Q4 2022 Iovance Biotherapeutics Inc Earnings Call
Speaker 2: The conference will begin shortly. To raise and lower your hand during Q&A, you can dial star 11.
Operator: and the
Operator: Welcome to the Iovans Biotherapeutics fourth quarter and full year 2022 financial results in corporate.
Operator: Update conference call. My name is Gigi, and I'll be your operator for today's call. At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session. Please note that this conference is being
Operator: Recorded. I will now turn the call over to Sarah.
Sara Pellegrino: Greeno, Senior Vice President of Investor Relations and Corporate Communications at Iovance. Sarah, you may begin.
Sara Pellegrino: Thank you, Operator. Good afternoon, and thank you for joining us. Speaking on today's call are Dr. Fred Vote, our interim president and chief executive officer; Dr. Igor Balinski, our chief operating officer; and Jim Ziegler, our executive vice president, commercial.
Speaker 3: Welcome to the IOVANDS Biotherapeutics fourth quarter and full year 2022 financial results and corporate updates conference call. My name is Gigi and I will be your operator for today's call.
Speaker 3: At this time, all participants are in a listen-only mode. Later, we will conduct a question-and-answer session. Please note that this conference is being recorded. I will now turn the call over to Sarah Pellegrino, Senior Vice President Investor Relations and Corporate Communications at IOVANTS. Sarah, you may begin.
Sara Pellegrino: Dr. Frederick Sincenstein, our chief medical officer, and John Mark Bellamyne, our chief financial officer. Dr. Raj Puri, our executive vice president, Regulatory Strategy and Translational Medicine, is also available for the Q&A sessions.
Speaker 4: Thank you, operator. Good afternoon and thank you for joining us. Speaking on today's call, we have Dr. Fred Vogt, our interim president and chief executive officer, Dr. Igor Balinski, our chief operating officer, Jim Ziegler, our executive vice president, commercial.
Sara Pellegrino: This afternoon, we issued a press release that can be found on our corporate website at iovance.com, which includes the financial results for the three and 12 months ended on December 31st as well as recent 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 and transactions, free commercial activities, clinical trials and results, regulatory interactions, plans and strategies, research and pre-clinical activities, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance, payers, interactions, licenses and collaborations, cash position and expense guidance, and future updates.
Speaker 4: Dr. Frederick Finckenstein, our Chief Medical Officer, and Jean-Marc Bellamy, our Chief Financial Officer. Dr. Raj Puri, our Executive Vice President, Regulatory Strategy and Translational Medicine, is also available for the Q&A session.
Speaker 4: This afternoon, we issued a press release that can be found on our corporate website at IOVANCE.com, which includes the financial results for the three and 12 months ended on December 31st, as well as recent 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.
Speaker 4: Business focus, business plans and transactions, pre-commercial activities, clinical trials and results, regulatory interactions, plans and strategies, research and pre-clinical activities, potential future applications of our technologies, manufacturing capabilities, regulatory feedback and guidance.
Sara Pellegrino: 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.
Speaker 4: payer interactions, licenses and collaborations, cash position and expense guidance, and future updates.
Speaker 4: 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.
Speaker 4: Our results may differ materially from those projected during today's call. We undertake no obligation to publicly update any forward-looking statement.
Frederick G. Vogt: I am pleased to highlight the positive milestones and significant progress at I advanced in 2022 and into the beginning of 2023. We are close to completing our Biologics License Application, or BLA, for our lead TIL therapy, Lysal, and advanced melanoma before the end of this quarter. We are also preparing for commercialization, developing our robust immune oncology pipeline, and integrating Prolucan upon the close of our planned acquisition. The BLA for Lafalusa remains our number one priority on behalf of patients with advanced melanoma who progress after anti-PD1 therapy.
Speaker 4: With that, I will turn the call over to Fred.
