Good morning, ladies and gentlemen, and welcome to the Humacyte Fourth Quarter and Year-End 2022 Results Conference Call. Currently, all participants are in a listen-only mode. Later we will conduct a question-and-answer session and instructions will follow at that time. As a reminder, this conference call is being recorded. I will now the call over to Lauren Marek with LifeSci Advisors. Please go ahead.

Thank you, operator. Before we proceed with the call, I would like to remind everyone that certain statements made during this call are forward-looking statements under U.S. federal securities laws. These statements are subject to risks and uncertainties that could cause actual results to differ materially from historical experience or present expectations. Additional information concerning factors that could cause actual results to differ from statements made on this call is contained in our periodic reports filed with the SEC. The forward-looking statements made during this call speak only as of the date hereof, and the company undertakes no obligation to update or revise the forward-looking statements, except as required by law. Information presented on this call is contained in the press release we issued this morning and in our Form 10-K, which will be filed today and may be accessed from the Investors page of the Humacyte website. Joining me on today's call from Humacyte are Dr. Laura Niklason, President and Chief Executive Officer; Dale Sander, Chief Financial Officer and Chief Corporate Development Officer; and Dr. Heather Prichard, Chief Operating Officer. Dr. Nikalson will provide a summary of the company's progress during the quarter and recent weeks; and Dale will review the company's financial results for the quarter and year ended December 31, 2022. Following their prepared remarks, the management team will be available for your questions. I will now turn the call over to Dr. Nikalson.

Thank you, Lauren. Good morning, everyone, and thank you for joining us for our fourth quarter and year-end 2022 financial results and business update call. Humacyte has made significant progress throughout 2022 in advancing our universally implantable, bioengineered human tissue product candidate, the HAV or Human Acellular Vessel. We're very close to completing enrollment in two trials of the HAV both in vascular trauma and in arteriovenous access, and we also continue to advance our earlier stage programs. As we begin 2023, we remain focused on advancing our HAV towards regulatory milestones and commercialization, beginning with the vascular trauma indication. During this call, I will review our recent highlights and the progress of our key programs before turning the call over to Dale for a review of our financial results, then we'll be happy to open up the call to your questions. I'll begin with our HAV program in vascular trauma. We're pleased that our Phase 2/3 V005 trial is nearing enrollment completion. We currently have a total of 63 patients, who received the HAV in the V005 trial, and an additional 17 patients, who've been treated with the HAV under our humanitarian program in Ukraine, bringing the total patients treated with the HAV for traumatic injury to 80. All patient results will be included in our upcoming BLA filing with the FDA. The efficacy of the endpoint of the HAV and trauma will be based on the 30-day patency in 50 patients from the V005 trial, who suffered vascular trauma in an extremity, either the arm or the leg. The primary efficacy analysis will not include torso injuries or iatrogenic trauma, which is trauma caused by physicians in patients, who were enrolled in the V005 trial. Although data from these patients will contribute to the safety database. Currently, in…

Thank you, Laura. As of December 31, 2022, we had cash, cash equivalents and short-term investments of $151.9 million, compared to the $225.5 million as of December 31, 2021. The $73.6 million net use of cash, cash equivalents and short-term investments for the year ended December 31, 2022, resulted from spending related to net operating activities for the period, including clinical and earlier stage research and development programs and preparation for our anticipated commercial launch. We have been prudent with our expenditures and our use of cash for 2022 was approximately $8 million less than we had budgeted. We will continue to monitor our rate of expenditure, and we believe that our cash, cash equivalents and short-term investments are adequate to fund operations through the end of 2024, past our current expected time lines for potential approval of the HAV in vascular trauma. There was no revenue for the fourth quarter of 2022, compared to $177,000 of revenue for the fourth quarter of 2021, and revenue was $1.6 million for the year ended December 31, 2022, compared to $1.3 million for the year ended December 31, 2021. Revenue in all periods related to grants supporting the development of HAV. Research and development expenses were $15 million for the fourth quarter of 2022, compared to $16.3 million for the fourth quarter of 2021, and they were $63.3 million for the year ended December 31, 2022, compared to $61.3 million for the year ended December 31, 2021. The decrease for the quarter ended December 31, 2022, compared to the prior year quarter resulted primarily from a decrease in non-cash stock-based compensation expenses. The increase during the year ended December 31, 2022, compared to the prior year resulted primarily from increased personnel and materials expenses designed to support expanded clinical and research initiatives…

Thank you, Dale. To conclude, we've made significant progress throughout 2022 in both our clinical and our preclinical programs. We're excited to move closer to our BLA filing in vascular trauma, and we will be pleased to close the enrollment soon in our AV access trial, the V007 trial. 2023 is shaping up to be a significant year for Humacyte, and we are poised to build on our momentum from the past year, and we look forward to providing further updates as we approach clinical and regulatory milestones. Operator, we're now ready to take questions.

