Q1 2021 Iovance Biotherapeutics Inc Earnings Call

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Hello, and welcome to the ideal dance Biotherapeutics first quarter 2021 financial results Conference. My name is Michelle and I will be the operator on today's call.

Operator: Hello and welcome to the Iovance Biotherapeutics First Quarter 2021 Financial Results Conference. My name is Michelle, and I will be the operator on today's call. At this time, all participants are in a listen-only mode.

At this time all participants are in a listen only mode. Later, we will conduct a question and answer session and during the question and answer session. If you have a question. Please press Star then one on your Touchtone phone.

Operator: Later, we will conduct a question-and-answer session, and during the question-and-answer session, if you have a question, please press star, then one, on your touch-home phone. I will now turn the call over to Miss Sarah Pellegrino. Ma'am, you may begin.

I will now turn the call over to Mr. Pellegrino Ma'am you may begin.

Thank you operator, good afternoon, and thank you for joining US speaking on today's call, we have Maria Florida, Our President and Chief Executive Officer, Fredrik Finkelstein, our Chief Medical Officer, and John Mark Melamine, Our Chief Financial Officer. We're also joined by Jim Ziegler Senior Vice President commercial.

Sara Pellegrino: Thank you, Operator. Good afternoon, and thank you for joining us. Speaking on today's call, we have Maria Fartis, our President and Chief Executive Officer, Frederick Sincenstein, our Chief Medical Officer, and Jean-Marc Belomene, our Chief Financial Officer. We are also joined by Jim Ziegler, Senior Vice President, Commercial.

Sara Pellegrino: This afternoon, we issued a press release that can be found on our website at iovance.com, which includes the financial results for the three months ended March 31st, 2021, as well as corporate updates. Before we start, I would like to remind everyone that statements made during this conference call will include forward-looking statements regarding Iovance's goals, business focus, business plans, pre-commercial activities, clinical trials, and regulatory plans and results, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, payer interaction, collaborations, cash position and expense guidance, and future updates. Forward-looking statements are subject to numerous risks and uncertainties, many of which are beyond our control, including the risks and uncertainties described from time to time and in our SEC filing.

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 months ended on March 31st 2021, as well as corporate update.

Before we start I would like to remind everyone that statements made during this conference call will include forward looking statements regarding idled assets goals business focus business plans pre commercial activities clinical trials and regulatory plans and results potential future applications of our technologies.

Factoring capabilities regulatory feedback and guidance payer interaction collaboration cash position, an expense 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.

Maria Fartis: Our results may differ materially from those projected during today's call. We undertake no obligation to publicly update any forward-looking statements. With that introduction, I will turn the call over to Sarah. Thank you, Sarah, and good afternoon, everyone. I am pleased to highlight our first quarter 2021 progress at Ayovans during today's conference call. During 2021, we have continued to advance and expand our Ayovans, tumor, infiltrating, lymphocyte, or TIL platform across multiple indications, including metastatic melanoma, cervical, head and neck, and non-small lung cancer.

Undertakes no obligation to publicly update any forward looking statements.

With that intro I will turn the call over to Maria.

Thank you Sarah and good afternoon, everyone I am pleased to highlight our first quarter 2021 progress at all you that during today's conference call.

During 2021 we have continued to advance and expand that all events tumor infiltrating lymphocyte or til platform across multiple indications, including metastatic melanoma cervical head and neck and non small cell lung cancers.

Maria Fartis: For our lead to product candidate, Lysol, and Metastatic Melanoma, we completed the submission of additional information related to our potency assays to FDA in support of a planned biologics license application or BLA submission. Resolution of the potency assay with FDA is our top priority for 2021. We also reported new and updated data from our ongoing C-14401 clinical study, demonstrating durable responses in our cohort two for one-time treatment with Lysil. The Cohort 2 data was presented at AACR 2021, and additional data updates will be presented at ASCO 2021.

For our lead product candidates like the news flow in metastatic melanoma, we completed the submission of additional information related to our potency assay to FDA in support of the planned biologics license application or BLA submission.

Resolution of the potency assays, if FDA is our top priority for 2021.

We also reported new and updated data from our ongoing C. One fourth for fetal one clinical study demonstrating durable responses and a cohort two for one time treats ended likely useful.

The cohort two data was presented at ACR 2021 and additional data updates will be presented at Astro 2021.

Maria Fartis: And additional indications, the completed patient dosing in cohort 2 for life-inducal in advanced cervical cancer. For our registration, directed study of LN-145 in non-small cell lung cancer, we continue to activate sites for I-O-V-L-UN-2 and consented multiple patients.

And additional indications be completed patient dosing in cohort two for life and do so in advanced cervical cancer for a registration directed study of L and 145 in non small cell lung cancer. We continue to activate sites for I O V Dash L. U N gosh, two O two and consented multiple patients.

Maria Fartis: We believe that the growing body of Iovans TIL clinical data across multiple late-stage cancers, coupled with results from the combination of our TIL and anti-PB1 therapy at earlier stages of the disease, validate the significance and broad potential for Iovans TIL therapies. We also continue to execute toward all manufacturing and pre-commercial activities and further our commitment to address the critical need of cancer patients. I am very confident in the quality of our internal team to deliver on this mission.

We believe that the growing body of audio line was til clinical data across multiple late stage cancers, coupled with results from combination of til and anti PD one therapy in earlier stages of the disease validate the significant and broad potential for til therapy.

We also continue to execute toward all manufacturing and pre commercial activities and furthering our commitment to address the critical need of cancer patients.

I am very confident in the quality of our internal team to deliver towards this mission.

Maria Fartis: An impressive 76% of our more than 250 employees have at least a year of cell therapy experience. On the call today, I would like to spend a few minutes highlighting our lead indications and manufacturing progress. Then, I will let Frederick review our recent clinical data update, and I will begin with our first pivotal program, Life and Usil, for Advanced Melanoma. As discussed in our previous calls, metastatic melanoma is a common type of skin cancer.

An impressive 76% of our more than 250 employees, how 'bout leased a year of cell therapy experience.

On the call today, I would like to spend a few minutes highlighting our lead indications and manufacturing progress then I will let friedrichs review, our recent clinical data updates.

I will begin with our first pivotal program. They can do so fried basketball at a low as discussed in our previous calls metastatic melanoma is a common type of skin cancer and <unk>.

The U S alone metastatic melanoma accounts for approximately 100000 patients diagnosed are 7000 deaths each year in the United States.

We are focused on the growing population of metastatic melanoma patients that have exhausted their most common to use available care options and need alternative therapies in our C. One full force needle one study.

Maria Fartis: In the U.S. alone, metastatic melanoma accounts for approximately 100,000 patients diagnosed and 7,000 deaths each year in the United States. We are focused on the growing population of metastatic malanoma patients that have exhausted their most commonly used available care options and need alternative therapies in our C-14401 study. At the American Association for Cancer Research, or AACR annual meeting, the updated data for cohort two from the C14401 clinical study were presented at a clinical trial plenary session. The long-term follow-up data showed that median duration of response was not reached at 28.1 months of median study follow-up.

At the American Association for cancer research or ACR annual meeting the updated data from cohort two from C. One full force needle one clinical study was presented at the clinical trial plenary session.

The long term follow up data showed that median duration of response was not reached at 28. One months of median study follow up. Furthermore, overall response rate remained at $36 four per cent and we saw a continued deepening of response and 17% of the patients.

We as well as kols, including the physicians, who highlighted the data at ACR continued to be very enthusiastic about the durability of response following onetime treatment that they can do so in a very difficult to treat metastatic melanoma patients.

For the post anti PD, one patient population enrolled in cohort two chemotherapy is the only currently available option and offers a 4% to 10% response rate and overall survival of only seven to eight months.