Speaker 5: Thank you, Sarah. And good afternoon, everyone. I am pleased to highlight the positive milestones and significant progress that I advanced in 2022 and into the beginning of 2023.
Speaker 5: We are close to completing our biologics license application, or BLA, for our lead till therapy, Lifelucil, and advanced melanoma before the end of this quarter. We are also preparing for commercialization, developing our robust immuno-oncology pipeline and integrating per-lucan upon the close of our planned acquisition.
Speaker 5: The BLA for Lympho-Lusso remains our number one priority on behalf of patients with advanced melanoma who progress one or after anti-PD-1 therapy. This represents a significant unmet medical need given that there are currently no FDA-approved treatment options in this setting.
Frederick G. Vogt: This represents a significant unmet medical need given that there are currently no FDA-approved treatment options in this setting. I feel very confident going into the BLA review process given the strength of our clinical data and I'm at need, as well as several positive interactions with and feedback from the FDA during 2022. These included FDA alignment on the Potency Essay Matrix last April and a successful pre-BLA meeting in July where the FDA provided favorable feedback on the clinical efficacy data from cohorts 2 and 4 of our C-14401 clinical trial, including duration of follow-up and that the clinical and safety data set was sufficient for a BLA review.
Speaker 5: I feel very confident going into the BLA review process given the strength of our clinical data and unmet need, as well as several positive interactions with and feedback from the FDA during 2022.
Speaker 5: These included FDA alignment on the potency assay matrix last April and a successful pre-BLA meeting in July where the FDA provided favorable feedback on the clinical efficacy data from cohorts 2 and 4 of our C14401 clinical trial, including duration of follow-up and that the clinical and safety dataset was sufficient for a BLA review.
Frederick G. Vogt: In the fourth quarter, we also reached a grant with the FDA on our recently started TILVANCE 301 Phase 3 trial, Frontline Advanced Melanoma, the service of registrational trial on that indication, as well as a confirmatory study supporting full approval of Leifelusil in post-antypd1 advanced melanoma. We expect TILVANCE 301 to be well underway at the time of potential approval. And Frederick will talk about additional details of the trial on today's call.
Speaker 5: In the fourth quarter, we also reached a grant with the FDA on our recently started TIL-VANCE 301 Phase III trial, Frontline Advanced Melanoma, to serve as a registrational trial and identification as well as a confirmatory study supporting full approval of Lifelucil in post-antipedian advanced melanoma.
Speaker 5: We expect TILVANCE 301 to be well underway at the time of potential approval. Frederick will talk about additional details of the trial on today's call.
Frederick G. Vogt: Overall, the FDA continues to be engaged and supportive. We look forward to continuing this level of collaboration in 2023. We're also preparing to integrate ProLucon upon the close of our planned acquisition of this product. As a reminder, we announced last month that we had entered into a strategic transaction with Clinogen to acquire worldwide rights to ProLucan, an IL2 product with currently approved indications that is importantly also used to promote T-Sel activity following till infusion.
Speaker 5: Overall, the FDA continues to be engaged and supportive. They look forward to continuing this level of collaboration in 2023.
Speaker 5: We are also preparing to integrate Proleukin upon the close of our planned acquisition of this product.
Speaker 5: As a reminder, we announced last month that we have entered into a strategic transaction with Clinagen to acquire a worldwide rights to Proleukin, an IL-2 product with currently approved indications that is importantly also used to promote T-cell activity following TIL infusions. We have a strong strategic fit and rationale for this transaction, which provides immediate and future revenue and full control of the IL-2 supply chain and logistics surrounding TIL.
Frederick G. Vogt: We have a strong strategic fit and rationale for this transaction, which provides immediate and future revenue and full control of the IL2 supply chain and logistics surrounding TIL therapy and is expected to lower clinical trial expenses and future costs of goods for Lysol. In addition to Leifluso and Melanoma, we are building a deep and diverse Till Therapy pipeline and multiple solid tumor types that have the potential to create significant value for cancer patients as well as our shareholders.
