow us to add opportunistically to support our development objectives and growth initiatives.

And with that, I will turn the call back over to Charles.

Thank you, Patricia. As we noted, we expect a significant number of potential value-creating milestones in the near future. These include Phase II data including updated median PFS stratified by tumor endoglin expression from our ongoing trial of TRC105 in combination with Votrient in soft tissue sarcoma patients including an angiosarcoma; full Phase I data for the ongoing NCI trial of TRC102 and Temodar; a determination of orphan drug designation in GTN; and initiation of dosing of TRC105 in trials of hepatocellular, breast, and lung cancer, as well as the initiation of dosing in additional TRC102 trial funded by the NCI.

Further, later this year, we expect randomized Phase II data as well as the initiation of trials in angiosarcoma and GTN that may be registration enabling. I look forward to providing further updates regarding our upcoming key milestones throughout 2016. I'm confident that we have the right strategy in place to deliver on our development and business plans for the benefit of patients (inaudible - microphone inaccessible).

We'd be happy to answer your questions.

(Operator Instruction)

Our first question comes from Jim Birchenough of Wells Fargo. Your line is open.

Hi, guys, and congrats on all the progress. A few questions, I guess the first one is just regards to endoglin levels and how they may correlate with response. Is this something you'll be looking at in other cancers as well like hepatocellular? I think it would be interesting to know if the 45% that responded to 105 had higher endoglin levels than, say, the 55% that didn't. Could you maybe lay that out in terms of broader evaluation of endoglin expression?

Yes. Thanks for the question, Jim. So, endoglin is always expressed on the tumor vessels, and the degree of expression on tumor vessels maybe prognostic as a separate consideration. There are certain tumors where it's directly expressed on tumor cells, and those are not the epithelial tumors quite like liver cancer, for example, but there are more than the mesenchymal tumors, including sarcoma. There are tumors like melanoma. There is certain leukemia that's an example. There are certain subsegments of myeloma, where you see densely expressed endoglin tumor cells in addition to the tumor vessels.

And those are the tumor types including choriocarcinoma, for example, where we thought we might see particularly dramatic activity. And we have done a study, for instance, in sarcoma a translational study about a multitude or archival tumor specimens where we demonstrated the dense endoglin expression, for instance, in angiosarcoma and also on certain other sarcoma subtypes that gave us the idea that certain subtypes may be more responsive especially within sarcoma than other sarcoma subtypes. I think gratifying to see angiosarcoma where you do see expression on tumor and tumor vessels in virtually every single specimen to see the level of response that we've seen in the study.

In other sarcoma subtypes, it's going to be less common in the 20% to 40% range, and those are the general sarcoma subtypes where informing with respect to patient expression may help select patients for a Phase III trial. In epithelial tumors, it is not going to be the direct tumor expression. It's going to be the expression of tumor vessels that may make the difference. So, that's kind of segregates the tumor expression versus the vessel expression in terms of predicting potential response.

Thanks for that, Charles. And then maybe just following up on TRAXAR, could you remind us in terms of powering that study, what you're expecting to see? What sort of baseline assumptions you're making for the Inlyta alone?

Sure. Yes. Fair enough, Jim. Yes.

And also whether there might be any confounding from subsequent therapies on the endpoints you're looking at?

Right. Yes. So, fair enough. So on TRAXAR, it's a randomized study, 150 patients one-to-one randomization to Inlyta single agent or Inlyta plus TRC105. And the endpoint is progression-free survival, which has the advantage that it should not be influenced by subsequent therapies and to be clear as a progression-free survival that is independently verified by central radiograph review.

It's a -- the expected PFS for Inlyta is 4.8 months, which is exactly what they achieved in their pivotal access trial in patients who received one and only one prior VEGF inhibitor. We're looking to increase that with a hazard ratio of 0.67. So we can go 4.6 months to 6.9 months and that we have 80% power to do so.

