Q4 2021 Iovance Biotherapeutics Inc Earnings Call

Yes.

Okay.

Welcome to the ILD biotherapeutics fourth quarter and full year 2021 financials yourself.

My name is Sherry 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 stuff.

During this session.

If you would like to ask a question. Please press Star then one on your Touchtone phone.

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 Ireland.

Sarah you may begin.

Thank you operator, good afternoon, and thank you for joining US speaking on today's call. We have Dr. Fred vote, our interim President and Chief Executive Officer, Dr. Igor Bilinski.

Chief operating officer, Jim Ziegler, our senior Vice President commercial Dr Fragrance, Benkenstein, our Chief Medical Officer, and John Martin, Our Chief Financial Officer, Dr. <unk> <unk>, our senior Vice President Medical Affairs is also on the call to participate in.

Q&A. This afternoon, we issued a press release that can be found on our website at <unk> Dot Com, which includes the financial results for the three and 12 months ended on December 31, 2021, as well as corporate update before.

Before we start I would like to remind everyone that statements made during this conference call will include forward looking statements regarding <unk> goals business focus business plan pre commercial activities clinical trials and regulatory plans and results research and preclinical activity potential future applications of our.

Our technologies manufacturing capabilities.

Regulatory feedback and guidance payer interaction collaboration cash position.

<unk> guidance and future update.

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.

Thanks, Sarah and good afternoon, everyone.

I am pleased to highlight our fourth quarter and full year 2021 progress that I have answering today's conference call.

In 2021, we continue to advance toward our first BLA submission.

Expanded our til platform into new indications and earlier treatment settings.

For a lethal therapy life of Leucyl, our top priority remains our planned BLA submission in metastatic melanoma.

We have continued ongoing work developing and validating our potency assays.

We are also engaged in discussions with the FDA during the second half of 2021, and we're confident in our current guidance, we anticipate a BLA submission during the first half of 2022.

Resolution of the potency assay.

Melanoma is also a key step towards regulatory plans in other indications.

2021 was our busiest year yet in terms of still data presentations over the past 12 months, we presented data in 118 patients across five indications and four solid tumor types.

<unk> medical meetings.

<unk> The American Association for cancer research or ACR meeting the American Society of clinical oncology or Astro meeting the society for immunotherapy of cancer or <unk> meeting.

We believe that this growing set of clinical data continue to demonstrate the power of the potential power of Vyvanse til therapy to become the next paradigm shifting treatment regimen for solid tumors.

Last year, we also opened the eyes and cell therapy center or <unk> in Philadelphia.

We have made significant progress in our internal manufacturing capabilities that ICT, SEC, which eagle will highlight further.

And we grew our organization to prepare for commercial manufacturing and launch.

Today, we have approximately 350 employees at the company who have on average for the four years of cell therapy experience.

We believe that the breadth and depth of talent within our organization. During this important time of <unk> growth is a testament to the potential of our IV, it's still therapy in solid tumors and our ability to maintain leadership within the field.

Looking towards 2022, our milestones include submitting our BLA for life Leucyl metastatic melanoma in the first half of the year.

Advancing til therapy in non small cell lung cancer, which Frederic will highlight.

Executing an update a registrational strategy in cervical cancer based on FDA dialogue and feedback in reflection of the evolving landscape of care in this indication.

Defining our strategy for til plus Pembroke combinations in early lines solid tumors, beginning with melanoma.

Initiating the first clinical study for <unk> 4001.

Genetically modified til product in which PD one as an activated.

And further advancing our research and next generation til programs to remain at the forefront of til therapy in solid tumors.

Operator: Welcome to the Iovance Biotherapeutics 4th Quarter and Full Year 2021 Financial Results call. My name is Cherie, and I will be your operator for today's call. At this time, all participants are in a listen-only mode.

Overall, we are confident the strength of vyvanse is positioned to be the global leader in developing delivering an innovative til therapies for patients with cancer.

We're well on our way to becoming a fully integrated organization to launch the first onetime cell therapy in solid tumors.

Operator: Later we will conduct a question and answer session. During the session, if you would like to ask a question, please press stars and 1 on your touchtone phone. 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.

Owning our manufacturing capability is the key to our success.

I'll hand, the call to your now to talk more about our progress there.

Thank you Fred.

During 2021, which is several multiples of the item til therapy center, or ICC, which is a 136000 square foot cell therapy manufacturing facilities.

We completed commissioning activities.

<unk> initiated two clinical supply from the ICC in the third quarter of 2021.

Sara Pellegrino: Thank you, Operator. Good afternoon, and thank you for joining us. Speaking of today's call, we have Dr. Fred Vogt, our Interim President and Chief Executive Officer, Dr. Igor Bilinsky, our Chief Operating Officer, Jim Ziegler, our Senior Vice President, Commercial, Dr. Frederick Finckenstein, our Chief Medical Officer, and Jean-Marc Bellemin, our Chief Financial Officer. Dr. Madan Jagazia, our Senior Vice President, Medical Affairs, is also on the call to participate 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 December 31, 2021, as well as corporate updates.

The first patient with cancer received til manufactured at ICD.

September 2021, as part of our ongoing clinical trial.

In parallel with clinical manufacturing, we are in truck and preparing the ICT seat for the BLA submission and commercial manufacturing upon the potential BLA approval.

Several important activities are now underway, such as validation activities and process performance qualification or <unk>.

In addition, we are getting ready for FDA pre approval inspections at both ICD.

And our contract manufacturing partners facilities, which we expect to occur soon after the BLA filing.

Turning to intellectual property or IP portfolio, we continue to build a robust and growing the portfolio to support our proprietary manufacturing processes as well as.

Sara Pellegrino: 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, research and preclinical activities, potential future applications of our technologies, manufacturing capabilities, Regulatory Feedback and Guidance, Payor Interaction, Collaboration, Cash Position, 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.

Our knowhow surrounding til therapy.

We currently own more than 35 granted or allowed U S antigen national tenants.

This IP covers two compositions and methods of treatment and manufacturing in a broad range of cancers, including jumped to patent rights that I expect it to provide exclusivity into 2038.

Oh granted patents as well as our filed patent applications are directed towards Gen. III manufacturing selected til products stable and transient genetic until modifications tumor digest and fragment compositions and methods, including cryopreservation.

Combinations of checkpoint inhibitors and <unk> products.

I would now like to hand, the call to Jim Ziegler to highlight our commercial launch preparations Jim.

Fred Vogt: With that, I will turn the call over to Fred. Thanks, Sara, and good afternoon, everyone. I'm pleased to highlight our fourth quarter and full year 2021 progress that I have answered in today's conference call. In 2021, we continue to advance toward our first BLA submission and expanded our TILT platform into new indications and earlier treatment settings. For our lead co-therapy, Lifelucel, our top priority remains our planned BLA submission in metastatic melanoma. We have continued ongoing work developing and validating our potency aspects.

Fred Vogt: We have also engaged in discussions with the FDA during the second half of 2021, and we are confident in our current guidance for the anticipated BLA submission during the first half of 2022. Resolution of the potency assay in melanoma is also a key step towards regulatory plans and other indications. 2021 was our busiest year yet in terms of TIL data presentations.

Thank you Igor throughout 2021 and into 2022.

<unk> team has made steady progress in our commercial launch preparations while maintaining financial discipline.

Our launch priorities include the Onboarding of our authorized treatment centers, our ATC payer engagement and related operational readiness activities.

Our cross functional teams continue to partner with leading U S cancer centers to build their tail service line capability.

Our training program is designed to ensure cross disciplinary teams can administer the LIFO leasehold treatment regimen upon FDA approval.

Our goal is to onboard at least 40 atc's for launch.

This number is informed by our assessment of the car T market, where claims data indicate that the top 10 centers account for.

Fred Vogt: Over the past 12 months, we've presented data in 118 patients across five indications and four solid tumor types at multiple medical meetings, including the American Association for Cancer Research, or AACR, meeting, the American Society of Clinical Oncology, or ASCO, meeting, and the Society for Immunotherapy of Cancer, or CITSI, meeting. We believe that this growing set of clinical data continues to demonstrate the power and potential power of IV antiteltherapy to become the next paradigm-shifting treatment regimen for solid tumors.

About 50% of the car T treated patients.

And the top 40 centers account for about 80% of the car T treated patients.

We expect a similar concentration across our atc's for the potential commercialization of LIFO leucyl.

Our longer term goal is to have enough sites.

That most patients in the U S can be within a few hours drive 2000, ATC offering LIFO Leucyl til therapy.

Fred Vogt: Last year, we also opened the Iovance Cell Therapy Center, or ICTC, in Philadelphia. We have made significant progress in our internal manufacturing capabilities at ICTC, which Igor will highlight further, and we are growing our organization to prepare for commercial manufacturing and launch. Today, we have approximately 350 employees at the company who have, on average, more than four years of cell therapy experience. We believe that the breadth and depth of talent within our organization during this important time of growth is a testament to the potential of our Iovance pill therapy in solid tumors and our ability to maintain leadership within the field. Looking towards 2022, our milestones include submitting our BLA for lifelucel and metastatic melanoma in the first half of the year, and Advancing Pill Therapy in Non-Small Cell Lung Cancer, which Frederick will highlight.