Frederick G. Vogt: We are conducting six active clinical trials, preparing to randomize patients in the frontline melanoma treatment setting in our first phase three study and advancing several genetically modified telotherapies, which Frederick will also highlight on today's call.
Speaker 5: conducting six active clinical trials, preparing to randomize patients in the frontline melanoma treatment setting in our first phase three study and advancing several genetically modified telotherapies. Frederick will also highlight on today's call.
Igor P. Bilinsky: As we grow our organization to prepare for our first potential launch, we currently have more than 500 I-Avance employees who have expertise in developing and commercializing oncology and cell and gene therapy products. I look forward to addressing your questions later during this call, and we'll now ask Igor to address our manufacturing updates and preparations to supply commercial teletherapeutics upon potential approval. Thank you, Fred.
Speaker 5: As we grow our organization to prepare for our first potential launch, we currently have more than 500 i-Advanced employees who have expertise in developing and commercializing oncology and cell and gene therapy products.
Speaker 5: I look forward to addressing your questions later during this call and will now ask EGLE to address our manufacturing updates and preparations to supply commercial teletherapies upon potential approval.
Igor P. Bilinsky: Manufacturing is critical for any commercial launch, particularly for autologist deltera, so I'll discuss priorities to prepare for commercial supplies to meet patient needs while continuing to scale up our internal capabilities and We are focused on operational excellence and maintaining a consistent steel manufacturing success rate of more than 90% in more than 600 patients treated with IVN steel therapy today. We are currently supplying clinical studies from ICTC, which is operating flex suites for clinical manufacturing and core suites for BLA readiness activities in preparation for commercial manufacturing.
Speaker 6: Thank you Fred. Caring is critical for any commercial launch, particularly for autologous cell therapies.
Speaker 6: So our top priority is to prepare for commercial supply to meet patient needs while continuing to scale up our internal capabilities and staffing.
Speaker 6: We are focused on operational excellence and maintain a consistent steel manufacturing success rate of more than 90% in more than 600 patients treated with ION steel therapy to date.
Speaker 6: We are currently supplying clinical studies from ICTC, which is operating flex suites for clinical manufacturing and core suites for PLA resonance activities in preparation for commercial manufacturing. We have done significant work to ensure that ICTC is a safe and effective solution for
Igor P. Bilinsky: We have done significant work to ensure that ICD and our contract manufacturers facility are well prepared for launch, with many of our current efforts focused on the FDA pre-approval inspection that we expect to occur during the BLA review. The ICT is expected to supply most of the commercial tilt therapies upon approval, with contract manufacturers to provide additional flexibility to optimally balance capacity and patient demand. Beyond our initial launch of Laosol, we are planning for future capacity needs as we look to establish Laosol still as the next paradigm-shifting class of cancer therapy.
Speaker 6: Our contract manufacturers facility are well prepared for launch with many of our current efforts focused on the FDA pre-approval inspections that we expect to occur during the BLA review process. The ICBC is expected to supply most of the commercial tilt therapies upon approval.
Speaker 6: with contract manufacturers to provide additional flexibility to optimally balance capacity and patient demand. Beyond our initial launch of LIFELUSO, we are planning for future capacity needs, as we look to establish TIL as the next paradigm shifting class of cancer therapy.
Igor P. Bilinsky: The ICDC is currently built, and has annual capacity to supply products for more than 2,000 patients, with available shell space that we can build out to supply products for more than 5,000 patients annually from this facility, longer term by adding new facilities as well as streamlining and automating manufacturing processes. Our vision is to build capacity for more than 10,000 patients and Our intellectual property or IP is also a critical component to support and protect our proprietary manufacturing processes and know-how and to further solid We currently own at least 60 granted or allowed US and international patents, including Gen 2 patent rights that I expect to provide exclusivity into 2038.
