Good day, ladies and gentlemen, and welcome to TRACON Pharmaceuticals First Quarter 2023 Earnings Conference Call. [Operator Instructions].

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 runaway, our development plan and strategy and the timing and results of our arbitration with I-Mab.

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, 2022, and subsequent quarterly reports on Form 10-Q.

You are cautioned not to place undue reliance on these forward-looking statements, and unless required by applicable law, we disclaim any obligation to update such statements. Now I'd 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 TRACON's first quarter 2023 financial results and business update call. I will begin with an update on our pipeline and then review our recent activities. Following that, Scott Brown, our Chief Financial Officer, will discuss our financial results for the three months ended March 31, 2023.

Finally, we will conclude by taking your questions. I'll begin with an update on our continued progress with the ongoing ENVASARC pivotal trial, evaluating ENVA as a single agent and in combination with Yervoy. We have now enrolled more than 92 patients with refractory UPS, or MFS, into ENVASARC, which is accruing at 29 sites in the U.S.

and one site in the U.K. Accrual continues to exceed projections and the completion of enrollment of 160 patients treated at the 600-milligram ENVA dose is anticipated to occur before the end of 2023.

In December, we announced that the DMC reviewed interim safety and efficacy data from 18 patients enrolled into each of the two cohorts, who completed a minimum of 12 weeks of efficacy evaluations that included two on-treatment scans.

The double-digit objective response rate assessed by blinded independent central review in each cohort more than satisfied the pre-specified futility rule. ENVA monotherapy in combination with Yervoy was well tolerated with only a single related serious adverse event reported in 36 patients.

Responses were noted in patients regardless of weight at the 600-milligram dose of ENVA, that was instituted following the previous DMC review of interim safety and efficacy data from patients in the ENVASARC trial treated at the 300-milligram dose of ENVA. The DMC recommended the trial continue as planned at the 600-milligram ENVA dose.

As a reminder, the primary endpoint in each cohort is objective response rate by RECIST confirmed by central blinded independent review, and 9 out of 80 objective responses, in either cohort or an 11.25% objective response rate, defines a level of response that satisfies the primary endpoint of the study to statistically exceed the 4% objective response rate of Votrient, the only approved treatment for patients with refractory UPS or MFS.

Therefore, a double-digit response rate at the time of interim analysis is meaningful, indicating that we are on track to achieve the primary endpoint of the study. Notably, Votrient is a drug with a black box warning for fatal liver toxicity.

Our goal in ENVASARC, therefore, is to demonstrate that ENVA is both safer and more efficacious than Votrient. Given the robust accrual of more than 92 patients into the ENVASARC trial, we are on track for the DMC to perform the protocol mandated second interim efficacy analysis in the third quarter.

At that time, the DMC will review safety and efficacy data from 46 patients in each cohort, who have been followed for at least three months to prevent two on-study scans for evaluation by blinded Independent Central review.

During the interim efficacy assessment, committee will apply a futility rule that requires at least three responses in 46 patients in order to continue accrual into that cohort. In addition to the mandated DMC efficacy review in the third quarter, there will be an Ad Hoc DMC review in the second quarter.

The DMC charter stipulates that available safety and efficacy data be reviewed at a minimum of every six months. Since the last DMC review occurred in December, we have scheduled a meeting in the second quarter to assess safety and efficacy in each of the two cohorts.

This review will not invoke a formal futility rule and will not include central review of all available scans. Based on the data from trials of other checkpoint inhibitors in refractory UPS or MFS, we are targeting a 15% response rate for single-agent ENVA and up to a 30% response rate for ENVA in combination with Yervoy.

Furthermore, we plan to approach the FDA to discuss a BLA filing strategy as soon as we determine 9 responses in either cohort.

As a reminder, we have received Fast Track designation for ENVA in the sarcoma subtypes of UPS and MFS that have progressed on one or two prior lines of therapy, and have received orphan drug designation in soft tissue sarcoma based on activity observed in ENVASARC.

These designations provide important advantages that might expedite regulatory review and commercialization of ENVA. Moving on to our second checkpoint inhibitor, YH001, a potentially best-in-class CTLA-4 antibody that we licensed from Eucure Biopharma in October of 2021.