Maria Fartis: Furthermore, overall response rates remained at 36.4%, and we saw a continued deepening of response in 17% of patients. We, as well as KOLs, including the physicians who highlighted the data at AACR, continue to be very enthusiastic about the durability of response following one-time treatment with Lycanusel in very difficult-to-treat metastatic melanoma patients. For the post-anti-Ped1 patient population enrolled in cohort 2, chemotherapy is the only currently available option and offers a 4-10% response rate and overall survival of only 7 to 8 months.

Further update for cohort two will be highlighted at the upcoming American society of clinical oncology or ethical annual meeting in June.

Cohort two data has also been accepted for publication in a forthcoming a manuscript in a peer reviewed high impact oncology journal.

Turning to til in earlier lines of therapy at the upcoming <unk> 2021 meeting.

Excited about sharing clinical data for life and diesel in combination with Kimberly oven Entre PD, one naive metastatic melanoma patients.

Combination of Io that pill with available therapies and anti PD. One naive patients is one of <unk> main critical goal toward moving to into earlier treatment settings.

What is the second clinical setting in which such combination is tested and data are being provided.

Maria Fartis: Further updates for cohort 2 will be highlighted at the upcoming American Society of Clinical Oncology or Asco Annual Meeting in June. Details Cohort 2 data has also been accepted for publication in a forthcoming manuscript in a peer-reviewed high-impact oncology journal.

As previously mentioned, reaching agreement with FDA on the potency assays for life and diesel is a top priority for all your value.

While the length of time until BLA submission depends on feedback from the agency. We continue staying prepared for a BLA submission in 2021 B plan to provide updates when available.

Our second pivotal program is investigating L. And 1.5 now also known as they send useful in the C 145 legal force study to support a BLA submission in metastatic cervical cancer.

Maria Fartis: Turning to TIL in earlier lines of therapy, at the upcoming ASCO 2021 meeting, we are excited about sharing clinical data for Life and Lucille in combination with Cumberlusimab and AntipD1-N-Na-Matic melanoma patients. Combination of Iovans' TIL with available therapies and anti-PD1 naive patients is one of Iovans' main clinical goals toward moving T Malanoma is the second clinical setting in which this combination is tested, and data are being provided.

During the first quarter cohort two patient dosing is in life of Newfield was completed and post anti PD, one cervical cancer patients.

We believe that a BLA submission that includes both who pivotal cohort one which is evaluating LIFO neutral post chemotherapy. In addition to cohort two may strengthen the potential label and reflect the expected accounting treatment landscape and cervical cancer.

As we have mentioned before the resolution of the potency assay for life and do fill in melanoma and dialogue with FDA around the amount of clinical data follow up are key steps toward our BLA submission in the cervical cancer indications.

As a reminder, the FDA has previously granted both breakthrough therapy and fast track designations for life and do so in cervical cancer.

Maria Fartis: As previously mentioned, reaching agreement with FDA on the potency assays for life in Lucille is a top priority for IVAN. While the length of time until BLA submission depends on feedback from the agency, we continue to stay prepared for a BLA submission in 2021. We plan to provide updates when available.

Turning to our manufacturing facility, our events cell therapy center or ICT C. We have completed construction of the exterior core and shell as well as initial clean room on behalf moved in.

Process equipment unnecessarily utilities are now in place and day available clean room on activities have commenced the support the start up til clinical manufacturing in late 2021 <unk>.

Maria Fartis: Our second pivotal program is investigating LN145, now also known as Laifian Usil, in the C14504 study to support a BLA submission for metastatic cervical cancer. During the first quarter, cohort two patient dosings in Life and Lucil were completed in post-anti-Ped1 cervical cancer patients. We believe that a BNA submission that includes both Pivotal cohort 1, which is evaluating life and neutral post-chemotherapy, in addition to cohort 2, may strengthen the potential label and reflect the expected upcoming treatment landscape for cervical cancer.

Commercial manufacturing of Ireland's chilled remains on track for 2022 with capacity to meet the demand for up to thousands of patients in multiple indications.

Iphones has transformed til manufacturing from a lengthy academic process to a shorter scalable centralized GMP process, yielding a cryopreserved product.

Our Gen. Two process of 22 days to date more than 450 patients have received either hill with a continuing success rate above 90%.

We are also looking forward to the potential to further improve the til manufacturing timelines on efficiencies.

It's shorter 16 day third generation til manufacturing process or Gen. Three is being explored in two of our clinical studies.

Maria Fartis: As we have mentioned before, the resolution of the potency assay for life and useful in melanoma and dialogue with FDA around the amount of clinical data follow-up are key steps toward our B&A submission in the cervical cancer indication. As a reminder, the FDA has previously granted both Breakthru Therapy and Fast Track designations for Life Alusel and Serbical Center. Turning to our manufacturing facility, Iovans Cell Therapy Center, or ICTC, we have completed construction of the exterior core and shell as well as initial clean rooms, and we have moved in.

Patients receiving gen. Three til include a cohort of metastatic melanoma patients in the I O V Dash C. O M Dash two O two clinical study where patient dosing has initiated.

As well as a cohort of a non small cell lung cancer patients and the I O V cash L. U N dash two O two study.

We have also built and continue to augment our intellectual property, which is covered by more than 25 granted or allowed U S uninsured national patents.

Granted patents include composition and methods of treatment in a broad range of cancers from leading to the Gen. Two manufacturing process with expected exclusivity through 'twenty 38.

Maria Fartis: Process equipment and necessary utilities are now in place in the available clean rooms, and activities have commenced to support the start of chilled clinical manufacturing in late 2021. Commercial manufacturing of Iovans still remains on track for 2022, with capacity to meet the demand for up to thousands of patients and multiple indications. Iovance has transformed till manufacturing from a lengthy academic process to a shorter, scalable, centralized GMP process yielding a credit reserve product. Our GEN2 process is 22 days.

I announced patent applications and granted patents are also directed towards Gen. III manufacturing selected til product stable on transient genetic modification of til tumor digest and fragment composition and methods, including cryopreservation and combination of til the checkpoint inhibitors.

In addition, as noted in this afternoon's press release, we have licensed additional patent rights from National Institutes of health or NIH Force cytokines, Heather Hille technology, including IL, 15, and IL 21, and similar technology.

Also expanded our worldwide field of use to all cancers be believed that this expanded license and relationship with NIH may further solidify our leadership and the advancement of til and the related intellectual property.

Maria Fartis: To date, more than 450 patients have received eye advanced treatment still with a continuing success rate above 90%. We are also looking forward to the potential to further improve till manufacturing timelines and efficiencies. A shorter 16-day third-generation Iovansil manufacturing process, or Gen 3, is being explored in two of our clinical studies. The patients receiving GEM-3 TIL include a cohort of metastatic melanoma patients in the I-O-V-C-O-M-202 clinical study where patient dosing has begun, as well as a cohort of non-responding lung cancer patients in the I-O-V-L-U-N-2 study.

Turning to our pre commercial launch preparations we remain disciplined in our gated approach to commercial readiness. Our core commercial team continues to build the foundation for site training patient access payer coverage and other commercialization readiness activities.

We are well positioned to rapidly scale and expand our efforts across these areas pending alignment with the FDA on our calls we see I see.

Our medical Affairs team maintains a clinical site engagement in preparation for commercial launch.

This team continues to work with key opinion leaders and patient advocacy groups until awareness and educational programs and to ensure scientific communication at major conferences and in peer reviewed publications.

Commercial team is partnering with the leading U S cancer centers to build their til service line capabilities.

Maria Fartis: They have also built and continued to augment our intellectual property, which is covered by more than 25 granted or allowed U.S. and international patents. Patented inventions include composition and methods of treatment in a broad range of cancers relating to the Gen 2 manufacturing process with expected exclusivity through 2038. IAvance patent applications and granted patents are also directed towards Gen 3 manufacturing, selected TIL products, stable and transient genetic modification of TIL, tumor digest and fragment composition, and methods including cryopreservation and combination of TIL with checkpoint inhibitors.

They treat our training and Onboarding program, which we will further expand upon BLA submission is designed to ensure cross disciplinary teams can administer the life a lethal treatment regimen upon FDA approval.