Speaker 6: The ICDC is currently built as annual capacity to supply and sell products for more than 2000 patients.
Speaker 6: with available shelf space that we can build out to supply products for more than 5,000 patients annually from this facility.
Speaker 6: Longer throw by adding new facilities as well as streamlining and automating manufacturing processes.
Speaker 6: Our vision is to build capacity for more than 10,000 patients annually.
Speaker 6: Our intellectual properties or IP is also a critical component to support and protect our proprietary manufacturing processes and know-how and to further solidify our global leadership in tilt therapy.
Speaker 6: We currently own at least 60 granted or allowed US and international patents, including Gen2 patent rights that are expected to provide exclusivity into 2038.
James Ziegler: Extensive detail on IAVN, ODIP is highlighted on our corporate website and within our annual report on form. I would like to hand the call to Jim Ziegler to highlight our commercial launch preparer, Thank you, Igor. Duell 2020, the commercial team made steady progress towards long. With the ongoing BLA submission, our launch priorities include onboarding our authorized treatment centers or ATCs, securing appropriate access, and achieving operational readiness. Our cross-functional teams continue to partner with and onboard ATCs to develop new workflows that are unique to TIL therapy while leveraging workflows within existing cell therapy service lines at the center.
Speaker 6: Extensive detail on IOD IP is highlighted on our corporate website and within our annual report on Form 10-K .
Speaker 6: I would now like to hand the call to Jim Ziegler to highlight our commercial launch preparations.
Speaker 7: Thank you, Igor. Throughout 2022, the commercial team made steady progress towards launch.
Speaker 7: With the ongoing BLA submission, our launch priorities include onboarding of our authorized treatment centers or ATCs to cure inappropriate access and achieving operational readiness.
Speaker 7: Our cross-functional teams continue to partner with and onboard ATCs to develop new workflows that are unique to TIL therapy while leveraging workflows within existing cell therapy service lines at these centers.
James Ziegler: Our ATC operations and regional account director teams have structured interactions to support an efficient ATC onboarding process, and we have developed a training curriculum to ensure multidisciplinary teams can administer the LIFALUSO treatment regimen upon FDA approval. The timing and execution of key onboarding activities and training at each center are aligned to our regulatory timeline. We support each center in developing their TIL service line, and we plan just-in-time training to ensure launch readiness. Our reimbursement strategies are focused on securing coding, coverage, and payment.
Speaker 7: Our ATC operations and regional account director teams have structured interactions to support an efficient ATC onboarding process. And we have developed the training curriculum to ensure multidisciplinary teams. Can administer the life of Lucille treatment regimen upon FDA approval.
Speaker 7: The timing and execution of key onboarding activities and training at each center are aligned to our regulatory timeline.
Speaker 7: We support each center in developing their TIL service line, and we plan just-in-time training to ensure launch readiness.
James Ziegler: Our market access team continues to engage key national and regional payers. As we transition from the clinical trial to the commercially approved setting, our goal is to ensure patients have appropriate and timely access to lipalus. Our cross-functional team is also assessing our needs and capabilities and developing our implementation plan for Proluc. We are also fortunate to have several cross-functional team members with prior Pro Lucan leadership experience who are leading and developing our end-to-end integration process.
Speaker 7: Our reimbursement strategies are focused on securing coding, coverage, and payment.
Speaker 7: Our market access team continues to engage the key national and regional payers.
Speaker 7: As we transition from the clinical trial to commercially approved setting, our goal is to ensure patients have appropriate and timely access to lipo-lucil.
Speaker 7: Our cross-functional team is also assessing our needs and capabilities and developing our implementation plan for ProLUCAN.
Speaker 7: We are also fortunate to have several cross-functional team members with prior ProLUCAN leadership experience who are leading and developing our end-to-end integration processes.
