Good afternoon, and welcome to the Iovance Fourth Quarter and Full Year 2020 Financial Results Conference Call. [Operator Instructions] Now, I would like to turn the call over to speaker Sara Pellegrino, Vice President, Investor and Public Relations at Iovance. Please go ahead..

Thank you, Operator. Good afternoon, and thank you for joining us. Speaking on today's call, we have Maria Fardis, our President and Chief Executive Officer; Friedrich Finckenstein, our Chief Medical Officer; and Jean-Marc Bellemin, our Chief Financial Officer. We are also joined by Jim Zigler, Senior Vice President, Commercial.

This afternoon, we issued a press release that can be found on our website at iovance.com, which includes the financial results for the 3 and 12 months ended on December 31, 2020, 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 trial plans and results, potential future applications of our technologies, manufacturing capabilities, regulatory plans, feedback and guidance, 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 introduction, I will turn the call over to Maria..

Thank you, Sara, and good afternoon, everyone. I am pleased to highlight our 2020 progress as well as our 2021 priorities and all events during today's conference call.

During 2020 we continue to advance and broaden our tumor infiltrating lymphocytes or TIL platform across multiple indications including metastatic melanoma, cervical, head and neck and non-small cell lung cancers.

For lethal product candidate like the metastatic melanoma, we reported new and updated data from our ongoing C14401 clinical study demonstrating durable responses and our core two for one time treatment that like to do. So initiated a dialogue with FDA and learned that we need to continue refining the information from our potency essays.

We continue our work to refine existing assays as well as to develop new assays in pursuit of our biologics license application, or BLA, which is our top priority for 2021. And additional indications as we completed enrollment in two cohorts for life [ph] and advanced cervical cancer.

We've reported the initial clinical data for TIL in combination with pembrolizumab and head and neck cancer and the activated site for registration directed study of LN-145 in non-small cell lung cancer.

We believe that the growing body of clinical data across multiple late stage cancers coupled with combination of TIL and checkpoint inhibitors in earlier stages of disease, validate the significance and broad potential for TIL.

We also continue to execute toward all manufacturing and pre commercial activities in furthering our commitment to address the critical needs of cancer patients. I am very confident in the strength of our employees to deliver on this mission. We have an impressive 76% of our nearly 250 employees who have at least a year of cell therapy experience.

On the call today I would like to spend a few minutes highlighting the main indication. Then I will let Frederick highlight our recent clinical study update. I will begin with our first pivotal program lifileucel in advanced melanoma.

Metastatic melanoma is a common skin cancer accounting for approximately 96,000 patients diagnosed and 7000 deaths each year in the United States alone. We are focused on metastatic melanoma patients that have exhausted their most commonly used available care options and need alternative therapies.

In early January of 2021, we provided a corporate update that median duration of response, though has not been reached at 28.1 month of median steady follow up or Cohort 2 from our C-14401 clinical study. We as well as KOLs continue to be very enthusiastic about the durability of response following one time treatment like you saw.

For the post anti PD1 patient population similar to Cohort 2, chemotherapy is only currently available option and offering a 4% to 10% response rate and overall survival of only 7% to 8%. We intend to present the long term follow up data from Cohort 2 at an upcoming medical conference.

As previously mentioned, reaching agreement with FDA on the potency assay is a top priority for all events. Following a Type B meeting with the US FDA, during fourth quarter of last year, we reached agreement on the duration of clinical data follow up for our pivotal cohort for to support the BLA.

We did not reach an agreement with the agency on the potency assays to define TIL and continue our work to refine existing potency assays while developing new assays. While the length of time until BLA submission depends on future dialogue with the agency. We continue staying prepared for a BLA submission in 2021.

You plan to provide updates when available. Our second pivotal program is investigating LN-145 now also known as lifileucel in this C-145-04 study to support BLA submission in metastatic cervical cancer. Enrollment in both cohorts one and two of this study have been completed.

Patients in our pivotal Cohort 1 are post chemotherapy, whereas Cohort 2 includes posts anti PD1 patients. We believe that inclusion of both cohorts in the BLA may strengthen the potential label and reflect the expected upcoming treatment landscape in cervical cancer.