Our market access team continues to engage payers to ensure patients have access to liquidity so very.

Very recently the centers for Medicare and Medicaid services or CMS proposed two new international classification of diseases tenths revision procedure coding system or ICD 10 codes for life and useful.

Additionally, CMS proposed to map like the new salt existing M. S. DRG 18.

CMS also proposed to expand M. S. DRG 18 from car T cell immunotherapy to car T cell and other Immunotherapies, including Islands Hill.

We believe that Cms's proposal to include likes to lead flow and existing M. S. EOG 18 is recognition of the value of I've asked Phil I'm cell therapies for patients and the need to ensure appropriate reimbursement for providers beyond car T.

Maria Fartis: In addition, as noted in this afternoon's press release, we have licensed additional patent rights from the National Institutes of Health for cytokine tethered TIL technology, including IOL-15 and IL-21, and similar technology. We also expanded our worldwide field of use to all cancers. We believe that this expanded license and relationship with NIH may further solidify our leadership in the advancement of TIL and related intellectual property.

The proposal if finalized has the potential to strengthen hospital reimbursement for life useful therapy at the time of launch. We appreciate CMS is leadership and commitment to access to care.

The audio lines team is also developing our <unk> cares program, which remains on track. Our goal is to deliver a best in class chain of custody and chain of identity system sell ordering platform and patient support capabilities.

I have asked cares is designed to be both customer and patient centric throughout the life of news flow treatment journey.

I will now pass the call to Friedrich to also in our clinical update Frederic.

Maria Fartis: Turning to our pre-commercial launch preparations, we remained disciplined in our gated approach to commercial readiness. Our core commercial team continues to build the foundation for site training, patient access, payer coverage, and other commercialization readiness activities. We are well positioned to rapidly scale and expand efforts across these areas pending alignment with the FDA and our potency. Our medical affairs team maintains clinical site engagement in preparation for commercial launch. This team continues to work with key opinion leaders and patient advocacy groups on TIL awareness and educational programs and to ensure scientific communication at major conferences and peer review publication. Commercial Team is partnering with the leading U.S. Cancer Centers to build their TILS. service line capabilities

Jim Maria.

Just to highlight recent and upcoming clinical data updates from til alone and in combination with <unk>.

In melanoma.

The status of our four ongoing clinical studies.

Drug development strategy focuses on cancer populations with high unmet need with substantial opportunities for til to make a meaningful impact.

First as Maria mentioned, we provided an update for cohort two and our C. 14401 clinical study of ACR in approximately 28, one months of median study follow up longer term updates have been accepted for oral presentation at the high school.

Also looking forward to an upcoming peer reviewed publication of detailed cohort two data.

At the upcoming Astro meeting we are also looking forward to the poster presentation of initial clinical data in the <unk> Com 202 study from cohort one eight which is evaluating lucky leucyl in combination with Pembina has them up in melanoma.

Maria Fartis: Our training and onboarding program, which we will further expand upon BLA submission, is designed to ensure cross-disciplinary teams can administer the Lifealuso Treatment Regiment upon FDA approval. Additionally, our Market Access team continues to engage payers to ensure patients have access to Leifal. Very recently, the Centers for Medicare and Medicaid Services, or CMS, proposed two new international classification of diseases, 10th revision, procedure coding system, or ICD10 codes for Life Illusil. Additionally, CMS proposed to map Lysol to existing MS DRG 18.

This would represent the second indication with clinical data for <unk> two in combination with Campbellism up earlier treatment settings. Following the encouraging data in head and neck cancer presented at last year's society for the immunotherapy of cancer.

Answer or S ITC meeting.

Well up yields 33% response rate, 6% of which are complete responses in patients with melanoma.

40% to 65 per cent of patients still progress on or after treatment.

For an anti PD, one naive metastatic melanoma, there remains a need to increase the overall response rate and then in particular the complete response rate.

Maria Fartis: CMS also proposed to expand MSG18 from Cartycell Inunotherapy to Karty Cell Inmunotherapy and other immunotherapies, including Iovans Hill. We believe that CMS's proposal to include Lifeal and Usel in an existing MS DRG 18 is recognition of the value of Iovans pill and cell therapies for patients and the need to ensure appropriate reimbursement for providers beyond T. The proposal, when finalized, has the potential to strengthen hospital reimbursement for life-elisotherapy at the time of law.

We also continue to recruit patients across four clinical studies with <unk>.

Sure. She one flow five or four clinical study in advanced cervical cancer has completed patient dosing in the first two cohorts we.

We continue to recruit the third cohort of anti PD, one naive patients to receive <unk> plus.

<unk>.

We have now activated a total of 10 sites and consented multiple patients for a registration supporting study Iot.

202 in second line non small cell lung cancer.

Maria Fartis: We appreciate CMS's leadership and commitment to access to care. The Ayovance team is also developing our Ayovans CARES program, which remains on track. Our goal is to deliver a best-in-class chain of custody and chain of identity system, cell ordering platform, and patient support capabilities. IAVANC cares is designed to be both customer and patient-centric throughout the life cycle and useful treatment journey. I will now pass the call to Friedrich to outline our clinical update. Thank you, Maria. I am pleased to highlight recent and upcoming clinical data updates for Iovans still alone and in combination with Pembralizumab in melanoma.

We believe that the patient population in ILD as U N. Two O two as well as the three in non small cell lung cancer cohorts and the basket study allow us to broadly address the unmet needs for non small cell lung cancer.

Recruitment also continues in our IV come to two study of Io events until until combinations across melanoma head and neck and non small cell lung cancers. In addition to the ILD.

Zero, one study and CLO.

Oh.

As the impact of the COVID-19 pandemic on hospitals results. Following the rollout of the COVID-19 vaccines and that's the virus abates, we hope to be able to provide additional data at future medical meetings.

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

Friedrich Graf Finckenstein: as well as the status of our four ongoing clinical studies.

Thank you for it.

Friedrich Graf Finckenstein: Our drug development strategy focuses on cancer populations with high unmet need, with substantial opportunities for Till to make a meaningful impact. First, as Maria mentioned, we provided an update for cohort 2 in our C-14401 clinical study at AACR at approximately 28.1 months of median study follow-up, and longer-term updates have been accepted for oral presentation at ASCO. We are also looking forward to an upcoming peer-reviewed publication of detailed core 2 data.

My comments will reflect the high level financial results from the first quarter of a point to point to one.

Additional details can be found in this afternoons press release.

Our SEC filings.

I will begin with our cash position.

As of March 31st 2021.

$632 million in.

Josh cash equivalents investments and route.

Restricted cash compared to $635 million on December 31st towards.

2020.

Our strong cash position is expected to be sufficient through 'twenty towards from free to deliver on our pipeline programs.

Moving on to the income statement net.

Loss for the first quarter ended March 31st 2021 was $75 4 million.

Oh 51 cents per share.

Friedrich Graf Finckenstein: At the upcoming ASCO meeting, we are also looking forward to the poster presentation of initial clinical data from the Iov-Com. Com-202 study from cohort 1A, which is evaluating lifeelousal in combination with pambulizumab and melanoma. This will represent a second indication with clinical data for Iovans still in combination with pambulismab in earlier treatment settings, following the encouraging data for head and neck cancer presented at last year's society for the treatment of cancer or SITC meeting. While Pambrilysmap yields a 33% response rate, 6% of which are complete responses in patients with melanoma, 40 to 65% of patients still progress on or after treatment

From a net loss of $69 6 million Daus force.

Two five cents per share for the first quarter ended March 31st pointed towards.

Research and development expenses were $55 9 million for the first quarter ended March 31st 2021.

Cruise of $1 million compared to $57 million for the first quarter.

Marshall T force pointed towards.

The year over zero day cruise in research and development expenses.

Primarily attributable to decreases.

Manufacturing and clinical costs following the completion of enrollment in the pivotal calls for melanoma and cervical cancer.

General and administrative expenses were $19 6 million.

For the first quarter ended March 31st 2021.

An increase of 5.8 million daus.

