Welcome to the Iovance Biotherapeutics Second Quarter 2021 Financial Results. My name is Josh, and I will be your operator for today’s call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session. . Please note that this conference is being recorded. I will now turn the call over to Sara Pellegrino, Vice President, Investor and Public Relations at Iovance. Sara, you may begin.

Thank you, operator. Good afternoon and thank you for joining us. Speaking on today's call we have Fred Vogt, our Interim President and Chief Executive Officer; Igor Bilinsky, Chief Operating Officer; Jim Zigler, Senior Vice President, Commercial; Dr. Friedrich Finckenstein, our Chief Medical Officer; and Jean-Marc Bellemin, our Chief Financial Officer. Dr. Madan Jagasia, our Senior Vice President of Medical Affairs is also on the call to participate in the question-and-answer session. This afternoon, we issued a press release that can be found on our Web site at iovance.com, which includes the financial results for the three and six months ended on June 30, 2021, as well as corporate update. Before we start, I would like to remind everyone that statements made during this conference call will include forward-looking statements regarding Iovance's goals, business focus, business plans, pre-commercial activities, clinical trials and regulatory plans and results, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, payer interaction, collaboration, cash position and expense guidance and future updates. Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filings. Our results may differ materially from those projected during today's call. We undertake no obligation to publicly update any forward-looking statements. With that, I will turn the call over to Fred.

Thank you, Sara, and good afternoon, everyone. I'm pleased to highlight our progress in the second quarter and first half of 2021 at Iovance during today's conference call. During this year, we have continued to advance our tumor-infiltrating lymphocyte, or TIL, pipeline. We've reported clinical data across for metastatic melanoma program, including our first clinical data in early line melanoma, as well as the new indications such as metastatic non-small cell lung cancer. For our lead TIL product candidate lifileucel in metastatic melanoma, our top priority remains our ongoing work to address FDA feedback regarding the potency assays for lifileucel to support our planned BLA submission. We are confident in our ability to address FDA’s feedback and complete our work on additional assays in a timely manner. We're engaged in ongoing dialogue with the FDA that we plan to continue through the second half of the year to support a BLA submission in the first half of 2022 as guided. Resolution of the potency assays is also an important next step towards progress in other late-stage clinical programs. Turning to our clinical pipeline updates. We now have clinical data showing the promise of TIL therapy in four different solid tumor types across their treatment settings to strengthen our confidence in TIL as a broad platform in next class of cancer treatment. Friedrich will summarize the key updates in a moment, but overall we are really excited about three key takeaways. First, our initial data in metastatic non-small cell lung cancer demonstrated 21.4% overall response rate in a heavily pretreated patient population. All of them have progressed on prior immune checkpoint inhibitor, or ICI therapy, which represents a significant unmet need for that patient population in non-small cell lung cancer. Next, lifileucel in post-anti-PD-1 melanoma continues to show increasing long-term durability.…

Thank you, Fred. I'm pleased to speak today about the progress of Iovance’s manufacturing and our in-house manufacturing facility, Iovance’s Cell Therapy Center, or iCTC at the Navy Yard, Philadelphia. Today, nearly 500 patients have received Iovance TIL with a continuing manufacturing success rate above 90%. Iovance has transformed TIL manufacturing from a lengthy single center academic process to a shorter, scalable, centralized GMP process yielding a cryopreserved product for shipment back to the sites where the patients are treated. Our current Gen 2 process is 22 days. We're also continuing to advance our TIL leadership position. We are already investigating in the clinic our Gen 3 process, which is 16 days to further improve Iovance TIL manufacturing efficiencies and deliver Iovance TIL to patients even sooner. We believe that our Gen 3 16-day TIL manufacturing process is the fastest in the industry at this time. We're excited to be completing the commissioning of our iCTC where all activities are proceeding as planned. As noted in today's press release, we have received IND clearance and plan to commence clinical manufacturing at iCTC in the near future to supply investigational items through therapies to cancer patients enrolled in our clinical trials. In addition, we’re now moving to commercial manufacturing readiness activities for Iovance TIL at iCTC. Commercial supply remains on track for 2022 with capacity to meet the demand for up to thousands of patients in multiple indications. To support our Iovance TIL manufacturing capabilities and pipeline, we have been sharply focused on building our robust and growing intellectual property, or IP portfolio. Our Gen 2 IP portfolio is covered by more than 25 granted or allowed U.S and international patents with expected exclusivity through 2038. In total, we have more than 700 patents and patent applications filed globally across major pharmaceutical markets and other key geographies. Iovance’s granted patents and patent applications include compositions and methods of treatment in a broad range of relating to the Gen 2 manufacturing process. Gen 3 manufacturing selected TIL products produced from core biopsies, stable and transient genetic modifications of TIL, tumor digest and fragment compositions and methods, including cryopreservation, and combinations of TIL with checkpoint inhibitors. We believe that our internal manufacturing and IP position have firmly established our leadership in developing and delivering TIL therapies for patients with cancer. I would now like to hand the call to Jim Zigler, our SVP Commercial to highlight our commercial lunch preparations. Jim?

