TRACON Pharmaceuticals Inc (TCON) 2016 Q4 法說會逐字稿

Good day, ladies and gentlemen, and welcome to the TRACON Pharmaceuticals Fourth Quarter and Full Year 2016 Earnings Conference Call. At this time, all callers are in 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 development 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, 2016. You are cautioned not to place undue reliance on these forward-looking statements, and we disclaim any obligation to update 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 2016 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 financial results for the three months and year ended December 31, 2016. Finally, we will conclude by taking your questions.

Let's begin with our lead product candidate TRC105, which is also known as carotuximab. It has received orphan drug designation in sarcoma, including angiosarcoma, in both the EU and the U.S. As a reminder, we received valuable protocol systems from the EMA and have a special protocol assessment agreement from the FDA regarding Phase 3 development in angiosarcoma an orphan indication with high unmet need. Following these very positive regulatory interactions, we initiated the randomized Phase 3 TAPPAS trial of TRC105 in angiosarcoma and very recently began dosing patients.

Several trial details are noteworthy. First, PFS rather than overall survival is the primary endpoint; second, the trial enrolled treatment naive patients in addition to the patients who have received prior therapy; third, the trial incorporates an adaptive design, which preserves type I error and protects the power to detect a clinically meaningful survival benefit. The initial sample size of 124 patients provides more than 80% power to detect an improvement and meeting PFS from 4.0 to 7.3 months using a two-tailed alpha of 0.05.

We expect to conduct an interim analysis when 40 events have occurred in approximately 70 patients. At that time, the results we categorized belong to either the favorable promising, enrichment, or unfavorable zones based on conditional power. The sample size in [TF] events needed to complete the trial will be left unchanged in the favorable and unfavorable zones but will be increased to a total 200 patients in the promising zone. This will allow more than 80% power to detect a less robust improvement in PFS between the two arms. In the enrichment zone, the trial will enroll an additional 100 patients with cutaneous disease only to a maximum of 170 patients, which will preserve power to detect the original treatment effect between the two arms in patients with cutaneous disease.

The TAPPAS trial was recently selected as a 2017 finalist for Most Innovative Clinical Trial Design by the Clinical and Research Excellence or CARE Awards in recognition of its novel design. We expect to present further details of the study at a scientific meeting later this year and expect to report the interim analysis in the first half of 2018.

We believe that TRC105 has broad potential. And as such, TRACON continues to execute on its tiered development strategy that includes orphan drug indications, mid-size market indications, and large market indications. In addition to the pivotal trial in angiosarcoma, we've recently initiated dosing in a Phase 2 trial in gestational trophoblastic neoplasia or GTN, which includes choriocarcinoma. The primary endpoint of the Phase 3 trial is response rate, and we believe the study has the potential to be registration-enabling.

We recently reported update on randomized Phase 2 trial in glioblastoma and renal cell cancer, both of which are mid-size market indications. We learned from the NCI's Cancer Therapy Evaluation Program or CTEP that the combination of TRC105 and Avastin did not improve PFS when compared to single-agent Avastin in recurrent glioblastoma patients although the combination was associated with a non-significant increased in overall survival. We expect detailed results of this randomized Phase 2 trial to be presented by the NCI at a scientific conference later this year.

We also expect to report PFS data from our randomized Phase 2 trial in renal cell cancer, the TRAXAR trial, in the second half of 2017. As a reminder, this trial compares treatment with TRC105 and Inlyta to treatment with single-agent Inlyta in patients with clear cell renal cell cancer.

Turning to our efforts in liver cancer. We expect the NCI to publish their Phase 1/2 trial results that indicate a significant response rate for TRC105 and Nexavar in a peer review journal later this year. We also expect response rate data from TRACON's ongoing multi-center Phase 2 trial of TRC105 in Nexavar in early 2018.

Finally, enrollment continues in trials in two large market indications: our Phase 1 trial of TRC105 in combination with Avastin and chemotherapy for the first line treatment of patients with lung cancer; and the Phase 1/2 trial of TRC105 in combination with Afinitor and Femara for the new adjuvant treatment of patients with breast cancer.

We believe there is also a significant opportunity for endoglin antibodies to improve treatment options for patients with wet AMD. Notably, companies conducting two separate studies targeting the PDGF pathway, in combination with VEGF inhibitors and wet AMD, recently reported negative Phase 2 and Phase 3 data. We believe this leads substantial opportunity for the development of agents that target essential angiogenic pathways like endoglin to be developed in combination of VEGF inhibitors for wet AMD.

