Good day, and thank you for standing by. Welcome to the Alaunos Therapeutics Fourth Quarter 2022 Financial Results Conference Call. At this time, all participants are in a listen-only mode. After the speakers' presentation, there will be a question-and-answer session. [Operator Instructions] Please be advised that today's conference is being recorded. I would now like to hand the conference over to your speaker today, Danielle Dudgeon with Stern IR. Please go ahead.

Good morning, and welcome to Alaunos Therapeutics fourth quarter and full year 2022 financial results conference call and audio webcast. Earlier this morning, Alaunos issued a press release announcing financial results for the three months and full year ended December 31, 2022. We encourage everyone to read today's press release, as well as the Alaunos annual report on Form 10-K for the quarter ended December 31, 2022, which was filed with the SEC this morning. The company's press release and annual report will also be available one the Alaunos' website at alaunos.com. In addition, this conference call is being webcast through the Investor Relations section of the company's website, and will be archived there for future reference. Please note that certain information discussed on today's call is covered under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Participants are cautioned that this conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, March 7, 2023. Actual results could differ materially from those stated or implied by the forward-looking statements made today due to risks and uncertainties associated with the company's business. Information on potential risks and uncertainties are set forth in our most recent public filings with the SEC at sec.gov. The company undertakes no obligation to revise or update any forward-looking statements to reflect events or circumstances after the date of this webcast, except as may be required by applicable securities law. With me today are Kevin Boyle Senior, Chief Executive Officer; Drew Deniger, Vice President of Research and Development; Abhi Srivastava, Vice President of Technical Operations; and Mike Wong, Vice President of Finance. With that said, I would like to turn the call over to Kevin.

Thank you, Danielle. Good morning, and thank you for joining us today for an update on the exciting progress we are making here at Alaunos. 2022 was a transformational year for Alaunos Therapeutics, as we achieved several meaningful corporate milestones including advancing our library TCR-T cell program into the clinic and subsequently achieving our first objective clinical response. We are a highly focused company, committed to leading the scientific development of T-cell receptor therapies to revolutionize solid cancer treatment and improve patient outcomes. I'm extremely proud of our team's work and realizing the promise of our novel technologies and R&D efforts with clinical execution. We believe TCR-T targeting high frequency driver mutations is potentially the most promising advanced immunotherapy to kill solid tumors. We are proud to be on the leading edge of cell therapy. We are the first company to demonstrate an objective clinical response in a patient with a solid tumor using a non-viral TCR-T cell therapy. We are encouraged and motivated by the significant interest these results have since generated among physicians, patients, investors, potential partners and other key stakeholders. Every day, multiple patients are reaching out to inquire into our clinical study from across the country. This growing momentum provides a tremendous foundation for the year ahead. We have been hard at work to ensure that we can meet our TCR-T Library Phase 1/2 program milestones in 2023. In the fourth quarter, we filed an IND amendment for the trial. As part of this amendment, we made several critical enhancements to our enrollment and manufacturing processes. First, we combined our treatment and screening protocols, streamlining enrollment, making it easier for both patients and physicians. Second, we are no longer required to retest the patient's tumor mutation if more than six months has passed between screening and…

Thank you, Kevin. I'm excited to share today that we were pushing full speed ahead in our R&D efforts. We continue to ramp up our Hunter TCR discovery platform to increase the number of patients, who can benefit from TCR-T cell therapy. We are generating foundational data from the translational assessments in our treated patients. And we are using the translational data to guide our next generation TCR-T cell endeavors that will fuel our pipeline for the long-term. Let me start with Hunter. We continue to strongly believe that Hunter is at the cutting edge of innovation and has significant advantages over traditional TCR discovery methods. We have been very successful in identifying novel exclusively owned mutation reactive TCRs and are emboldened to increase throughput and focus on high value targets. Our TCRs are sourced from T-cells infiltrating the tumor expressing the driver mutation in the natural context of HLA. We can then use the TCR to add to the library for the benefits of another patient who has the same target. At the 2022 SITC conference, we presented proof-of-concept data supporting Hunter's ability to evaluate hundreds of thousands of HLAs mutations and TCR combinations in a high throughput setting with our proprietary technology. As Kevin referenced, in the fourth quarter, we added two new TCRs to our library targeting frequent driver mutations and HLAs. The addition of these two TCRs has had a major impact on the potential addressable market for our TCR-T program effectively doubling. We are pleased to show now a greater than a 10% match rate and the patient prescreening process. The addition of these new TCRs is a prime example of our two pronged library expansion strategy. On one hand, we are working to add more HLAs to the existing KRAS, TP53 and EGFR mutations…