James Ziegler: We are preparing for a smooth transfer and operational readiness for ProLucan upon the close of our planned acquisition. We understand that launching in autologous cell therapy requires sustained operational excellence. And I want to acknowledge the critical thinking, problem solving, and tireless efforts of our cross-functional team. Our team has set a high bar for themselves to ensure the highest quality of operations. We are well positioned to scale our efforts to ensure commercial launch readiness.
Speaker 7: We are preparing for a smooth transfer and operational readiness for ProLucan upon the close of our planned acquisition.
Speaker 7: We understand that launching an autologous cell therapy requires sustained operational excellence.
Speaker 7: And I want to acknowledge the critical thinking, problem solving, and tireless efforts of our cross-functional team.
Speaker 7: Our team has set a high bar for themselves to ensure the highest quality of operational excellence.
Friedrich Graf Finckenstein: I will now pass the call to Friedrich Finkinstein, our chief medical officer, to highlight our clinical, Thank you, Jim. Today I would like to summarize our TIL therapy pipeline and next generation technology. I'll begin with our multi-promp strategy in advanced melanoma.
Speaker 7: We are well positioned to scale our efforts to ensure commercial launch readiness.
Speaker 7: I will now pass the call to Friedrich Finkenstein, our Chief Medical Officer, to highlight our clinical progress.
Speaker 8: Thank you, Jim. Today I would like to summarize our TIL therapy pipeline and next generation technology.
Friedrich Graf Finckenstein: Our ongoing rolling BLA submission for Lyphilus and post-anti-PD1 advanced melanoma is based on the results from our C-14401 trial, the largest single clinical study ever conducted for a child therapy in post-I-I-Menoma. In the fourth quarter, we presented positive data from C14401, cohorts 2 and 4, to the medical community for the first time at the Society for Imminotherapy of Cancer annual meeting last November, and published results from the study in the Journal of Imminotherapy of Cancer.
Speaker 8: I'll begin with our multi-pronged strategy in advanced melanoma. Our ongoing rolling DLA submission for Lifel-Lusol and post-antipd1 advanced melanoma is based on the results from our C14401 trial, the largest single clinical study ever conducted for cell therapy in post-ITA melanoma.
Friedrich Graf Finckenstein: We are confident that the strength of the clinical data from 153 patients in the C14401 trial, including our pivotal cohort 4 and supportive cohort 2, support approval. Following the recent posting of our Phase 3, TIL-VAN 3-3 trial in Frontline Advanced Melanoma on Clinical Trials.gov, I would like to highlight additional details on this trial today. We reached agreement with the FDA for TILD-R-1 to serve as our registrational trial for accelerated and full approvals of LIFELUILIN combination with PEMLAS in Frontline Advanced Melanoma, as well as a confirmatory trial to support full approval of Lyphililand-P-D-1 for advanced melanoma, as well as a confirmatory trial to support full approval of Lyphilililin post-PT-D Number
Speaker 8: results from the study in the Journal of Immunotherapy of Cancer, or JITC, in December . We are confident that the strength of the clinical data from 153 patients in the C14401 trial, including our pivotal COVID-19 cohort 4 in support of cohort 2, support approval.
Speaker 8: Following the recent posting of our Phase III TILDANS 301 trial and frontline advanced melanoma on clinicaltrials.gov, I would like to highlight additional detail on this trial today. We reached agreement with the FDA for TILDANS 301 to serve as our registrational trial for accelerated and full approval of LIFO-Lusol and combination of temblizumab in frontline advanced melanoma.
Speaker 8: as well as a confirmatory trial to support full approval of Lactiluthrin CoA and PD-1 I don't have any more number on Lecture.
Speaker 8: Notably, we were very pleased that the FDA agreed to dual primary endpoints of Blinded Independent Review Committee, or BIRC, Assist Objective Response Rate, or ORR, and Progression-Free Survival, or PFS. Till then, 3-1 also includes several secondary endpoints.