We have partnered global rights to develop our endoglin antibodies in eye disease, including wet AMD, with Santen. DE-122 is the ophthalmic formulation of TRC105, and we expect Santen to report data from the Phase 1/2 PAVE trial that assesses safety and bioactivity of DE-122 in refractory wet AMD patients later this year.

Notably, Santen recently posted the randomized Phase 2 AVANTE study to the Philippine Health Research Registry. This trial compares treatment with DE-122 and Lucentis to treatment with single-agent Lucentis in patients with wet AMD. And we anticipate that Santen will initiate dosing in AVANTE later this year.

Fibrosis is the third therapeutic area where our endoglin antibodies have demonstrated activity. TRACON's endoglin antibodies have been active in number of pre-clinical models including cardiac fibrosis, liver fibrosis, and nonalcoholic steatohepatitis or NASH. And we observed a reduction in cutaneous neurofibromatosis in a patient treated as part of sarcoma trial. Neurofibromatosis is an incurable genetic disorder that affects more than 100,000 Americans. And we will explore options for dosing TRC105 in additional patients in neurofibromatosis in 2017.

We'll turn now to our second product candidate, TRC102. TRC102 is a novel small molecule inhibitor of the DNA base excision repair pathway that reverse the resistance to certain chemotherapeutics. Importantly, TRC102 has demonstrated the ability to potentiate the activity of PARP inhibitors in preclinical tumor models. And the NCI presented positive safety, PK, and efficacy data from its all comers Phase 1 trial of the combination of TRC102 and Temodar at ASCO 2016. The combination was well tolerated, and partial responses were observed in patients with ovarian, lung, and KRAS-positive colorectal cancer.

Expansion cohorts have now been added in each of these three tumor types. The study is also designed to assess biomarkers associated with TRC102 susceptibility in the patients enrolled in each of the expansion cohorts. These data, which we expect to be presented at a scientific conference in mid 2017, may provide valuable information for patient selection into future clinical studies.

Enrollment in additional NCI funded trials of TRC102 is underway. The NCI is sponsoring a Phase 2 trial TRC102 with Temodar in patients with glioblastoma; and a dual arm Phase 1/2 trial consisting of a Phase 2 cohort of TRC102 with Alimta in patients with mesothelioma; and a Phase 1 cohort of TRC102 with Alimta and cisplatin in patients with solid tumors. We expect to release data from these Phase 2 trials in 2018.

Finally, our collaborators at Case Western recently began dosing patients in a Phase 1 trial of TRC102 in combination with chemotherapy and radiation therapy in patients with lung cancer. As we previously announced late last year, we inlicensed two oncology assets from Janssen. The first is TRC253, which was discovered at Janssen as a novel potential treatment for prostate cancer. It is a small molecule, competitive inhibitor of wild type androgen receptor and androgen receptor mutations that confer resistance to Xtandi and other drugs approved to treat prostate cancer.

We have moved quickly on TRC253 since inlicensing the asset in September 2016. TRACON found the IND in December. The IND was cleared by the FDA in January, and we expect to initiate at Phase 1/2 proof of concept study in the first half of the year. Following completion of the initial proof of concept study, Janssen will have the exclusive option to reacquire full rights to TRC253 for an upfront payment of $45 million, potential regulatory and commercialization milestones totaling up to an additional $137.5 million, and a low-single digit royalty.

If Janssen does not exercise its exclusive option to reacquire the program, TRACON would retain worldwide development and commercialization rights to the program. And if TRACON continuous development of 253, we'd be obligated to pay Janssen potential development and regulatory milestones totaling up to $45 million in addition to a low-single digit royalty on net sales.

The Janssen deal also brought TRC694, a novel small molecule potent inhibitor of NF-kB inducing kinase or NIK that is intended for the treatment of patients with hematologic malignancies including myeloma. TRC694 is currently in pre-clinical development, and TRACON expects to file an IND in 2018.

In completion -- upon completion of an initial proof -- clinical proof of concept study, Janssen will have a right of first negotiation to reacquire the program on terms agreed upon at that time. If we cannot come to terms following negotiations or Janssen does not exercise its rights of negotiation and TRACON wishes to continue development of TRC694, TRACON will be obligated to pay Janssen potential development and regulatory milestones totaling up to $60 million and a low-single digit royalty on net sales. Pre-clinical data on TRC694 are scheduled for presentation at the Annual Meeting of the American Association for Cancer Research in Washington, D.C. on April 4.

As you can see, we remain very active on the development front and look forward to a highly productive year with multiple potential value-enhancing events, including a number of key pipeline-related milestones. Importantly, we continue to achieve our progress in a cost-effective manner by leveraging the TRACON clinical operations team that will manage our international Phase 3 trial for TRC105 in angiosarcoma without the significant cost or complexity associated with outsourcing to a full service CRO. We believe the Janssen licensing agreement validates this model and our drug development expertise. And we will continue to evaluate additional assets that can leverage our product development platform for the benefit of TRACON and its stakeholders.