In August, 2022; the FDA approved our IND to initiate a Phase I/II clinical trial of YH001 for the treatment of sarcoma patients, including patients who have not received prior therapy. Last October, we initiated the first site in the trial.

Several sites are now open, and we have dosed multiple patients using TRACON's product development platform of CRO-independent research. Our initial YH001 trial leverages data from two completed Phase I trials conducted by our partner, Eucure.

These two trials demonstrated the recommended Phase II dose of YH001 as a single agent and in combination with the PD-1 antibody, toripalimab. Our sponsored Phase I/II clinical trial will evaluate a triplet that includes YH001, ENVA and doxorubicin chemotherapy as doxorubicin is the current frontline standard of care treatment for sarcoma.

The Phase I portion of the trial assesses the tolerability of the combination of the ENVA and YH001 doublet as well as the triple therapy that includes doxorubicin. And we expect to report Phase I data in the second half of this year.

Thereafter, the Phase II portion of the trial will assess the response rate in common and rare sarcoma subtypes to combination treatment, with the intent of demonstrating superior response rates compared to historical data using standard of care agents.

In leiomyosarcoma and liposarcoma, we plan to compare the response rate of triple therapy to the historical 10% to 15% response rate of single agent doxorubicin.

In the case of rare sarcoma subtypes like chondrosarcoma and alveolar soft part sarcoma, where chemotherapy is not highly effective, we intend to study the doublet of YH001 and ENVA to assess the response rate compared to historical response rates for chemotherapy or single-agent checkpoint inhibition.

One of the objectives of this Phase I/II trial is to determine the subtypes of sarcoma that best respond to the combination of ENVA, YH001 and doxorubicin. Assuming positive trial results in the ENVASARC pivotal trial and potential accelerated approval of ENVA, the FDA will require a randomized trial to demonstrate a survival benefit.

We expect this Phase III post-approval trial will compare single-agent doxorubicin to the triplet combination of doxorubicin with ENVA and YH001, with PFS as the end point.

This trial would be expected to enroll patients with UPS and MFS as well as other sarcoma subtypes shown to respond to triple therapy based on data from the Phase I/II trial that I described earlier.

We expect to discuss the design of a frontline trial with the FDA and initiate accrual prior to our planned BLA submission of ENVA for accelerated approval in refractory sarcoma based on data from ENVASARC. Our strategic goal is to commercialize two in-licensed immuno-oncology therapies together in sarcoma.

It is important to understand the sales potential in sarcoma with ENVA at parity pricing is not solely the forecasted $200 million in peak annual ENVA revenues expected in the initial indications of refractory UPS and MFS and the $100 million in annual revenue in rare sarcoma subtypes where the activity of checkpoint inhibition is demonstrated.

Our clinical development strategy is designed to create the opportunity for ENVA to broadly benefit patients with sarcoma in the front-line adjuvant and neoadjuvant settings by seeking supplemental indications.

Moreover, we believe TRACON's total sarcoma-driven sales revenue would be significantly enhanced by marking ENVA and YH001 together as part of a treatment combination in sarcoma. In addition to our two checkpoint inhibitors, we are pleased that the National Cancer Institute continues to fund development of our DNA, damage repair inhibitor, TRC102.

The NCI has initiated a randomized Phase II trial, assessing TRC102 in stage three, non-squamous, non-small cell lung cancer in combination with chemoradiation.

The 2-arm trial will enroll 78 patients to assess the benefit of adding TRC102 to current standard of care treatment of pemetrexed, cisplatin and radiation therapy followed by consolidated durvalumab maintenance treatment. The primary endpoint of the trial is PFS, and the trial is designed to detect an improvement in PFS at one year from 56% to 75%.

Multiple sites are open in the U.S. for enrollment, which was initiated in 2022 and final results are expected in 2025. Next, I will provide an update on our arbitration with I-Mab.

On April 24th, we were informed the International Chamber of Commerce Tribunal ruled in our favor for certain claims and rendered an award to TRACON in the aggregate amount of approximately $23 million.

Among other findings, the tribunal declared the TJ4309 trial complete as of January, 2022, which entitled TRACON to $9 million plus Interest and also awarded legal fees and costs to TRACON. The award is made pursuant to a binding arbitration in both thet fourth nine agreement and the vice agreement are now terminated.