Thanks, Igor. We continue our launch preparations with U.S. cancer centers, payers and others key stakeholders in anticipation of our first BLA submission in the first half of 2022. Our cross-functional team is focused on operational excellence to ensure a strong launch. The commercial organization maintains our dated approach to commercial readiness, and we are well positioned to scale our efforts based upon internal milestones and timing. Our medical affairs team continues robust KOL and clinical site engagement in preparation for commercial launch through education and scientific communication activities that are essential to building a strong foundation for launch. This team works closely with leading medical association, and partners with patient advocacy groups to increase awareness for Iovance TIL and lifileucel. In addition, we have increased scientific communication through publication and high impact journal and presentations at leading medical meetings that Friedrich will cover in more detail. Our commercial team is deepened on oncology and cell therapy experience. We are partnering with the leading U.S. cancer centers to build their TIL service line capabilities. We are also seeing a strong level of engagement and commitment by a significant number of sites. As we approach our BLA submission, we will ramp up our training and onboarding processes so that these sites are ready to treat patients upon approval. I would like to recognize our public policy and market access teams who are working to ensure timely and appropriate access for TIL cell therapy. Specifically this week, the Centers for Medicare & Medicaid Services, or CMS, finalized its proposal to expand the existing MS-DRG 18 to include lifileucel and other cell therapies. With this significant change, we expect that our TIL centers will experience a much more stable and predictable Medicare in-patient reimbursement landscape at launch. In turn, we anticipate that Medicare patients will have timely access to lifileucel. We thank key stakeholders who supported this approach and appreciate the steps CMS has taken to improve Medicare patient access to cell therapies. We look forward to working with CMS and other key stakeholders in the future, as refinements may be needed for this emerging class of therapies. In addition to CMS, we continue to engage national and regional payers to ensure patients with private insurance will have timely and appropriate access to lifileucel. The team also remains on track to deliver IOVANCECares at launch, which includes our proprietary chain of identity and chain of custody system. Our fully integrated patient management approach and our integrated approach to quality, IOVANCECares cell ordering platform and patient support programs reinforce our commitment to customer and patient centricity, which means understanding, anticipating and addressing their needs. I will now pass the call to Friedrich to outline our clinical updates.

Thank you, Jim. I am pleased to highlight recent clinical data updates as well as the status of our four ongoing clinical studies. Our drug development strategy focuses on cancer populations with high unmet need with substantial opportunities for TIL to make a meaningful impact. Since we have held recent conference calls to focus on the ASCO data and the non-small cell lung cancer data, I will briefly recap the highlights. First, as Fred mentioned, our clinical data updates and plenary presentations this year at AACR and ASCO included lifileucel in advanced melanoma patients who have progressed on anti-PD-1 therapy. And at ASCO, our first set of clinical data for lifileucel in combination with pembrolizumab in an earlier treatment setting was melanoma patients who were not used to anti-PD-1 therapy. In post-anti-PD-1 patients from Cohort 2 in our C-144-01 study, the long-term follow-up data showed an overall response rate, or ORR, of 36.4% and median duration response was still not reached at 33.1 months of median study follow up. Results from additional analyses suggest that early intervention was lifileucel at the time of initial progression on anti-PD-1 therapy may maximize benefit. For the post-anti-PD-1 patient population enrolled in Cohort 2, chemotherapy is the only currently available option and offers a 4% to 10% response rate and overall survival of only seven to eight months. We as well as KOLs continue to be very enthusiastic about the durability of response following one-time treatment with lifileucel in this very difficult to treat metastatic melanoma patients. We are very excited about the high impact publication of our Cohort 2 data in JCO in May 2021, with an accompanying editorial that outlines the transformative potential of TIL therapy. This publication will further help communicate our melanoma data to a broad international audience of oncologists.…

