Q4 2020 Iovance Biotherapeutics Inc Earnings Call
Ladies and gentlemen, todays conference is scheduled to begin shortly please continue to standby and thank you for your attention.
Yeah.
[music].
Good afternoon, and welcome to the other banks fourth quarter and full year 2020 financial results Conference call.
At this time all participants are in a listen only mode. After the Speakers' presentation. There was the question and answer session to ask the question during that portion of the call you don't need the press star one of your tongue.
If you require any further assistance please press star zero.
I would like to turn the call all of their two year Sneaker, Sarah Byrnes, Vice President Investor and public relations and other than this.
Gotcha.
Thank you operator, good afternoon, and thank you for joining US speaking on today's call we of Maria <unk>, Our President and Chief Executive Officer, Fredrik thinking Stein, our Chief Medical Officer.
John Mark Bellamy, our Chief Financial Officer.
Also joined by Jim piece of our senior Vice President commercial.
This afternoon, we issued a press release it can be found on our website at <unk> Dot com.
The financial results for the three and 12 months ended on December 31st 2020, that's.
Well the corporate update.
Before we start I would like to remind everyone that statements made during this conference call will include forward looking statements regarding I'll pass the school business focused business plan pre commercial activities clinical trials and regulatory Torri plans and results.
Actual future applications of our technologies manufacturing capabilities regulatory feedback and guidance payer interaction collaboration cash position, an expense guidance and future updates.
Forward looking statements are subject to numerous risks and uncertainties many of which are beyond our control, including the risks and uncertainties described from time to time in our SEC filings.
Our results may differ materially from those projected during today's call. We undertake no obligation to publicly update any forward looking statements with that introduction I will hand, the call over to Maria.
Thank you Sarah and good afternoon, everyone.
I'm pleased to highlight our 'twenty 'twenty progress as well as our 2021 priorities at all events during today's conference call.
During 2020, we continue to advance and broaden our tumor infiltrating lymphocyte or true platform across multiple indications, including metastatic melanoma cervical head and neck of non small cell lung cancers for our lead product candidate each like the new store in metastatic melanoma, the reported new and updated day.
From our ongoing the one full force needle one clinical study demonstrating durable responses in our core two for one time treatment that they can do so.
We initiated the dialog, but the FTA and learned that we need to continue to finding the information from our potency assay.
We continue our work to refine existing guests as well as they thought about the U S. As in pursuit of other biologics license application, albeit of a which is our top priority for 2021.
And the additional indications the completed enrollment in two cohorts for life of diesel and advanced cervical cancer. We reported the initial clinical data for children combination, but temporarily lose them up and head and neck cancer and the activated sites for our registration directed study of <unk> 145 in non small cell lung cancer.
We believe that the growing body of choke clinical data across multiple late stage cancers, coupled with companies just kill and checkpoint inhibitors in earlier stages of disease validate the significant and broad potential for chill.
We also continued to execute towards all manufacturing and pre commercial activities in furthering our commitment to address the critical needs all of the cancer patient.
I am very confident in the strength of our employees to deliver on the submission. We have an impressive 76 per cent of our nearly 250 employees, who have at least a year of cell therapy experience.
On the call today, I would like to spend a few minutes highlighting the lead indication then I will let fredrik highlight a recent clinical study update.
I will begin with the first pivotal program like the new sofa, and a basketball and Obama.
Metastatic melanoma is the common skin cancer accounting for approximately 96000 patients diagnosed in the southern thousand deaths each year in the United States alone.
We are focused on metastatic melanoma patients that have exhausted their most common use of available care options and <unk>.
The alternative therapies.
In early January of 'twenty 'twenty, one be provided of corporate update the median duration of response has not been reached at 28. One months of median study follow up of core two from our C. One full force needle one clinical study.
We as the one S. Kols continue to be very enthusiastic about the durability of response following onetime treatment the life and useful.
For the post anti PD, one patient population similar to the core to chemotherapy is all the currently available option and offering of four to 10 per cent response rate and overall survival of only seven to eight months.
We intend to present the long team for the long term follow up data from cohort two at an upcoming medical conference.
As previously mentioned, reaching agreement to the FDA on the potency assay is the top priority for all of that.
Following the type B meeting with the U S. FDA during the fourth quarter of last year. We've reached agreement on the duration of clinical data follow up where our pivotal cohort four to support the BLA.
We did not reach an agreement with the agency on the potency assay used to define til and continue our work to define existing potency assays why is developing new assays.
While the length of time until the any submission depends on future dialogue with the agency. We continue staying prepared for a BLA submission in 2021.
The plan to provide updates when available.
Our second pivotal program is investigating and then one four of five now also known as like the neutral and the C. One 450 force study to support the BLA submission and metastatic cervical cancer.
Enrollment in both cohorts, one and two of the study has been completed patients in our pivotal cohort one or post chemotherapy, whereas cohort two includes post PD one patients.
We believe that inclusion of both cohorts at the BLA make strengthened the potential label and reflects the expected upcoming treatment landscape in cervical cancer.
The resolution of the potency assay for life and do flow of melanoma is a key step towards our BLA submission planned in the cervical cancer indication I spoke.
Reminder, the S. D of has previously granted both breakthrough therapy and fast track designation for like the useful in cervical cancer.
Turning to our manufacturing facility all of the bounds of cell therapy center or I see the.
The construction of clean rooms was completed in late 2020, probably.
Process equipment on now in place and the available clean rooms and activities in support of clinical manufacturing unexpected to initiate in the coming months.
Commercial manufacturing remains on track for 'twenty 'twenty, two with capacity to meet the demands of up to thousands of patients.
I have found such transformed til manufacturing from the Nike academic process of shorter scalable centralized GMP process, yielding of Cryopreserved product.
Our Gen. Two process is 22 days.
To date more than 400 patients have received all your loans til with the continuing success rate above 90% we.
We have also built on continued to our arguments are intellectual property, which is covered by more than 20 granted or allowed U S and international patents for compositions and methods of treatment and a broad range of cancer from eating to the gen. Two manufacturing process.
Or are you that's the IP portfolio includes patents applications and granted patents directed toward Gen. Two manufacturing selected til products stable and transient genetic until modifications cryopreservation and combination of chill with checkpoint inhibitors.
Turning to our commercial launch preparation the value of Ams team is currently focused on cable engagement site activation and training till education and awareness patient access and other readiness activities.
Our priority is to ensure launch success, while taking a gated approach to commercial readiness expenses.
And head counts prior to BLA submission.
Our medical Affairs team works with a network of treating health care professionals or H C piece and patient advocacy groups to ensure that the information about till it's available to interest that organization.
Our core commercial team continues to partner with the leading U S cancer centers to build their til service line capabilities from the intent to scale of training and Onboarding of upon be any submission of.
Our market access team continues to meet with the private payers and the centers for Medicare and Medicaid services or CMS to ensure patients have appropriate and timely access to like of diesel.