We expect payment promptly and the award includes a high single digit interest on the awarded amounts. The award did not exceed the pre-specified threshold under the non-recourse financing agreement entered into in December, 2022, and therefore we will not receive any additional funds under such agreements.

Given the challenging capital markets, the arbitration award is important. Our current cash funds accompany into quarter three and given our capital efficiency net proceeds from the arbitration award when collected are expected to fund the company into early 2024.

Our runway may be further extended by the equity credit line we recently entered into with Lincoln Park Capital.

That yields at our request $1 million when all conditions to commencement are met, including that a resale registration statement is filed and declared effective, and the equity line can provide subject to compliance with its terms and at our discretion of further $25 million to support the robust accrual of the Pivotal ENVASARC trial.

As we have noted in the past, we expect to further supplement our cash position through opportunities for capital enabled through our CRO independent product development platform, that we believe positions us as one of the most efficient clinical development organizations.

In particular, we believe a company with an emerging pipeline who plans to conduct multiple trials would be an ideal collaboration partner, given our ability to execute multiple trials using our team and advanced clinical trial management, data management and safety reporting system infrastructure.

At this time, Scott will provide an update on our financials..

Thank you, Charles, and good afternoon everyone. TRACON's research and development expenses were $5 million for the first quarter of 2023 compared to $3 million for the comparable period of 2022. The increase was related to Envafolimab drug purchase in the first quarter of 2023 for use in ENVASARC in the YH001 and Envafolimab trial.

General and administrative expenses $2.3 million for the first quarter of 2023 compared to $6.5 million for the comparable period of 2022. The decrease was due to lower legal expenses in the first quarter of 2023. Our net loss was $8.5 million for the first quarter of 2023 compared to $9.5 million for the comparable period of 2022.

Turning to the balance sheet. Turning to the balance sheet at March 31st, 2023, our cash and cash equivalence totaled $6.6 million compared to $17.4 million at December 31, 2022. We expect our current capital resources to fund the company into Q3 and with net proceeds from the arbitration award when collected into early 2024.

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

First, in the second quarter, we expect to report an ad hoc DMC safety and efficacy assessment of available ENVASARC data to comply with the six month review requirements specified by the DMC charter.

Second, in the third quarter, we expect to report the second and final mandated DMC interim efficacy assessment for each of the two ENVASARC cohorts of 46 patients dosed with 600-milligrams of ENVA. That includes a formal futility rule.

Third, in the second half of the year, we expect to report phase one data of the combination of ENVA and our CTLA-4 antibody YH001 as well as the triple therapy that includes doxorubicin.

Fourth, this year, we also expect to further leverage our unique product development platform to enable companies tired of being beholden to zeros to potentially benefit from our capabilities and realize for themselves the substantial time and cost savings we enjoy at TRACON.

Thank you for your time and attention and we are now available to answer your questions..

Thank you. [Operator instructions]. Our first question will come from Ed White of HC H.C Wainwright. Your line is open..

Good afternoon. Thanks for taking my question.

So Charles, just first question is on the arbitration is there any thoughts you can give us about the timing to receiving the $23 million in payments and how is that going to be recorded on the company's income statements or balance sheet? You know, the $9 million and the $13.5?.

Yeah, I can answer the first portion. Then Scott can take the second portion. Thanks for the question. So we do expect payment in the near term IAB indicated they will confirm the award, which is binding on both parties, and I would also point out in the meantime the award is accruing interest and Scott can comment on the accounting issues..

Yeah, hi Ed. So the $9 million should be recorded as collaboration revenue since that was due to the termination of TJ4309, and the rest will be recorded as other income below the line..

Okay, great. Thanks Scott. And then Charles, just a, a question on the, the product development platform you know, yeah, you, you've mentioned this several times in the past.

I'm just wondering has there been any in investor interest in it or any, anything you can tell us about you know, do you think that you are going to have your first client this year or is this something later in the future?.

That's a great question, Ed. You know, I can't specify an exact time table, but I will just say that there's extreme interest in, in what TRACON does that's very different than other companies that are beholden the CROs. You know, when you think about TRACON, I think about two major value propositions.