Thank you, Friedrich. My comments will reflect the high level financial results from the second quarter of 2021. Additional details can be found in this afternoon's press release as well as in our SEC filings. I will begin with our cash position. As of June 30, 2021, Iovance held $708.7 million in cash, cash equivalents, investments and restricted cash compared to $665 million on December 31, 2020. A strong cash position is expected to be sufficient well into 2023 to advance our operating plan, including pipeline development, commercial manufacturing readiness and launch preparations. Moving on to the income statement, our net loss for the second quarter ended June 30, 2021 was $81.4 million or $0.53 per share compared to a net loss of $63 million or $0.47 per share for the second quarter ended June 30, 2020. Net loss for the six months ended June 30, 2021 was $156.8 million or $1.04 per share compared to a net loss of $132.6 million or $1.02 per share for the same period ended June 30, 2020. Research and development expenses were $62.1 million for the second quarter ended June 30, 2021, an increase of $12.8 million compared to $49.3 million for the second quarter ended June 30, 2020. Research and development expenses were $118.1 million for the six months ended June 30, 2021, an increase of $11.8 million compared to $106.2 million for the same period ended June 30, 2020. The increase in research and development expenses in the second quarter 2021 over the prior year period was primarily attributable to growth of the internal research and development team and increase in cost related to manufacturing and our internal iCTC facility. The increase in research and development expenses in the first half of 2021 over the prior year period was primarily attributable…

Thank you. . Our first question comes from Michael Yee with Jefferies. You may proceed with your question.

Hi, guys. Thank you. Congrats on the progress. And thank you for the question. We had a question on clarifying the next steps on the potency assay. When you say you're going to submit data and meet with the FDA by the end of the year, can you walk through generally what you're focused on submitting? And then when you submit it, do you have to wait a certain number of days to get a meeting? And then you have to wait for the meeting minutes and then to update us, and therefore that fall into actual calendar 2022? Maybe just walk through the chronology of how that works, because that would explain when you'd be able to come back to the street and tell us the next steps. Thank you.

Michael, it’s Fred. I can answer that for you. The FDA interaction process is -- we're not disclosing the details of what we're doing right now with the FDA. But in general, as you know, there's different types of meetings you can hold with the FDA. They have submission timelines, and then the FDA responds after those timelines. And you host a meeting, for example, for a Type A meeting, it’s 30 days; for a Type B meeting, it's 60 days. You get feedback from the FDA ahead of the meeting. You have the meeting. And then typically 30 days later, you get a written response from FDA for most of these categories. We're not disclosing any of the detail of exactly what we're doing right now with the FDA, but we are executing on the plan that we described earlier, which is to have these interactions in the second half of 2021, which we're in right now. So please stay tuned. And we'll -- as soon as we can get some information that we think is significant and we can communicate, we'll certainly be communicating it.

But to clarify, you would probably not come back to the street on what the result of this stuff is until after you've met with them and all of that, which you're saying is by end of '21. So if I just do math on that, that’s calendar '22. Is that a fair conclusion?

No, I don't think that's fair. It very well could be -- and our intention is to have interactions in '21. And we very well could be communicating in '21. We just don't know right now.

Got it. Okay. Thank you.

Thank you. Our next question comes from Mark Breidenbach with Oppenheimer. You may proceed with your question.

Hi, guys. Congrats on the progress and thanks for taking the question. Just wondering, aside from the more detailed lung data from the basket study that you guys present later this year, should we be expecting any additional clinical presentations? And kind of a second part of the question is, do you see any sort of silver lining in the sense that your regulatory filings are kind of like synching up with your in-house manufacturing capabilities? So I guess I'm wondering how much of a COGS reduction we can expect from manufacturing once you translate the bulk of that to your own facility. Thanks for taking the questions.

Hi, Mark. It’s Fred. Why don’t I take the first part and then I'll ask Igor to answer the second part. On the first part, we're always looking for opportunities to communicate at medical meetings and there's some coming up end of the year. We haven't guided towards anything specifically there beyond the fact that we do hope to present more on the, call it, 3B data in non-small cell lung this year. But yes, we are looking. We're all trying to -- we're always trying to take advantage of that. And seeing the history of the company, we've made major use of medical meetings where we possibly could. Igor, do you want to answer some questions about the availability of iCTC?

Yes, happy to. Hi, Mark. Thanks for the question. So as we mentioned on the call today, we are pleased that the IND has been accepted by the FDA and we're getting ready to start clinical manufacturing at our iCTC facility in Philadelphia. We are also getting ready for commercial manufacturing in 2022 that could support multiple indications and potentially thousands of patients commercially. And the importance of running in-house manufacturing is really threefold. We can control our capacity, which in the industry is short, so we’re in control of our fate. We can reduce the cost of goods compared to what one could potentially achieve with contract manufacturing. And we believe we can also achieve higher quality by controlling the facility. So, Mark, I wouldn't be commenting specifically on the cost percentages, but as you can imagine the in-house facility can allow us to achieve lower COGS than outsourcing.