We're up to 13 9 million for the first quarter ended March 31st 2020.

The year over year, and crews and general and administrative expenses was primarily attributable to growth of total general and administrative team.

Stock based compensation expenses.

As of March 31st 2021, there were approximately 149 3 million common shares outstanding.

Friedrich Graf Finckenstein: Therefore, in anti-PD1 naive metastatic melanoma, there remains a need to increase the

Looking ahead, we remain focused on investments in four key areas to ensure the growth and strength of our value creation.

Friedrich Graf Finckenstein: need to increase the overall response rate, and in particular, the complete response rate. We also continue to recruit patients across four clinical studies with Iovans-Till. Our C-14504 clinical study in advanced cervical cancer has completed patient dosing in the first two cohorts, and we continue to recruit the third cohort of anti-PD1 naive patients to receive Iovans tilt plus pambrolismap. We have now activated a total of 10 sites and consented multiple patients for our registration supporting study, I-O-V-L-U-N-202 and second-line non-smolancans.

First advancing our current clinical programs from indication.

Second scaling a margin.

Fracturing capacity to support our clinical and manufacturing while preparing for expected commercial supply in 2022.

Third ensuring launch readiness and fourth maintaining a strong balance sheet and cash position.

I remain confident that by managing our investments across these four priorities. We will continue to stay focused on the line, they're all spending was our corporate priorities.

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

Thank you we will now begin the question and answer session. If you have a question. Please press Star then one on your Touchtone phone if you wish to be removed from the queue. You may press, the pound sign or the hash key.

Friedrich Graf Finckenstein: We believe that the patient population in I-O-V-L-U-N-2, as well as the three non-small lung cancer cohorts in the basket study, allow us to broadly address the unmet needs in non-small lung cancer. Recruitment also continues in our Iovicom 2 study of Iovans' Till and Till combinations across melanoma, headernecked, and non-smolza lung cancers, in addition to the Iov-C-L-01 study in CLL and SLL, as the impact of the COVID-19 pandemic on hospitals' results following the rollout of the COVID-19 vaccine continues to be evaluated.

So if youre using a speakerphone you may need to pick up on your handset before pressing the numbers. We do respectfully ask that you limit. Your question to one question and should you have a follow up please re enter the queue by pressing star one.

The first question in the queue comes from Peter Lawson, Sir Your line is open. Please proceed.

Okay. We'll go to the next question Michael <unk>. Your line is open. Please proceed.

Okay. Thank you can you hear me Okay Maria.

Yes, we can hi, Michael Hey, Hey, guys. Thanks, and I appreciate the update and the interest of I guess one question. Our question was regarding the commentary around the.

Friedrich Graf Finckenstein: Vaccines, and as the virus abates, we hope to be able to provide additional data.

The progress from submitting additional data for assays.

Jean-Marc Belomene: I hope to be able to provide additional data at future medical meetings. I will now hand the call over to Jean-Macht to discuss our first quarter 2021 financial results.

It was around.

Your confidence level that things are absolutely moving on a pace to get an agreement and if there wasn't agreement you would just be able to come out and say that.

That was not going along the right path.

Second is to be able to either engage with the broader <unk> team.

Jean-Marc Belomene: My comments will reflect the high-level financial results from our first quarter of 2021. Additional details can be found in this afternoon's press release as well as in our ACC filing.

Or do other things to just be able to go ahead and push a little harder sorry for the different questions here, but it's all kind of related to the conference from long time line. Thank you.

Understood. Thank you so much Michael.

We have submitted as we noted we have submitted our prior responses from the agency.

Jean-Marc Belomene: I will begin with our cash position. As of March 31, 2021, Iovans held $610.2 million in cash, cash equivalents, investments, and restricted cash, compared to $635 million on December 31st, 2012. A strong cash position is expected to be sufficient into 2023 to deliver on our pipeline program. Moving on to the income statement, our net loss for the first quarter ended March 31, 2021 was $75.4 million, or 51 cents per share, compared to a net loss of $69.6 million, or $55 per share, for the first quarter ended March 31st, 2020.

The questions that were issued as part of the type B meeting. We also have now provided the validation data that'd be hard committed to provide to FDA as part of our responses in Q1 of 2021, we have not heard back from the agency and I think that the degree of confidence would depend on feedback from them you really do need to hear from them in.

In terms of mechanism of escalation there are definitely mechanisms by which mechanics can eat we have been talking to them FTE management to ensure that you're able to at least get a response in a timely matter. So yes. There are then used and we certainly have considered them.

Thank you very much.

Yes.

Yeah.

Okay and Peter Lawson. Your line is open. Please proceed.

Great. Thank you so much.

Sorry, I joined late so I apologize if you run through this.

In lung cancer, when you think about the subset.

Jean-Marc Belomene: Research and development expenses were $55.9 million for the first quarter ended March 31st, 2021, a decrease of $1 million compared to $57 million for the first quarter ended March 31st, 2020. The year-over-year decrease in research and development expenses was primarily attributable to a decrease in manufacturing and clinical costs following the completion of enrollment in the pivotal cohorts for melanoma and cervical cancer. General and Administrative Expenses were $19.6 million for the first quarter and March 31st, 2021, an increase of $5.8 million compared to $13.9 million for the first quarter and March 31st, 2021.

Post T K Ireland.

Hi.

So what did you say til therapy could potentially fit in and what do you think you can go to the best shots.

Generation efficacy or is it both.

Existing and emerging therapies coming through.

Okay.

Hi, Peter Thank you for the question.

The study that was conducted by Moffitt and was published at ACR 2020 was incredibly helpful. In showing that really didn't seem to be particular subpopulations that was responding to tell or not responding to tell would you might've seen as patients who had a PD L. One low expression level, we're still among the response.

All patients never post T. I, if you had an oncogene driver mutation. So that's highly encouraging is quite consistent with the cig distress chilled, where theres not a specific from a population that may not respond to till now our study designed to share the specific I O V com two O two or L. U N two O two.

Jean-Marc Belomene: The year-over-year increase in general and administrative expenses was primarily attributable to growth of the internal general and administrative team and higher stock-based compensation. As of March 31, 2021, there were approximately 149.3 million common shares outstanding.

Is more designed it with a registration program in mind. So L. You went to two specifically as a potentially supportive of registration I suppose it's low population that'd be selected there is trying to identify a patient population that is both an unmet medical need and yet early enough in lines of therapy. The patients don't line up.

For Trinity to benefit from until it's not selected based on where we think till may be active or not active.

Jean-Marc Belomene: Looking ahead, we remain focused on investment in four key areas to ensure the growth and strength of our value creation. First, advancing our current clinical programs and indications. Second, scaling up our manufacturing capacity to support our clinical manufacturing while preparing for expected commercial supply in 2022. Third, ensuring launch readiness, and fourth, maintaining a strong balance sheet and cast. I remain confident that by managing our investments across these four priorities, we will continue to stay focused and align our spending with our corporate priorities.

Really what we see is still seems to be active regardless of the subpopulations that a degree do you have data in non small cell.

Got you. Thank you.

Just maybe maybe addressed but.

What was the last time you spoke to the FDA I know the FDA has kind of not all of the.

Tun talk with.

With you.

But what was the last time you spoke about.

That would be a lie.

Yep.

And when do you anticipate speaking again.

Do you think things are moving forward.

Polls, though just.

Your sense around that dialogue.

Sure.

So F D is a pretty large body the review team or formal meetings as one venue for communication. There certainly are informal other ways of talking to FDA, who either regulatory or project managers or other venues. So the dialogue with the agency is very much ongoing it doesn't necessarily mean just is.

Operator: I will now end the call back to the operator to kick off the Q&A session. Thank you. We will now begin the question and answer session. If you have a question, please

No your standard sort of the you Tycho the meeting like a type B meeting well there are definitely used dialogue between our regulatory team and F. D. A to make sure that they have received the package that would be so does my time to review it and they will respond to us in a timely manner.