Thank you. [Operator Instructions] Our first question comes from the line of Ryan Zimmerman with BTIG. Please proceed with your question.

Good morning. Thanks for taking the questions, Laura and Dale and appreciate it. I want to talk about the V005 trial a little bit. It sounds like the FDA maybe had some feedback for you guys in terms of how you think about usage of the HAV in trauma? Or I was wondering if you could kind of speak to that specifically and how that impacts both utilization going forward and commercialization once you get that product to the market?

Yes. So we're really happy that we've gotten clarity and direction from the FDA as far as number of patients and the analysis in V005, as well as the targeted indication statement. The indication statement is really based on the fact that our V005 trial has always been designed for patients, who do not have autologous vein/saphenous vein for treatment of their vascular injuries. The contraindication for saphenous vein and for synthetic graph really falls out of both the V005 trial design, but also the fact that most traumatic injuries actually are not deemed suitable for synthetic grafts. So for example, penetrating injuries, but also many blunt injuries that are -- have contaminated wounds are all known to be at high risk for infection. And so if you speak with most vascular or trauma surgeons, most of these people will indicate that a synthetic graft is really not suitable in many or most cases of trauma. So the limitation as far as the indication really speaks to patients who do not have available saphenous vein, which is the enrollment criteria in the V005 trial. Something that we didn't speak to in our comments earlier is the fact that, with an accelerated approval, the FDA also asked that we perform a confirmatory study after we gain approval -- after we're granted approval in the trauma indication. And we're currently designing that Phase 4 confirmatory study with the FDA right now. Our anticipation is that the design of the confirmatory study would, sort of, throw the gates open to a broader patient population, and completion of that study, we would anticipate would allow us to broaden the indication. But that said, the indication statement, we do not believe, is very narrowing from the standpoint that having something that's immediately available that doesn't require the hour of saphenous vein harvesting and that resists infection is going to be highly sought after for surgeons who are treating acute traumatic injury.

Okay. And just to be clear though, what is the new -- what is the -- is it limited -- the HAV is limited to extremity injuries because your -- I appreciate that you're including some of those other injuries in the safety data, but I just want to be clear about where you can -- or you think potentially you can or cannot use the HAV after BLA?

So the indication statement is focused on extremity injury, because the data subset that we're analyzing in the trauma trial focuses on patients, who have at least one anastomosis in an extremity. So some of these patients have an anastomosis also in the pelvis or the thorax, but at least one anastomosis is in the extremity. This is -- the FDA asked us to do this because traumatic injury, as you would imagine, is very heterogeneous. And the focus on extremity injury was a way of, sort of, focusing on a slightly more homogeneous group of patients, although these patients still have a wide variety of injuries. The reality is that the current 6 millimeter diameter of the HAV is suitable for the anatomies that I've talked about. But if you talk about, for example, aortic traumatic injury, the HAV really isn't suitable there, because the diameter isn't a good match. So we believe that the extremity focus in the indication really doesn't change functionally where the HAV will be used very much.

Yes. Now that makes sense. Okay, and then just last question for me and then I'll hop back in queue. In terms of timing, I think we're, kind of, thinking middle of this year previously in terms of getting enrollment complete. I know you're bringing up some sites in Israel and Ukraine. Do you think the timing for the HAV V005 trial and still maintain completion kind of mid- ‘23? Or do you think you're maybe push it back a little bit just because of the nature of the patients you're targeting?

Well, it's always hard to predict enrollment in a trauma trial. Certainly, we're going to work as hard as possible to get the remaining six patients enrolled. We're targeting six. Technically, we need a minimum of four more enrollments. So I will say that our prior enrollment rate of one per month has picked up a little bit recently with the addition of the Israeli sites. If we're able to bring up the Ukrainian sites, I would expect that the enrollment would tick up above one per month, because frankly, the Ukrainian sites all by themselves enroll 1 per month or more. So again, hard to predict, but I would hope that in the next couple of months that we'll complete enrollment and then about 120 days after that, we would file.

Okay. Thank you for taking the questions, Laura.