The planned timing and execution of key Onboarding and training is aligned to BLA related milestones to ensure just in time training and readiness at our ATC.

Although there is a significant amount of work that will occur between our BLA submission and launch our core commercial team has built the foundation to scale rapidly and efficiently.

Reimbursement is also a critical factor for patient access at launch.

And the last year, our market access team engaged commercial and Medicare payers responsible for more than 90%.

The covered lives as well as Medicaid states responsible for approximately 50% of the covered lives.

Based on these interactions we believe that payers appreciate the unmet need and the potential clinical value of <unk> for patients with.

Fred Vogt: Executing an updated registrational strategy in cervical cancer based on FDA dialogue and feedback in reflection of the evolving landscape of care in the syndication, defining our strategy for TIL plus PEMBRO combinations and early line solid tumors beginning with melanoma, and finally, initiating the first Iovance clinical study for IOV4001. Genetically Modified Till Product in which PD-1 is inactivated, and further advancing our research in next-generation till programs to remain at the forefront of till therapy in solid tumors.

<unk> melanoma cancer.

Our reimbursement strategies are designed to secure coding coverage and payment.

In 2021, Medicare expanded DRG 18 to include car T and other immunotherapies, including LIFO Luzon.

This is an important milestone achievement because upon <unk> approval hospitals will have more appropriate payment for Medicare beneficiaries.

Fred Vogt: Overall, we are confident in the strength of Iovance's position to be the global leader in developing, delivering, and innovating pill therapies for patients with cancer. We are well on our way to becoming a fully integrated organization to launch the first one-time cell therapy in solid tumors. Owning our manufacturing capability is the key to our success, so I will hand the call to Igor now to talk more about our progress there. Thank you, Fred.

We continue to engage payers and CMS as we planned for BLA submission and prepare for commercialization.

We are also pleased with the progress of our <unk> cares program, which remains on track for launch.

Our goal is to deliver a best in class cell ordering and patient support system that assist the patient.

Igor Bilinsky: During 2021, we achieved several milestones at the Iovance Cell Therapy Center, or ICTC, which is a 136,000 square foot cell therapy manufacturing facility. We completed commissioning activities and initiated TIL clinical supply from the ICTC in the third quarter of 2021. The first patient with cancer received TIL manufactured at ICTC in September 2021 as part of our ongoing clinical trial. In parallel with clinical manufacturing, we are on track in preparing the ICTC for the BLA submission and commercial manufacturing upon potential BLA approval. Several important activities are now underway, such as validation activities and process performance qualification, or PPQ runs.

<unk> and ATC every step of the process.

<unk> includes our proprietary chain of identity and chain of custody system.

Our patient management approach and our integrated approach to quality.

I will now pass the call to Friedrich taken Stein, our Chief Medical officer to highlight our clinical progress.

Thank you Jim.

Please to share highlights from our two clinical programs across the various data presentations from 2021.

Norma we presented updated cohort two data <unk> 2021 we've reported 36, 4% overall response rate or <unk> and the median duration of response or deal that was not reached 33. One months of median study follow up as assessed by investigators.

Igor Bilinsky: In addition, we are getting ready for FDA approval inspections at both ICTC and our contract manufacturing partners' facility, which we expect to occur soon after the BLA filing. Turning to our intellectual property or IP portfolio, we continue to build our robust and growing IP portfolio to support our proprietary manufacturing processes, as well as our know-how surrounding till therapy. We currently own more than 35 granted or allowed U.S. and international patents.

Each cohort two data continue to demonstrate the durability of onetime treatment with license and metastatic melanoma patients after anti PD one therapy.

Looking ahead for this year, we plan to report data from the pivotal cohort four and our other nano amongst on the FSS side as you can.

Review comedy in connection with the BLA submission.

We are also excited about the data for <unk> in combination with <unk> and checkpoint inhibitor naive melanoma patients.

Igor Bilinsky: This IP covers till compositions and methods of treatment and manufacturing in a broad range of cancers, including Gen 2 patent rights that are expected to provide exclusivity into 2038. Our granted patents, as well as our filed patent applications, are directed towards Gen III manufacturing, selected till products, stable and transient genetic till modifications, tumor digest and fragment compositions and methods, including cryopreservation, and combinations of checkpoint inhibitors and till products. I would now like to hand the call to James Ziegler to highlight our commercial launch preparations. Jim.

The most recent results presented.

<unk> 2021 demonstrated a 60%.

And 30% complete response and support the potential for this combination as earlier treatment for melanoma.

We look forward to enrolling additional patients to further defining our strategy in frontline melanoma during the coming year.

Also very excited about the proof of concept fulfill plus <unk> is an early treatment option.

Our vehicles and head and neck cancer patients, which we also highlighted.

Seems like you said tomorrow.

Overall response rates for till September well above the published response rates from timber alone in melanoma cervical and head and neck patients.

James Ziegler: Thank you, Igor. Throughout 2021 and into 2022, the Iovance team has made steady progress in our commercial launch preparations while maintaining financial discipline. Our launch priorities include the onboarding of our authorized treatment centers or ATCs, payer engagement, and related operational readiness activities. Our cross-functional teams continue to partner with leading U.S. cancer centers to build their kill service line capability. Our training program is designed to ensure that cross-disciplinary teams can administer the lipoleucel treatment regimen upon FDA approval.

So PD one therapies.

In additional solid tumor indications lung cancer patients continue to have an unmet need for new treatment options.

We presented our first clinical data set for <unk> as treatment for non small cell lung cancer.

We were very encouraged by the observed responses in heavily pretreated non small cell lung cancer patients who received one hallmark.

That makes therapies, including anti PD one therapy.

This data set was an important proof of concept.

Small cell lung cancer and provide us valuable learnings general earlier line patients in our ongoing ione as USD 202 study.

James Ziegler: Our goal is to onboard at least 40 ATCs for launch. This number is informed by our assessment of the CAR T market, where claims data indicate that the top 10 centers account for about 50% of the CAR T-treated patients, and the top 40 centers account for about 80% of the CAR T-treated patients.

We are enrolling second line metastatic non small cell lung cancer patients and the ILD.

202 study of 30 sites when engaging with the FDA about parameters will further legislation.

In cervical cancer as Phil mentioned, we are actively engaged in regulatory discussions.

James Ziegler: We expect a similar concentration across our ATCs for the potential commercialization of Life Esquire. Our longer-term goal is to have enough sites so that most patients in the U.S. can be within a few hours' drive of an ATC offering lipoleucel kill therapy. The plan, timing, and execution of key onboarding and training is aligned to BLA-related milestones to ensure just-in-time training and readiness at our ATC. Although there is a significant amount of work that will occur between our BLA submission and launch, our core commercial team has built the foundation to scale rapidly and efficiently.

Lastly, I am excited by the growth of our research pipeline as we look to enter the clinic. This year with our first genetically modified til therapy candidate <unk> 4001.

<unk> 4001 is a tiered product and activated PD one using the talent technology licensed from select us and has the potential to deliver until a PD one inhibition within a single therapy.

I will now hand, the call over to John Mark to discuss our fourth quarter 2021 financial results.

Thank you.

My comments will reflect the high level financial results from our fourth quarter and full year 2021.

James Ziegler: Reimbursement is also a critical factor for patient access at launch. In the last year, our market access team engaged commercial and Medicare payers responsible for more than 90% of the covered lives, as well as Medicaid states responsible for approximately 50% of the covered lives.

Details can be found on this afternoon's press release as well other.

The SEC filings.

I will begin with our cash position.

As of December 31, 2021.

$602 1 million.

Cash cash equivalents investments and restricted cash compared to $655 million on December 31, 2020.

James Ziegler: Based on these interactions, we believe that payers appreciate the unmet need and the potential clinical value of lipoleucel for patients with metastatic melanoma cancer. Our reimbursement strategies are designed to secure coding, coverage, and payment. In 2021, Medicare expanded DRG 18 to include CAR T and other immunotherapies, including lipoleucine.

Our strong cash position is expected to distributions into 2020 full to advance our mobility plan, including pipeline the government commercial manufacturing readiness and launch preparation.

Moving onto moving on to the income statement.

James Ziegler: This is an important milestone achievement because, upon life-or-death approval, hospitals will have more appropriate payment for Medicare beneficiaries. We continue to engage payers and CMS as we plan for BLA submission and prepare for commercialization. We are also pleased with the progress of our Iovance CARES program, which remains on track for launch. Our goal is to deliver a best-in-class cell ordering and patient support system that assists the patient. Physicians and APCs at every step of the process. Iovance Cares includes our proprietary chain of identity and chain of custody system.

Net loss for the fourth quarter ended December with your first one into 'twenty, one was $99 3 million.

<unk> 53 per share of which approximately $6 $3 million or more than <unk> <unk> per share were one time expenses.

This compared to a net loss of $68 4 million.