The resolution of the potency assay for life and new for melanoma is a key step toward our BLA submission plan in the cervical cancer indication. As a reminder, the FDA has previously granted both breakthrough therapy and fast track designation for lifileucel and cervical cancer.

Turning to our manufacturing facility or advanced Cell Therapy Center, or ICTC, the construction of clean rooms was completed in late 2020. Process equipment are now in place in the available clean rooms and activities in support of clinical manufacturing are expected to initiate in the coming months.

Commercial manufacturing remains on track for 2022 with capacity to meet the demand for up to 1000s of patients. Iovance have transformed to manufacturing from a lengthy academic process to a shorter, scalable, centralized GMP process, yielding a cryo-preserved product. Our Gen 2 process is 22 days.

To date, more than 400 patients have received Iovance TIL with a continuing success rate above 90%.

We have also built on continued to our arguments our intellectual property which is covered by more than 20 granted or allows U.S and international patents for compositions and methods of treatment in a broad range of cancers leading to the GEN 2 manufacturing process.

Our Iovance IP portfolio includes patent applications and granted patents directed toward gently manufacturing, selected TIL products, stable and fancy and genetic TIL modification, cryopreservation and combination of TIL with checkpoint inhibitors.

Turning to our commercial launch preparation, the advance team is currently focused on KLO [ph] engagement, fight activation and training, TIL education and awareness, patient access and other readiness activities.

Our priority is to ensure launch success while taking a gated approach to commercial readiness, expenses and headcount prior to be in a submission. Our medical affairs team works with a network of treating healthcare professionals or HCPs, and patient advocacy groups to ensure that the information about tools available to interest that organization.

A core commercial team continues to partner with the leading U.S cancer centers to build their TIL service line capabilities and the intensive skill of training and onboarding upon submission.

Our market access team continues to meet with the private payers and the Centers for Medicare and Medicaid Services, or CMS to ensure patients have appropriate and timely access to lifileucel.

We believe that CMS and payers recognize the unmet need and clinical value of lifileucel as well as the potential benefits for patients with metastatic melanoma. We are also pleased that the development and progress of our events [ph] cares program.

Our goal is to deliver a best in class, sell ordering and patient support system that assists the patients at every step of the process. I will now pass the call to Frederick to outline our clinical study updates including the enrollment status, as well as introduction of new cohorts and treatment regimens into our existing studies.

Frederick?.

Thank you Maria. I am pleased to highlight today that we are currently recruiting patients for four clinical studies. Our drug development strategy focuses on cancer populations with high unmet need with substantial opportunity fulfill to make a meaningful impact.

Our C-145 or clinical study in advanced cervical cancer has completed and closed enrollment in the first two cohorts while we continue to recruit a third cohort of anti PD1 naive patients to receive two plus pembrolizumab. Recruitment also remains underway in our IOV-COM-202 study in solid tumors.

The IOV-COM-202 study and second line non-small cell lung cancer and the IOV-CLL01 study and CLL SLL.

As we move ahead with TIL alone and in combination with approved treatments in different indications and various stages of cancer, the COVID-19 pandemic may impact the pace of enrollment, particularly across cohorts with earlier line patients, which may improve as COVID-19 abates.

A lot for this call I focused on the activation of IOV-LUM 202 clinical studies. Today I will highlight our current data and strategy and head and neck cancer as well as the recent updates and inclusion of new cohorts in the IOV-COM-202 basket study.

Head and neck cancer remains an important indication for Iovance and we are particularly encouraged by the initial clinical data for two therapy LN145 in combination with pembrolizumab that was presented at the society for the immunotherapy of cancer or should see annual meeting in November of 2020.

We are also excited about the potential Foothill in combination with pembrolizumab and other solid tumors. The city poster highlighted nine patients with head and neck squamous cell carcinoma or HNSEC from cohort to 2A and the IOV-COM-202 basket study.

These patients had not previously received treatment with checkpoint inhibitors, but may have received prior chemotherapy. Following LN-145 in combination with pembrolizumab overall response rate for ORR was 44% and median duration of response have not been reached at 8.6 months of median study follow up.

As these are small patient numbers, we find the results to be very promising or with checkpoint inhibitor monotherapy and checkpoint may its head and neck cancer patients ranges from 15% to 18% in the literature. We look forward to gathering additional data to present an upcoming conference in the future.