Friedrich Graf Finckenstein: Notably, we were very pleased that the FDA agreed to dual primary endpoints of blinded independent review committee or BIRC to assess objective response rate for ORR and progression-free survival or PFS. Tidans 3A also includes several secondary endpoints, such as overall survival and duration of response. In terms of trial design, we plan to randomize 670 patients who are naive to therapy, and they will be done equally to either a life-elucline combination of Pembrylism Up in the experimental arm or Pembrolysmab monotherapy in the control arm.
Speaker 8: combination of pembrolizumab in the experimental arm or pembrolizumab monotherapy in the control arm.
Speaker 8: We are including an appropriate number of global sites such as many large US and European cancer centers and in numerous other countries where we expect from the moment.
Speaker 8: In the control arm patients will have the option to receive children monotherapy upon confirmed disease progression, five-by physidertes.
Friedrich Graf Finckenstein: We are including an appropriate number of global sites, such as many large US and European cancer centers and innumerable other countries where we expect the results from a moment. In the control arm, patients will have the option to receive chill monotherapy upon confirmed disease progression verified by BIRC. Additional information on trial design, outcome measures, and eligibility criteria is available on clinicaltrials.gov.
Speaker 8: Additional information on trial design, outcome measures, and eligibility criteria are available on clinicaltrials.gov.
Speaker 8: Our confidence in the success of TIL-VAM3A1 is based on results from cohort 1A in our IOV-COM 202 trial of Lifelucilin combination with Tambulizimab in ICI-naive endocrine melanoma. In addition to prior data at the NCI for TIL monotherapy and types in anti-PD-1-naive melanoma generated in the pre-
Friedrich Graf Finckenstein: Our confidence in the success of TILVAN 3A is based on results from cohort 1A in our I.OV-2 trial of Lyphaluslan in combination with pambulism maps in ICI-nais melanoma, in addition to prior data at the NCI for TIL monotherapy and type in AntipD1 naive melanoma generated in the pre-I era. We look forward to advancing our frontline melanoma strategy throughout 2023, including site activation and patient randomization in Tillvance 301. As Fred mentioned, Tillvance 301 is expected to be well underway at the time of potential BLA approval for LIF solution and post anti-PD1 advanced melanin.
Speaker 8: Today, approval for like-illucent post-ant–NHIK PD-1ad? már her allegiance.
Speaker 8: We continue to execute on our non-small cell lung cancer, or NSDLC, pipeline at IOVAM, with six cohorts across three IOVAM studies to investigate multiple treatment regimens in various populations at various stages of disease.
Speaker 8: We recently shared top line initial data from GoHo 3A of the IOV come to a two trial, which we highlighted in a press release an investor conference called last month.
Speaker 8: Based on initial COVID-3a positive results in patients with advanced NSDLC who are naive to ICI treatment, particularly within the treatment-naive and post-chemotherapy subsets, we plan to meet with FDA in 2023.
Friedrich Graf Finckenstein: We continue to execute on our non-smol-cell lung cancer or NSCL pipeline at Iovans, with six cohorts across three Iovans studies to investigate multiple treatment regimens in various populations at various stages of disease. We recently shared top-line initial data from cohort 3A of the IOP2 trial, which we highlighted in a press release, an investor conference call NAP. Based on initial cohort 3A positive results in patients with advanced NSDLC, who are naive to ICI treatment, particularly within the treatment naive and post chemotherapy subsists, we plan to meet with FDA in 2023, to discuss data and a potential registration path for Life Alouzlan, Frontline Advance, and a CLC, Enrollment to Cohort 3A is ongoing, and we plan to present details and updated results at a medical meeting this year.
Speaker 8: to discuss data and the potential registration path for lipo-lutein from Planet Dance and a CLC patient.
Speaker 8: Enrollment to COVID-3a is ongoing and we plan to present details and updated results at the medical meeting this year.
Speaker 8: Our IOV-LUN-202 trial is investigating LN145 monotherapy in patients who have received prior anti-PD-1 and chemotherapy.