<unk> 47 per share for the fourth quarter.

<unk> 2000 twins.

Net loss for the full year.

<unk> 2021 was $342 $3 million.

$2.

23 per share.

Compared to a net loss of $259 6 million.

Friedrich Finckenstein: Our patient management approach and our integrated approach to quality. I will now pass the call to Friedrich Finckenstein, our Chief Medical Officer, to highlight our clinical progress. Thank you, Jim.

Wonderful.

<unk> per share for the full year period.

<unk> 2000 twins.

Research and development expenses were $75 6 million.

Friedrich Finckenstein: I am pleased to share highlights from our TILL clinical programs across the various data presentations from 2021. For example, in melanoma, we presented updated cohort 2 data at ASCO 2021. We reported a 36.4% overall response rate, or ORR, and a median duration of response, or DOR, that was not reached at 33.1 months of median study follow-up as assessed by investigators. These two data continue to demonstrate the durability of one-time treatment with lifeducal and metastatic melanoma patients after anti-PD-1 therapy.

For the fourth quarter ended December 31, 2021, an increase of $23 $1 million compared to $52 5 million.

For the fourth quarter ended December 31st two.

2020.

Research and development expenses were $259 million for the full year period.

December 31, 2021, an increase of $57 3 million compared to $201 7 million for the full year ended December sorts of first 2020.

The increase in research and development expenses in the fourth quarter of 2021 over the prior year period.

Friedrich Finckenstein: Looking ahead for this year, we plan to report data from the pivotal cohort 4 in our melanoma study as assessed by an independent review committee in connection with the BLA submission. We are also excited about data for TIL in combination with Pembrolizumab in checkpoint inhibitor-naive melanoma patients. The most recent results presented at SITC 2021 demonstrated a 60% ORR and a 30% complete response and support the potential for this combination as an earlier treatment for melanoma.

Primarily attributable to an increase in costs associated with growth of the internal research and development team, including stock based compensation expenses and increasing.

Cruising clinical trial costs and personnel related costs associated with <unk>.

The increase in research and development expenses in the full year of 2021 over the prior full year period was primarily attributable to growth of the internal research and development teams and then improve in the clinical trial cost and facility related cost associated with us.

Friedrich Finckenstein: We look forward to enrolling additional patients and to further defining a strategy in frontline melanoma during the coming year. We are also very excited about the proof-of-concept for Till Plus Pembro as an early treatment option in cervical and heterocytic cancer patients, which we also highlighted at ITC 2021. Overall, response rates for Till Plus Pembro were above the published response rates for Pembro alone in melanoma, cervical, and heteronect patients who are not used to anti-PD-1 therapies.

Sure.

<unk> expenses were up $23 million for the fourth quarter ended December 31st 2021, an increase of $7 7 million.

Compared to $16 1 million for the fourth quarter ended December 31 2020.

General and administrative expenses were $83 7 million for the full year period ended December 31, 2021, an increase of $23 5 million compared to $60 2 million.

Friedrich Finckenstein: In additional tumor indications, non-cancer patients continue to have an unmet need for new treatment of... Last year, we presented our first clinical data set for Iovance-TIL as treatment for non-small cell lung cancer at SIDC. We were very encouraged by the observed responses in heavily pre-treated non-small cell lung cancer patients who received one or more prior systemic therapies, including anti-PD-1 therapy.

For the full year ended December <unk> was the first one.

The increases in general and administrative expenses in the fourth quarter and full year 2021 compared to the period.

Prior year periods were primarily attributable to an increasingly cost associated with growth of the intermodal general and administrative team.

Friedrich Finckenstein: This data set was an important proof of concept for TIL in non-small cell lung cancer and provided valuable learnings to enroll early-aligned patients in our ongoing IOV-LUN202 study. We are enrolling second-line metastatic non-small cell lung cancer patients in the IOV-LUN-202 study at 30 sites while engaging with the FDA about parameters for further registration. In the service of cancer, as Fred mentioned, we are actively engaged in regulatory discussions. Lastly, I am excited by the growth of our research pipeline as we look to enter the clinic this year with our first genetically modified pill therapy candidate, IOV4001. IOV4001 is a TIL product with inactivated PD-1 using the TALENT technology licensed from Selectus and has the potential to deliver TIL and PD-1 inhibition within a single therapy.

These stock based compensation expenses and an increase in <unk> related costs.

As of December 31, 2021, there were approximately 157 million common shares outstanding.

We continue to focus on investments in four key areas outlined previously to ensure the growth on the strength of our value creation.

This include advancements and expansion of our clinical pipeline launch readiness, a strong cash position and manufacturing anti CTC, which will provide new cost efficiencies as we are able to shift work currently being done through contract manufacturers towards Cds.

I remain confident that by managing our investments across these priorities. We will continue to stay focused on the line of our funding with our corporate priorities.

With late stage clinical assets in our pipeline as well as a strong balance sheet and focused investment on loans preparation, we're also well positioned to execute our operating plan.

Jean-Marc Bellemin: I will now hand the call over to Zhamak to discuss our fourth quarter and full year 2021 financial results. Thank you. My comments will reflect the high-level financial results from our fourth quarter and full year 2021. Additional details can be found in this afternoon's press release, as well as in our SEC 5. I will begin with your cash position. As of December 31, 2021, Iovance held $602.1 million in cash, cash equivalents, investments, and restricted cash, compared to $635 million on December 31, 2020.

Jean-Marc Bellemin: A strong cash position is expected to be sufficient into 2024 to advance our operating plan, including pipeline development, commercial manufacturing readiness, and launch preparation. Moving on to the income statement, our net loss for the fourth quarter and December 31st, 2021 was $99.3 million, or $0.63 per share, of which approximately $6.3 million, or more than $0.04 per share, were one-time expenses. This is compared to a net loss of $68.4 million, or $0.47 per share, for the fourth quarter and December 31, 2020.

Ill now hand, the call back to the operator to kick off the Q&A session.

Thank you as a reminder to ask a question you will need to press star one on your telephone.

I ask that you. Please limit yourself to one question and one follow up question. You May then return to the queue to withdraw your question press the pound.

Jean-Marc Bellemin: The net loss for the full year period under December 31st 2021 was $342.3 million or $2.23 per share compared to a net loss of $259.6 million or $1.88 per share for the full year period under December 31st 2020.

Please standby, while we compile the Q&A roster.

Okay.

Our first question will come from Tyler Van Buren with Cowen. Please go ahead.

Hey, guys. Congrats on the progress thanks very much for taking the question.

Jean-Marc Bellemin: Research and development expenses were $75.6 million for the fourth quarter and December 31, 2021, an increase of $23.1 million compared to $52.5 million for the fourth quarter and December 31, 2020. Research and development expenses were $259 million for the full-year period under December 31, 2021, an increase of $57.3 million compared to $201.7 million for the full year under December 31, 2020. The increase in research and development expenses in the fourth quarter of 2021 over the prior year period was primarily attributable to an increase in costs associated with the growth of the internal research and development team, including stock-based compensation expenses, an increase in clinical trial costs, and facility-related costs associated with ICD.

Don't you have to have resolution on the potency assay front in the next month or two in order to be able to run the assay or assays with the cohort four patient samples and generate the data to submit the BLA by the end of the first half and I guess my follow up to that would be is it possible that you've already started testing the cohort four patient samples.

Jean-Marc Bellemin: The increase in research and development expenses for the full year of 2021 over the prior full year period was primarily attributable to growth in the internal research and development team and an increase in clinical trial costs and facility-related costs associated with ICD. General and administrative expenses were $23.8 million for the fourth quarter and December 31st, 2021, an increase of $7.7 million compared to $16.1 million for the fourth quarter and December 31st, 2020.

With the latest iteration of the potency assay, our assays in anticipation of the filing.

Yes, Thanks, Tyler I can I can answer some of that.

We haven't disclosed the detail of how those interactions are going with the SBA and whether we've commenced testing or that at that level, but in general yes, we have to get some.

Have to be moving towards the BLA filing I should note that it's important to understand that we could be holding conversations with FDA in parallel while we do work.

We could be staging it so that we manage the risk really well.

But it could come write downs relative relatively late in the game.

For us to really feel comfortable but regardless right now what we've been saying publicly and clearly again here on this earnings call is that we're comfortable filing a BLA in the first half of this year. So that should give you some indication of where we think we are with the FDA.

That's great. Thank you very much.

Thank you. Our next question will come from Michael <unk> with Jefferies. Please go ahead.

Alright, Thank you and thanks for the update guys.

I have one question and a follow up my question is.

In relation to the filing is there a scenario where you file and meet your guidance and go ahead and do that and that you have to tell the street or will tell the street that the.

Final agreement with the final sign off for the final validation is obviously, an ongoing process and ultimately everything gets filed finalized at the Paducah date can you maybe just talk about that scenario I think like Wall Street thinks you have to screen light on a piece of paper and then you just filed can you maybe talk to that a bit that scenario yet.

Thanks.

One quick follow up on you did say clearly that Youll announced the cohort four melanoma data can you just when that gets done can you just remind me do you have.