The belief that CMS and payers recognize the unmet need and clinical value of life and useful as one of the potential benefits for patients with metastatic melanoma.
We're also pleased with the development and progress of our Io bonds of cares program. Our goal is to deliver a best in class of cell ordering and patient support system, but assist the patients at every step of the process.
I will now pass the call to Fredrik to outside non clinical study updates, including them Goldman status as one of the introduction of new cohorts in treatment regimens into our existing studies Frederic.
Thank you Maria.
I am pleased to highlight today that we are currently recruiting patients for four clinical studies of law.
Drug development strategy focuses on cancer populations with high unmet need with substantial opportunity of fulfill to make a meaningful impact.
All of our C. One four of five Oh for clinical study in advanced cervical cancer has completed.
Those enrollment of the first two cohorts will be continue to recruit the third cohort of anti PD, one naive patients to receive two plus kind of losing them up.
Recruitment also remains underway and all of it will be called to a true study in solid tumors.
The other you'll be loans two of two study in second line non small cell lung cancer.
The I O vs yellow zero, one study of yellow F. L O.
As we move ahead with two alone and the combination with the proof treatments in the different indications in various stages of cancer. The COVID-19 pandemic may impact the pace of enrollment, particularly of course cohorts with earlier line patients, which may improve the school with 19 of beats.
On last quarter's call I focused on the activation of all of our it'll be tell you in two of two clinical studies.
I will highlight the occurred day, though and strategy in head and neck cancer as well as the recent updates and the inclusion of new cohorts of the IOP column two of true basket study.
He doesn't that cancer remains an important indication for Io them. So we are particularly encouraged by the initial clinical data from our til therapy L and wonderful five in combination with Campbellism up the book presented at the society for the immunotherapy of cancer or since the annual meeting in November of 2020.
We are also excited about the potential full tilt in combination with the campbellism up another sort of attempt.
The since the poster highlight the nine patients with head and neck squamous cell carcinoma voyage in S. E. C from cohort two eight and the audio will be come two of two basket study. These patients had not previously received treatment with checkpoint inhibitors, but may have received prior chemotherapy.
Following the island 145 in combination with symbolism of over the swaps rates or are with 44% and median duration of response had not been reached the $8 six months of median study follow up.
Well these are small patient numbers, we find the results could be very promising.
Of our with checkpoint inhibitor of monotherapy and shake Glenn, but you've heard of that cancer patients ranges from 15% to 18% in the literature.
Core TUI has now been expanded to include up to 19 patients.
Before I hand, the cultures are Marc I would like to highlight the additional updates and all of I O E. Com two of two basket study, which now includes seven total courts across the melanoma head and neck and non small cell lung cancers.
As Maria mentioned, we are very excited about the potential for true to offer an option for many different patient populations in multiple indications.
This basket study the that'd be line patients in each indication received to the realism.
The nine months' small cell lung cancer patients receive to stipulate move up the volume.
And later of lung cancer patients with melanoma, non small cell lung cancer of receipts kill alone.
Recent updates include the addition of of the new melanoma cohort of new lung cancer cohort and as mentioned previously the expansion of the head and neck cancer cool.
Our newly added cohort one C will investigate other than one full floor manufacturer with a 16 day third generation of old Gen. Three process and metastatic melanoma patients who have received one or more prior systemic therapies.
Cohort two eight and head of that cancer, which is evaluating and then one full price in combination with Campbellism of was extended to true up to 19 heads at the cancer patients who are not used to the immune checkpoint inhibitors.
And all of new cohort three C will provide an alternative options of standard chemotherapy of non small cell lung cancer offering to close the prelim them up the of all of them up and non small cell lung cancer patients who have received one prior systemic therapy.
The three non small cell lung cancer cohorts in the basket study together with the second line patient population and our I O V. A U N. Two registration supporting study allow us to cast the broad enough to address the unmet needs the non small cell lung cancer.
I will now hand, the call over to zone, Mark to discuss all of fourth quarter and full year 2020 financial results.
Yeah.
Thank you Farooq.
My comments really reflect the high level of financial results from a full squadron of full year of 2020.
Additional details can be found in this afternoon's press release as well as you know annual report on form 10-K filed with the system.
I will begin with our cash position.
As of December 31st of 'twenty to 'twenty.
Once all of the 635 million.
Cash cash equivalents short terms in the basement and restricted cash.
To treat pruned rhythm 12.5 million on December.
When she mentioned.
The strong cash position delivered on our commitment to them last year was at least 600 sort of $2 million in cash.
Our current cash positions include net proceeds of $567 million all from of June 2020 of common stock public offering of <unk>.
Financial strength is expected to be sufficient into 'twenty, two 'twenty three to deliver on the pipeline programs.
Moving to the income statement of net loss for the fourth quarter ended December so to the first went to the 'twenty was $68.4 million or 47 cents per share.
The net loss of $63 6 million zone.
The 50 cents per share for the fourth quarter ended December so it's the first 20 mentioned.
Net loss for the 12 months ended the December so to the from 'twenty to 'twenty was 269 6 million all of one dollar and 88 cents per share.
Compared to a net loss of $197.6 million of $1 59 per share for the 12 months of December.
The December 31st two months of medicine.
Operator: Ladies and gentlemen, today's conference is scheduled to begin shortly. Piano Sonata No. 1 in B-flat Major, Op. 67 No. 2 in B-flat Major, Op. 67 No.
Research and development expenses were $52.4 million of for the fourth quarter of the disarm Bruce what's the first 2020.
<unk> of 1.8 million co broke true 50, forborne $2 million for the fourth quarter on the December sort of two for 'twenty.
She mentioned.
Research and development expenses were $201.7 million for the full year ended December of sorts of the first two months of 'twenty, an increase of $35 7 million.
Operator: 2 in B-flat Major, Op. 67, Good afternoon, and welcome to the Iovance fourth quarter and full year 2020 financial results conference call. At this time, all participants are in a listen-only mode. After the speaker's presentation, there will be a question and answer session. To ask a question during that portion of the call, you will need to press star 1 on your telephone. If you require any further assistance, please press star zero.
Compared to $166 million for the full year and the December of 'twenty.
2019.
The decrease in research and development expenses in the fourth quarter of 2020 over the prior year of your period was primarily attributable to of the crews and manufacturing in the clinical cost following the completion of enrollment in the pivotal calls for melanoma and cervical cancer.
The increase in research and development expenses in the full year of 'twenty to 'twenty overrode. The part of your full year period was primarily attributable to all of your clinical cost licensing fees and gross of the internal research and development of them.
Moving on to.
General and administrative expenses were $16 $1 million of for the fourth quarter of 2020, an increase of $5 2 million compared to 10 9 million for the.
Fourth quarter of 2019.
General and administrative expenses were $62 million for the 12 months on the.