Speaker 8: in combination or sequentially, and includes an option for pre-progression tumor harvest. We involve patients for 2022 and expect to continue involvement this year.
Speaker 8: Moving to cervical cancer, enrollment is underway in our expanded Cohort 2 in the ongoing C14504 trial in patients who have progressed after chemotherapy and anti-PD-1 therapy. As a reminder, Cohort 2 is intended to be pivotal to support regulatory submissions following dialogue and feedback from the FDA.
Friedrich Graf Finckenstein: Our Iov, LUN-2 trial is investigating LN-145 monotherapy and patients who have received prior antipid1 and chemotherapy, in combination or sequentially, and includes an option for pre-progression tumor harvest. We will enroll patients throughout 2022 and expect to continue enrollment this year. Moving to cervical cancer, enrollment is underway in our expanded cohort two in the ongoing C-14504 trial in patients who have progressed after chemotherapy and anti-PD1 therapy. As a reminder, cohort two is intended to be pivotal to support regulatory submissions following dialogue and feedback from the FDA, and we look forward to continuing court to enrollment during the year.
Speaker 8: licensed from selectors to optimize pill therapy by inactivating immune checkpoint proteins that inhibit anti-tumor response. IOV4001 is our first genetically modified PD-1 inactivated pill therapy candidate.
Speaker 8: In the third quarter of last year, we treated the first patient with IOV4001 in our first in-human IOV-GM1-201 trial in patients with previously treated advanced melanoma or NFCLC.
Speaker 8: Additional programs using the TALEN technology are expected to enter clinical development in 2024, including genetically modified TIL therapy with multiple inactivated immune checkpoint targets. Earlier-stage research and preclinical studies include additional approaches to increase TIL potency.
John Mark Bellamyne: We are excited about our next generation TIL therapies. We are developing several genetically modified TIL therapies that utilize gene editing talent technology licensed from Selectors to optimize TANTEL therapy by inactivating immune checkpoint proteins that inhibit anti-tumor results. Iov-401 is our first genetically modified, PD1 inactivated kill therapy can. In the third quarter of last year, we treated the first patient with Iov-401 in our first in human Iov GM1 201 trial in patients with previously treated advanced melanoma or NSCLC.
Speaker 8: including the selection of CD3969 double negative tilts and enhancements.
Speaker 8: of CD3969 double negative tilts and enhancements such as tethered cytokines.
Speaker 8: As part of our strategy to optimize the TIL treatment regimen, we also continue IND-enabling studies.
Speaker 8: of our Nobel Interluchin Amelok IOB-3001. I am available during the question and succession. For now, I will hand the call over to Sam Mark to discuss a lot of thought, quarter, and full of your 2022 financial results.
John Mark Bellamyne: Additional programs using the TEPTAN technology are expected to enter clinical development in 2024, including genetically modified TIL therapy with multiple inactivated immune checkpoint targets. Earlier stage research in preclinical studies includes additional approaches to increase TILCOP, including the selection of CD 39-69 double negative tilks and enhancement such as Pether Psychic. As part of our strategy to optimize the TIL treatment regimen, we also continue IND enabling studies of our novel interleucan analog Iob 301. I will be available during the question and answer session. For now, I will hand the call over to Jean-Marc to discuss our fourth quarter and full year 2022 financial results.
Speaker 9: Thank you, Philippe. My comments will summarize our planned acquisition of Polukin as well as high-level financial results from our fourth quarter and full year ended on December 31, 2022.
Speaker 9: More details can be found in this afternoon's press release as well as in your SEC filings.
Last month we announced that we have entered into an agreement to require polluting from pages.
Terms of the agreement include an upfront payment of £167.7 million GBP.
the 41.7 million British pounds milestone payment upon first approval of Liferousol in Advanced Melanoma and double-digit co-looking global sales realities from IFA to decades.