Previously you had an interim.

And can you just tell me where cohort four is and when you do it it will be an independent review when you presented in and Thats supposed to be similar response rate data as cohort just remind us about that status. Thank you. Thank you.

Sure Michael let.

Let me take the last one first actually cohort cohort four data as part of the BLA submission, it's IRC read data and as part of the BLA submission.

In conjunction with that we would we would talk more about that cohort four data because that's the time to go in with the BLA and obviously its important information to put that out.

Jean-Marc Bellemin: General and administrative expenses were $83.7 million for the full year period under December 31, 2021, an increase of $23.5 million compared to $60.2 million for the full year under December 31, 2020. The increases in general and administrative expenses in the fourth quarter and full year 2021 compared to the prior year periods were primarily attributable to an increase in costs associated with the growth of the internal general and administrative team, including stock-based compensation expenses, and an increase in intellectual property filing-related costs. As of December 31st, 2021, there were approximately 157 million common shares outstanding.

Cohorts, who is already out there we've been talking about it for a while you can see that data we don't know court for yet so it's something we're still working on.

But you know the data is.

Yes.

A very similar study in many respects so it could give some guidance as to what we what we expect in these populations although of course they can differ.

On the assay part, let me try to answer the whole question, there because I don't.

<unk> always sort of the Paducah date.

Which could could would be in early 'twenty three.

Potentially or very late 'twenty, two depending on when we submit the BLA this year.

There can be conversations with the FDA during the entire pendency of the BLA. After it gets accepted as to sort of the specifications in some aspects of your potency assay or assays that you're you're proposing for your products. So things can change during that period I think that's what you might be asking.

Of course, I can comment on validation and you could present additional data you could.

Provide them with more information about the the specifications that you are proposing.

Jean-Marc Bellemin: We continue to focus on investment in four key areas, as outlined previously, to ensure the growth and strength of our value creation. This includes advancement and expansion of our clinical pipeline, launch readiness, a strong cash position, and manufacturing at ICTC, which will provide new cost efficiencies as we are able to shift work currently being done through contract manufacturers to ICTC. I remain confident that by managing our investments across these priorities, we will continue to stay focused and align our funding with our corporate priorities.

They ask questions about any aspect of the validation package during that period and you could go back and forth to come on that so you're absolutely right in thinking that you don't really know for sure.

The BLA is approved at all this is done and Thats the way. It just is in drug development.

Earlier in the process. So we submit the BLA when we had the pre BLA meeting prior to that.

Trying to get as much clarity as we can from the FDA. So we can make sure we're successful.

On the <unk> date.

And getting that approval. So we're not submitting something that has.

Gaps in it that we should we could have filled have listened to the FDA. So that's a big old leading up to the.

Operator: With late-stage clinical assets in our pipeline, as well as a strong balance sheet and focused investment in launch preparation, we are also well-positioned to execute our operating plan. I will now hand the call back to the operator to kick off the Q&A session. Thank you. As a reminder, to ask a question, you will need to press star one on your telephone.

Leading up to the BLA submission itself and of course some of that includes successfully completing validation.

And a lot of the work that eventually gets reviewed during the pendency of the BLA.

That was a long winded answer, but I hope I got what you were trying to get there Michael.

I think that makes sense and I can see that thank you.

Okay.

Thank you. Our next question will come from Peter Lawson with Barclays. Please go ahead.

Operator: We ask that you please limit yourself to one question and one follow-up question. You may then return to the queue. To withdraw your question, press the pound key.

Great. Thanks for taking the questions.

So wondering if you could walk through kind of timelines and kind of what's changing around.

Operator: Please stand by while we compile the Q&A roster. Our first question will come from Tyler Van Buren on Cowan. Please go ahead.

The potential for funding for <unk> that we should be thinking about.

Yes.

Tyler Van Buren: Hey guys, congrats on the progress. Thanks very much for taking the time to ask a question. Don't you have to have resolution on the potency assay front in the next month or two in order to be able to run the assay or assays with the cohort 4 patient samples and generate the data to submit the BLA by the end of the first half? And I guess my follow-up to that would be, is it possible that you've already started testing the cohort 4 patient samples with the latest iteration of the potency assay or as Yeah, thanks, Tyler.

Yes, Fredric do you want to answer that one.

Perhaps two good questions. So basically obviously, we are always an option.

Treatment landscape in cervical cancer has changed quite a bit the approval of checkpoint inhibition as part of first line standard of care was a paradigm shift in this <unk> immunotherapy to enter that field for the patients.

That obviously now changed the landscape and opportunities. After first line first line chemo and we saw that with how this impacted some of the additional checkpoint inhibitors that we're going after that second line after chemotherapy only spud.

Fred Vogt: I can answer some of that. We haven't disclosed the details of how those interactions are going with the FDA and whether we've commenced testing or that at that level. But in general, yes, we have to get some, you know; we have to be moving towards a BLA filing. I should note that it's important to understand that we could be holding conversations with the FDA in parallel while we do the work. We could be staging it so that we manage the risk really well, but it can come right down relatively late in the game for us to really feel comfortable.

Til therapy is differentiated from from checkpoint inhibitors, we know that.

We see activity in patients that have received checkpoint inhibitor therapy from our melanoma data.

Early based on a differentiated mechanism of action.

We knew that because we were foreseeing the changes from the first line landscape.

Fred Vogt: But regardless, right now, what we've been saying publicly and clearly, again, here on this earnings call is that we're comfortable filing a BLA in the first half of this year. So that should give you some indication of where we think we are with the FDA. That's great.

And the symptoms of checkpoint inhibition as standard of care, we started a post checkpoint or.

Cohort early in 2019 already.

And.

We do think that that is.

An area of unmet need that we would be able to address data in that setting.

We.

Our planning to execute Registrational strategy.

Michael Yee: Thank you very much. Thank you. Our next question will come from Michael Yee with Jeffrey. Please go ahead. Hi, thank you, and thanks for the update, guys. I have one question and a follow-up. My question is, in relation to the filing, is there a scenario where you file and meet your guidance and go ahead and do that, and you have to tell the street, or will tell the street, that the final agreement or the final sign-off or the final validation is obviously an ongoing process, and ultimately, everything gets filed and finalized at the PDUFA date? Can you maybe just talk about that scenario? I think Wall Street just thinks you have the screen light on a piece of paper, and then you just file it.

Addressing feedback from the FDA.

Fred Vogt: Should maybe talk about that a bit, that scenario. Yeah. One quick follow-up. You did say clearly that you'll announce the Cohort 4 melanoma data. Can you just, when that gets done, can you just remind me, you've previously had an interim, and can you just tell me where Cohort 4 is, and when you do it, will it be an independent review? When you present it, and that's supposed to be similar response rate data as Cohort 2. Just remind us about that status. Thank you. Sure, Michael. But I'll take the last one first, actually.

And addressing the changed landscape and we do think that we do have some some.

In the post checkpoint inhibitor.

Setting.

Perfect. Thank you and then just with the addition of Dr. Perry does that change the process in any way for filing.

Is there any chance you have funds at risk.

No I don't I don't.

No that's not really the plan there Peter he he's he's essentially.

Great addition to our team that's not really it's not really tied to the BLA or how we would handle the BLA of course, having him join us is going to be very helpful. In doing anything from a regulatory perspective.

That's not really something we're thinking about.

Got you okay. Thank you so much and thanks for taking the questions.

Thank you. Our next question will come from Nick Abbott with Wells Fargo. Please go ahead.

Good afternoon.

Thanks for taking my questions.

Fred Vogt: The Cohort 4 data is part of the BLA submission. It's IRC-RED data. And as part of the BLA submission, in conjunction with that, we would talk more about that Cohort 4 data, because that's time to go in with the BLA. And obviously, it's important information to put that out. Cohort 2 is already out there. We've been talking about it for a while. You can see that data. We don't know Cohort 4 yet.

I appreciate the clarity firm as always.

First one just going back following up on Mike's question familiar so have you closed the cohort four database being cleaned and ready for analysis.

Yes.

We haven't announced that yet Nick we are.

Without getting into details there obviously were very late in the game. So that's something we would need to do and it's been a relatively short time period here, but what we haven't spoken directly about that yet.

Fred Vogt: That's something we're still working on. But, you know, the Cohort 2 data is a very similar study in many respects, so it can give some guidance as to what we should expect in these populations, although, of course, they can differ. On the assay part, let me try to answer the whole question there, because going all the way through to the PDUFA date, which could be early 23, potentially, or very late 22, depending on when we submit the BLA this year, there can be conversations with the FDA during the entire pendency of the BLA after it gets accepted as to sort of the specifications and some aspects of your potency assay or assays that you're proposing for your product So things can change during that time.

Okay.

And then.

Maybe thinking forward.

A potential approval of NEVA and we'll outline that.

Fred Vogt: I think that's what you might be asking. Of course, they can comment on validation, and you could present additional data; you could..., provide them with more information about the specifications that you're proposing. And they could ask questions about any aspect of the validation package during that period, and you could go back and forth with them on that. So you're absolutely right in thinking that you don't really know for sure until the BLA is approved that all this is done. And that's the way it just is in drug development.