Decembers, what's the first ones to 'twenty, an increase of $19 3 million.
Operator: I would like to turn the call over to your speaker, Sara Pellegrino, Vice President, Investor, and Public Relations at Iovance. [inaudible] Thank you, operator. Good afternoon, and thank you for joining us on today's call. Speaking on today's call are Maria Fardis, our President and Chief Executive Officer, Frederick Finckenstein, our Chief Medical Officer, and John Mark Bellamine, our Chief Financial Officer. We are also joined by Jim Ziegler, Senior Vice President.
Compared to $49 million for the 12 months and the same.
So to the first 2019.
The increases in general and administrative expenses in the fourth quarter and full year of 2020 compared to the per year of your periods were primarily attributable to growth of the internal general and administrative team and now you're of stock based compensation expenses.
As of December so it's the first 2020, there were approximately the Li $146 9 million common shares outstanding.
Sara Pellegrino: This afternoon, we issued a press release that can be found on our website at iovance.com. This announces the financial results for the 3 and 12 months ended on December 31st, 20, as well as corporate.
Looking ahead, we are open to opportunities to top off of cash balance while being mindful of dilution of <unk>.
We of food or not the market or ATM facility in place to raise of true trend with $15 million.
The ATM much like of shelf as a good housekeeping measure of the mirror laws to be opportunistic.
Two of our already strong balance sheet.
I will now under called back to the opioid or do kick off of the Q&A session.
Thank you I don't know as I reminder, ladies and gentlemen, if you have a question simply press star one on your telephone.
To withdraw your question press, the pound or high school.
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. Matthew Matthews,,,,,,,,,,,,,,,,,,,,,,, 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. We undertake no obligation to publicly update any forward. With that introduction, I will hand the call over to Maria.
One moment, while we compile the Q&A roster.
Our first question is from my Freedom back with Oppenheimer. Your question. Please.
Hey, Thanks for taking the question and congrats on the or the the price.
Yes this quarter.
Maria I was hoping you could clarify whether or not the first patient has been treated in the Iot all of you went into it.
The study.
Or can you offer any thoughts as to when we might see lung cohort data from the basket trial.
Hi, Mark good afternoon. Thank you for the questions. We have not started patient dosing in L. U N. Two O. Two although we do have a few sites that are activated.
We have not committed to a data flow timeframe for our lung data. If you recall, there's only two cohorts and of our program that actually have Ah patients and the one is cohort three a M. One of score of three b in the Com two of two study behalf highlighted in core three a V have had challenges in patient enrollment and of course.
Maria Fardis: Thank you, Sara. And good afternoon, everyone.
Maria Fardis: I am pleased to highlight our 2020 progress as well as our 2021 priorities at Iovance during today's conference call. During 2020, we continued to advance and broaden our tumor infiltrating lymphocyte, or TIL, platform across multiple indications, including metastatic melanoma, cervical, head and neck, and non-small cell lung cancers. For our lead TIL product candidate, lipoleucine, and metastatic melanoma, we reported new and updated data from our ongoing C14401 clinical study, demonstrating durable responses in our cohort two for one-time treatment with Lifelucidol. We initiated a dialogue with FDA and learned that we need to continue refining the information from our potency assays.
Three b, we are hoping to of additional patients with long enough follow up to be able to present, the data will be of not committed to the timeframe for data flow.
Okay. Thanks, that's helpful.
And then just turning to the cervical program.
You know, obviously there might be more focused on cohort two given the evolving standard of care.
In frontline in cervical cancer.
Can you give us a sense from what you see is a meaningful efficacy bar for for that you'd need to clear for checkpoint experienced patients in cervical and if we can expect to see data from the second cohort.
Maria Fardis: We continue our work to refine existing assays as well as to develop new assays in pursuit of our Biologics License Application, or BLA, which is our top priority for 2021. In additional indications, we completed enrollment in two cohorts for lifelucid and advanced cervical cancer. We reported the initial clinical data for TIL in combination with pembrolizumab in head and neck cancer, and we activated sites for our registration-directed study of LN145 in non-small cell lung cancer.
Of this trial.
Sure.
So currently the way we have designed to critical for cohort two behalf. These patients of course PD one unexpectedly the would've received chemotherapy as of prior line because that's just the available care for them. So if you think about as third line therapy. The best we are aware of and there is no data that I'm aware of I know you start the Frederick in just a minute.
Maria Fardis: We believe that the growing body of TIL clinical data across multiple late-stage cancers, coupled with the combination of TIL and checkpoint inhibitors in earlier stages of disease, validate the significance and broad potential for TIL. We also continue to execute toward all manufacturing and pre-commercial activities in furthering our commitment to address the critical needs of cancer patients. I am very confident in the strength of our employees to deliver on this mission.
That is sort of post PD, one patients, but I believe for chemo in third line. This the bar is around 3% response rate Mark in terms of cohort two data itself, we have blinded ourselves the same way as behalf of with our pivotal cohorts such as Covid, one in cervical and we have not read out that cohort since we have talked.
F D a.
Don't know if you want to add anything on the expected response rate for all of two patient or similar of patients.
Maria Fardis: We have an impressive 76% of our nearly 250 employees who have at least a year of cell therapy experience. On the call today, I would like to spend a few minutes highlighting the lead indications. Then, I will let Frederick highlight our recent clinical study update, and I will begin with our first pivotal program, Life and Youth in Advanced Melanoma. Metastatic melanoma is a common skin cancer, accounting for approximately 96,000 patients diagnosed and 7,000 deaths each year in the United States alone.
That's correct.
Is that his numbers for third line treatment.
The same percentage is about right and that is interestingly true across a number of different therapies all of them being chemotherapy. So it's all ranging in of the about 33% range.
Maria Fardis: We are focused on metastatic melanoma patients that have exhausted their most commonly used available care options and need alternative therapies. In early January of 2021, we provided a corporate update that median duration of response still has not been reached at 28.1 months of median study follow-up for cohort 2 from our C14401 clinical study. We, as well as KOLs, continue to be very enthusiastic about the durability of response following one-time treatment with life-giving salts.
Okay Super helpful. Thanks for taking the questions and congrats again.
Thanks Mark.
Our next question comes from Peter Lawson with Barclays. Your question. Please.
Hey, Thanks of taking my questions Mary just on the.
F D a.
Potency assay one.
Are the next steps in the in any way kind of asking for a more defined product.
Hi, Peter.
Thank you for your question.
On behalf of from the time he met with the agency, which was back in early October of 2020, we have submitted a couple of packages to the agency and we.