Thank you. Our next question comes from the line of Matthew O'Brien with Piper Sandler. Please proceed with your question.

Hey, this is Phil on for Matt. Thanks for taking our questions. I guess just to piggyback off Ryan's question there. For the V005 trial, that 63 patient number is current and not at the end of 2022, which would imply you're adding, what, 7 over, call it a 1.5 quarters, almost two quarters. Can you just speak to the current pace of additions here for that remaining six? And then can you just touch on the delta between needing only four more, but you guys are going to go for six there?

Sure. Well, as I mentioned, the -- historically, the pace of enrollment in V005, which was negatively impacted by COVID for sure, just like every other trial in North America, but previously, we've been around one patient per month. That has picked up a little bit in the last couple of months with addition of these sites. So again, all I can say is that we think it will take a few months to enroll the four to six patients. The reason we're saying six right now is because with each of these patients and having very heterogeneous injuries. Our current strategy is to provide a little bit of a buffer or cushion slightly above the targeted number of patients of 50 that we've discussed with the FDA. But the reality is that we currently have 46 patients that fall into the category that the FDA would like us to focus on. And so, at a minimum, we would need four more patients to hit that target number of 50. I think one thing I do want to emphasize is that we've really been able to partner very well in recent months with the FDA and have had a very active dialogue with them. And getting clarity on the subset of patients that they were most focused on and the types of analysis they would like us to do and the patient number has really allowed us to be -- to provide a lot more clarity on our glide path for filing.

That's helpful. Thank you. And then just shifting gears really quickly. Are you preparing in any way for commercial activities? What's going on, on that front as you prepare for this stage and eventually making it to market for trauma?

Well, I'll answer that a little bit, and then I'll ask Dale and also Heather to weigh in a little bit more. But essentially, as you may recall, we began filling out our commercial team even in the latter part of 2021. So currently, we have staff in place to lead the commercialization effort with really a focus on health economics and market access and reimbursement, although we are bringing on a VP of Marketing in the next few weeks. So the groundwork that we're laying now is really around the cost-benefit analysis and the health economic analysis that we'll be able to bring to payers and to health care providers around the benefits that the HAV can provide the patients into the system. But I'll let Dale speak to staffing up for commercialization. And I'll also ask our COO, Heather Prichard, to speak to our commercial manufacturing readiness.

Yes. Thanks, Lauren, in that, certainly, beyond W. J. Scheessele, our Chief Commercial Officer, we did have a core marketing team in right now in addition to the budget impact model that Laura described, much of the emphasis are on the longer lead time items that need to be prepared for in advance of launch, and that includes preparing for the NTAP, pass-through reimbursement from CMS, which we think will be important to us. And also things that may seem mundane, like naming the product, but there are long lead time items that work is underway right now, which requires going through both trademark issues, as well as the FDA. Beyond that, there's certainly a great deal of effort going on to prepare from a manufacturing point of view, and I'll let Heather address that.

Thanks, Dale and Laura. From a manufacturing standpoint, we are on track, as you know, to be able to produce our product for commercialization. And we don't anticipate any complications, but we continue to prepare for our preapproval inspection and also update our modules to our BLA filing.

Very helpful. Thanks so much.

Thank you. Our next question comes from the line of Josh Jennings with TD Cowen. Please proceed with your question.

Hi, good morning. Thanks for taking the questions. Sorry to bring trauma indication again. But just wanted to make sure that the -- or get an update or just reiteration of the total addressable market. That hasn't changed, has it? And just with this update from the FDA, I assume no, but just wanted to get clarity there. And also, any incremental thoughts on ultimate pricing of the HAV once you get BLA approval.

Yes. We -- again, we don't see the total addressable market really being materially impacted by this initial indication statement. As you know, the HAV at 6 millimeters in diameter really is most suited for injuries in the upper and lower extremities. And as I mentioned earlier, aortic injury was never anything that we really contemplated in any of our financial models. So I think that the TAM really isn't impacted here. And again, although Humacyte would never advocate or market the product for any off-label use, I think the reality is that in trauma centers, the HAV will get pulled off the shelf and will get used in instances where surgeons feel it's best for the patient, independent of the letter of the indication statement. So I don't think the TAM is really addressed by these clarifications. I'll let Dale speak to product pricing.