Operator: Thank you. We will now begin the question and answer session. If you have a question, please press star, then one on your touchstone phone. If you wish to be removed from the queue, you may press the pound sign or the hash key. Also, if you're using a speaker phone, you may need to pick up on your handset before pressing the numbers.

Great Okay.

The next question in the queue comes from Mark Breidenbach. Your line is open. Please proceed.

Hey, good afternoon, and thank you for taking our question.

Just switching over to the upcoming data from licensing so.

Operator: We do respectfully ask that you limit your question to one question, and should you have a follow-up, please, we enter the queue by pressing star 1. The first question in the queue comes from Peter Lawson. Sir, your line is open, please proceed. Okay, we'll go to the next question. Michael Yee, your line is open. Please proceed.

Line with timber living up and in frontline melanoma.

I'm curious how many patients we're likely to see in in that presentation, maybe ballpark how much how much follow up we can expect.

Most of my thoughts on what you see as likely next steps for development in an early line setting with this with this.

Michael Jonathan Yee: Okay, thank you. Can you hear me okay, Maria?

Basket trial cohort potentially balloon into a randomized study versus single agent Umbro are or what do you have in mind.

Maria Fartis: Yes, we can. Hi Michael.

Michael Jonathan Yee: Hey, hey guys, thanks, and I appreciate the update. In the interest of, I guess, one question. Our question was regarding the commentary around the progress in submitting additional data for assays, and the question was around your confidence level that things are absolutely moving at a pace to get an agreement, and if there was an agreement, you would just be able to come out and say that, and if that was not going along the right path, there are mechanisms to be able to either engage with the ODAC team or do other things to just be able to go Thank you.

These initial data looked at.

Maria Fartis: I understand. Thank you so much, Michael. We have submitted, as we noted, we have submitted our prior responses to the agency to the questions that were issued as part of the type B meeting. We also have now provided the validation data that we had committed to provide to FDA as part of our responses in Q1 of 2021. We have not heard back from the agency, and I think a degree of confidence would depend on feedback from them.

Maria Fartis: We really do need to hear from them. In terms of the mechanism of escalation, there are definitely mechanisms by which we can escalate. We have been talking to FDA management to assure that we are able to at least get a response in a timely matter. So yes, there are venues, and we certainly have considered them. Thank you.

Comes from Borst peak or your line is open. Please proceed.

Great just wanted to ask in terms of the of lung cancer cohorts when should we be expecting updates from nose and what are some of the factors that go into a kind of deciding the timing of those updates.

Maria Fartis: Thank you very much.

Hi, Boris good afternoon, yes, absolutely. So we have two cohorts to have lung cancer patients. One is in our basket study they come to O. Two study has two cohorts course can be a M. P. B four three a which is early line patient the treatment naive Laci P. D. One night you from <unk>.

Operator: Okay, and Peter Lawson, your line is open, please proceed. Great, thank you so much. Sorry, I joined late, so I apologize if you already went through this.

Peter Richard Lawson: But when, in lung cancer, when you think about the subsets, kind of post-TKI and P1 high and low and failed, where do you think teal therapy could potentially fit in? Where do you think you've got the best shot? at generating efficacy over both existing and emerging therapy is coming through. Hi, Peter, thank you for the question.

Is there has been a little bit sore jungle. During COVID-19. This may very well be the impact of hospitals hasn't been impacted by COVID-19 as well as the fact that these patients obviously have available therapy to receive a day are local institutions Incor three b. We do have some patience you have not committed to a specific date of low timeline vs drew to come.

<unk> that patients that are second line are certainly much better in terms of non small cell that patient.

Maria Fartis: The study that was conducted by Moffitt and was published at AACR 2020 was incredibly helpful in showing that there really didn't seem to be a particular subpopulation that was responding to tell or not responding to tell. What you might have seen is patients who had a PDR1 low expression level were still among the responders or patients that were post-TKI if they had an oncogene driver mutation. So that's highly encouraging.

Isn't that assertion from first like a second line and non sponsor lung cancer is quite large unfortunately, many patients around 70 per cent of the patients don't make it. The second line. So we are trying to limit our subsequent upcoming cohorts to second line non small cell will be do have some patience and that two or three b, which once you have long enough model will be.

Could disclose the data you haven't committed to a specific venue or a timeframe yet.

Great. Thank you very much for taking my question.

Maria Fartis: is quite consistent with the signature of TIL, where there's not a specific subpopulation that may not respond to TILs. Now, our study designs, such as the specific I-O-V-COM 2 or LUN-202, are more designed with a registration program in mind. So LUN-202 specifically is potentially supportive of registration, and so the subpopulation that we selected there is trying to identify a patient population that is both an unmet medical need and yet early enough in lines of therapy that the patients have an opportunity to benefit from TIL.

Thank you force.

And the next question day cute comes from Mara Goldstein. Please proceed.

Great. Thank you so much for taking the questions. Just a couple of things first I just wanted to circle back to make sure that I understood correctly on the submission that was made to the F. D. A around the assay that the that day is not obligated to respond to you within a specific time frame for that submission uhm and on a cervical program.

Can you give us a bit more background on how the decision was made to combine the two cohorts and was that made based on discussions with F. D. A and where does that leave a potential filing time line and then the last thing I had was just a curiosity more than anything on on the reimbursement from and the and the and the.

Maria Fartis: It's not selected based on where we think TIL may be active or not active. It's really what we see is TIL seems to be active regardless of the subpopulations to the degree we have data in non-small cell.

And the determination that have been made around codes and whatnot is there a specific time limit and which those must be made active such.

Peter Richard Lawson: Gotcha, thank you. And then this may be addressed, but what was it?

Such that you don't have to reapply back to the agencies.

More than just need your first two questions from you answered them, but I didn't catch quite your third question, Let me try and answer the first grade and then I'll ask you to repeat number three.

Peter Richard Lawson: But when was the last time you spoke to the FDA? I know the FDA is kind of not on a time clock with you, but when was the last time you spoke and about the BLA? And when do you anticipate speaking again? And do you think things are moving forward or if they paused or, your sense around that dialogue. Sure. So FTA is a pretty large body.

In terms of the assay you're correct agency is not on the Paducah o'clock to answering it in a given timeline. However, when is C. M. C. I N. D Amendment is submitted to the agency. There's guidelines that's typically limit the duration of time do you review, it's usually one to two months and so that guideline is what we are sort of referring to an <unk>.

Maria Fartis: The review team or formal meetings are one venue for communication. There certainly are informal other ways of talking to FTA through either regulatory project managers or other venues. So the dialogue with the agency is very much ongoing. It doesn't necessarily mean this is a standard sort of a view type of meeting, like a type D meeting.

And for the agency to respond within that window of opportunity.

In terms of cervical the.

<unk>, we have been quite committed to combining the course I just wanted to be sure that you're clear we gave the visibility to investors that'd be have the possibility of combining force wanted to it's certainly a subject of discussion with F. D. A who would one where patient number post chemotherapy metastatic setting and cohort to where michelle's that also.

Maria Fartis: But there definitely is dialogue between our regulatory team and FDA to make sure that they have received the package, that they have set aside time to review it, and they will respond to us in a timely manner. Great. Okay. The next question in the queue comes from Mark Breedenbach. Your line is open.

Could have received onto P. D. One in a medicine that exciting now the reason V. We kind of went down the policies you wanted to make sure that the investors are aware that there was a possibility given the potential change in the landscape of cervical cancer. There's a possibility that the agency may request for two and or I have asked me want to include that day, though so it's very <unk>.

Operator: Please proceed. Hey, good afternoon, and thank you for taking our question. Just switching over to the upcoming data from Lifealusville combined with Pemberlizumab in Frontline Melanoma, I'm curious how many patients were likely to see in that presentation, maybe ballpark, how much follow-up we can expect. And, Maria, I'm also curious to get your thoughts on what you see as likely next steps for development in an early stage. setting with this basket trial cohort potentially balloon into a randomized study versus single agent Pembro, or what do you have in mind assuming these initial data look good? Sounds good.