Maria Fardis: For the post-anti-PD-1 patient population similar to cohort 2, chemotherapy is the only currently available option and offers a 4 to 10 percent response rate and overall survival of only 7 to 8 months. We intend to present the long-term follow-up data from Cohort 2 at an upcoming medical conference. As previously mentioned, reaching agreement with FDA on the potency assay is a top priority for Iovance. Following a type B meeting with the U.S. FDA during the fourth quarter of last year, we reached agreement on the duration of clinical data follow-up for our Pivotal Cohort 4 to support the BLA. We did not reach an agreement with the agency on the potency assays to define TIL but will continue our work to refine existing potency assays while developing new assays.
We have not received additional comments or questions from FDA. So if you haven't received specific requesting anyway. The continue with our validation work with additional assays and the expected you're providing that information to the agency in the coming weeks or months. So we don't have anything new from the agency of no additional questions have arrived.
Okay. Thank you and then just with the Gen three manufacturer and does that in any way kind of generate a more defined product and just kind of of <unk>.
The question around that as well as.
How many T cell clones other than most of the fuel products.
I'm really good topic. Our Gen. Three is expected to be released under the same type of criteria of the Gen. Two.
So from it's one of the type of diversity perspective, we don't expect it to be different than our gen. Two in terms of how many of prosperous corner types. There are we have released a repertoire of data from all of our melanoma program in cervical program.
Maria Fardis: While the length of time until BLA submission depends on future dialogue with the agency, we continue to stay prepared for a BLA submission in 2021. We plan to provide updates when available. Our second pivotal program is investigating LN145, now also known as rifenucle, in the C14504 study to support a BLA submission in metastatic cervical cancer. Enrollment in both Cohorts 1 and 2 of this study have been completed. Patients in Arpeggio Cohort 1 are post-chemotherapy, whereas Cohort 2 includes post-anti-PE1 patients.
The average of what we seize around somewhere between 10000 to 17000 quanta types per patient product.
Okay. Thank you.
Sure.
Our next question of song.
Birhan Amin with Jefferies. Your line is open.
Yeah, Hi, guys. Thanks for taking my questions on the cervical study a.
Maria Fardis: We believe that inclusion of both cohorts in the BLA may strengthen the potential label and reflect the expected upcoming treatment landscape in cervical cancer. The resolution of the potency assay for lipoleucine melanoma is a key step toward our BLA submission plan for cervical cancer.
Cross both cohort one and two Maria can you just talk about the lower bound of of 95% confidence confidence interval that you need to treat for regulatory purposes.
Thank you for the question of beer and good afternoon, you Havent change.
Changed our statistical plans in any way. So we are still going with the existing clients that we had before so the haven't changed anything I'm. The only thing that we are basically communicating to investors is.
Maria Fardis: As a reminder, the FDA has previously granted both breakthrough therapy and fast-track designations for lipoleucine and cervical cancer. Turning to our manufacturing facility, Iovance Cell Therapy Center, or ICTC, the construction of cleanrooms was completed in late 2020.
There is a possibility of using cohort two in addition to cohort one we stand ready should that'd be a need from the agency and we are wondering whether that might be an ask because of the landscape is expected to change list of potential chemo immunotherapy, becoming frontline therapy. So we haven't changed our statistical planning anyway.
Maria Fardis: Process equipment is now in place in the available clean rooms, and activities in support of clinical manufacturing are expected to initiate in the coming months. Commercial manufacturing remains on track for 2022 with capacity to meet the demand for up to thousands of patients. Iovance has transformed pill manufacturing from a lengthy academic process to a shorter, scalable, centralized GMP process, yielding a cryopreserved product. Our Gen 2 process is 22 days.
So the.
First of all plan was based on cohort one so is cohort two then.
You know I'm sure you've made some assumptions that you need to exceed a certain level of efficacy for cohort two as well.
And given the patient populations of PD one experience.
There's probably differences in terms of what your assumptions are between call of one and two is that is that accurate.
Maria Fardis: To date, more than 400 patients have received Iovance TIL with a continuing success rate above 90%. We have also built and continued to augment our intellectual property, which is covered by more than 20 granted or allowed U.S. and international patents for compositions and methods of treatment in a broad range of cancers relating to the Gen 2 manufacturing process. Our Iovance IP portfolio includes patent applications and granted patents directed toward Gen 3 manufacturing, selected TIL products, stable and transient genetic TIL modifications, cryopreservation, and combination of TIL with checkpoint inhibitors.
I can't speak to the date of U as I noted the are blinded to both cohort one and cohort two data. So it's hard for me to tell you. What we are seeing them I can tell you and I've commented on this before when we read out the 27 patients before we had met with the agency and blinded ourselves. We did have patients have had prior.
Checkpoint therapy, and we had responders in that group and that was on the slides that we presented at <unk>.
But aside from that we are not planning on changing our statistical approach in any way. We just are making sure that the already should the agency request cohort two to be added into the BLA, that's all of you're saying.
Maria Fardis: Turning to our commercial launch preparation, the Iovance team is currently focused on KOL engagement, site activation, and training, tele-education and awareness, patient access, and other readiness activities. Our priority is to ensure launch success while taking a gated approach to commercial readiness expenses and a headcount prior to BLA submission.
Okay, and then maybe just one question on cohort III fee in the basket study, where you're combining with it would be knievel, what's the rationale with this combination and this is a Simon two stage design. So is there a thought that you could develop this into a pivotal cohort if youre seeing encouraging data.
Just to make sure. We are on the same page bearing are you asking about the contour of two program or still the surgical program. The comp two of two sorry of cop two of two of the basket study the combination with <unk>.
Maria Fardis: Our medical affairs team works with a network of treating healthcare professionals, or HCPs, and patient advocacy groups to ensure that information about TIL is available to interested organizations. A core commercial team continues to partner with leading U.S. cancer centers to build their tilt service line capabilities with the intent to scale out training and onboarding upon BLE submission. Our market access team continues to meet with private payers and the Centers for Medicare and Medicaid Services, or CMS, to ensure patients have appropriate and timely access to Leica Lucille.
Sure why don't ask me the two comments on this.
I think one thing to mention here is the population and this and the scoreboard is non overlapping with the ILD along too low too. So I think that is one one rationale of years that we are broadening.
And covering additional populations across the non small cell lung cancer patient population.
Maria Fardis: We believe that CMS and payers recognize the unmet need and clinical value of life-renewal as well as the potential benefits for patients with metastatic melanoma. We are also pleased with the development and progress of our Iovance CARES program. Our goal is to deliver a best-in-class cell ordering and patient support system that assists patients at every step of the process. I will now pass the call to Frederick to outline our clinical study updates, including the enrollment status, as well as the introduction of new cohorts and treatment regimens into our existing study. Friedrich
The the further rationale for E&P needle.
Is is that with this regimen we're exploring.
Priming of the tumor anti science filtration by way of administering a P. Knievel prior to resection. So this is different from how we are doing this in ILD along to a true for example, so here. The dosing is the single dose of AP and AR knievel, probably onto the resection and then afterwards.
Section, we are continuing needs of both comparable to the whole way of doing this and the Pembroke combination studies. So this is exploring of priming approach that's at the national rationale for this.