You know, first is ENVA, you know, late stage clinical asset being studied in a indication where the standard care is absolutely abhorrent, whereby we know the mechanism of action is relevant in those sarcoma subtypes that are enrolling in the end of ENVASARC trial, and that's a late stage asset with near term commercialization potential.

The other major value proposition is the platform and just to be clear, a company that accesses the Tracom platform literally would save approximately 70% to 80% of every trial they ever do. That's not lost on companies, especially in this environment where capital efficiency is so important.

So again, I can't exactly give you a timetable, but I would just say that there's extreme interest in the platform and that's regarded as a significant part of the TRACON value proposition, as is our late stage clinical asset..

Okay, thanks Charles.

And my last question is just concerning the Ad hoc analysis in the second quarter since it's not based on futility, what can you actually tell us after this ad hoc analysis? Will you just tell us that the study is going to continue as planned? Or is, is, is there any data point that you can, will be releasing?.

No, great point, Ed.

Yeah, our goal with the ad hoc analysis you mentioned that's coming up, you know, this quarter would be to be able to report similar to what we reported in December, that the drug is tolerated a single agent and tolerated when combined with your boy, and that we remain with a double digit response rate in each cohort knowing that we won't have two months of date on every single patient enrolled at this time.

But we'll be able to report on the available data for patients, but it will be short of 46 patients in each cohort to be clear..

Thank you. [Operator instructions] Our next question will come from Joel Beatty with Baird. Your line is open..

Great. Thanks for the updates and for taking the question.

The, the first one is, is a follow-up on the efficacy analysis from or analysis coming from ENVASARC in this quarter, next quarter from an efficacy point of view, I mean when we think about both of them as, as similar to the December update in the amount of data provided and, and the main difference is just kind of the number of patients or are, are there other differences in the level of detail that will be provided to, to consider?.

Hi Joel. No, I appreciate the question. So, you know, the formal interim efficacy analysis in third quarter is, is a very regimented data set, if you will.

So it's 46 patients in each cohort and each of those patients is followed for at least three months so that they each have at least two scans on study so that you can get a reasonable understanding of what the general response rate will be knowing it still could grow with time, but you'll at least have the ability to assess response rate based on at least two scans in each of those 46 patients.

You know, the assessment this quarter will not have that degree of follow up on these patients, so we'll have all the available data not every scan will be, have undergone central review, for example, in the second quarter analysis.

So what we expect to report is, is data on patients up to 46 patients knowing that many of them may not have been followed for three months and knowing that not all those patients have had two scans, nor will all of those scans been assessed by central review.

So we'll caveat, if you will, the, the expected pressure release in quarter two with respect to safety, but also efficacy to give an understanding of of what the response rate is in patients that have had, for instance, two scans, knowing that not every scan will have undergone central review and knowing that that denominator will not be 46 patients as it will be in third quarter..

Yeah, appreciate that. And then a question on the potential for collaborations regarding the, the CRO independent model.

You know, in, in light of the, the IMA arbitration that that seems, you know, somewhat lengthy is, is there a way to kind form the, the, the feature agreements regarding the CRO independent model in, in, in such a way to kind of help, you know, minimize the, the possibility of kind of future arbitration that that might you know, be, be cumbersome for TRACON as, as well as potentially de deter potential partners?.

Yeah, I, I think, you know, we have multiple partners, Joel, and going forward, we expect to work with partners as well that will be similar to the, the partners we're currently engaged with includes Alpha Oncology, includes 3D medicines, includes biopharma.

Yeah, I think we're an excellent partner and I think the efficiency with which we conduct trials and the manner of this team makes this incredibly attractive partner for people who are looking to accelerate the timeline, decrease the cost, and improve the quality of their clinical trials.

You know, I would point out in the past we've had collaborations around our platform with companies like Johnson and Johnson and that was a, a very fruitful, productive collaboration for both best and for them..

Thank you again. [Operator instructions] I am seeing no further questions in the queue. I would now like to turn the conference back to Dr. Charles fur for closing remarks..

I would like to thank the participants for your time and attention, and we look forward to speaking and updating you at their next quarterly call. Have a good day..

This concludes today's conference call. Thank you all for participating. You may now disconnect and have a pleasant day..