That's very helpful. And just finally, Charles, on GTN, could you maybe just break out what the opportunity there looks like if you were to get an accelerated path through approval there? What's your opportunity?

Yes. In terms of the overall opportunity in GTN, in terms of the commercial opportunity it is fortunately treated very well in most cases. It's one of the great success stories in terms of treating cancer with chemotherapy. The opportunity is to treat refractory patient population and to have two parallel, if you will, pivotal programs in place, the angiosarcoma and in parallel the GTN opportunity.

And so, I think that helps us have two potential registration pathways with orphan drug indications. That could be an advantage worth as we talk with payers. And so, the overall commercial opportunity, there's larger advantages to (inaudible) than it is in GTN, but it is still something that will help us, I think, in terms of building up enthusiasm around the program to understand that there are certain tumors that may be very responsive in this therapy where they're seeing potential for durable complete response. And I think that's an important element of the program in GTN.

Great. Thanks for taking the questions.

Thank you for the questions.

Our next question comes from the Tom Shrader of Stifel. Your line is open.

Hi. Good afternoon. Thanks for taking the questions. I had a question on the sarcoma trial. You may have said it but you added a cohort of angiosarcoma there. Didn't you -- when does that read out? And will you see that before the Phase III trial? Is that going to be part of the Phase III trial? Just remind us what's going on.

It's a great question, Tom. We did add -- so the Phase I/II trial initially was (inaudible) 81 patients which had completed enrollment. Given the activity we've seen in angiosarcoma, we have amended to enroll additional cohort of 13 patients with angiosarcoma. That is actually enrolling at this time. And those data expect to be updated midyear with the expected overall trial results.

Okay. And then -- so you don't know yet if the undifferentiated pleomorphic sarcoma patient had high endoglin levels or --

We do not -- that full interrogation of every patient enrolled in the trial will be presented at a major conference this year, expect at midyear.

Okay. And just -- it's a little vague, but if in fact you did wind up with a pivotal trial in sarcoma with endoglin expression above some staining level or whatever, what would that look like? Is there any lay of the land for what a trial would look like in terms of size and terms like that?

It's a great question. So I think with respect to -- the Phase II data is really going to inform us in terms of the Phase III design. So with respect to the Phase II trial, when we correlate PFS with endoglin expression, we'll have, I think, a baseline for what we expect to see in the Phase II trial in terms of treatment effect. And so, I think patients that don't expect them versus patients that do expect them will give us an idea that certain patients are more responsive. We'll look at the PFS in that group. We'll compare it to historical data with Votrient as a single agent to help us design the Phase III trial, if you will. And I think that's what's so important as a Phase II result. They really will inform us as to the Phase III design in terms of sample size and in terms of hazard ratio assumptions we want to make.

Okay. And then just finally, real quickly on the newest HCC trial, that's another non-randomized trial kind of repetition. What's the thought there rather than doing a randomized trial? Is it just that the standard of care is so clear? Or what's the thought there?

Yes. Our thought is we're really impressed with the NCI data, single institution data. Our thought is to verify that robust response rate in a multi-institution setting as we -- and the other thing we're doing is try and build momentum to move this into a randomized study, the next logical step. And I think the multi-center nature of the study that would verify a robust response would help create that momentum to push us into a potential pivotal randomized trial.

All right. I got it. Okay. Great. Thanks a lot, Charles.

My pleasure, Tom. Thank you.

Our next question comes from Chad Messer of Needham. Your line is open.

Great. Thanks. Thanks for taking my question, and as always, I need to write fast to keep up with all the stuff going on with you guys every quarter. Can you just remind me how the stratification of endoglin is working in that analysis?

Yes. That's a very great question, Chad. So, this really was set up in terms of the overall analysis through some translational work that was done out of Mayo Clinic and presented in 2013 at EORTC Meeting. And the stratification was to look at tumor endoglin expression and was categorized as 1, 2 or 3-plus, and that was done across seven different sarcoma subtypes. And that's exactly how we plan to do the analysis for the patients now that are enrolled in the Phase I/II trial, and then we'll look at what level of endoglin expression you think is most predictive for improved benefits and therapy and make that cut point as potentially the cut point to enroll patients into a separate general sarcoma Phase III trial.