Friedrich Graf Finckenstein: Thank you, Maria. I am pleased to highlight today that we are currently recruiting patients for four clinical studies. Our drug development strategy focuses on cancer populations with high unmet need, with substantial opportunity for TIL to make a meaningful impact. For example, our C14504 clinical study in advanced cervical cancer has completed and closed enrollment in the first two cohorts, while we continue to recruit a third cohort of anti-PD-1 naive patients to receive TILD plus pembrolizumab.
Great. Thank you.
Our next question comes from Ren Benjamin with JMP Securities. Your question. Please.
Hey, good afternoon, guys. Thanks for taking the questions and congrats on the progress.
Maria I'd like to maybe get a sense of the timing of the potential filings I think before at least I had I was thinking about you know both melanoma and cervical going in.
Friedrich Graf Finckenstein: Recruitment also remains underway in our IOV-COM202 study in solid tumors, the IOV Lung 202 Study and Second Line Lung Small Cell Lung Cancer, and the IOV CLL 01 Study and CLL SLO. As we move ahead with TILT alone and in combination with approved treatments and different indications in various stages of cancer, the COVID-19 pandemic may impact the pace of enrollment, particularly across cohorts with earlier line patients, which may improve as COVID-19 abates.
We're very very close to each other it seems to me just kind of based on how things could unfold the melanoma could be a 2021 type of filing in cervical kind of based on the work that needs to be done might be more 2022 of my thinking about that correctly or is there another way to think about it.
Hi, Randy good afternoon.
I don't know if I can I can necessarily deduct out I think it really depends on a resolution of the potency assay matter of an F D. A.
Given the do you have completed enrollment into the surgical program both cohorts one and two in cohort. One was completed if you recall around third quarter 2020, we think we have sufficient amount of follow up possibly just for cohort one if the actual core to then of course, we need the additional follow up but I don't think I can rule out submission of a potential.
Friedrich Graf Finckenstein: Last quarter's call, I focused on the activation of our IOV-LUN-202 clinical study. Today, I will highlight our current data and strategy in head and neck cancer as well as the recent updates and inclusion of new cohorts in the IOV-COM 202 basket study. Head and neck cancer remains an important indication for Iovance, and we are particularly encouraged by the initial clinical data for our chill therapy, LN145, in combination with pambulizumab, that was presented at the Society for the Immunotherapy of Cancer, or CITSI, annual meeting in November of 2020. We are also excited about the potential for TILT in combination with PAMBULISM and other physics.
The BLA for both indications in 'twenty and 'twenty one.
Got it Okay and then.
The notice of course, the and it makes sense the combination studies with checkpoints, but is there are other is there any other work that's being done to evaluate other combinations of outside of checkpoints of these in these indications.
Yeah. That's of Great question, we've actually thought about a number of different alternative combinations and different settings of mines.
Typically we are looking to see where we can take the til product into earlier lines.
Friedrich Graf Finckenstein: The CITSE poster highlighted nine patients with head and neck squamous cell carcinoma, or HNSEC, from cohort 2A in the IOV-COM-202 basket study. These patients had not previously received treatment with checkpoint inhibitors, but may have received prior chemotherapy. Following LN145 in combination with Pembrolizumab, the overall response rate, or ORR, was 44%, and median duration of response had not been reached at 8.6 months of median study follow-up. While these are small patient numbers, we find the results to be very promising.
Looking at Steve Rosenberg's data and the PD one naive patients. This is highly encouraging it showed us that if chillers in earlier line of therapy, there may be additional responders and additional C. R said, one can have and.
So the initial thinking wasn't necessarily going into combination, but going into an earlier line now once we decide they're going to earn your line typically of regulatory path is offered the patient available care. In addition to chill and so since in most of the diseases. We are in available care and frontline <unk>.
Friedrich Graf Finckenstein: ORR with checkpoint inhibitor monotherapy in checkpoint nave head and neck cancer patients ranges from 15 to 18 percent in the literature. We look forward to gathering additional data to present at an upcoming conference in the future.
Tends to be checkpoint inhibitors in combination with checkpoint inhibitors, but I do want to remind there has been data published in combining chill plus other agents teekay is come to mind BRAF combinations have been published and that data appears to have been possibly additive. Although many of these studies are not statistically significant.
Friedrich Graf Finckenstein: Court 2A has now been expanded to include up to 19 patients. Regarding our C.1.4.5.03 clinical study of L.N.1.4.5.11 head and neck cancer, we achieved target enrollment and closed the study to enrollment. Before I hand the call to Jean-Marc, I would like to highlight additional updates in our IOPCOM202 basket study, which now includes seven total cohorts across melanoma, heteronych, and non-small cell As Maria mentioned, we are very excited about the potential for TILT to offer an option for many different patient populations in multiple indications.
Again in terms of the number of patients, but there appears to be additivity there.
Got it I guess one final one from me in the melanoma study you know you continued to to not reached the.
Median duration.
Do you have any sort of the census to what the patients who are progressing kind of what theyre moving onto and have any of them ever been.
Retreated with with the tools.
Yes, we do collect that information as part of our database of certainly in certain cohorts.
Friedrich Graf Finckenstein: In this basket study, early-line patients in each indication received KIL plus pembrolizumab. Second-line non-small cell lung cancer patients received KIL plus ipilimumab, and nivolumab, and later-line cancer patients with melanoma and non-small cell lung cancer received KIL alone.
We also do have the re treatment cohort you might recall, it's called cohort three in our melanoma program. So they do have the opportunity to get retreated should they choose to do that so yes.
Okay, and we haven't seen any of that totally get out of our coronary we haven't seen any data from from those patients or is there any sort of an update that we have from that cohort.
Jean-Marc Bellamine: Recent updates include the addition of a new melanoma cohort, a new lung cancer cohort, and, as mentioned previously, the expansion of the head and neck cancer cohort. Our newly added cohort 1C will investigate LN144, manufactured with our 16-day 3rd generation or Gen 3 process, in metastatic melanoma patients who have received one or more prior systemic therapies. Cohort 2A and Head and Neck Cancer, which is evaluating LN145 in combination with pambulizumab, was expanded to include up to 19 head and neck cancer patients who are naive to immune checkpoint inhibitors.
Yeah, we haven't presented data from that cohort typically do you want to have sufficient number of patients before we can present data on long enough follow up.
But the yes that cohort three allows for the treatment of patients that may be coming from cohorts, one two and four.
Excellent. Thank you very much thanks for taking the question of course, Thank you Randy.
Our next question comes from Mara Goldstein with Mizuho. Please go ahead.
Great. Thanks for taking the question I mean, I think that's kind of dovetail from the last question about earlier lines of therapy, but in the.