Cohort 2A has now been expanded to include up to 19 patients. Regarding our C-145 or three clinical study of LN-145 alone head and neck cancer, we achieve targeted enrollment and close the study to enrollment.

Before I hand the call to Jean-Marc I would like to highlight additional updates in our IOV-COM-202 basket study, which now includes seven total cords across melanoma head or neck and non-small cell lung cancers.

As Maria mentioned, we are very excited about the potential for to offer an option for many different patient populations in multiple indications.

In this basket study, early line patients in each indication received two plus pembrolizumab second to nine months small cell lung cancer patients receive two plus ipilimumab, nivolumab and later lung cancer patients with melanoma and non-small cell lung cancer receive TIL alone.

Recent updates include the addition of the new melanoma cohort, the new lung cancer cohort and as mentioned previously, the expansion of the head and neck cancer cohort.

Our newly added Cohort 1C will investigate LN-144 manufactured with our 16 day third generation or Gen3 process and metastatic melanoma patients who have received one or more prior systemic therapies.

Cohort 2A and head and neck cancer which is evaluating LN-145 in combination with pembrolizumab was expanded to include up to 19 head and neck cancer patients who are not used to immune checkpoint inhibitors.

And our new Cohort 3C will provide an alternative option to standard chemotherapy and non-small cell lung cancer offering two plus pembrolizumab, nivolumab and non-small cell lung cancer patients who have received one prior systemic therapy.

The three non-small cell lung cancer cohorts in this basket study together with the second line patient population and our IOV-LUN-202 registration supporting study allow us to cast a broad net to address the unmet needs of non-small cell lung cancer.

I will now hand the call over to Jean-Marc to discuss our fourth quarter and full year 2020 financial results..

Thank you, Frederick. My comments will reflect the high level financial results from a fourth quarter and full year 2020. Additional details can be found in this afternoon's press release, as well as in our annual report on Form 10-K filed with SEC. I will begin with our cash position.

As of December 31, 2020 Iovance held $635 million in cash, cash equivalents, short term investment and restricted cash compared to $312.5 million on December 31, 2019. This current cash position delivered on our commitment to end last year with at least $630 million in cash.

Our current cash positions include net proceeds of $567 million from a June 2020 common stock public offering. Our financial strength is expected to be sufficient into 2023 to deliver on our pipeline programs.

Moving to the income statement, our net loss for the fourth quarter and December 31 2020 was $68.4 million or $0.47 per share, compared to a net loss of $63.6 million, or $0.50 per share for the fourth quarter ended December 31 2019.

Net loss for the 12 months ended December 31 2020 was $259.6 million or $1.88 per share, compared to a net loss of $197.6 million, or $1.59 per share for the 12 months ended December 31 2019.

Research and Development expenses were $52.4 million for the fourth quarter ended December 31, 2020; a decrease of $1.8 million compared to $54.2 million for the fourth quarter ended December 31, 2019.

Research and Development expenses were $201.7 million for the full year ended December 31, 2020; an increase of $35.7 million compared to $166 million for the full year ended December 31, 2019.

The decrease in research and development expenses in the fourth quarter of 2020 over the prior year period was primarily attributable to a decrease in manufacturing and clinical cost following the completion of enrollment in the pivotal cohorts for melanoma and cervical cancer.

The increase in research and development expenses in the full year 2020 over the prior four year period was primarily attributable to IR clinical cost, licensing fees and growth of the internal research and development.

General and administrative expenses were $16.1 million for the fourth quarter of 2020, an increase of $5.2 million, compared to $10.9 million for the fourth quarter of 2019.

General and administrative expenses were $16.2 million for the 12 months ended December 31, 2020 an increase of $19.3 million, compared to $40.9 million for the 12 months ended December 31 2019.

The increases in general and administrative expenses in the fourth quarter and full year 2020 compared to the previous year periods were primarily attributable to growth of the internal general and administrative team and our stock based compensation expenses. As of December 31 2020, there were approximately $146.9 million common shares outstanding.

Looking ahead, we are open to opportunities to top off a cash balance while being mindful of dilution. As such we have put at the market or ATM facility in place to raise up to $350 million. The ATM much like a shelf is a good housekeeping measure that may allow us to be opportunistic, in addition to an already strong balance sheet.