Yes, Josh, good to talk to you. As you know, the pricing is a complex decision that generally isn't announced until the time of launch. I guess, if you were to dig back to our earliest SEC filings where we were required to put placeholders in there, there is commentary about potential price ranges, which at that time suggested something in the $25,000 per HAV range, although decisions around pricing will be made at the time of launch. That being said, I can tell you that the work we've done to date in terms of looking at the budgetary impact of using the HAV versus standard of care or other treatments. And also our discussions with hospital administrators would suggest that the price kind of strawman that we originally had is certainly acceptable and pricing could be even somewhat higher than that, particularly within the vascular trauma market. So that's everything we've seen kind of progressed since our original SEC filings close to two years ago, and nothing has changed that other than to indicate even more so the viability of pricing at that level within this indication due to the major cost savings associated with things such as avoidance of amputation and avoid some infection and the impact those have on length of stay in the hospital and other costs.

Excellent. And thanks for that and I want to just follow-up on -- just about we get some questions on the pace of enrollment for V005. And our understanding just in terms of connecting the dots with the ultimate market opportunity. I mean, can you just review some of the hurdles and enrollment? I mean our understanding talking to vascular surgeons, these patients are very hard to consent. And so once you have approval, that total addressable market that you guys have laid out is realistic. But just wanted to get your thoughts on just the pace of enrollment and how that translates into the total addressable market and some of the hurdles that your investigator sites face enrolling these patients.

Yes, Josh, that's a really excellent question. So the number of vascular injuries in the U.S. is what it is. It's tens of thousands per year even in peace time. But again, the hurdles and the difficulties that we've encountered enrolling V005 really just highlights the reason that extremely few interventional trials have ever been done in this type of traumatic injury. By definition, if a patient is injured enough that they require acute repair of an artery that is big enough to be treated by the HAV, that means that this patient is essentially bleeding to death. Typically, these events occur in the off hours in the middle of the night. And also, by definition, if a patient is bleeding that much, they're typically not able to provide consent. So targeting patients with injury severe enough to require acute repair, but finding patients, who are not sedated or who are conscious and able to give consent or have a family member standing right next to them who can give consent that just becomes a vanishingly small pool. So the realities of human clinical research are that, of course, we have to abide by all regulations and consent every patient. But for this type of trial, it just places enormous hurdles on enrollment. So Humacyte continues to believe that the realities of the marketplace are very different from that sort of tightly constrained limitations that we've had to deal with in this trial.

I appreciate that. And just lastly, thinking on the pipeline and the different indications that you're pursuing for HAV, is there any way to think about the prioritization or is it in terms of how you're going to allocate investment dollars to each of those pipeline projects? Thanks for taking all the questions.

Well, the pipeline products that we're focused on most intensely are the coronary artery bypass graft, the small-caliber vessel as well as the biovascular pancreas. Now both of those -- both of those product candidates are in large animal trials. So we're in primates for both of those candidates, which is very exciting. We're certainly pushing forward with large animal implantations in the CABG application and really filling out the preclinical database for that indication. And the same thing is true on the biovascular pancreas. That said, the total dollars, even for primate work, because the numbers of primates aren't hundreds, it's on -- it's single digits or low double digits, so that's on the order of several million dollars for those programs, which is really a small total fraction of our total spend. Because obviously, with active Phase III clinical programs in a couple of different areas and fully scaled manufacturing, the vast majority of the spend is still going there. So we've made strategic decisions to continue to push forward what we believe are incredibly important programs for building the value in the company. But the total spend for 2023 on these pipelines as a fraction of the total budget is actually pretty small. But we think there's outsized value there.

Thanks a lot, Laura.

Thank you. Our next question comes from the line of Suraj Kalia with Oppenheimer. Please proceed with your question.

Good morning, Laura Dale, can you hear me all right?

Yes.

Yes. Perfect. Congrats on all the progress. So Laura, just following up on V005, and forgive me if I got my numbers wrong, wasn't the trial originally supposed to enroll 75? I guess, where I'm headed is, during your discussions with the FDA, were there any questions about efficacy in non-extremities, which led to the 50 number? Just trying to understand this new number and the difference in adjudication for efficacy versus safety, if at all.