Jean-Marc Bellamine: And our new cohort, 3C, will provide an alternative option to standard chemotherapy and non-small cell lung cancer, offering TILL plus epilimumab, nivolumab, and non-small cell lung cancer patients who have received one prior systemic therapy. The three non-small cell lung cancer cohorts in this basket study, together with the second line patient population in our IOV-LUN-202 registration supporting study, allow us to cast a broad net to address the unmet needs in non-small cell lung cancer. I will now hand the call over to Jean-Marc to discuss our fourth quarter and full year 2020 financial results. Thank you, Frederick.
And the non small cell lung cancer study the inclusion criteria really just specify that patients have a single line of systemic therapy that includes checkpoint and chemo and so I'm just curious as to is that your anticipation that you will essentially be second line or our.
Are you taking patients who had more than one.
The prior line of therapy.
Tomorrow in the contour of two study where a chemo immunotherapy is defined as prior line. We are asking patients to be second line does that answer the question Yeah. No I appreciate that thank you sure sure. Thank you.
Jean-Marc Bellamine: My comments will reflect the high-level financial results from the fourth quarter and full year 2020. Additional details can be found in this afternoon's press release, as well as in our annual report on Form 10-K. First, I will begin with our cast position. As of December 31, 2020, Iovance held $635 million in cash, cash equivalents, short-term investment, and restricted cash, compared to $312.5 million on December 31. The current cash position delivered on a commitment to end last year with at least $630 million. Our current cash positions include net proceeds of $567 million from a June 2020 Common Stock Public Offering. Our financial strength is expected to be sufficient into 2023 to deliver on our pipeline program.
Alright, and the last question comes from Nick Abbott with Wells Fargo. Your question. Please.
Good afternoon. Thank you for taking my questions.
Some of them great can I just confirm that the.
The next set of submission to FDA on the potency assay what occurred this quarter you said the next few weeks so I'm not sure of that you mean this quarter.
Hi, Nick Good afternoon, Yes, we have said that we are on track with completion of the validation work to provide day. The the data to agency I have always said in the upcoming weeks two months. So that's not an incorrect statement still of you're still on target with our own internal activities.
Okay.
And then.
In terms of the you mentioned that you've been validated some of the assay. So by that because that can we conclude that you've tested all of the melanoma cohort cohort pool products the.
Jean-Marc Bellamine: Moving to the income statement, our net loss for the fourth quarter and the December 31st, 2020 was $68.4 million or $0.47 per share, compared to a net loss of $63.6 million or $0.50 per share for the fourth quarter and the December 31st, 2019. The net loss for the 12 months under December 31, 2020 was $259.6 million, or $1.88 per share, compared to a net loss of $197.6 million, or $1.59 per share, for the 12 months ended December 31st, 2020.
Of that assay and I guess, where I'm going with this is what would be the timeline between an agreement with FDA on the potency assay and the filing.
So just the kind of clarify the validation of you're talking about does not apply to our frontrunner assay that assay had been validated them fairly a few years ago and the data was provided to the agency and the clinical samples where in fact to release based on that assay. So that work was complete.
When we're talking about validation of additional assays. These are subsequent assays that we were talking to the agency, but to answer. The second question. If that's what your question is yes, one would have to run the clinical samples with the validation of I see them provide that to the agency.
Jean-Marc Bellamine: R&D expenses were $52.4 million for Q4 and Dec. 31, 2020, a decrease of 1.8 million dollars compared to 54.2 million dollars for the fourth quarter and Dec. 31st. Research and development expenses were $201.7 million for the full year ended December 31st, 2020, an increase of $35.7 million compared to $166 million for the full year ended December 31st, 2020. The decrease in research and development expenses in the fourth quarter of 2020 over the prior year period was primarily attributable to a decrease in manufacturing and clinical costs following the completion of enrollment in the pivotal cohorts for melanoma and cervical cancer.
Depending on how many samples are asked them. This is something that takes a few months to do it shouldn't be a rate limiting step for submission from the way we're thinking about it.
So just.
Just to be clear then you have run those clinical samples, where you would you'd wait until you get agreement with FDA that the.
The assay sufficient.
I don't know if I can disclose the details there are ways of doing both at the same time. So not every single sample needs to be run in advance of getting some degree of agreement, but some samples can be run and we do run them just to test the range of an assay.
Okay. Okay. So it is.
Sorry to belabor the point.
So if we go ahead and we file in the next few weeks then FDA agrees some weeks after that it's still possible you could file the BLA before the middle of the year.
Hum.
Jean-Marc Bellamine: The increase in research and development expenses for the full year of 2020 over the prior full year period was primarily attributable to higher clinical costs, licensing fees, and growth of internal research and development. General and administrative expenses were $16.1 million for the fourth quarter of 2020. An increase of $5.2 million compared to $10.9 million for the fourth quarter of 2020. General and administrative expenses were $60.2 million for the 12 months under December 31, 2020.
Going into too much detail, because you're right. It depends on what exactly the request of how clear day provide a feedback on I do want to remind you we still need to read out data by IRC, the clinical data still needs to be read out by the IRC.
I've been waiting to make sure that the agencies comfortable with our approach and then read the clinical data by IRC.
Okay.
And then just.
It's intriguing that you might be able to combine the cervical data cohort one with not just kind of going to the melanoma, the potentially but am I right.
Jean-Marc Bellamine: An increase of $19.3 million compared to $40.9 million for the 12 months ended December 31st, 2020. The increases in general and administrative expenses in the fourth quarter and full year 2020 compared to the prior year periods were primarily attributable to growth of the internal general and administrative tax and other stock-based competitions. As of December 31, 2020, there were approximately 146.9 million common shares outstanding.
And assuming the only cohort one.
The the breakthrough therapy designation, Hello, Hello, mum profiling surgical applies only to cohort one so how.
How do you combine.
The mission that has part of it is has breakthrough therapy and part of it doesn't.
Really great question breakthrough therapy generally is the designation it doesn't dictate your label so theres not a direct correlation of whatever it is you received breakthrough therapy has to be exactly your label. All it says is that the agency of recognizes that this particular therapy for this patient population is unmet need.
Operator: Looking ahead, we are open to opportunities to top off our cash balance while being mindful of dilution. As such, we have put an at-the-market, or ATM, facility in place to raise up to $350 million. The ATM, much like a shelf, is a good housekeeping measure that may allow us to be opportunistic in adding to our already strong balance. I will now hand the call back to the operator to kick off the Q&A session.
And they are willing to work with the sponsor to expedite the development program.
Okay.
Okay.
Thank you.
Sure.
From here and Theres no part of your questions I would like to turn the call back to my EFI book for final remarks.
Operator: Thank you. And as a reminder, ladies and gentlemen, if you have a question, simply press star 1 on your telephone. To withdraw your question, press the pound or hash key. Please wait while we compile the Q&A. Our first question is from Mark Breidenbach with Oppenheimer. Your question, please. Hey, thanks for taking the question, and congrats on the progress this quarter. Maria, I was hoping you could clarify whether or not the first patient has been treated in the IOV-LUN-202 study, and can you offer any thoughts as to when we might see lung cohort data from the BASQ-IT trial?