Thank you, Drew. As Kevin and Drew has discussed, we continue to be very excited about the progress we are making in our TCR-T library trial. Last year was a critical year for us, as we initiated several efforts to advance and accelerate our clinical program. I'd like to highlight three major efforts. First, we have successfully manufactured at cGMP suite, three (ph) patients' product using three different TCRs in three different tumor indications. All three manufactured products had fantastic characteristics, relating to viability, purity and TCR positivity. Our manufacturing process works consistently for the TCR in our library, irrespective of mutations, part HLA's. Second, we have doubled our manufacturing capacity by implementing new SOPs that allow for simultaneous production of multiple products in our GMP suite. And third, we continue to invest to improve process development, further refining our manufacturing platform. In the fourth quarter of 2022, we worked to further optimize our manufacturing process to an IND amendment to move from fresh to cryopreserved cell products. Cryo enabled us to reduce the manufacturing process time from 30 to 26 days representing a 13% decrease. I'm happy to report that we have already implemented the cryo manufacturing process this year. This new process now provides us with greater flexibility for patients scheduling and treatment with the possibility to collect the patient's phrases (ph) earlier in their treatment journey. We can then manufacture the drug product and cryopreserve it until the patient is ready for the infusion. This is a good start and our long term goal is to further reduce the manufacturing time to 15 days. I'm so proud of our fully committed technical operations team and our universal TCR manufacturing platform. And I remain excited about the investment we are making in process development that will close the system, automate the process and decrease the cost while preparing us for Phase 2. I would now like to turn the call over to Mike Wong to review the financial results for the fourth quarter and full year. Mike?

Thank you, Abhi. Allow me to review our financials for the three months ended December 31, 2022. For the fourth quarter of 2022, we reported a net loss of approximately $9.2 million or a $0.04 net loss per share compared to a net loss of approximately $11.8 million or a $0.05 net loss per share for the same period in 2021. Research and development expenses were approximately $5.6 million for the fourth quarter of 2022 compared to approximately $8.2 million for the fourth quarter of 2021, a decrease of 32%. The decrease was primarily due to reduced program related costs and lower employee related and consulting expenses. General and administrative expenses were approximately $2.9 million for the fourth quarter of 2022 compared to approximately $2.1 million for the fourth quarter of 2021, an increase of approximately $800,000, which was primarily due to higher legal and accounting expenses. Our operating cash burn for the fourth quarter of 2022 was approximately $7.1 million compared to approximately $15.1 million in the fourth quarter of 2021, a decrease of approximately $8 million or 53%. And now, I will review the results for the full year ended December 31, 2022. For the year ended December 31, 2022, we reported a net loss of approximately $37.7 million or $0.17 net loss per share, compared to a net loss of approximately $78.8 million or $0.37 net loss per share for the year ended December 31, 2021, an impressive year-over-year reduction of 52%. Collaboration revenue was approximately $2.9 million for the year ended December 31, 2022 compared to approximately $400,000 for the year ended December 31, 2021. The increase in collaboration revenue was primarily due to the achievement of sales based milestones of darinaparsin in Japan, which was largely offset by a 1 time research and development expense…

Thank you, Mike. As we look to the year ahead, we are dedicated to revolutionizing how solid tumors are being treated using our disruptive technology and the clinical, manufacturing and research teams are committed to this objective. Through the groundwork we have laid in our recent IND amendment, where we added additional TCRs and transition to cryopreservation, we will greatly enhance patient throughput and treatment flexibility for our TCR-T library Phase 1/2 trial. We remain confident the positive momentum we have built among patients and physicians will lead to even greater accomplishments as we expect to treat the remaining balance of patients in the Phase 1 portion of our TCR-T library trial, share additional patient data and become Phase 2 ready by the end of the year. Looking beyond 2023, we envision being in the Phase 2 stage of our existing IND. Our IND enables us to conduct multiple independent indication specific Phase 2 trials simultaneously. Often times, certain TCRs may be associated with specific cancer types. For instance, non-small cell lung cancer commonly has EGFR and KRAS mutations. So we may expect to enroll lung cancer patients with predominantly these TCRs. Colon cancer on the other hand is associated with KRAS and TP53 mutations, which could be a second Phase 2 trial. Over time, we expect to initiate multiple Phase 2 trials across several solid tumor indications. As we believe our TCR-T cell therapy has applicability across a broad range of solid tumor types. To our knowledge, we are the only company taking this type of unique approach, utilizing a TCR library targeting driver mutations against solid tumors. As we continue to build a long term potential of TCR-T cell therapies from Alaunos, we are actively developing next generation treatments, which hold the potential to deepen clinical responses through combination approaches and multiplexed TCR-T cell therapies. We are working to conduct translational assessments of treated patients to guide these next-gen approaches. In the near-term, our membrane-bound IL-15 TCR-T cell therapy program is advancing towards an IND, which we anticipate submitting later this year. We remain very optimistic about our Hunter TCR discovery platform, which is firing on all cylinders. By expanding the library with proprietary TCRs, we increased the addressable market and the number of patients that might benefit from our single or multiplex TCR-T cell therapies. It is truly astonishing what this platform is capable of and I look forward to what the future holds for Hunter. In sum, bolstered by the early and encouraging clinical results, we believe 2023 will prove to be an exciting year filled with promise and progress for Alaunos as we advance our pipeline of innovative TCR therapies. I want to express my deepest gratitude to our patients, shareholders and employees for their support as we continue our mission to improve the lives of patients with solid tumors. We will now open the call to questions. Michelle?