Thanks so much.

Thank you. Our next question comes from Ben Burnett with Stifel. You may proceed with your question.

Hi. Thank you very much. I was wondering if you could just talk about the regulatory strategy for cervical cancer. And I guess are we right to assume that the potency assays are rate limiting, and should we therefore be thinking about sort of a single BLA covering both indications?

Hi, Ben. It’s Fred. I don't know if people want to think about a single BLA. We haven't gotten to that and that's something that could go either way. We talked a little bit before about this I think. Right now, the potency assay is the gating item for all of our clinical programs, all of our registrational strategy. We think once we resolve the potency assay issue with FDA for melanoma, that should allow us to proceed with other clinical programs. However, we have multiple registrational programs now and we'd have to evaluate exactly how to bring those in front of the FDA. Our first priority above all is getting the potency assay resolved for melanoma.

Okay, understood. And then I guess just one more question. Is there a chance that we could see the results of the pivotal, like melanoma and cervical studies, prior to the BLA submission?

Yes. Well, when we get close to the BLA submission, that would be around the time where we would typically want to do an IRC read -- a more formal cut plus the IRC read of the data. And so at that point, it's fairly typical for companies to disclose something. I can't commit to anything at this point given where we are on the regulatory process. But you could foresee strategies where we might have that available not long before filing, for example.

Okay, makes sense. Thank you. I appreciate it.

Thank you. Our next question comes from Madhu Kumar with Goldman Sachs. You may proceed with your question.

Thanks. This is Rob on for Madhu. Just wondering, do you guys have any plans for updated assays? To what degree are points to address related to the actual assays to use versus the effect size or effect ranges for the current assays?

You got cut off partway through there, Rob. There is a big blank in your question there. Would you mind just repeating the first part of it?

Sure. So any updated plans for head and neck data? And then to what degree are the assays related to the actual assay to use versus the effect size of current assays?

The head and neck part got cut off. Sorry. So head and neck right now, we haven't indicated any plans on that right now. We're always looking for opportunities to do medical meetings where we can present that kind of data. So stay tuned on that. The effect sizes and the sort of the details of the assays, well, we're still in the conversation with FDA about which assay or assays we would use to evaluate potency. So the effect or whatever you're measuring in the assay, that could vary wildly by choice of assay, depending on the detection method what we actually look at, what we use systemically as stimulation for the method. So that's still stuff that we would work out with FDA typically later in the process. Once we've got agreement on an assay, we start to talk about the performance of the assay in quantitative terms, including acceptance criteria, and I think that's what you're asking about. Is that right?

Yes, for sure. That answers my question. Thanks so much.

And your next question comes from Boris Peaker with Cowen. You may proceed with your question. If your line is on mute, please unmute.

Operator, I can’t hear anything.

We’ll go to our next question from Mara Goldstein with Mizuho. You may proceed with your question.

Hi. This is Gabriel for Mara. Thank you for taking the question. I have a question around the next generation two that was discussed, IOV-3001 and 4001. I was wondering about the status of that and how should we think about how they are differentiated from current generations when translating into clinic? Thank you.

Sure. IOV-3001 is a monoclonal antibody product that's designed to offer an alternative to . So don't think of that as a TIL product. It's part of its whole regimen. IOV-4001 is in fact a TIL product. That's a TIL that has a genetic knockout or silencing of the PD-1 gene that we think will help -- we hope will help improve efficacy because it will . The cells will carry a bit of an immunity, if you will, to an inhibitory mechanism in the tumor microenvironment.

Thank you.

Thank you. . Our next question comes from Nick Abbott with Wells Fargo. You may proceed with your question.

Good afternoon. Thank you for taking my question. So, first one is, and I think I know the answer to the first one, but I have to ask it anyways. When we might see more of the first line melanoma data? But more importantly, if the data continue to support that scene at ASCO, what are the next steps in the frontline and perhaps more broadly, lifecycle management? You could be doing a second line trial, for example. And then I have a follow on. Thank you.