Okay.

As I pointed out, angiosarcoma is in a different league. Angiosarcoma in that translational study over 20 specimens, the majority had 3 or 3-plus dense expression on endoglin [on] tumor. And so that in a sense is its own biomarker which is why we moved it to Phase III in angiosarcoma without the need for a companion diagnostics.

Okay. So you have the ability to kind of look at the data and look and see if there extensible sort of cut-off point. You're not pre-hypothesizing one like median high and low or something like that?

Yes. It will definitely be empiric based on the data, Chad.

Okay. And maybe this is an over simplistic way of thinking about it. But if you hypothesize that there is some reasonable effect of endoglin, in patients with some level of endoglin expression that encompasses a decent number of patients, wouldn't you rather, wouldn't you prefer to have seen the PFS be a little higher for the whole population? Or is that not the right way to think about that?

Yes. I think if single-arm trial is much more influenced by the [spike] and the nature of patient enrollment, then it will be by the exact number of patients that have endoglin tumor expression. I need to be clear. Most sarcoma patients are not going to have endoglin tumor expressions. I think that will dominate the trial in a similar way that I think if you look at breast cancer patients and treated them all with Herceptin, you probably would not see a signal either until you segregate the patient that are truly going to respond.

Okay. Understood. So there's possibly a decent signal there, but it's in a small enough portion of the patients that's being drowned [out].

Okay. My next one is on the finances. I was hoping to get a little bit of help as I think about 2016. I know you guys didn't give any formal guidance. But here is my specific problem. R&D in the fourth quarter was 10.5. That's quite a big jump. And in your remarks, you attributed that to [three-stage] manufacturing, R&D, and headcount. And I think of all of those things and you guys and your need for '16, I don't see any reason why those would go down at all, maybe even up at any day, but I guess directionally. And if I could just take that 4Q, fourth quarter, and carried it across, I, and this is just a matter of arithmetic, can't match that up with your statement that your cash is going to get you -- to roll the endpoints you stated you're [going] to get you into '17. So is there something going on in that quarter that maybe it was one time? Or is there any kind of color you could give me about where expenses go in 2016? I really think that we have really big numbers in my model because I know how passionate (inaudible) you guys are.

Right. Chad, thanks for the question. So, as you know, manufacturing antibodies is expensive and it's kind of cyclical. So we did have a lot of manufacturing-specific activities in the fourth quarter. We will continue to have some manufacturing activities in 2016.

So in terms of how you look at 2016, I would look at the fourth quarter as an indication for the 2016, for each of the quarters in 2016 year with -- obviously, it's not going to be flat. There's going to be some ups and downs.

Okay. Thank you. That's very helpful.

(Operator Instruction) Our next question is a follow-up from Jim Birchenough of Wells Fargo. Your line is open.

Hi, guys. Thanks for taking my follow-up question. I hope this is an okay question to ask. But beyond looking at endoglin expression, does it make sense to look at gene polymorphisms or mutations to see if there is some pattern that emerges from that? Or is that just something that you wouldn't expect to impact responsiveness to the drug?

Great question, Jim. Yes. For endoglin, it's more a function that the gene isn't mutated very often at all. So it's more of function of whether it's expressed on the cell versus whether it's a mutated formula receptor; so, hence, the really -- [the minerals], the chemistry is a better way to assess for potential responsive patient than a genetic sequencing-based approach.

Got you. Speaking of VEGF polymorphisms with Avastin, that seemed to be predictive of outsized responses, so I didn't know if it was the same with endoglin.

No. I think it's a great question, Jim. And I think with VEGF, that feels -- evolved as drug targeting that pathway has been approved now for over 10 years. And there may be some evolution with endoglin. But right now, I think the real basic understanding is the receptor has a normal sequence, and it's being expressed on the cell surface making it a target for therapy as opposed to a mutant receptor.