Thank you. [Operator Instructions] Our first question comes from the line of Prakhar Agrawal with Cantor. Your line is open. Please go ahead.

Hi. Thanks for taking my questions and congrats on 4Q. So Kevin and team, my first question, have there been additional patients dose in patient number three in Q4 given enrollment progress as a key focus for the company. So appreciate any color here. And just to confirm that you have the green light from the FDA on the specific enhancements to the IND and there are no further regulatory approvals required? And I had a couple of follow ups.

Prakhar, good morning. Good to hear from you. With regards to patient enrollment, as we said, we are very excited about the progress that is being made and the interest in this trial stemming from our first objective clinical response. We are not going to report on a patient by patient basis, but we're going to look for the right venue to provide further updates on number of patients treated and the data associated with that. But we're feeling quite confident based on the interest that has grown and the excitement around the response and the data that we've seen thus far out of the first three patients. And with regards to the IND amendment in the fourth quarter where we added two additional TCRs and made certain enhancements in the clinical trial design to further facilitate and accelerate the enrollment, there are no outstanding questions from the IND, which is really shown our unique trial design and the relationship with the agency the fact that we have had multiple IND amendments with very minimal comments. So this is a unique trial design for sure, one that we believe is a differentiator for this company in quite a positive way and very excited about these driver mutations benefiting cancer patients.

Got it. Thank you. And the second question, the opportunity for multiplex TCR was noted in the press release and the comments for patients who are matching for more than one TCR. So maybe if you can expand on how this will be -- this could be implemented in the trial? Will it be a separate IND? And if you can expand on the scientific rationale for a multiplex TCR? Thank you.

Absolutely. I'll let Drew comment on that.

Yeah. Prakhar, good morning. Thank you for the question. We're very excited about the potential for multiplexing’s out of its TBD for now. But we're excited to see that roughly one in five of our patients that matched one of the TCRs, on our prescreening process have more than one match. So we do think that this is something that's feasible for us. We think that through our Sleeping Beauty non-viral system, we have a unique position to deliver more than one TCR. And then to your point about the rationale, just going back to more than one target at a given time has more than one chance to affect the cancer. So we're excited about that. And we're looking forward to bringing in IL-15 as our -- in the second half of this year for an IND amendment, maybe even potentially adding that to multiplexing in the long-term.

Got it. Thank you.

Thank you. And one moment for our next question. Our next question comes from the line of Yale Jen with Laidlaw. Your line is open. Please go ahead.

Good morning, and thanks for taking the questions. My first question is that in terms of you characterized the TCR sales that has certain characteristics. Could you elaborate more in terms of whether those aspects are functional or -- and then I have a follow-up as well?

Good morning, Yale. Yeah. It's a great question. Thanks for the question. We're very excited about what we're seeing in the translational assessments. And then specifically in regards to the cells that are persisting in the blood of our patients that have been treated are showing limited exhaustion. We're seeing team memory stem cells. And then within the tumor biopsies that have happened post treatment, we've seen retention of DHLA and the mutation by the tumor and T-cells that we've grown from those tumor subtills have had TCRT cells and those are indeed functional against the driver mutation. So really encouraged that our cells are getting there. They look to be functional and they look to have limited exhaustion.

Okay. Great. That's very helpful. Maybe a follow-up here, which is that giving you guys start to progress a little bit more into more patients and goes (ph). Are you guys thinking about any potential business development opportunities? And if so, how would those things could be define or characterize that you will still retain a good portion of the assets in house?

Sure, Yale. Like all biotechs, we're always in active discussion with potential partners and business development opportunities. We're very excited about the interest that our TCR-T platform targeting driver mutation has generated within discussions with other folks and we're also very motivated by the potential of our Hunter platform. We really believe that is quite interesting and novel because we can develop through this very high put -- throughput of single cell sequencing that Drew has mentioned, identify novel targets with proprietary IP, so a very strong patent position both to bolster our own TCR library of KRAS, TP53and EGFR mutations. But at the same time, Hunter identifies and has the capability of identifying other novel targets that would be of interest to potential partners. So we really have something special here and I believe strongly that others see that very opportunity and potential as well.

Okay. Great. That's very, very helpful. Maybe just squeezing one more. You currently assume you have a certain level of debt. How would -- what's your thought in managing that and thanks.