From our financial perspective, following an investment by JJDC in September and our subsequent equity financing in November, we believe that our current cash resources will fund operations in the Q2 2018 and be sufficient to deliver endpoints from the ongoing randomized Phase 2 renal cell cancer study, the Phase 1/2 data in wet AMD, and support manufacturing activities at Lonza required for regulatory approvals of TRC105.

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

Thank you, Charles, and good afternoon, everyone. TRACON reported collaboration revenue of $0.6 million for the three months ended December 31, 2016 and $3.4 million for the year ended December 31, 2016, compared to $1.4 million and $7.9 million respectively for the comparable periods of 2015. The decrease in the full year amounts is primarily attributable to a $3 million cash milestone triggered by Santen's filing of an IND in wet AMD received in 2015.

Research and development expenses were $4.8 million for the fourth quarter and $21.6 million for the year ended December 31, 2016, compared to $10.6 million and $25.7 million respectively for the comparable periods of 2015. The decrease in R&D expenses in the fourth quarter and full year 2016 compared to the corresponding 2015 period reflects lower TRC105 drug manufacturing cost in the 2016 period. The decrease in R&D expenses in the year ended December 31, 2016 was offset in part by increased TRC105 clinical study-related expenses and higher personnel cost resulting from increased headcount.

General and administrative expenses were $1.9 million for the fourth quarter and $7.9 million for the year ended December 31, 2016, compared to $1.7 million and $5.7 million respectively for the comparable periods of 2015. These increases were primarily attributable to higher personnel costs resulting from increased headcount in 2016.

Our net loss was $6.3 million for the fourth quarter and $27 million for the year ended December 31, 2016, compared to $11 million and $24.4 million respectively for the comparable periods of 2015.

Turning to the balance sheet at December 31, 2016, our cash, cash equivalents, and short-term investments totaled $44.4 million compared to $35.1 million and $52.2 million at September 30, 2016 and December 31, 2015 respectively. In November, we received net proceeds of approximately $16.1 million from the sale of approximately 3 million shares at our common stock in a follow-on financing.

In addition in January 2017, we entered into an agreement with Silicon Valley Bank to revert to interest-only payments on our $8 million of debt outstanding until December 31, 2017, with the possibility of a six-month extension upon the achievement of certain clinical and capital milestones. As Charles mentioned, we expect our capital resources to be sufficient to fund our currently planned operations into the second quarter of 2018.

With that, I'll turn the call back over to Charles.

Thank you, Patricia. As we noted, 2017 will be an eventful year full of multiple potential value-creating milestones. We recently initiated dosing in the pivotal Phase 3 TAPPAS trial of TRC105 in angiosarcoma and soon expect to initiate dosing in a Phase 1/2 study of TRC253 in prostate cancer. We expect to report TRC102 data mid-year and report randomized TRC105 data in renal cell cancer in the second half of the year. We also expect Santen to report Phase 1/2 data from the PAVE trial and to initiate dosing of the Phase 2 AVANTE wet AMD trial later this year.

I look forward to providing further updates regarding our upcoming key milestones, and I am confident that we have the right strategy in place to deliver on our development and business plans to the benefit of stock patients and stockholders.

With that, we will be happy to answer your questions.

(Operator Instructions) Our first question comes from Brian Abrahams with Jefferies. Your line is now open.

Hi, this is [Maury] on for Brian. Thank you for taking our questions. To start, for the glioblastoma study, now that you've had a little bit more time to look at the data, can you comment on whether you have a clear understanding of whether the PFS analysis was confounded by zero progression and/or edema in some patients.

Hi, Maury. First of all, thanks very much for the question. We don't have insight into the data. It's really CTEP's data package, and we do hope we'll see that data midyear. What we can say is we didn't see a prolongation of PFS. We did see a non-significant improvement in overall survival, which I think is interesting. And in terms of why PFS was not prolonged in OS, again non-statistically significant was prolonged, we'll have to really investigate that data carefully and hopefully can do that at ASCO.

I would point out that in GBM compared to other indications, we are in the spectrum of disease indications with this drug. We're in, what we call, [lower skin indications]. Angiosarcoma is a perfect example of that. It's a blood vessel tumor. And as you well know, endoglin is a blood vessel target. And so that's the indication where you expect the most robust activity, and that's where we see durable complete responses in the trial, TRC105 and Votrient.