Do you think you need to show benefit in these patients.

It is similar magnitude to what you have shown.

<unk>.

Cohort, two and presumably what youre showing total.

It could it could be important in the future landscape of course, because there'll be patients coming off that line of therapy that would potentially be candidates for life of leucyl, but don't assume that we havent seen some of those patients already because those patients are out there right now in the clinical trials getting.

So it's something we're looking at closely I can tell you that that's something we've considered closely and we'll try to provide updates at medical meetings on how we might how we might address those patients.

Terrific. Thank you.

So can I just sorry.

I think one thing to keep in mind is that.

The data that we have presented indicating benefit that's comparable between patients who have failed the PD one monotherapy in patients who have failed PD one and.

Fred Vogt: Earlier in the process, so when we submit the BLA, when we have the pre-BLA meeting prior to that, we're trying to get as much clarity as we can from the FDA so we can make sure we're successful on the PDUFA date and get that approval, so we're not submitting something that has gaps in it that we could have filled had we listened to the FDA. So that's our big goal leading up to the BLA submission itself.

<unk> four blockade combination so I think that might be indicative of what we might be seeing in patients.

Patients will go field other combinations as well, obviously you don't have data on that.

Yes.

<unk> fashion, but I think that's something to keep in mind for that setting.

Fred Vogt: And of course, some of that includes successfully completing validation, doing a lot of the work that eventually gets reviewed during dependency of the BLA. That was a long-winded answer, but I hope I got what you were trying to get there.

Yes, that's a good point fredric.

Thank you. Our next question will come from Mara Goldstein with Mizuho. Please go ahead.

Thanks for taking the question.

Peter Lawson: Thank you. Okay. Thank you. Our next question will come from Peter Lawson with Barclays. Please go ahead.

On the initiation of the trial for.

<unk> 4001.

Peter Lawson: Great. Thanks for taking the questions. Just on cervical cancer, I wonder if you could walk through kind of timelines and kind of what's changing around the potential for filing for cervical cancer that we should be thinking about. Yeah, Frederick, do you want to answer that one? You're happy to. Good question.

This year that you've indicated can you talk about the clinical plan for that and what indications you might look at it and then I just wanted to ask about the sequential R&D spend and what that run rate looks like going forward given.

Now the delta in the fourth quarter versus the prior quarters.

Yes, maybe I can take the first one to have John Mark follow up on the second one so we haven't disclosed that yet merits, but that's something we'll obviously talk about the clinical plan for that asset as soon as we can because thats tied once once we get the regulatory filing through I think will you'll hear a lot more from us on that.

Friedrich Finckenstein: So obviously, obviously, we are acknowledging that the treatment landscape in cervical cancer has changed quite a bit. The approval of checkpoint inhibition as part of first-line standard of care was a paradigm shift, and it's great to see immunotherapy enter that field for patients. So that's good news.

We're obviously indicated interested and indications that we know and can.

Friedrich Finckenstein: That obviously has changed the landscape for opportunities after first line, first line chemo. And we saw that with how this impacted some of the additional checkpoint inhibitors that were going after that second line after chemotherapy only spot until therapy is differentiated from checkpoint inhibitors.

Can benchmark against as well as potentially new indications that might benefit from the having to combine.

Combined effects of the checkpoint inhibition like mechanism built into the til cell itself, which can theoretically infiltrate better into the tumor then the antibody.

As well as R. R.

Polyclonal T cell platform combined with the same asset. So we're looking for indications that would benefit from that approach and then hopefully we'll be able to talk about that pretty soon.

Friedrich Finckenstein: We know that we see activity in patients that have received checkpoint inhibitor therapy from our melanoma data, and that's really based on a differentiated mechanism of action. Because we knew that and because we were foreseeing the changes in the first-line landscape and acceptance of checkpoint inhibition as standard of care, we started a post-checkpoint inhibitor cohort early in 2019, and we do think that that is an area of unmet need that we would be able to address with data in that setting. We are planning to execute a registrational strategy, addressing feedback from the FDA and addressing this changed landscape. And we do think that we do have some, some headway in that post-treatment setting. Perfect.

Mark do you want to talk a little bit about the R&D spend.

<unk>.

Fred Vogt: Thank you. And just for the addition of Dr. Puri, does that change the process in any way for filing? Is there any chance you'd file at risk?

Yeah.

Yes sure. Thanks for the question.

Look honestly of course, or we are focusing our spending on the on the building pipeline.

The research will be bulk of it and so forth I was on one is only one aspect of the program that we are building.

And we're spending perspective.

We are definitely looking at reallocation of expenses with US if you think about what we do.

Should you see for example in 2021.

Be reallocated to research or for 2000 for instance through so we have.

Increases in our research and development spending in Q4.

And during the script that we have the.

Onetime $6 3 million so it was rover.

For expenses there.

Yes.

There is no real concern will keep steady on the research and development spending for 2023.

Okay, and if I could just also ask a question around the CEO a permanent.

And what that looks like from this but at this point in time from a timing perspective.

Okay.

Basically our board is conducting a search and we're still looking for candidates.

Fred Vogt: No, I don't. I don't. No, that's not really the plan there, Peter. He's essentially a great addition to our team.

It continues to be on growing our top priority for our board and we'll announce the outcome as soon as we can.

Fred Vogt: That's not really, it's not really tied to the BLA or how we would handle the BLA. Of course, having him join us is going to be very helpful in doing anything from a regulatory perspective. That's not really something worth thinking about.

I don't really have anything else.

Thank you.

Thank you. Our next question will come from Mark Breidenbach with Oppenheimer. Please go ahead.

Fred Vogt: Okay, thank you so much. Thanks for taking the question. Thank you. Our next question will come from Nick Abbott with Wells Fargo. Please go ahead. Good afternoon.

Hey, guys. Good afternoon. Thanks for taking our question just one from me maybe directed at <unk> I was hoping you could provide a little more color on the nature of these parameter changes to the <unk> two trial that you've been discussing with the FDA and maybe a little bit more detail on that.

Nick Abbott: Thanks for taking my questions and I appreciate the clarity, Fred, as always. First one, so just going back, following up on Mike's question from earlier, so have you closed the cohort for the database? It is being cleaned, ready for analysis.

Would be appreciated.

I don't think that we have spoken about the exact details of our discussions with the FDA in regards to <unk> too.

Fred Vogt: We haven't announced that yet, Nick. Without getting into the details there, obviously, we're very late in the game, so that's something we would need to do in a relatively short time period here, but we haven't spoken directly about that yet. Okay. Um, and then.

So.

I'm not sure I can I can't really comment on that.

Just just as a reminder, what we're doing with <unk>.

Fred Vogt: You know, maybe thinking forward, you know, the potential approval of NEEVO and RLATLIN, perhaps. Do you think you need to show benefit in these patients that's of a similar magnitude to what you've shown currently from cohort two and, presumably, what you're showing in cohort four? It could be important in the future landscape, of course, because there will be patients coming off that line of therapy that would potentially be candidates for Lifelucid, but don't assume that we haven't seen some of those patients already because those patients are out there right now and the clinical trial is getting...

We are.

<unk>, specifically patients that have failed the single line of.

Checkpoint plus standard of care chemotherapy. So this is.

Already online.

Sedation, then than the population that was enrolled for those.

Concept cohort of three B from our basket study.

Thats the parameter changes that you're referring to so that's really the main point is focus on the earlier earlier line population with a desk prior therapy.

Okay that wasn't already part of the protocol that so it was originally designed.

Fred Vogt: So that's something we're looking at closely. I can tell you that's something we've considered closely, and we'll try to provide updates at medical meetings on how we might address those patients. Thank you. Fred, can I chime in here?

No that was that was the design of the study if we opened it.

And we have we have not.

<unk> changed the design.

Friedrich Finckenstein: So I think one thing to keep in mind is that the data that we have presented clearly indicate benefit that's comparable between patients who have failed PD-1 monotherapy and patients who have failed PD-1 and CTLA-4 blockage combination. So I think that might be indicative of what we might be seeing in patients who have failed other combinations as well. Obviously, we don't have data on that, but yes, in a controlled fashion, but I think that's something to keep in mind for that setting.

Since then.

Okay.

Yeah.

Thank you. Our next question will come from Colin <unk> with Baird. Please go ahead.

Great. Thanks, so much for taking my question.

Are there any characterizations you are able to provide as to how the latest conversations with the FDA have progressed regarding the potency assay.

Yes sure.

They've given us a lot of good advice detailed advice and we feel like we really understand.

What they're looking for and we think we were going to be able to address that.

Friedrich Finckenstein: Yeah, that's a good point, Frederick. Thank you. Our next question will come from Mara Goldstein with Mizuho. Please go ahead.

At the technical level. The details of that are still confidential and that's not something we're quite ready to talk about but as a general matter, it's at the level where.