Thanks for the question. As of year-end, our outstanding debt balance was approximately $16.7 million. We started principal repayments in September of 20 22 and we expect to have that fully repaid by August of this year.

Okay. Great. Thanks a lot. I really appreciate it.

Thank you. And one moment for our next question. Our next question comes from the line of Thomas Flaten with Lake Street. Your line is open. Please go ahead.

All right. Good morning. Thanks for taking the questions. Kevin, I was wondering if you could expand a little bit more on what qualifies you as Phase 2 ready aside from the patient number? Any other things we should be looking for there?

Thomas, good morning. When we look towards what we want to accomplish in the Phase 1, first and foremost, it's about safety. It's identifying a maximum tolerated dose and then it's also identifying the recommended Phase 2 dose. So those are going to be the three items that we look for, safety, maximum tolerated dose, recommended Phase 2 dose. And what's really nice is this patient design allows us to accelerate achieving this objective and that is why a relatively low patient number in Phase 1 is all that's required to achieve these objectives. So as you may recall, Thomas, we only had to dose one patient at the first dose level and because of the favorable safety profile that we've seen, we were able to accelerate that to the second dose level. So we're very excited. We also have a higher dose level you may recall because of the safety profile should be rather favorable. The targets we're going after these driver mutations by definition are at the core of the heart of the cancer and do not appear on healthy tissue cells like some of our other TCR competitors that are targeting different targets. So we believe we have a superior target in our driver mutation with our TCRs going after these targets that are only in the cells of the cancer. And therefore we can use higher doses and we believe that will lead to greater efficacy.

That's great. I appreciate the color. And the enrollment target that you have of 12 to 15, can we assume that, that would be achievable with the current stable of TCR? So the 12 or does that imply that you're going to add a few more during the year in order to hit that enrollment goal?

I tell you, we feel very confident with the number of patients that we're seeing in our pipeline. Any additional TCRs are just building towards the future, building towards our goal of multiplexing. So as a reminder, anytime we add a TCR we can absolutely use it to start treating patients right away. But we're very confident with what we see right now with the engagement of our PIs at MD Anderson that with our Phase 1 we will be successful in treating the required number of patients. And we'll do so in a very expeditious manner. And we have our own manufacturing capacity with our own employees being able to execute on that, being able to manufacture multiple products at the same time and what's nice with this as well with the cryopreservation, Thomas, is we're able to start manufacturing now earlier in the patient's journey. So we can manufacture products. It can be waiting in the freezer for when unfortunately, if a treatment fails a patient. We can then take that product that we made early in 2023 and then fuse that patient when they're ready. So it's really a very important enhancement that we made. We believe we're going to end up with more fit cells by taking the [indiscernible] earlier in the patient's journey. We can manufacture that product, cryopreserved the cells and then be ready for that patient when unfortunately if their failure -- if their current therapy fails them.

Excellent. And then just one final one, just a segue off of manufacturing. I believe that Abhi said during the call that the goal was to reduce the manufacturing timeline from 26 to 15 days. I was just wondering if you could comment on what's required to hit that goal and over what timeframe we might expect to see you guys kind of whittle that timing down?

Sure. And I do think Abhi hit some of the aspects, the kind of three aspects within that we're working on in addition to reducing costs. But Abhi, why don't you go ahead and talk to Thomas today?

Yeah, Tom. So we are investing in multi-pronged manufacturing strategy to really cut down our manufacturing time. We are constantly investing in process development, closing the system, providing the automation in our manufacturing platform, And by doing so, we are very confident that we'll be able to reduce the manufacturing time to the 15 days as we reach to the commercialization space.

[Multiple Speakers] Sorry, sorry, go ahead.

And just wanted to highlight that how much cryopreservation has provided us the power of flexibility by utilizing that cryopreservation will be able to manufacture the better product and overall efficacy of the -- what I'll call overall quality of the bucket. (ph)

Thomas, just important I think to highlight here is one of the things that cryopreservation does, when fresh cells you had a patient that was ready to be infused immediately. So timing really mattered, right? Now the fact that we're able to manufacture the cells ahead of time in this Phase 1 portion of the trial with the cryopreservation, whether it's 26 days or 15 days, it's still earlier in the patient's journey where they're not quite ready to be infused yet. So the time is less relevant at this stage. So we have the time to be able by the time, as Abhi said, when we hit commercial, it will be reduced. That will be very important. But as of right now, the timeframe taking the manufacturing to cells is less relevant because the cells will be frozen down and be available immediately when the patient is ready.

Excellent. Appreciate it. Thank you guys.

Thank you, Thomas.

Thank you. And this does conclude today's question-and-answer session. Ladies and gentlemen, this also does conclude today's conference call. Thank you for participating. You may now disconnect. Everyone have a great day.