Yes. Suraj, those are very good questions. So guidance that we've been providing to yourself and to the market, really since the summer of 2021 has been that we expected to enroll approximately 75 patients give or take, in V005 before we could file. And that was really an estimate based on what was then ongoing discussions with the FDA about which patient subset and -- we would focus on and what the total number of patients required would be. So currently, as I mentioned, we're at 63 total patients. But the 50 number, as a subset, again, was really an effort by the FDA to focus on a set of patients that was more homogeneous. So the number of -- so just to be specific, the number of torso injuries that we have in the trial is actually pretty small. It's only five patients. And the extent of the injury in those patients is really a very different ball game because if you have vascular disruptions, significant vascular disruptions in your torso, by definition, your survival and mortality is just a very different thing than if you have a limb vascular injury. So the FDA wanted to focus again on a more homogeneous set of patients. And that's also why they had us exclude the iatrogenic patients. So we have -- gosh, I don't know, 10 or 12 iatrogenic injury patients, which the FDA views as actually a healthier patient subset because these wounds tend to be in a more sterile environment. They tend to be more discrete. So the FDA actually asked us for purposes of statistical analysis to carve out patients with severe, oftentimes fatal injuries, which were the torso patients, and then perhaps more discrete injuries, which were the iatrogenic patients. So that left sort of the majority of the patients in the middle with limb injuries. And vascular injuries in the limb really are the majority of vascular injuries that occur in both the civilian and military settings. So again, this is focusing on the majority, but trying to get a slightly more homogeneous population. But the number of -- yes. So -- but the 75 number was not a hard number. It was always our estimate.

Fair enough. Laura, on V007, two additional patients remaining to be enrolled. Obviously, this is an open label. So I'm curious just given what's happened in V005, why do we still need -- is there some statistical issues that we are still -- we need to get to 240? Just trying to understand the difference between in the FDA's approach here also.

Well, certainly, the V007 trial is “open-label," but I just want to emphasize that Humacyte is not privy to the results. This is a prospective randomized trial that is open label to the investigators, but Humacyte and Humacyte staff are blinded. And we are just following the trial protocol that we agreed to with the FDA a number of years ago. And the target patient number of 240 was based on the power calculations that we performed at the outset of the trial. So we've just been trying to hue to what we agreed to with the FDA. And again, these patients are obviously -- dialysis patients are obviously not as acute as trauma patients. These surgeries are elective and the enrollment rate really took a hit during COVID, as we know. So we're just pleased to be finally wrapping up this trial and getting to the enrollment target that we agreed to with the agency.

Fair enough. And Laura, finally from my side, I'll hop back in queue, with JDRF, congratulations on that partnership. The BVP, is that going to involve, I shouldn't say plain vanilla iPSCs, but are you all going to edit in any genes, knock out any genes, any time lines? Any additional color would be greatly appreciated. Thank you for taking my questions.

Yes. So we are focusing on stem cell-derived islets. I mean we're taking a sort of a multiplexed approach. We're looking at the potential of using cadaveric native islets as part of the BVP program, but we're also looking very closely at stem cell-derived islets because, obviously, these -- that brings in manufacturability and control of islet supply, which is going to be very important in any commercial setting. We are certainly looking at immune privileged iPS cells. I do not believe we've yet shared with the broader investment community what exact types of immune privilege we're looking at. But I will generally say that as a general rule, overexpressing genes and adding in new stuff into a cell line that's then going to be therapeutic for a patient is generally a little harder from a regulatory standpoint than taking stuff out. So in other words, removing genes that might be immunogenic, we anticipate will be an easier path forward rather than overexpressing or adding in new proteins, which might add more regulatory hurdles.

Got it. Thank you.

Thank you. [Operator Instructions] Our next question comes from the line of Bruce Jackson with The Benchmark Company. Please proceed with your question.

Hi, good morning, and thank you for taking my questions. Quick follow-up on the pre-approval net inspection for manufacturing, is that scheduled yet?

Heather, do you want to take that?

No Bruce we -- I'll go ahead. Yes.

No, Bruce. Nice to talk to you. We have not had that scheduled yet. So that pre-approval inspection will be scheduled by the FDA after they get our filing, our BLA filing. So it will be scheduled by them after we file.

Okay. Great. And then one quick follow-up on the earlier stage programs. Will there be any publications, presentations, et cetera, on the CABG program or the BVP program this year?

Yes. So we certainly expect that. We are -- we have made submissions to various national, international meetings already on the BVP program, and we expect to continue to present on the CABG program. I'm not really in a position to let you know which meetings we're presenting at, but these are both active primate level programs. And so we're going to continue to keep the market appraised.

Okay, great. That’s it from me. Congratulations again on the progress during the quarter.

I'm showing no further questions in the queue at this time. This concludes Humacyte fourth quarter and year-end 2022 results conference call. Thank you all for participating. You may now disconnect your lines.