I will now turn the call back to the operator to kick off the Q&A session..

[Operator Instructions] First question is from Mark Breidenbach with Oppenheimer. Your question please..

Hey, thanks for taking the question and congrats on the progress this quarter.

Maria, I was hoping you could clarify whether or not the first patient has been treated in the IOV-LUN-202 study? And can you offer any thoughts as to when we might see long cohort data from the basket trial?.

Hi, Mark. Good afternoon. Thank you for the questions. We have not started patient dosing in LUN-202 although we do have a few sites that are activated, we have not committed to a data flow timeframe for our long data. If you recall, there's only two cohorts in our program that actually have patients in them.

One is cohort 3A and one is cohort 3B in the comp to acute study, we have highlighted in cohort 3AV, we have had challenges in patient enrollment and in cohort 3B, we are hoping to have additional patients with longer follow up to be able to present the data, but we have not committed to a timeframe for data flow..

Okay, but thanks, that's helpful in just turning to the cervical program.

You know, obviously, there might be more focused on Cohort 2, given the evolving standard of care, in frontline, cervical cancer, can you give us a sense for what you see as a meaningful efficacy bar for that you'd need to clear for checkpoint experienced patients in cervical and if we can expect to see data from the second cohort of this trial?.

Sure. So currently, the way we have designed the protocol for Cohort 2 we have these patients as post PD 1 unexpectedly they would have received chemotherapy as a prior line because that's just available care for them. So if you think about a third line therapy, the best we are aware of and there is no data that I'm aware of.

And I'll refer to Frederick in just a minute, that is for post-PD1 patients; what I believe for chemo and third line, this the bar is around 3% response rate mark.

In terms of cohort 2 data itself, we have blinded ourselves the same way as we have with our pivotal cohorts such as COVID, one in cervical, and we have not read out that cohort since we have talked to FDA. Frederick, I don't know if you want to add anything on the expected response rate for cohort 2 patient, similar patient..

No, that's correct. There is numbers for third line treatment. The three percent support right and that is interestingly true across a number of different therapies, all of them being chemotherapy. So it's all ranging in the about 33% range. .

Okay, super helpful. Thanks for taking the question. .

Our next question comes from Peter Lawson with Barclays. Your question, please..

Hey, thanks for taking my questions.

Mary, just on the FDA and the potency assay, what are the next steps and then in any way kind of asking for a more defined product?.

Hi, Peter, thank you for your question. We have from the time we met with the agency, which was back in early October of 2020. We have submitted a couple of packages to the agency. We have not received additional comments or questions from FDA. So we haven't received specific requests in any way.

We continue with our validation work with additional assets. And we expect to be providing that information to the agency in the coming weeks or months. So we don't have anything new from the agency and no additional questions have arrived..

Okay, thank you.

And then just with Gen 3 manufacturing does that in any way kind of generate a more refined product? And just kinds of a question around that as well as how many T cell clones are there in most of your products?.

Really good topic. Our Gen 3 is expected to be released under the same type of criteria as Gen 2. So from a clonotypes diversity perspective, we don't expect it to be different than our Gen 2. In terms of how many approximants clone types there are, we have released our repertoire data from our melanoma program and cervical program.

As an average what we see is around somewhere between 10,000 to 17,000 clonotypes per patient product..

Okay, thank you..

Our next question is from Biren Amin with Jefferies. Your line is open. .

Yes. Hi, guys.

Thanks for taking my questions on the cervical study across both Cohort 1 and 2, Maria, can you just talk about the lower bound on the 95% confidence interval that you need to exceed for regulatory purposes?.

Thank you for the question. Biren good afternoon. We haven't changed our statistical plans in any way. So we are still going with the existing plans that we had before. So we haven't changed anything.

The only thing that we are basically communicating to investors is there is a possibility of using Cohort 2 in addition to Cohort 1 we stand ready, should that be a need from the agency. And we are wondering whether that might be an ask because the landscape is expected to change with a potential chemo immunotherapy becoming frontline therapy.

So we haven't changed our statistical plan in any way..