More subject to discussion with with F. D. A if that address is your questions one and two do you mind repeating your question three.

Sure not a problem, but on on question too. If you do if if the determination is that those cohort will be combined from you know potential filing perspective does that <unk> you know what does that do to city. The internal timeline that you have.

<unk> the one that you share.

Understood understood from a timing perspective, just to kind of <unk> what is required to reach a service will be in a let me just.

Sort of lay out the steps that are needed <unk> first and foremost be operating if you want to make sure that our potency ask the issue was resolved with the melanoma team, which is right now the dialogue that is ongoing.

Mark Alan Breidenbach: Thank you, Mark. The number of patients has not quite been disclosed once the abstracts come out away from embargo. We can certainly discuss how many patients are in there. What I can say is that the cohort itself was designed for 12 patients, and the cohort is still open. So it's still continuing to enroll patients into the cohort. In terms of what the next steps would be, it is important for us to understand with a larger number of patients and longer follow-up what the real data is.

As a next step you still do need to meet with the surgical review team to discuss the amount of follow up they're going to request and whether COVID-19. One plus four two is something they want or they want to stay just a cold one and subsequent to that we can we can think about who lived to be at a time line is scenario during which this submission can happen later.

Of this year is still in the picture from my perspective, it really depends on when we get the code can see athlete resolved.

Okay. That's great and then I was just curious as you were discussing in the at the top of the call around having determination from C. M S and whatnot around potential code such that you could get reimbursed I know typically those needs to be in the book I believe by August and so I'm just curious.

Mark Alan Breidenbach: These early looks are really helpful for us to understand what the potential may be. But at the same time, we recognize that we want to make sure we have a large enough sample size that we understand what the product is or is not doing. In terms of the next step, I think once the data is visible, it's a little bit easier to speak to it. In general, I'll answer your question in a general sense.

Do you have to have a commercialized product within a certain amount of time at those are still valid. So would you have to go through this exercise again, you know next year.

Sure, Let me ask Jim actually address that question using the room with me. Thanks, Maria Amara High respect D. R. G. If it's a free be approved upon product approval I think your real question is around income Super products or technologies that are <unk> are ones you.

Maria Fartis: Typically, when you have a combination in early line, the next step typically is a randomized study that would show the contribution of each element. I do not rule out single arms in general. If the contribution of elements is extremely high in that single arm, there may be possibilities of talking to the agency and defining a registration path with that single arm. It's not very common, though. So typically, a randomized phase three type would be the next step to take.

They would be implemented in the next fiscal year beginning one October show in this case 20 twenty-two for products that I don't need that one July approval day would have February 5th.

There are two separate processes right. So when's. The day are you on the Wednesday.

Maria Fartis: Got it. Thanks for taking the question.

Okay I appreciate the clarification on that thank you.

Thank you and the next question in the queue comes from S ticket Gonna work from your line is open. Please proceed.

Operator: And the next question in the queue comes from Boris Peaker. Your line is open. Please proceed.

Boris Peaker: Great, I just wanted to ask in terms of the lung cancer cohorts, when should we be expecting updates from those? And what are some of the factors to look into?

Hi, This is avi for on for all to go can you hear me.

Yes account.

Hi, Good afternoon. So one quick question about the license agreement with the NIH can you give a little color.

Maria Fartis: go into kind of deciding the timing of those updates. Hi Boris, good afternoon.

On so.

<unk> excuse me ma'am and.

Maria Fartis: Yes, absolutely. So we really have two cohorts that have lung cancer patients. One is in our basket study; the Com202 study has two cohorts, cohorts 3A and 3B. Cohort 3A, which is early line patients, the treatment naive, or actually, PD1 naive patients, has been a little bit slower to unify during COVID, and this may very well be the impact of hospitals that haven't been impacted by COVID, as well as the fact that these patients obviously have available therapies to receive at their local institutions.

Every time, there's a D O a approval.

Your subject to pay now a.

Low single digit million dollar payment right.

That's correct.

Okay got it.

And one last thing just certainly back with the F D. A.

Lot of.

Clarity today, Thank you, but one so you mentioned that it was one to two months.

General guidelines, but it's you know not required by the typical day to day. So you lost when you can you give a little more 30 on like the day or the week.

You guys submitted.

The most recent state doctor them.

Thank you all before the question.

Maria Fartis: In cohort 3B, we do have some patients, but we have not committed to a specific data flow timeline. We draw the conclusion that patients who receive our second line are certainly much better in terms of non-small cell. The progression from first line to second line in non-sponsal lung cancer is quite large. Unfortunately, many patients, around 70% of the patients don't make it to second line. So we are trying to limit our subsequent upcoming cohort.

So we didn't disclose the exact date will be did say that'd be have submitted the validation package to the agency in Q1, we had committed to and that's okay too that I've dealt with complete it in on time.

Alright, thanks, Thanks for our questions.

Thank you so much.

The next question the queue comes from <unk> Kumar. Your line is open. Please proceed.

Hey, everyone can you guys hear me okay.

I'm a do yes, we can.

Okay, great. So I'm kind of thinking about the from line melanoma travel a little bit.

Kind of a very simple question, where do you think are the gaps and from line melanoma on P. D. One blockade where pills can provide specific benefit of like duration of response complete responds, where do you think there's a kind of window <unk> P. D. One two to give edge.

Maria Fartis: to second line non-small cell, but we do have some patients in that former 3B, which once we have long enough follow-all, we could disclose the data. We haven't committed to a specific venue or a time frame yet.

Maria Fartis: Great, thank you very much for taking my question.

That's a great question I do some at all and it was at a disease that is fairly well addressed with check my inhibitors. However, I think that it really depends on the day to itself and I think we can call them into a little bit more once the data for chill plus hambro shows up at Osco, There's still there's always room from.

Operator: And the next question to queue comes from Mara Goldstein. Please proceed. Great, thanks so much for taking the questions. Just a couple of things.

Mara Goldstein: First, I just wanted to circle back to make sure that I understood correctly in the submission that was made to the FDA around the assay that the FDA is not obligated to respond to you within a specific time frame for that submission. And on the cervical program, can you give us a bit more background on how the decision was made to combine the two cohorts and was that made based on discussions with FDA, and where does that leave us potential? The filing timeline. And then the last thing I had was just a curiosity more than anything.

Improvement if the patients on not reaching a complete response or that their duration of response could be improved so from my perspective, a patient that experienced as a deep durable response in front line did you offers a lot of benefit to the patient.

Clear second unmet need is exactly moving have been doing which is opposed P. D. One patient population I'm Gonna ask fridrich to comment just is anything to did you want to add to this.

And from agreement <unk>, what we shouldn't forget although a lot of progress has been made with the check whether the <unk> and the various indications the majority of patients still little progress.

Maria Fartis: On the reimbursement front and the determinations that have been made around codes and whatnot, is there a specific time limit within which those must be made active such that you don't have to reapply to the agencies? Maura, I understood your first two questions; let me answer them, but I didn't catch your third question quite. Let me try and answer the first two and then I'll ask you to repeat question number three.

Either primarily or secondarily because of resistance mechanisms. You will you will make that looks like me and you will increase benefit by pushing down the responses, even deeper and and complete responses are are real real good gold here. So I think I I totally agree with Maria that got it it's really <unk>.

Maria Fartis: In terms of the assay, you're correct. The agency is not on a pedupe o'clock clock to answer in a given timeline. However, when a CMC-I-N-D amendment is submitted to the agency, there's guidelines that typically limit the duration of time they review it. It's usually one to two months, and so that guideline is what we are sort of referring to and waiting for the agency to respond within that window of opportunity. In terms of cervical cancer, we haven't quite committed to combining the cohort. I just want to be sure that we are clear.

There's room for improvement.

Okay, great and kind of them to follow up on some of the questions around the the cell phone. So yeah. So your issues.