And maybe just a final question and you may or may not be able to answer it, but in terms of ASCO, it seems like you guys have the potential to share a lot of data over the course of the year. Any preview you can provide in terms of what might get submitted to ASCO?

Yes. I think the -- many of the data points we've talked about on the call, you know, full sarcoma data as an example, GTN as an example for TRC105, TRC102 data with Temodar as an example, are all presentations we hope to see probably presented in the midyear time frame.

Great. Well, thanks for taking the follow-ups.

I appreciate the questions. Thank you, Jim.

Our next question comes from George Zavoico of Jones Trading. Your line is open.

Hey, Charles. Hi, Patricia. Good afternoon.

Good afternoon.

Thanks for the update and [all]. Two questions -- one regarding cancer, one regarding wet AMD. For cancer, you're doing combination trials with a number of different drugs. Do you think -- if you do you do IHC and check for endoglin expression after Inlyta or after Votrient, if you do a before and after IHC? Do you have any -- do you see any changes in endoglin expression?

Yes, George, it's a great point of in terms of inhibiting the VEGF pathway will up-regulate endoglin, we've seen that pre-clinically and we've seen that clinically as well. So you could -- I think with respect to IHC, I think our view is if we see expressed endoglin on the tumor, that just clues us in that this could be responsive tumor and that it maybe more responsive after you introduce the VEGF inhibitor which should operate delayed endoglin expression. So that we feel is a positive in terms of the interaction of the two drugs.

Great. So you may see -- you're bringing it in with the first use of the drug. So it sounds like a second line, right? So you felt like you have fewer patients first line and more patients second line (multiple speakers) [TRC105].

Right. So sarcoma, it will be -- our paradigm with sarcoma is that this will be a second-line therapy, which is exactly the positioning where Votrient is currently approved [for].

Okay. Well, doxorubicin is used in sarcoma.

Correct. Standard first line --

Do you see any -- yes, for first line. Do you see any changes in -- let me ask you it this way. Do you see any changes in endoglin expression with doxorubicin before and after?

It's a great question. We have not done those studies.

Okay. All right. And then with regard to wet AMD, I mean it's hard to get tissue biopsies there. So, I mean, are you going to be able to test for endoglin expression in wet AMD (multiple speakers) for patients?

Yes. So wet AMD, it's the -- we know in wet AMD that endoglin is overexpressed on [core], the neovessels that the drive the entire disease. So we -- and that's also true in tumors. It's always expressed on the tumor vessels; it's always expressed on the CNV membranes in AMD. If it's proliferating vessels, they're going to overexpress endoglin. So it's on the target tissue in AMD as they drive the entire disease, if you will, every time. That's what makes it such a beautiful disease, for instance, to use VEGF inhibitors, which should become an incredible dominant standard of care. It will make it a great disease in order -- to add an endoglin-based therapy on top of those VEGF inhibitors because it's all vascular biology that's driving that entire disease.

The variability and expression that you see in cancer is not seen in the eye?

No, there's no cancer there. It's just all vessels.

That's right.

So you have a perfect, if you will, test tubes to use an endoglin-based therapy to treat wet AMD as you've got a perfect, if you will, test tube to initially develop the VEGF inhibitors in that disease.

Okay. So you should -- taking that to the next step further, you should see more uniform response then (multiple speakers) --

Exactly. I mean in one sense, George, you can say AMD may be the low-hanging fruit because it's a disease driven by angiogenesis and the two essential targets out there, one VEGF and another one is endoglin.

Okay. There you go. Thank you very much for taking my question.

Thanks, George. Yes.

There are no further questions at this time. I will turn the call back over to Dr. Charles Theuer for any closing remarks.

Well, thanks, everyone, for your participation and your questions. Please have a nice day. We look forward to speaking with you again soon.

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