Your GBM is on the exact opposite of that spectrum. It's an incredibly tough disease to treat. There's one approved drug in GBM, Temodar, based on a survival advantage in the past 20 years. We didn't have any preliminary evidence of activity in GBM based on preexisting data, and the trial was a small underpowered trial.

So we know it's a tough indication. Yes, I think because it's a high unmet need and we want to support the NCI and try to advance therapeutics and indication, we explored it. And the data will be interesting. And we hope to see that midyear but we just don't have insight into that data quite yet.

Sure, okay. And then for the Phase 3 trial, I was wondering if cutaneous patients sometimes progress to become systemic. And does it mean anything on efficacy if you show a difference in preventing cutaneous patients from becoming systemic?

So cutaneous patients, to your point -- the cutaneous patient is defined based on the primary disease starts in the skin and it can metastasize. In many times, you'll have cutaneous patients that are represented with, for instance, local lymph node metastases and they can also proven to have distant metastases. So they'll be followed by RECIST criteria, and that could mean that they progress based on either increase in the area of the cutaneous lesion or it could mean they progress based on the progression of internal lesions; for instance, an internal lymph node or an internal visceral metastasis. So, it will be the standard RECIST criteria to define progression whether it's cutaneous as a primary or whether the tumor started as a visceral lesion.

Got it, okay. And then last for the Phase 2 trial with the DE-122, I was wondering if you can comment more on the trial size and design, and if any specific effects on endoglin or biomarkers will be measured.

Yes. So the design of the study is now posted, and I will send you the link after the study. But the initial design is a randomized study, which I think is important. So it's a DE-122 Lucentis versus Lucentis alone. And I'll have to look carefully at the sample size, but we're expecting, I think, in the 50- to 100-patient rough sample size. But we will send you the link more so you can have that exact information.

In terms of biomarkers, this will be a classic AMD trial, which I think it'd be typical to expect that OCT will be employed to assess macular edema as an example; visual acuity clearly will be assessed. I think those will be two of the most important endpoints coming out of Phase 2 trial. And also those are being assessed even as part of the Phase 1/2 PAVE study that we expect to see data later this year.

Okay. Great, thank you.

Our next question comes from Tom Shrader with Stifel. Your line is now open.

Good afternoon. Thanks for the update. I had one question. I just want to make sure I heard it correctly. The TAPPAS trial will have treatment-naive patients as well?

Yes, it will. It was actually where we thought, Tom, was a great recognition of the unmet need in that indication. So there is a classic first line therapy for angiosarcoma. And frequently it's chemotherapy and the two chemotherapeutics that are frequently used first line or either taxanes or adriamycin.

That said, the response rate is poor and the PFS is poor. And based on the fact that we've seen durable complete responses, we were able to argue persuasively that if patients are eligible for a clinical trial and have not seen chemotherapy, they should have the opportunity to enroll in the trial and not have to go through a round of chemotherapy just to get into the trial. And I think that was, again, a sign from regulators that there is a need for new therapy in this disease to the point that treatment-naive patients should come straight into the trial.

And then there is -- will you stratify on treatment-naive or they all lumped together just to become two trials.

Great question, Tom. It is one of the key stratification factors in the trial. So the two stratification factors in the trial, one is cutaneous versus non-cutaneous as the site of origin of the angiosarcoma; and second is treatment-naive versus patients have been treated previously. That was important stratification.

Well, that is a complicated trial. No wonder you won an award.

Actually, what's beautiful about the design, though, is it really gives us the flexibility to do one trial the right way in angiosarcoma and prove benefit in the entire population if that's where the benefit is or to prove the benefit in the cutaneous patients if that's where the benefit is. So it's really a nicely designed and flexible trial that really lets us -- lets the drug direct us to the patients that are most likely to benefit.

Okay, perfect. And the TRC253 program, so if you're going to start dosing soon, is there any guidance on when J&J might have to make a decision? Is it a year or is it longer than that?

So it is a Phase 1/2 trial, Tom. Our general expectation of that trial is that we hope to report the Phase 1 portion of the study and complete that portion this year, and then to complete the Phase 2 proof of concept portion from an efficacy perspective by the end of 2018. And then that would define the opt-in period although Janssen has the ability to opt in at any time up until that time.

All right. Okay. And just -- and any thoughts about hepatic HCC? What's the time line to --

Sure.

-- start to think about a pivotal trial? And what would it look like today? Is it (multiple speakers) same thing a trial like that would look like five years ago or are things changing?

There definitely are new agents being studied in liver cancer.

Yes.