Thank you again for joining the idea of us fourth quarter and full year 2020 results conference call. Please feel free to reach out to our IR team. If you wish to follow up have a great rest of the day.
And ladies and gentlemen, thank you for participating in today's program.
Disconnect.
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Maria Fardis: Hi Mark. Good afternoon.
Maria Fardis: Thank you for the questions. We have not started patient dosing in LUN202, although we do have a few sites that are activated. We have not committed to a data flow timeframe for our lung data. If you recall, there are only two cohorts in our program that actually have patients in them. One is Cohort 3A, and one is Cohort 3B in the COM202 study. We have highlighted in Cohort 3A that we have had challenges with patient enrollment. And in Cohort 3B, we are hoping to have additional patients with long enough follow-up to be able to present the data, but we have not committed to a timeframe for data flow.
Maria Fardis: Okay, thanks. That's helpful. And just turning to the cervical program, you know, obviously, there might be more focus on Cohort 2 given the evolving standard of care in frontline cervical cancer. Can you give us a sense for what you see as a meaningful efficacy bar that you'd need to clear for checkpoint-experienced patients in cervical cancer and if we can expect to see data from the second cohort of this trial?
Maria Fardis: I'm sure. Currently, the way we have designed the protocol for cohort 2, we have these patients as post-PD-1, and expectedly, they would have received chemotherapy as a prior line because that's just available care for them. So if you think about a third-line therapy, the best we are aware of, and there is no data that I'm aware of, and I'll defer to Frederick in just a minute, that is for post-PD-1 patients, but I believe for chemo and third-line, the bar is around the 3% response rate mark.
Maria Fardis: In terms of cohort 2 data itself, we have blinded ourselves the same way as we have with our pivotal cohorts, such as cohort 1 in cervical, and we have not read out that cohort since we talked to FDA. Frederick, I don't know if you want to add anything on the expected response rate for cohort 2 patients.
Friedrich Graf Finckenstein: I know that that's correct. There are numbers for third-line treatment. The 3% is about right, and that is interestingly true across a number of different therapies, all of them being chemotherapies. So they're all ranging in the about 3% range.
Maria Fardis: Okay, super helpful. Thanks for taking the questions and congrats again. Thanks, Mark. Our next question comes from Peter Lawson with Barclays. Your question, please. Maria, just on the FDA and the potency aspect, what are the next steps, and are they in any way kind of asking for a more defined product?
Maria Fardis: Hi Peter. Thank you for your question. From the time we met with the agency, which was back in early October of 2020, we have submitted a couple of packages to the agency. We have not received any additional comments or questions from FDA, so we haven't received specific requests in any way. We continue with our validation work with additional assays, and we expect to be providing that information to the agency in the coming weeks or months. As a result, we don't have anything new from the agency, and no additional questions have arrived.
Maria Fardis: Thank you. And then just with the Gen 3 manufacturing, does that in any way kind of generate a more defined product? And just kind of a question around that as well is, how many T cell clones are there in most of your products?
Maria Fardis: Really good topic. Our Gen 3 is expected to be released under the same type of criteria as Gen 2. So from a chronotype diversity perspective, we don't expect it to be different than our Gen 2. In terms of how many approximate chronotypes there are, we have released our repertoire data from our melanoma program and cervical program. As an average, what we see is somewhere between 10,000 to 17,000 chronotypes per patient product.
Maria Fardis: Okay, thank you. Our next question is from Biryan Amin with Jeffrey. Your line is open. Yeah, hi, guys. Thanks for taking my questions. On the cervical study, you know, across both Cohort 1 and 2, Maria, can you just talk about the lower bound on the 95% confidence interval that you need to exceed for regulatory purposes?
Maria Fardis: Thank you for the question, Biren, and good afternoon. We haven't changed our statistical plans in any way, so we are still going with the existing plans that we had before. So we haven't changed anything. The only thing that we are basically communicating to investors is that there is a possibility of using Cohort 2 in addition to Cohort 1. We stand ready should that be a need from the agency, and we are wondering whether that might be an ask because the landscape is expected to change with potential chemoimmunotherapy becoming frontline therapy. So we haven't changed our statistical plan in any way.
Maria Fardis: So the statistical plan was:
Maria Fardis: was based on Cohort 1. So is Cohort 2 then, you know, I'm sure you've made some assumptions that you need to exceed a certain level of efficacy for Cohort 2 as well. And given the patient population's PD-1 experience, yeah, there's probably differences in terms of what your assumptions are between Cohort 1 and 2. Is that accurate?
Maria Fardis: I can't speak to the data. As I noted, we are blinded to both Cohort 1 and Cohort 2 data, so it's hard for me to tell you what we are seeing. But I can tell you, and I've commented on this before, when we read out the 27 patients before we met at the agency and blinded ourselves, we did have patients that had prior checkpoint therapy, and we had responders in that group.
Maria Fardis: And that was on the slides that we presented at ASCO. But aside from that, we are not planning on changing our statistical approach in any way. We just are making sure that we are ready should the agency request Cohort 2 to be added to the BLA. That's all we are saying.
Maria Fardis: And then maybe just one question, on cohort 3C in the basket study where you're combining with ipinivo, what's the rationale for this combination? And this is an assignment two-stage design, so is there a thought that you could develop this into a pivotal cohort if you're seeing encouraging data?
Maria Fardis: Just to make sure we are on the same page, Biren, are you asking about the COM202 program or the cervical program still?
Maria Fardis: The Comb-202, sorry Comb-202, the basket study, and the combination with Epi-Nevo.
Friedrich Graf Finckenstein: I think one thing to mention here is the population in this cohort is non-overlapping with the ILV Lung 202, so I think that is one rationale here is that we are broadening and covering additional populations across the non-small cell lung cancer patient population. The further rationale for ipinevo is that with this regimen we're exploring priming of the tumor and T-cell infiltration by administering ipinevo prior to resection, so this is different from how we are doing this in ILV Lung 202, for example, so here the dosing is a single dose of ipi and nevo prior to resection and then after resection we are continuing nevos comparable to how we are doing this in the PEMBRO combination studies, so this is exploring a priming approach that's an additional rationale for the...
Operator: Our next question comes from Ren Benjamin with JMP Securities. Your question, please. Hey, good afternoon, guys.
Maria Fardis: Thanks for taking the questions and congrats on the progress. Maria, I'd like to maybe get a sense of the timing of the potential filings. I think before, at least I had, I was thinking about, you know, both melanoma and cervical going in, you know, very, very close to each other. It seems to me, just kind of based on how things could unfold, that melanoma could be a 2021 type of filing, and cervical, kind of based on the work that needs to be done, might be more 2022. Am I thinking this?