Yes, Nick, in the frontline melanoma data that we reported at ASCO, we’re always going to be looking for another conference to hopefully update that data and provide more information about how we're seeing things in that study. Obviously, the data was very promising with 86% ORR right now and some really -- 43% CR rate, very significant numbers in a patient population that in check only gets 33% response rate with pembro with a 6% CR rate. So these are things that are really, really interesting to us. We do view the future of TIL therapy as transitioning to frontline or early line therapy. However, of course, our focus remains on the late line indications where we think we have fast approval routes. And then over time, we can develop studies and work with the FDA on study designs that might allow us to economically bring forward the frontline indication.

Okay. Thanks. And then we mentioned 4001 just a minute ago. Can you talk about how that electroporation step is being integrated into the manufacturing process? Where that's occurring? And is this being inserted into Gen 3 type process or Gen 2? Just what does that overall timeline look like for 4001?

Yes. We haven't disclosed the details of exactly what we're doing in that process yet. Hopefully, we can do that at some point at a scientific conference. So don't assume it is electroporation. However, what we're doing there is, we think is very similar in terms of timing to Gen 2. So we view Gen 2 as sort of the optimal commercial timing for a product these days with a -- approximately 22-day manufacturing cycle. So this is something we're focused on. We’ll hopefully provide more detail on 4001 in a future meeting.

Okay. Thank you.

Thank you. Our next question comes from Asthika Goonewardene with Truist Securities. You may proceed with your question.

Hi. This is Bill on for Asthika. You have given some good anecdotes and insights on your FDA discussions for potency assays. For example, you don't require antigen specific reactivity and also you don't need a new study. And we really appreciate that. But are there any new anecdotes or takeaways that you can share at this time?

We're telling you when we have our meetings with all the analysts and all the investor community is what we're hearing from FDA as much as we possibly can, what they are saying roughly to us or what they've said in their guidance to industry, especially they're potency assay guidance that they put out about a decade ago now, which is effectively at the statement on this whole sole potency assay situation in the industry. I don't have any new anecdotes for you or anything that I can tell you specifically. All I can say is that we're engaged in a lot of discussions with them. And we think we can find a reasonable path to solution here on the potency assay situation, as we've been saying. And FDA, when you collaborate with them, they tend to want to work with you. So we're looking forward to having that collaboration with them and moving this forward.

Thank you. I appreciate it.

Thank you. Our next question comes from Colleen Kusy with Baird. You may proceed with your question.

Hi. Good afternoon. Thanks so much for taking our questions. So, obviously, work is well underway for Gen 3 manufacturing process. I guess how do you see the manufacturing process continuing to evolve and get better? What could a hypothetical Gen 4 manufacturing process look like?

Colleen, I can give you some thoughts on this. It's a little early to say exactly how this would play out. But the idea behind Gen 3 was we're trying to shorten the process more than anything. We want to speed it up. We're also trying to lower our COGS and make TIL manufacturing as efficient as we possibly can so that we can serve the maximum number of patients in the future. I don't know exactly what a Gen 4 would look like, whether it would be shorter or whether it be something more like IOV-4001 where we achieve some additional feature that has been integrated in the TIL manufacturing process. But all these things are on the table. Engineering is obviously something that's we're very interested in. As you can see, we've been licensing technology from NIH, as we announced recently. There's other modifications that we can make to TIL therapy. I don't know if that helps to answer your question, but it's something that we're heavily invested in and we've already launched the first -- Gen 2 really did change the game and Gen 3 is continuing to change the game. So I do expect more innovation here in the future. I'm just not sure exactly where it's going to be right now.

Great, that's helpful. Thank you. And for the retreatment arm in the basket study, how long will the interval be between TIL dosing and redosing? And would patients have received any other anticancer therapies?

For the retreatment in the basket study, we don't -- do you mean LUN-202?

Yes, sorry. Thank you.

Madan, do you happen to have that information?

Yes, absolutely. So the retreatment strategy is really on a case-by-case basis. So initially, patient should have had a response if they have subsequent progression. We definitely want the patient stabilized enough that they can do a resection, and that may or may not involve interim therapy before they can get ready for the second treatment with the TIL. So that's really -- it's a very case-by-case, and depending upon the treatment recommendation.

Great. Thanks for taking our questions.

Thank you.

Thank you. And I'm not showing any further questions at this time. I would now like to turn the call back over to Fred Vogt for any further remarks.

Thank you, operator. Thank you again for joining the Iovance second quarter and first half 2021 financial results conference call. We'd like to thank our shareholders and covering analysts for the support as well as Iovance employees for their hard work and contributions as we develop cell therapy for cancer patients. I think it's an exciting time at the company and we are unwavering in our commitment to advance and expand the TIL pipeline towards potential approval. Please feel free to reach out to our Investor Relations team if you wish to follow up. Thank you.

Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.