For instance, regorafenib will probably based on the Phase 2 data be approved in second line. Our current trial focuses on first line combining with Nexavar, which remains the only approved first line drug. That said, Nexavar is being taken head to head against the volume having an ongoing trial, and we'll see how that plays out.

So the landscape could change. But right now, we haven't seen as robust a response rate at least in the Phase 2 study with nivolumab in liver that we have in other indication. So where that trial plays out, time will tell.

So based on what we know right now, Nexavar remains the standard care of first line agent in liver cancer. And our current view is if we can replicate the response rate that we saw in the NCI study and show that, that also has encouraging survival data, would be to pair with Nexavar as the pivotal Phase 3 study compared to Nexavar single agent. That said, we'll continue to monitor the landscape.

And could that trial start in 2018?

So we expect the data from our multicenter study in 2018, which could allow a Phase 3 study to start in 2018.

All right, okay. Okay, great. Thanks a lot.

(Operator Instruction) Our next question comes from Bert Hazlett with BTIG. Your line is now open.

Thanks. Congratulations on the progress. Thanks for taking the question. Could you just discuss some of the potential material inflection points for TRC253 that changed a program? Obviously, significant program for you and significant licensing, but how important is the safety data with this program?

Yes, great question, Bert. I think the safety data is absolutely critical for this program. When you think about this asset, Xtandi is the standard of care currently in this space. Xtandi works very well on the wild type androgen receptor. This drug, TRC253, based on pre-clinical data, we expect it to work just as well in the wild type receptor. So it could directly compete with Xtandi or drugs that are in the pipeline that are very similar to Xtandi and that also inhibit the wild type receptor without inhibiting mutants.

So our view is that if this drug is safe, it immediately becomes potential best-in-class in the space of androgen receptor antagonist. And that means it can compete with any product that's currently out there. So if safe, we think the chances of J&J will opt in are increased substantially. But to be clear, the opt-in period extends to the completion of the Phase 2 portion study, which will then trigger the $45 million opt-in payment.

Okay. And we should get a view on the safety around yearend this year, early 2018. Is that correct?

Yes, we expect that. But we have really moved quickly on that program. IND was -- we just licensed in September with IND before the end of the year. We have cleared IND. So expect dosing in the near-term and expect safety data this year, correct.

Terrific. Then a couple of just blocking and tackling questions. Could you discuss maybe the pacing of R&D expense throughout 2017? There is a lot going on here, lot in the clinic, but you are very efficient. Could you just -- how should we think about modeling it? And does the Santen start of Phase 2 trigger a milestone with the DE-122?

So I'll take your last question first. So we can't disclose the exact milestones that are tied to exact clinical trials at Santen. We can't say there is $17 million in development-stage milestones, which we've disclosed publicly. With respect to the pace of the trial enrolment, I think we gave a general idea of the burn going into Q2 of 2018. We spent $27 million last year, roughly; actually, $29 million last year roughly, about $25 million in the year before.

So I think we're roughly going to stay with a little bit higher burn, but we're still well within I think with the very limited burn compared to similar companies doing this extent of work. But I think you can use the Q2 runway that we've given in 2018 as the general guidance on the pace of burn moving forward.

Okay. And just want one other one, you mentioned the neurofibromatosis program. Could you just describe a bit more about the effort and the types of patients you expect to enroll there?

That's a great question, Bert. So, we really were interested in the serendipitous response we saw in the sarcoma trial that enrolled a patient with cutaneous neurofibromatosis or neurofibromatosis type 1, which is the cutaneous form of the disease, which is a more common disease that many people expect and that patient had marked reduction in the cutaneous disease. They're treated with TRC105 and Votrient to be clear.

So, based on that, there are clinical consortiums that treat neurofibromatosis patients. So our goal is to explore a potential relationship with a consortium and to consider doing a pilot study, for example, where we would study TRC105 with or without VEGF inhibitor in patients with cutaneous neurofibromatosis to see if we can replicate that serendipitous finding that we saw as part of a sarcoma study.

Is that -- should we be able to get visibility? Is that an '18 potential visibility for the indication? Or is that earlier than that potentially?

Yes, our goal is to explore the opportunity in terms of when we would potentially see clinical data. Yes, it's hard to say, we're just in the early stage of potentially exploring that clinical opportunity, Bert. So, yes, it's hard for me to comment on the time frame at this point.

Okay. Thank you very much.

Yes, appreciate your questions.

And I'm showing no further questions. I would now like to turn the call back over to Dr. Theuer for any further remarks.

Great. Thank you so much. Thanks for your time and interest. Have a nice day. We look forward to speaking with you again soon.

Ladies and gentlemen, thank you for participating in today's conference. You may all disconnect. Everyone, have a great day.