Maria Fardis: Hi Reni, good afternoon. I don't know if I can necessarily deduce that. I think it really depends on resolution of the potency assay matter with FDA. Given that we have completed enrollment in the cervical program, both cohorts 1 and 2, and cohort 1 was completed, if you recall, around third quarter 2020, we think we have a sufficient amount of follow-up, possibly just for cohort 1. If they ask for cohort 2, then of course, we need additional follow-up. But I don't think I can rule out the submission of potential BLAs for both indications in 2021.
Maria Fardis: Got it. Okay. And then, you know, I notice, of course, the, and it makes sense, the combination studies with checkpoints, but is there, is there any other work that's being done to evaluate other combinations outside of checkpoints?
Maria Fardis: Yeah, that's a great question. We've actually thought about a number of different alternative combinations in different settings and lines. Typically, we are looking to see where we can take the TIL product into earlier lines. Looking at Steve Rosenberg's data in PD-1 naive patients, this is highly encouraging.
Maria Fardis: It showed us that if TIL is an earlier line of therapy, there may be additional responders and additional CRs that one can have. And so the initial thinking wasn't necessarily going into combination but going into an earlier line. Now, once we decide we're going to an earlier line, typically, a regulatory path is to offer the patient available care in addition to TIL. And so since in most of the diseases we are in, available care in the front line happens to be checkpoint inhibitors, we are in combination with checkpoint inhibitors.
Maria Fardis: But I do want to remind you that there has been data published combining TIL plus other agents. TKIs come to mind. BRAF combinations have been published. And that data appears to have been possibly additive. Although many of these studies are not statistically significant in terms of the number of patients, there appears to be additivity there.
Maria Fardis: Got it. I guess one final one for me. In the melanoma study, you continued to not reach the... Do you have any sort of sense as to what the patients who are progressing are progressing, kind of what they're moving on to, and have any of them ever been retreated?
Maria Fardis: Yes, we do collect that information as part of our database, certainly in certain cohorts. We also do have a retreatment cohort, you might recall, it's called Cohort 3 in our Malnomah program. So they do have the opportunity to be retreated should they choose to do that. So yes.
Maria Fardis: Okay, and we haven't seen any, I totally forgot about cohort 30, haven't we seen any data from those patients, or is there any sort of update that we have from that cohort?
Maria Fardis: Yeah, we haven't presented data from that cohort yet. Typically, we want to have a sufficient number of patients before we can present data and have long enough follow-up. But yes, cohort 3 allows for retreatment of patients that may be coming from cohorts 1, 2, and 4. Excellent.
Maria Fardis: Thank you very much. Thanks for taking the question. Of course. Thank you.
Maria Fardis: Of course. Thank you, Reni.
Operator: Our next question comes from Mara Goldstein with Mizzou. Please go ahead. Okay.
Maria Fardis: Thanks for taking that question. I think this kind of dovetails with the last question about earlier lines of therapy, but in the non-small cell lung cancer study, the inclusion criteria really just specify that patients have a single line of systemic therapy that includes checkpoint therapy and chemo. And so I'm just curious, is that your anticipation that you will essentially be a second line, or are you taking patients who've had more than one prior line of therapy?
Maria Fardis: So Mara, in the COM202 study where chemotherapy is defined as prior line, we are asking patients to be second line. Does that answer your question?
Maria Fardis: Yeah, no, I appreciate it.
Maria Fardis: I appreciate that. Thank you. Sure. Sure.
Maria Fardis: Sure. Thank you. All right. And our last question comes from Nick Abbott with Wells Fargo. Your question, please. Good afternoon. Thank you for taking my questions. First of all, Maria, can I just confirm that the next sort of submission to FDA on the potency assay will occur this quarter? You said the next few weeks, so I'm not sure if you mean this quarter.
Maria Fardis: Hi Nick. Good afternoon.
Maria Fardis: Yes, we have said that we are on track with completion of the validation work to provide the data to the agency, I have always said, in the upcoming weeks to months. So that's not an incorrect statement yet. We are still on target with our own internal activities.
Maria Fardis: Okay. And then, in terms of the, you mentioned that you've been validating the assay, so by that, does that mean we can conclude that you've tested all of the melanoma cohort for products? With that essay, and I guess where I'm going with this is, what would be the timeline between an agreement with FDA on the potency assay and the filing?
Maria Fardis: So just to kind of clarify, the validation that we are talking about does not apply to our front-runner assay. That assay was validated fairly a few years ago, and that data was provided to the agency, and the clinical samples were, in fact, released based on that assay. So that work was completed.
Maria Fardis: When we are talking about validation of additional assays, these are subsequent assays that we are talking to the agency about. But to answer the second question, if that's what your question is, yes, one would have to run the clinical samples with the validated assay and provide that to the agency. Depending on how many samples are asked, this is something that takes a few months to do. But it shouldn't be a rate-limiting step for submission, the way we are thinking about it.
Maria Fardis: So just to be clear, then, you have run those clinical samples, or would you wait until you get agreement with FDA? Yeah.
Maria Fardis: I don't know if I can disclose the details, but there are ways of doing both at the same time. So not every single sample needs to be run in advance of getting some degree of agreement, but some samples can be run, and we do run them just to test the range of an assay.
Maria Fardis: Okay, okay, so I'm sorry to belabor the point, but if we go ahead and we file in the next few weeks, then FDA agrees some weeks after that, it's still possible you could file the BLA before the middle of the year.
Maria Fardis: Without going into too much detail, because you're right, it depends on what exactly they request or how clear they provide feedback on. I do want to remind you that we still need to read our data by IRC. The clinical data still needs to be read out by IRC. We have been waiting to make sure that the agency is comfortable with our approach and then read the clinical data by IRC.
Maria Fardis: And then, just, you know, it's intriguing that you might be able to combine the cervical data cohort 1 with not just cohort 2, but melanoma potentially, but am I right in assuming that only cohort 1, the breakthrough therapy designation for LM145 in cervical cancer applies only to cohort 1? How do you combine, you know, a submission that has part of it as breakthrough therapy and part of it doesn't?
Maria Fardis: Really great question. Breakthrough therapy generally is a designation. It doesn't dictate your label, so there's not a direct correlation of whatever it is you receive. Breakthrough therapy doesn't have to be exactly your label. All it says is that the agency recognizes that this particular therapy for this patient population is an unmet need, and they are willing to work with the sponsor to expedite the development program.
Maria Fardis: Okay, okay, fair enough. I'll leave it there. Thank you. Sure. Thank you. And there are no further questions. I would like to turn the call back to Maria for her final remarks.
Maria Fardis: Thank you again for joining the Iovance fourth quarter and full year 2020 results conference call. Please feel free to reach out to our IR team if you wish to follow up. Have a great rest of the day.
Operator: And, ladies and gentlemen, thank you for participating in today's program. You may now disconnect.