Mara Goldstein: Just on the initiation of the trial for IOV4001 this year that you've indicated, can you talk about the clinical plan for that and what indications you might look at? And then I just wanted to ask about the sequential R&D spend and what that run rate looks like going forward given the different, you know, delta in the fourth quarter versus the prior quarter. Yeah, maybe I can take the first one and have John Mark follow up on the second one.

Really productive discussions can be had and we can respond to what they think their concerns are and we can provide them with data.

Assay is a set of assays that we think address their concerns.

In detail.

Yeah, it's advanced quite a bit over the past nine months.

In that respect.

Understood. Thank you that's helpful and then any comments on how the PD one combo in lung cancer is advancing and when we might see data from that combination.

Fred Vogt: So, we haven't disclosed that yet, Mara, but that's something we'll obviously talk about, the clinical plan for that asset, as soon as we can, because that's tied to, you know, once, once we get the regulatory filing through. I think you'll hear a lot more from us on that. We're obviously interested in indications that we, we, we know and can benchmark against, as well as potentially new indications that might benefit from the combined effects of a checkpoint inhibition-like mechanism built into the TIL cell itself, which can theoretically infiltrate better into the tumor than the antibody, as well as our Polyclonal T cell platform combined in the same acid. So we're looking for indications that would benefit from that approach, and hopefully, we'll be able to talk about that pretty soon. Jean-Marc, do you want to talk a little bit about the R&D spend? Yeah, sure.

Sure that that study is cocoa or three a and our account to a two study that study has been enrolling for a while now.

We haven't guided to specific conferences or anything where we would present, but it is it is one of those.

Studies, where obviously, we'd like to present some data at some point soon.

So we presented as much data as we possibly could last year.

I look forward to 'twenty, two where we will try to keep that up.

I, just can't say exactly when we'll be able to do that.

Great. Thanks for taking my question.

Sure.

Thank you. Our next question will come from Ben Burnett with football. Please go ahead.

Hey, Thank you very much I had a question regarding the melanoma BLA in the new manufacturing center.

Jean-Marc Bellemin: Thanks for the question. Look, honestly, of course, we are focusing spending on the building of the pipeline, and, you know, research will be part of it. So 4001 is only one aspect of the program that we're building. But from a spending perspective, I mean, we are definitely looking at reallocating expenses in a way that if you think about what we spent on building ICTC, for example, in 2021, and will be reallocated to research in 2022. So we have an increase in research and development spending in Q4. I mentioned during the script that we have this one time 6.3 million. So that's why you have a little bit more expenses there.

<unk> okay.

How much patient experience have you accrued from product manufactured here for late line melanoma, specifically and I guess can you provide just a little more color just regarding your expectations for what's likely needed in terms of validation data numbers of samples or anything like that.

Where do you want to you want to talk about at least the first part of that and I could maybe cover almost the last part.

Happy to so thanks for the question so.

Jean-Marc Bellemin: But honestly, there is no real concern; we will keep steady on the research and development spending for 2022. Okay, and you know, if I could also ask the question around the CEO permanency and what that looks like from this point in time from a timing perspective. Basically, our board is conducting a search, and we're still looking for candidates. It continues to be an ongoing top priority for the board, and we'll announce the outcome as soon as we can. I don't really have anything else.

The facility is focused on two things right. One is clinical manufacturing for ongoing clinical trials.

And that's primarily the Gen. Two process, that's a part of the cohorts for which we intend to problems in the BLA and then the other part is preparation for <unk>.

Commercialization.

And BLA filing including.

All including the filing and the subsequent inspection inspection, but we expect.

To take place soon enough with it falling.

Halloween, that's getting to capacity ready to meet key.

Commercial demand after the potential BLA approval.

So that's we're well on track alone all of them.

Those activities.

And I think when you Fred.

Go ahead you go if you wanted to know if you want to get the part about the <unk> I think that's what you were asking about that right.

Yes, if there is anything you can say about just the number of samples.

Fred Vogt: Thank you. Thank you. Our next question will come from Mark Bradenbach with Oppenheimer. Please go ahead. Hey guys, good afternoon. Thanks for taking our questions. Just one for me, maybe directed at Friedrich.

Ballpark in terms of validation data that's needed.

I mean, it's a good number of samples eager eager go ahead, if you want to answer it.

Fred go ahead, I'm not sure I understood the question poorly.

Mark Bradenbach: I was hoping he could provide a little more color on the nature of these parameter changes to the LUN202 trial that you've been discussing with the FDA. Maybe a little bit more detail on that would be appreciated. I don't think that we have spoken about the exact details of our discussions with the FDA in regards to LUN202, so I'm not sure I can really comment on that. Just as a reminder, what we're doing with LUN202 is we are enrolling specifically patients that have failed the single line of Checkpoint Inhibitor Plus Standard of Care Chemotherapy. So this is an earlier line population than the population that was enrolled for those proof of concept cohorts of 3B from our basket study. So those are the parameter changes that you're referring to.

I think what you're saying then is the number of samples needed to perform validation exercises both for the assays and for anything we need to do at the facilities is that right.

Yes, sorry for not being more clear I think to validate that the product is manufactured at the new site is similar to whats been manufactured.

So that's what we call comparability in and it's part of comparability in what we call P. B Q's a process performance qualification is it.

We have the good number of samples I don't have the exact numbers equal probably doesn't either but you know there's obviously a lot of work done to make sure a statistically.

Well justified with the FTA and so thats, what really drives as the number of samples and we're well we're set in that area we think.

Okay. Thank you very much.

Thank you our next question will come from.

Gordon with sure.

Please go ahead.

Hi, guys. Thanks for taking my questions.

Just maybe.

Friedrich Finckenstein: So that's really the main point is focused on an earlier line population with this prior therapy. Okay, that wasn't already part of the protocol as it was originally designed. No, that was the design of the study as we opened it, and we have not, we have not changed the design since then.

Logistical and here.

If I understand your answer to <unk>.

Tyler's question and you might be doing somebody somebody's potential potency assay work.

Included in the filing.

Prior to you getting the official okay from the FDA is that a scenario that the FDA comes back to you and says, but we wanted to do a couple of more things.

Run out of samples.

And then I've a follow up question about lung cancer after that.

Friedrich Finckenstein: Okay, thank you. Thank you. Our next question will come from Colleen Kusy with Baird. Please go ahead. Great.

Alright, let me Yeah, let me take the first one they can always come back and asked and asked and answered stuff and you could always just ran out of retained at some point, but we don't expect that to be the case, we think we've got the routines we need to answer their questions right now.

Colleen Kusy: Thanks so much for taking our questions. So are there any characterizations you're able to provide as to how the latest conversations with the FDA have progressed regarding the potency assay? Yeah, sure, Colleen, they've given us a lot of good advice, a lot of detailed advice, and we feel like we really understand what they're looking for. And we think we're going to be able to meet that. At the technical level, the details of that are still confidential, and that's not something we're quite ready to talk about.

<unk>.

We're comfortable we are performing the assays that we've developed and that we think are.

Bonds as to what the FDA wants.

<unk>.

I think maybe maybe sort of the core of your question is the timing of the whole thing in the east because you've mentioned the concept of the FCA given us to go what I was saying earlier to both Michael and the Tyler.

Fred Vogt: But as a general matter, it's at the level where really productive discussions can be had, and we can respond to what we think their concerns are, and we can provide them with data, assays, and sets of assays that we think address their concerns in detail. So yeah, it's advanced quite a bit over the past nine months in that respect.

<unk> was you don't really know its done until the Paducah date and they approve your BLA. That's when they've truly say go but what you are trying to do is be responsive to their feedback during the process and of course preserve your repaint and preserve your provide them with information as they ask for it.

Burnt stuff up on necessarily during the process. So that's something we're doing very carefully here.

Got it okay. Thanks.

Fred Vogt: I understand. Thank you. That's helpful.

And then a question for Peter.

Given what we've seen with the with the non small cell lung data that you presented earlier I wanted to get your thoughts on the.

Colleen Kusy: And then any comments on how the PD-1 combo and lung cancer is advancing, and what we might see data from that combo? Sure, that study is COCOA-3A in our COMP-202 study. That study has been enrolling for a while now. We haven't guided to specific conferences or anything where we would present, but it is one of those. Namaste.

The confidence that you have.

Oh, you're going to have to buy going.

Maybe a potentially earlier stage than the previous data that was presented that you could.

Better durability of the responses that you have there and then related to that is there.

Do you think that it could be an option for you to consider giving maybe adding another arm to Ellie went into a two way of combining the til with PD one with the goal to help.

Fred Vogt: Great. Thanks for taking my question. Thank you. Our next question will come from Ben Burnett with CFO. Please go ahead.

We want to.

Get the T cell.

Little bit more kick the can do them a persisting.

Ben Burnett: Hey, thank you very much. I had a question regarding the melanoma BLA in the new manufacturing center, ICTC. I guess, how much patient experience have you accrued from the product manufactured here for late-line melanoma specifically? And I guess, can you provide just a little more color regarding your expectations for what's likely needed in terms of validation data, numbers of samples, or anything like that? Yeah, Igor, do you want to talk about at least the first part of that, and I can maybe cover the last part? I'd be happy to.