I mean, I guess kind of ultimately to what extent is this whole situation about kind of educating the F. D. A about the differences between kills antenna earlier generation, Kansas total technology, Hoyt Cartier and to what extent is is about to kind of you mentioned, having a panel of cytokines type factors said.

Demonstrate kind of <unk> did you say you wanted just a single type of factor sorry to demonstrate to cell phone too.

Maria Fartis: We gave the visibility to investors that we have the possibility of combining Cohorts 1 and 2. It's certainly subject to discussion with FDA. Cohort 1 were patients that were post-chemotherapy in a metastatic setting, and cohort 2 were patients that also could have received anti-PD1 in a metastatic setting.

Uhm So great question May do.

I don't know if I can comment on educating the agency I mean, the agency Turkey on our review team. There are members who have been at M. C. I before now how much internal communication there. It it's a little hard for me to sort of comments on that I can tell you that they requested they have made so far have been reasonable in the sense that.

Maria Fartis: Now, the reason we kind of went down that path is we wanted to make sure that the investors are aware that there's a possibility, given the potential change in the landscape of cervical cancer, there's a possibility that the agency may request two and or Iovans may want to include that data. So it's very much subject to discussion with FDA. If that addresses your questions one and two, do you mind repeating your question, please?

They're not asking for example for a go find yourself an outage in specific as day that would have told me that World War, two it's gonna be very difficult to do but that's low put the request hasn't come see you said, which tells me that they do understand the power of kill the the the the fact that it ultimate the addresses multiple you on two gyms on it is highly <unk>.

Maria Fartis: Sure, not a problem, but on question two, if you do, if the determination is that those cohorts will be combined from a potential filing perspective, does that, you know, what does that do to sort of the internal timeline that you have? Or the one that you shared.

<unk>, so I think that.

Maybe education is not the right word maybe the way is to better define a first in class product with the sponsor there definitely is some time that needs to be spent between both the agency and the sponsor and trying to define how do we define such a complex product I think that that will be the true statement.

Maria Fartis: From a timing perspective, just to kind of outline what is required to reach a cervical BLA, let me just sort of lay out the steps that are needed. First and foremost, we absolutely want to make sure that our potency athlete issue is resolved with the melanoma team, which is right now the dialogue that is ongoing. As a next step, we still do need to meet with the cervical review team to discuss the amount of follow-up they're going to request and whether cohort 1 plus cohort 2 is something they want or not. to stages, the forward one.

Okay, great. Thanks, guys.

Thank you.

Thank you and the next question to cute comes from Nick habit. Your line is open. Please proceed.

Good afternoon, and thanks for taking my question.

<unk> <unk> <unk> <unk> <unk> <unk> J C O J solution colleagues reported.

Encouraging data for the culmination of P D one and C. Kelly.

For in patients, who really considered primary P. D. One failures and acknowledging these allergies second line C telephone or your patience and so.

Clearly north apples to apples with <unk> legislation cohort.

Do you think these day to change to use a total.

Maria Fartis: And subsequent to that, we can think about sort of the BLA timeline. A scenario during which this submission can happen later part of this year is still in the picture from my perspective. It really depends on when we get the potency athlete resolved. Okay, that's great. And then I was just curious, as you were discussing at the beginning of the call around having determinations from CMS and whatnot around potential codes such that you could get reimbursed. I know typically those need to be in the books, I believe, by August.

<unk> and so the second line setting and does it.

<unk> a barrier of coal <unk>. Thanks.

Hi, Nick Thank you for the question Uhm I'll do my best to give you a preliminary answers and I'm going to invite Frederick to also comment.

I do I'd be have seen the manuscript I'm glad you're it's it's getting noticed I highlighted a few differences between the manuscript in terms of the patient population the endpoint with what audio bathrooms doing the end point that is reported I've been that is the manuscript is all you're all resist not resist one <unk>.

Maria Fartis: And so I'm just curious, do you have to have a commercialized product within a certain amount of time? Those are still valid, so would you have to go through this exercise again, you know, next year? Sure. Let me ask Jim to actually address that question.

One does this 1.1 is a regulatory and point that has been very well understood and requested by F. D. A I I'll resist as an immune mediated type of and point and has not been really accepted by the agency as an appropriate endpoint interest you.

So the patient population this is strictly speaking.

Maria Fartis: Thanks, Maria. Hi Mara. Hi.

In line in some cases frontline metastatic patience because he could have had adjuvant therapy and subsequent to that day would have entered the study.

James Ziegler: With respect to the DRG, if it's approved, it would be approved upon product approval. I think your real question is around N-TAM. So for products or technologies that are approved by 1-July, they will be implemented in the next fiscal year, again in 1-October. So, in this case, 2022. For products that don't meet that 1-July approval date, they would have to resubmit for the N-TAP. They're two separate processes, right? So one's the DRG and the other ones are,

Mm I highlight a couple of other place the amount of I'm unpray around J P. D. One of the median was reported at four eight months, that's a pretty short duration of time at it probably looks like a primary refractory patient population.

What was also remarkable from my perspective was the times won't play around J P. D. One which was quite short mm mm that may yield to the previous.

James Ziegler: Okay, I appreciate the clarification on that. Thank you. Thank you, and the next question in the queue comes from Estika Gunnew Warden. Your line is open. Please proceed. Hi, this is Avi for On Forautica. Can you hear me?

There'll be on board given the long haul cycles per 1951.

The median duration of response had been.

Reported and some of the patients as I noted, we're coming from one address I'm kidding.

So I think that there's there's meaningful differences both between the end point as well as a patient population, making it very difficult to compare friedrichs did you want to add any comments to this.

Operator: Hi, good afternoon. So one quick question about this license agreement.

Asthika Sarith Goonewardene: license agreement with the NIH. Can you just give a little color?

Think maybe maybe a couple of comments kinda compare and contrast also uhm. This is academic day paper. This was generated within seven seven U S site.

Asthika Sarith Goonewardene: On So these are exclusive agreements, and every time there's a DLA approval, you're subject to paying out a low single-digit million-dollar payment, right? That's correct. Okay, got it. And one last thing, just circling back to the FDA, a lot of clarity today, thank you. But one, you mentioned that it was a one to two month general

The date of that we.

We are presenting for a program Mr Zone as a global Multicenter study I think that is relevant in this context as well and maybe one <unk> just one quick comment on the nature of the therapy. The the treatment that was explored in this menu still.

Maria Fartis: general guidelines, but it's not required, like a typical producer date. So your last, when can you give a little more priority to, like, the day or the week you guys submitted the most recent data back to them? Thank you, Avi, for the question. So we didn't disclose the exact date, but we did say that we submitted the validation package to the agency in Q1. We had committed to investors to that, and that was completed on time.

Still requires continuation November isn't up for up to two years, which is a big contrast to a one time treatment with so I'd like to move to a regimen that is meaningful those as well.

And other than that I think Maria summarize the the difference so sorry, well yeah <unk> just maybe one one more point Nick that I was reminded him again strictly speaking they're stuck in line at the latest many of the patients that per cent of the patients were first line just so let's just to make that up and then just <unk>.

Maria Fartis: All right, thanks for our questions. Sure. Thank you so much. The next question in the queue comes from Madhu Kumar. Your line is open. Please proceed.

Some of them were second line the patients had not received <unk> four or other therapeutic switches.

Operator: Well, hey everyone, can you guys get me okay?

Pretty much a reality of life, where decisions nowadays an outpatient ma'am.

Madhu Sudhan Kumar: I'm adieu. Yes, we can. Okay.

Madhu Sudhan Kumar: Okay, great. So, kind of thinking about the frontline melanoma trial a little bit, I guess it's kind of a very simple question: where do you think are the gaps in frontline melanoma on PD1 blockade where Tills can provide specific benefits, like duration of response, complete response? Where do you think there's a kind of window for Tills plus PD1 to get an advantage?

Okay. Thank you.

Thank you.

And we have one more question in the queue and that question comes from been burn it to your line is open and Mister Burnett.