So this statistical plan was based on Cohort 1, so is Cohort 2, then, you know, I'm sure you've made some assumptions that you need to exceed a certain level of efficacy for Cohort 2 as well. And given the patient populations PD1 experience, there's probably differences in terms of what your assumptions are between Cohort 1 and 2.

Is that is that accurate?.

I can't speak to the data view. As I noted, we are blinded to both Cohort 1 and Cohort 2 data. So it's hard for me to tell you what we are seeing.

I can tell you that I've commented on this before, when we read out the 27 patients before we had met that agency, and blinded ourselves, we did have patients that had prior checkpoint therapy, and we had responders in that group. And that was on the slides that we presented at ASCO.

But aside from that, we are not planning on changing our statistical approach in any way. We just are making sure that we are ready should the agency request cohort 2 to be added into the BLA that's all we're saying..

Okay. And then maybe just one question on cohort 3 fee in the basket study where you're combining with [indiscernible]. What's the rationale with this combination and this is an assignment to phase design.

So is there a thought that you could develop this into a pivotal cohort if you're seeing encouraging data?.

Just to make sure we are on the same page here and are you asking about the comp 202 program or still the cervical program?.

The comp 202, the basket study, the combination with [indiscernible]..

Sure, I'm going to ask Friedrich to comment on this?.

Sure, I think one thing to mention here is the population and in this cohort is non-overlapping with the IOV-LUN-202. So I think that is one rationale here is that we are broadening and covering additional populations across the non-small cell lung cancer patient population.

The further rationale for epinevo [ph] is that with this regimen, we're exploring priming of the tumor and T cell infiltration by administering enable prior to resection. So this is different from how we are doing this in IOV-LUN-202 for example.

So here the dosing is a single dose of EPI, and NIVO [ph], prior to resection, and then after resection, we are continuing the both comparable to how we are doing this and the temporal combination studies. So this is exploring a priming approach. That's the national rationale for this. .

Great, thank you..

Our next question comes from Reni Benjamin with JMP Securities. Your question please..

Hey, good afternoon, guys. Thanks for taking the questions and congrats on the progress. Maria, I'd like to maybe get a sense of the timing of the potential filings.

I think before at least I had, I was thinking about, you know, both melanoma and cervical going in very close to each other, it seems to me just kind of based on how things could unfold that melanoma could be a 2021 type of filing and cervical, kind of based on the work that needs to be done might be more 2022.

Am I thinking about that correctly? Or is there another way to think about it?.

Hi, Reni. Good afternoon. I don't know if I can necessarily deduct that. I think it really depends on resolution of the potency as a matter of FDA.

Given that we have completed enrollment into the cervical program, both cohorts 1 and 2 on and cohort 1 was completed if you recall, around third quarter 2020, we think we have sufficient amount of follow up possibly just for Cohort 1.If they asked record to that, of course we need additional follow up, but I don't think I can rule out submission of potential BLS for both indications in 2021..

Got it? Okay. And then, of course and it makes sense the combination studies with checkpoints.

But is there any other work that's being done to evaluate other combinations outside of checkpoints in these indications?.

Yes, that's a great question. We've actually thought about a number of different alternative combinations and different settings and lines. Typically, we are looking to see where we can take the tool product into earlier lines.

Looking at Steve Rosenberg data and PD1 naïve patients; this is highly encouraging, it showed us that it still is an earlier line of therapy, there may be additional responders and additional CRS that one can have. And so the initial thinking wasn't necessarily going into combination but going into an earlier line.

Now once we decide we're going to earn your line, typically a regulatory path is offered the patient available care in addition to TIL. And so since in most of the diseases we are in available care in front line, happens to be checkpoint inhibitors, we are in combination with checkpoint inhibitors.

But I do want to remind there has been data published in combining TIL plus other agents, TKI come to mind BRAF [ph] combinations have been published. And that data appears to have been possibly additive. Although many of these studies are not statistically significant in terms of the number of patients but there appears to be additively there..

Got it. I guess one final one for me in the melanoma study, you continue to do not reach the median duration.

Do you have any sort of a sense as to what the patients who are progressing kind of what they're moving on to and have any of them ever been retreated with TIL?.

Yes, we do collect that information as part of our database of certainly in certain cohorts. We also do have a retreatment cohort you might recall, it's called cohort three in our melanoma program. So they do have the opportunity to get retreated. Should they choose to do that? So yes..