Yes.

Two good questions obviously.

It's about the durability and are confident that doing it in earlier line will will both improve the durability. So number one.

That is that is to some extent clinical experience in knowing how to think.

Eight to nine non small cell lung cancer patients often are.

In regards to logging function and performance status, so going into an earlier line was somewhat.

Igor Bilinsky: So thanks for the question. We are the facilities focused on two things right now. One is clinical manufacturing for ongoing clinical trials.

Yes, you guessed.

That's our starting point.

Really the confidence comes from from the data that were presented by <unk>.

Igor Bilinsky: And that's primarily the Gen 2 process that's a part of the cohort 4 that we intend to file to the DLA. And then the other part is preparation for commercialization and, and DLA filing, including all including the filing and the subsequent inspection inspection that we expect to take place soon after the filing, and then following that, getting the capacity ready to meet the commercial demand after the potential DLA approval. So that we're well on track with all of those activities. Go ahead, Igor, if you want to get to the part about the retainers. I think that's what you were asking about, Ben, right?

And published by Dr.

And from the Moffitt.

See a slightly different design.

Single institution experience there.

In what was overall earlier line population of patients that have either received a single priority.

I eased.

Long term and loan durability responses were observed so that was informing that what's informing this too long to it where it is.

Actually we don't.

Obviously has to now run this clinical experiment and generate the data supporting that but that's the rationale.

A volunteer a question of adding PD lone blockade to til for better durability, that's something that we are active.

Igor Bilinsky: Yeah, if there's anything you can say about just the number of samples kind of ballparks in terms of the validation data that's needed. I mean, it's a good number of samples. Igor, go ahead if you want to answer it. Actually, Fred, go ahead.

Flooring in quarter three of the basket study.

Checkpoint inhibitor naive population, albeit but we are generating data in non small cell lung cancer with that combination.

So we are interested in that.

Whether that is something that one would want to translate into a checkpoint inhibitor pretreated population is a question that we can ask once a once they understand what we're seeing in let's say one other thing you keep in mind.

Fred Vogt: I'm not sure I understood the question fully. I think what you're saying, Ben, is the number of samples needed to perform validation exercises, both for the assays and for anything we need to do with the facility. Is that right?

Ben Burnett: Yeah. Sorry for not being more clear. I think it's important to validate that the product manufactured at the new site is similar to what's been manufactured elsewhere.

Non cancer docs do not tend to reduce checkpoint inhibitor. After failure of a checkpoint inhibitor is slightly different from melanoma.

Fred Vogt: So that's what we call comparability and part of comparability and what we call PPQs, or process performance qualification. It's a good number of samples, I don't have the exact numbers, Igor probably doesn't either. But you know, there's obviously a lot of work done to make sure it's statistically well justified with the FDA. And so that's what really drives the number of samples. And, you know, we're well; we're settled in that area, we think. Okay, thank you very much.

They're usually there is not a lot of confidence and checkpoint inhibitors.

It is not by themselves and reusing or failures for that.

Defense to the situation in auto.

Got it thanks guys.

Thank you. Thank you. Our next question will come from Reni Benjamin with JMP Securities. Please go ahead.

Fred Vogt: Thank you. Our next question will come from Asthika Goonewardene with Shewa Securities. Please go ahead. Hi guys, thanks for taking my questions. Just maybe a logistical one here.

Hey, good afternoon, guys. Thanks for taking my questions and I apologize I jumped on the call little late so I apologize. If you guys have already answered, but can you just tell us what how are you thinking about ex.

Ex U S or in specific specifically, a European filing, especially if the BLA you were able to pull up as BLA submission time here in the U S. What are the kind of gating steps going forward.

Asthika Goonewardene: If I understand your answer to Tyler's question, and you might be doing some of these potential potency assays to include in the filing prior to you getting the official OK from the FDA, is that a scenario where the FDA comes back to you and says, well, we want you to do a couple more things, and you run out of samples? And then After that, I have a follow-up question about lung cancer. All right, let me, yeah, let me take the first one.

And then also just to clarify.

Typically see.

Clinical data more as a review issues or is there any.

Is there any reason to think or I really consider that.

The potency assay or any part of this any part of the CMC could be part of the review issue. If there if there is one.

Sure I can I can pick those up.

Fred Vogt: They could always come back and ask and ask and ask for stuff, and you could always just run out of retainers at some point, but we don't expect that to be the case. We think we've got the retainers we need to answer their questions right now. Comfortable performing the Assays that we've developed and that we think are responsible for what the FDA wants. I think maybe sort of the core of your question is the timing of the whole thing, because you mentioned the concept of the FDA giving us the go. What I was saying earlier to both Michael and to Tyler in their questions, You don't really know it's done until the PDUFA date and they approve your BLA. That's when they've truly said go.

Our European strategy really hinges on the FDA outcome. So really we're focused on the FDA right now and then since we have European patients in the trials, we've talked about before.

If things go well with FDA, we think we can turnaround the ebay and hopefully move pretty quickly there.

Haven't announced any details on that yet so you just got to stay tuned on some of this but we did prepare for that eventuality and we do think we could do something there fairly quickly after we resolve the issues with the FDA.

Your second question.

Yes, I mean look there could be a review issue everything with FDA can always say that there is.

They sometimes use that language in every single question that you asked them.

Fred Vogt: But what you're trying to do is be responsive to their feedback during the process. And, of course, preserve your retains and preserve your, you know, provide them with information as they ask for it and not burn stuff up unnecessarily during the process. So that's something we're doing very carefully.

With that type of your type C meeting.

But.

Goal is to try and get it to whatever whatever is left its a review issue is still minor that we feel very comfortable that we'll get a successful approval when the proof of de hits, that's really the way we look at it. The fact that they could say that they can say that for the clinical side I can say from the CMC side, we can say for non clinical side, but you know we try to close that window as tightly at or close to completely close as we can.

Asthika Goonewardene: Okay, thanks. And then I have a question for Frederick, by the way. Frederick, given what we've seen with the non-small-for-lunk data that you presented earlier, I want to just get your thoughts on the confidence that you have that LUN202, by going at maybe a potentially earlier stage than the previous data that was presented, could have better durability of the responses that you have there. And then related to that, is there a... Do you think that it could be an option for you to consider giving, maybe adding another Yes, those are two good questions, obviously, about durability and our confidence that going into an earlier line will improve durability.

With with pre BLA filing interactions to make sure that we're not caught in a situation where during the review something that becomes a real problem.

Got it Okay, and just just as a quick follow up regarding the European filing is that something that you do.

Right after submitting the BLA, because you've worked everything out or waiting for the BLA to be accepted or is it something that you do after an approval here in the in.

In the U S.

How should we think about that.

Probably be more like the latter, but we haven't determined that fully yet so.

Again, our focus is on the U S market for melanoma first and foremost because thats the market, we want to be in but we would look at the European opportunity.

As much as we possibly could with the resources that we have.

Terrific. Thanks for taking the questions.

Thank you. Our next question will come from Madhu Kumar with Goldman Sachs. Please go ahead.

Friedrich Finckenstein: So number one, that is, to some extent, just clinical experience and knowing how sick, late-line, non-small cell lung cancer patients often are in regards to organ function and performance status. So going into an earlier line will somewhat get you into a slightly better starting point. Really, the confidence comes from the data that were presented by Dr. Krillin and published by Dr. Krillin from Moffitt, so it's obviously a slightly different design and a single institution experience, but there, in what was overall an earlier line population with patients that had either received a single prior line or were even treatment naive, long-term and long durability responses were observed, so that was informing this step 2, Lung We obviously have to run this clinical experiment and generate the data supporting that, but that's the rush hour for your question about adding PD-1 blockade to pills for better durability.

Hey, everyone. Thanks for taking our questions. So I apologize that I'm gonna deep does it dead horse.

How should we think about news flow through June 30th with regards to lift the Lucent post PD one in melanoma like we will have the BLA submission.

Have cohort four data analyze like how should we think about kind of like what information is going to come between now and June 30.

Yeah. It's a good question, but does it all that information comes out in that period basically you should come out in that period.

We expect it will come out in that period, so well how it comes out in the order. It comes out and is still it's still something that needs to be determined but those are the critical elements, which you mentioned there basically the cohort four data the clinical data that will be.

Or at least the topline for data the clinical data will be in the BLA package.

Where we stand with respect to the CMC issues as much as we know the actual occurrence of a pre BLA meeting.

And you know the actual currency filing all of that stuff has to has to happen.

We'll try to time, but well you know we don't know the details yet we can't predict exactly where all this is going to happen, but we'll try to time the news flow and then keeping those slow coming is that process.

Friedrich Finckenstein: That's something that we are actively exploring in CORD3A of the basket study in a checkpoint-embittered naive population. Albeit, but we are generating data on asthma and lung cancer with that combination. So we are interested in that. Whether that is something that one would want to translate into a checkpoint inhibitor-prescribed population is a question that we can ask once we understand what we're seeing in the checkpoint inhibitor-primed population. Keep in mind, lung cancer docs do not tend to reuse checkpoint inhibitors after failure of checkpoint inhibitors. This is slightly different from melanoma. Where usually there is not a lot of confidence in checkpoint inhibitors, at least not by themselves, then reusing them after failure. Unknown Attendee.