Hi cause that can only this is karina I'm <unk> I'm trying to ban for that my <unk> My cold up here. So my apologies thinks you'll have to try the patch on days. What we were wondering if you could talk hubby modem day under cohorts free I'm off the physical cancer study.

Maria Fartis: That's a great question, Madu. So, melanoma is a disease that is fairly well addressed with check-point inhibitors. However, I think that it really depends on the data itself, and I think we can comment a little bit more once the data for Till Plus Pembro shows up at ASCO. There's always room for improvement if the patients are not reaching a complete response or if their duration of response could be improved. So from my perspective, a patient that experiences a disease, deep durable response in the front line really offers a lot of benefit to patients.

Can you expect these would be needed for approval.

Hi, Kelly not if I understand let me make sure I understand the question where are you asking about <unk> three of cervical.

Yes, correct.

<unk> three his patients that are P. D. One naive and they get to click on taking P. D. One is that the cool wood, you're asking or are you asking back over to.

No I'm asking about cohort free I need to you find that this is what I'm, saying it it tore for approval.

Great question I don't believe so that was really an exploratory cohort that'd be started trying to understand what a combination of two plus hambro M. P. D. One day of patience with you. So this has not been subject to any regulatory discussions the patient population is in earlier line patient compared to force one and two cohort one was discuss with a free <unk>.

Maria Fartis: The clear second unmet need is exactly what we have been doing, which is the post-PD1 patient population. I'm going to ask Frederick to comment if he has anything to add. Did you want to add to this? I agree, Maria. What we shouldn't forget is that although a lot of progress has been made with check-clin inhibitors in various indications, the majority of patients still will progress, either primarily or secondarily because of resistance mechanisms. You will make that less likely, and you will increase benefit by pushing down the responses even deeper, and complete responses are a real, real good goal here. So I think I totally agree with Maria. That is really where there's room for improvement.

Colver too is a patient population beaches post P. D. One as what is supposed to chemotherapy and we think this is the landscape locations that is coming so we had added.

Into the program and you think it might be also important is submission of the B L. A.

Okay perfect. Thank you.

Thank you.

Uh-huh.

Okay, well, we have no further questions at this time.

Thank you ladies and gentlemen, this will conclude today's teleconference. Thank you for participating you may now disconnect.

Maria Fartis: Okay, great. And kind of to follow up on some of the questions around the cell potency assay issues, I mean, kind of ultimately, to what extent is this whole situation about kind of educating the FDA about the differences between kills and kind of earlier generation cancer cell technologies like CAR-T, and to what extent is this about, kind of, as you mentioned, having a panel of cytokine-type factors that demonstrate kind of T-cell potency beyond just It's a great question.

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Maria Fartis: It's a great question; I may do. I don't know if I can comment on educating the agency. I mean, the agency is certainly on our review team. There are members who have been at NCI before. Now, how much internal communication there is, it's a little hard for me to sort of comment on that.

Maria Fartis: I can tell you that the requests that they have made so far have been reasonable in the sense that they're not asking, for example, for you to go find yourself an antigen-specific assay. That would have told me that, well, for Till, it's going to be very difficult to do. But that type of request for you hasn't come to, which tells me that they do understand the power of till, the fact that it ultimately addresses multiple new antigens, and it is highly, highly polyclonal.

Maria Fartis: So I think that maybe education is not the right word. Maybe the way is to better define a first-in-class product with this sponsor. There definitely is some time that needs to be spent between both the agency and the sponsor in trying to define how we define such a complex product. I think that's probably true.

Maria Fartis: State. Okay, great, thanks, guys. Thank you. Thank you. And the next question, the Q comes from Nick Abbott. Your line is open. Please proceed. Well, good afternoon. Thanks for taking the question.

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Operator: Maria and Co. So, you know, in the current JCO, Jason Luke and colleagues, this board is encouraging data for a combination of PD1 and CTLA4 in patients who really are considered primary PD1 failure, acknowledging these are largely second-line C2A4 nae patients, and so clearly not apples to apples with lipolous cells, the St. O.O. Do you think these data changed their use of that doublet in the sort of second line setting, or does it create a barrier for Littalusel use?

Nick Abbott: Hi Nick, thank you for the question. I'll do my best to give you preliminary answers, and I'm going to invite Frederick to also comment. I do, we have seen the manuscript. I'm glad you're, it's getting noticed.

Maria Fartis: I highlight a few differences between the manuscripts in terms of the patient population and the endpoints with what Iovance is doing. The endpoint that is reported in the manuscript is IR resistence, not resist 1.1. Resist 1.1 is a right.

Maria Fartis: endpoints that have been very well understood and requested by FDA. IR is an immune-mediated type of endpoint and has not been really accepted by the agency as an appropriate endpoint. In terms of the patient population, this is strictly speaking second line and, in some cases, front-line metastatic patients, because they could have had adjuvant therapies, and subsequent to that, they would have entered this study. I highlight a couple of other points.

Maria Fartis: Their amount of time on prior antiped1, as the median, was reported at 4.8 months. That's a pretty short duration of time. It probably looks like a primary refractory patient population. What was also remarkable from my perspective was the third.

Maria Fartis: time from prior antipD1, which was quite short, and that may lead to the previous products still being on board, given the long half life of prior anti-PD1. The median duration of response had been reached and was reported. And some of the patients, as I noted, were coming from an adjuvant setting. So I think that there are meaningful differences both between the endpoints as well as between the patient population, making it very difficult to compare. Frederick, do you want to add any comments to this?

Maria Fartis: I think maybe a

Friedrich Graf Finckenstein: A couple of comments, kind of a compare and contrast. Also, this is an academic page.

Friedrich Graf Finckenstein: paper This was generated in seven US sites. The data that we are presenting for our program is

Friedrich Graf Finckenstein: is a global multi-center study. I think that is relevant in this context as well. And maybe one quick comment on the nature of the therapy is,

Friedrich Graf Finckenstein: The treatment that was explored in this manuscript still requires continuation.

Friedrich Graf Finckenstein: in this manuscript still requires continuation of hembilism for up to two years, which is a big contrast to a one-time treatment with the Lafalutu regimen. I think that is meaningful as well. And other than that, I think Maria summarized the differences very well.

Maria Fartis: Yeah, just maybe one more point, Nick, that I was reminded of. Again, strictly speaking, their second line at the latest, many of the patients, the percent of the patients were first-line, sort of systemic therapy, and then some of them were second line. The patients had not received higher doses of antistice-tay-4 or other therapeutics, which is pretty much a reality of life-borne patients nowadays, and our patients have a person. Okay, thank you. And we have one more question in the queue, and that question comes from Ben Burnett. Your line is open, Mr. Burnett? Hi, good afternoon. This is Carolina Ivane's Rental Zone for Ben Burnett.

Operator: My call dropped earlier, so my apologies if you already touched on this. We were wondering if you could talk a bit more about the cohort three arm of the cervical cancer study and if you expect this will be needed for approval. Hi Karolina, let me make sure I understand the question. Were you asking about cohort three of cervical cancer? Yes, correct. So, cohort three is patients that are PD1 naive, and they get two plus anti-PD1. Is that the cohort you're asking about, or are you asking about cohort two? No, I'm asking about cohort three, and if you find that this will be needed for approval. Great question!

Carolina Ibanez: I don't believe so. That was really an exploratory cohort that we started trying to understand what a combination of TIL plus PEMB in PD1 naive patients would yield. So this has not been subject to any regulatory discussions.

Maria Fartis: The patient population is an earlier line patient compared to cohorts 1 and 2. Cohort 1 was discussed at FDA. Cohort 2 is a patient population that is post-PD1 as well as post-chemotherapy, and we think this is the landscape of patients that is coming. So we have added that to the program, and we think it might be important in submission of the BLA.

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Maria Fartis: Okay, perfect. Thank you. Thank you. We have no further questions at this time. Thank you, ladies and gentlemen. This will conclude today's teleconference. Thank you for participating. You may now disconnect.

Operator: and and and and and Thank you Thank you Thee and and and Thank you Thank you, Thank you.