Okay.

And we haven't seen any type of cohort -- we haven't seen any data from those patients, or is there any sort of an update that we have from that cohort?.

Yes, we haven't presented data from that cohort. Typically, we want to have sufficient number of patients before we can present data and long enough follow up. But yes, that cohort 3 allows for retreatment of patients that may be coming from cohorts 1, 2 and 4. .

Excellent. Thank you very much. Thanks for taking the question. .

Our next question comes from Mara Goldstein with Mizuho. Please go ahead..

Hey, great. Thanks for taking the question. I mean, I think this kind of dovetails on the last question about earlier lines of therapy. But in the non-small cell lung cancer study, the inclusion criteria, really just specify that patients have a single line of systemic therapy that includes checkpoint and chemo.

And so I'm just curious as to is that your anticipation that you will essentially be a second line? Or are you taking patients who've had more than one prior line of therapy?.

So Mara in the contour to study where chemo immunotherapy is defined as prior line, we are asking patients to be second line.

Does that answer your question?.

Yes, no, I appreciate that. Thank you. .

All right. And our last question comes from Nick Abbott with Wells Fargo. Your question please..

Good afternoon. Thank you for taking my questions.

First one Maria, can I just confirm that the next sort of submission to FDA on the potency assay would occur in this quarter? You said the next few weeks, so I'm not sure if they mean this quarter?.

Hi, Nick. Good afternoon. Yes, we have said that we are on track with completion of the validation work to provide the data to agency. I have always said in the upcoming weeks, two months. So that's not an incorrect statement. Still, we are still on target with our own internal activities..

Okay. And then, in terms of the, you mentioned that you've been validating the essay, so by that, because that can be concluded that you've tested all of the melanoma cohort for products without essay and I guess where I'm going with this is what would be the timeline between an agreement with FDA on the potency assay and the filing..

So just to kind of clarify the validation that we're talking about does not apply to our frontrunner assay that assay had been validated fairly, a few years ago, and that data was provided to the agency. And the clinical samples were, in fact to release based on that assay.

So that work was completed, when we are talking about validation of additional assay these are subsequent assay that we are talking to the agency. But to answer the second question, if that's what your question is, yes, one would have to run the clinical samples with the validated assay and provide that to the agency.

Depending on how many samples are asked, this is something that takes a few months to do, it shouldn't be a rate limiting step or submission from the way we're thinking about it..

So just to be clear, then you have run those clinical samples, or you would be able to wait until you get agreement with FDA that the assay is sufficient?.

I don't know if I can disclose the details, there are ways of doing both at the same time. So not every single sample needs to be run in advance of getting some degree of agreement, but some samples can be run, and we do run them just to test the range of an assay..

Okay. So that is, I'm sorry to belabor the point. So if we go ahead and we file in the next few weeks, then FDA agrees.

Some weeks after that, it's still possible you could file BLA before the middle of the year?.

Without going into too much detail, because you're right, it depends on what exactly the requests are, how clear they provide a feedback. I do want to remind we still need to read our data by IRC, the clinical data still need to be read out by IRC.

We have been waiting to make sure that the agency is comfortable with our approach and then read the clinical data by IRC..

Okay. And then just it's intriguing that you might be able to combine cervical data, cohort 1 with, not just cohort 2 melanoma potentially. But am I right and assuming the only Cohort 1? The greatest therapy designation [indiscernible] only to Cohort 1.

So how do you combine submission that has part of it is a breakthrough therapy and part of it doesn't?.

Really great question. Breakthrough therapy generally is a designation it doesn't dictate your label. So there's not a direct correlation of whatever it is you receive breakthrough therapy has to be exactly your label.

All it says is that the agency recognizes that this particular therapy for this patient population is unmet need and they are willing to work with this sponsor to expedite the development program..

Okay, fair enough..

Thank you. And there are no further questions. I would like to turn the call back to Maria Fardis for your final remarks..

Thank you again for joining the Iovance, fourth quarter and full year 2020 results conference call. Please feel free to reach out our IR team if you wish to follow up. Have a great rest of the day..

And ladies and gentlemen, thank you for participating in today's program. You may now disconnect..