Continues.

Okay and then following up on the last question kind of a bigger picture question about accelerated approval in this context, what is the confirmatory trial look like to you and with Lyft to lose so as monotherapy and kind of advanced solid cancers.

In melanoma or just in general well I mean, as a confirmatory trial for the melanoma BLA previously it has been discussed the idea that a confirmatory trial doesn't necessarily need to be in the same indication, but like you said this the current view or is there a notion that there needs to be a confirmatory trials specifically in post PD one in melanoma.

I can actually think about now when a confirmatory trial it looks like.

So a couple of things there the FDA generally discourage you from having a confirmatory trial in the same indication you just got approval for.

They're more interested in different like going to an earlier line of therapy.

I need to point out that with your method. The nation. We don't know for sure where we are required to have a confirmatory trial, that's very important to make clear and we will be submitting as we've said many times cohort two data IRC read data for cohort two to the FDA as part of this as well, which FDA has said can be supporting.

Asthika Goonewardene: Got it. Thanks, guys. Thank you. Our next question will come from Reni Benjamin with JMP Securities. Please go ahead. Hey, good afternoon, guys.

Reni Benjamin: Thanks for taking the questions. And I apologize; I jumped on the call a little late. So I apologize if you guys have already answered this. Can you just tell us how you think about ex-US or, you know, specifically European filing, especially if this PLA, you know, you were able to pull up this PLA submission on time here in the US? What are the kind of gating steps going forward?

So all of that kind of goes into the same blender.

From that.

You will find out whether you need a confirmatory trial in the first place.

And if you do it is not likely to be in the same indication that you've just got your you just ran your pivotal data.

Is that ultimately it will have to do that and is there kind of like a natural data set you guys have in hand that serves that function kind of when would logically think something like the cervical cancer data set that you have developed over the last few years is that kind of like a natural kind of confirmatory population to submit as a confirmatory group.

Fred Vogt: And then also, just to clarify, you know, we typically see, you know, clinical data more as a review issue. Is there any reason to think or ever consider that, you know, the potency assay or any part of this, any part of the CMC could be part of the review issue if there is? Sure, I can. Pickers.

No that would be for a separate label on cervical so that's.

Would they be looking for for a confirmatory trial should they require one in melanoma would be in melanoma.

Fred Vogt: Unknown Speaker 0: It hinges on the FDA outcome. So really, we're focused on the FDA right now. And then, since we have European patients in the trial, as we've talked about before, if things go well with FDA, we think we can turn around the EMA and hopefully move pretty quickly there. We haven't announced any details on that yet. So you just have to stay tuned in on some of this. But we did prepare for that eventuality.

So you know maybe the natural one that you can think of would be an earlier line of.

Earlier line of therapy in melanoma like our cohort one eight comp two or two or something similar to that.

Fda's current thinking on this matter as they talked about publicly is that the sponsor should have that trial up and running at the time of approval.

Or earlier.

Thank you.

Fred Vogt: And we do think we can do something there fairly quickly after we resolve the issues with the FDA. Our second question. I'm going to go ahead and get started.

Ladies and gentlemen, thank you for participants.

Thank you for participating in today's question and answer session I would now like to turn the call back over to the Doctor.

Fred Vogt: Thank you. Yes, I mean, look, there can be review issues on everything with FDA. They can always say that there is, and they sometimes use that language in every single question that you ask them, you know, type B or type C meeting. But, you know, our goal is to try and get it to where whatever is left of the review issues is so minor that we feel very comfortable that we'll get a successful approval when PDUFA day hits. That's really the way we look at it.

No closing remarks.

Yeah.

Thank you operator, and thank you again for joining I advanced Biotherapeutics fourth quarter and full year 2021 financial results Conference call.

We're really grateful for the patients and physicians, who are participating in our clinical studies and moving the field of cancer Ford.

I want to acknowledge our employees and cross functional teams, who are working tirelessly to prepare for our BLA filing to bring life of leucyl of patients.

Fred Vogt: The fact is, they could say that they could pay for the clinical side, they can pay for the CMC side, they can pay for the non-clinical. But you know, we try to close that window as tightly or as close to completely closed as we can with pre-BLA filing interactions to make sure that we're not caught in a situation where during the review, something becomes a real problem. Okay, and just as a quick follow-up regarding the European filing, is that something you do, you know, kind of like right after submitting the BLA? You know, because you've worked everything out or waiting for the BLA to be accepted? Or is it something that you do after approval here in the US?

Also like to thank our shareholders and covering analysts for their collaboration and supported by events.

All of your key contributors in advancing our mission to be the global leader in developing delivering an innovative til therapy. Please feel free to reach out to our Investor Relations team. If you wish to follow up thank you.

Fred Vogt: How should we think? It'd probably be more like the latter, but we haven't determined that fully. So we want to, again, our focus is on the U.S. market for melanoma first and foremost because that's the market we want to be in. But, you know, we would look at the European opportunity as much as we possibly could with the resources that we have.

Ladies and gentlemen, this concludes today's conference call. Thank you for your participation you may now disconnect.

Okay.

[music].

Fred Vogt: Terrific, thanks for taking the questions. Thank you. Our next question will come from Madhu Kumar with Goldman Sachs. Please go ahead. Hey everyone, thanks for taking our questions. So I apologize that I'm going to beat this dead horse.

Madhu Kumar: How should we think about news flow through June 30th with regard to litho-leucillin post PD-1 melanoma? We will have the BLA submission, they'll have the cohort for data analyzed, like actually think about kind of like, what information is going to come between now and Yeah, it's a good question. All that information comes out in that period, basically, or should come out in that period. We expect it to come out in that period.

Fred Vogt: So how it comes out in the order it comes out in is still something that needs to be determined. But those are those are the critical elements, which you mentioned there, basically, the core four days of the clinical data that will be, or at least the top line core four data, the clinical data will be in the BLA package, where we stand with respect to the CMC issues as much as we know, the actual occurrence of a pre-BLA meeting, and the actual occurrence of a filing. All that stuff has to happen.

Madhu Kumar: And we'll try to time the news flow and keep the news flow coming as that process continues. Okay, and then following up on the last question, kind of a bigger picture question about accelerated approval in this context. What does a confirmatory trial look like to you with litholeucel as monotherapy in some kind of advanced... In melanoma or just in general?

Fred Vogt: Well, I mean, as a confirmatory trial for the melanoma of DLA. Previously, it has been discussed the idea that a confirmatory trial does not necessarily need to be in the same indication. But, like, is that the current view, or is there a notion there needs to be a confirmatory trial? Specifically, in post-PD-1 melanoma because we think about what a confirmatory trial looks like. So, a couple of things there. The FDA generally discourages you from having a confirmatory trial in the same indication you just got approval for. They're more interested in different types of therapy, going to an earlier line of therapy.

Fred Vogt: Another thing I need to point out is that with the R method definition, we don't know for sure whether we're required to have a confirmatory trial. That's very important to make clear, and we will be submitting, as we've said many times, cohort two data, IRC-RED data for cohort two, to the FDA as part of this as well, which the FDA has said it can support. So, all that kind of goes in the same blender.

Fred Vogt: You will find out whether you need a confirmatory trial in the first place, and if you do, it's not likely to be in the same indication that you just got your PIVL data. To that end, is there kind of like a natural data set you guys have in hand that serves that function? I mean, kind of, one would logically think something like the cervical cancer data set that you have developed over the last few years. Is that kind of like a natural kind of confirmatory population to submit as a confirmatory group?

Fred Vogt: Now, that would be for a separate label on cervical cancer. So that's what they'd be looking for for a confirmatory trial, should they require one in melanoma, would be in melanoma. And so, you know, maybe the natural one that you could think of would be an earlier line of therapy in melanoma like our Covert 1A at COM202 or something similar to that.

Fred Vogt: And FDA's current thinking on this matter, as they talk about publicly, is that the sponsor should have that trial up and running at the time of approval, or earlier. That's what they... Cool, thank you. Ladies and gentlemen, thank you for participating in today's question and answer session. I would now like to turn the call back over to Dr. Fred Vogt for any closing remarks. Thank you, operator. And thank you again for joining the Iovance Biotherapeutics fourth quarter and full year 2021 financial results conference call.

Fred Vogt: We are really grateful for the patients and physicians who are participating in our clinical studies and moving the field of cancer forward. I want to acknowledge our employees and cross-functional teams who are working tirelessly to prepare for our VLA filing to bring elusive life to patients. I would also like to thank our shareholders and the covering analysts for their collaboration and support of Iovance. All of you are key contributors to advancing our mission to be the global leader in developing, delivering, and innovating tilt therapy. Please feel free to reach out to our investor relations team if you wish to follow up. Thank you. Ladies and gentlemen, this concludes today's conference call. Thank you for your participation. You may now disconnect. [music]