The transaction will be financed with existing cash and is expected to close after all conditions are met, including regulatory approvals and clearance and other customary closing conditions.
As a late stage oncology company approaching potential commercialization this year, we are also investing in launch preparations, internal manufacturing and pipeline activities.
As of December 31, 2022, we held $478.3 million in cash, cash equivalents, investments and restricted cash.
compared to $602.1 million on December 31, 2021.
John Mark Bellamyne: My comments will summarize our planned acquisition of Polukin, as well as the high-level financial results from our fourth quarter and full year ended on December 31st and January 21st. More details can be found in this afternoon's press release as well as in your SEC. Last month, we announced that we have entered into an agreement to require poliqin from. Terms of the agreement include an upfront payment of 167.7 million British pounds, 41.7 million British pounds milestone payment upon first approval of life reversal in advanced melanoma, and double-digit royalties on global sales royalties from air advanced to kidney. The transaction will be financed with existing cash and is expected to close after all conditions are met, including regulatory approvals and clearance and other customary closing conditions.
Taking into account proceeds raised in 2023 from an at-the-market or ATM facility, our unedited cash position is approximately $670 million as of February 24, 2023, which include approximately $450 million in net proceeds raised through the ATM during the fourth quarter of 2020.
and pipeline advancement.
Transitioning to the financial results for the fourth quarter and full year on December 31, 2022, our net loss for the fourth quarter of 2022 was $105.3 million or 64 cents per share. Compared to a net loss of $99.3 million, our net loss for the fourth quarter of 2022 was $1.3 million.
or 63 cents per share for the fourth quarter of 2021. Net loss for the full year 2022 was $395.9 million or $2.49 per share.
John Mark Bellamyne: As a late stage of Cology Company approaching potential commercialization this year, we are also investing in launch preparations, internal manufacturing, and pipeline activities. As of December 31st, 2022, we held $478.3 million in cash, cash equivalence, investments, and restricted cash, compared to $602. $1 million at December 31st, 2021. Taking to account proceeds raised in 2023 from our at the market or ATM facility, the unaudited cash position is approximately $670 million on February 24, 2023, which includes approximately $450 million in net proceeds raised through the ATM during the fourth quarter of 22 and into the first quarter of 2020.
compared to net loss of $342.3 million or $2.23 per share for the full year of 2021.
Research and development expenses were $80.6 million for the fourth quarter of 2022, an increase of $5 million compared to $75.6 million for the fourth quarter of 2021. Research and development expenses were $294.8 million for the full year 2022.
an increase of $35.8 million compared to $259.0 million for the full year of 2021.
The increasing research and development expenses in the fourth quarter and four year 2022 over the prior year of periods were primarily attributable to cost associated with the gross attentional research and development team, including start-based compensation expense, as well as fast-meeting related expenses and internal research programs.
million for the fourth quarter 2022, an increase of $2.7 million compared to $23.8 million for the fourth quarter 2021.
General and administrative expenses were $104.1 million for the full year 2022.
John Mark Bellamyne: This current transformed cash position is expected to found our operating plan into the second half of 2024, including the product acquisition, manufacturing activities, launch readiness and execution, plan clinical trial, and pipeline advance. Positioning to the financial results for the fourth quarter and four years on December 31st, 2022, a net loss for the fourth quarter of 2022 was $105.3 million, 64 cents per share, compared to a net loss of $99. or 63 cents per share for the fourth quarter of 2021.
An increase of $20.4 million compared to $83.7 million for Fourier 2021.
The increase in general and administrative expenses in the fourth quarter and full year 2022 compared to the prior year periods were primarily attributable to costs associated with the growth of the internal general and administrative and commercial teams, including stock-based compensation expense, the build-out of the new corporate headquarters, as well as pre-commercial activities.
As of December 31st, 2022, there were approximately 187.8 million common shares outstanding.
I will now hand the call back to the operator to kick off the Q&A session. Thank you. As a reminder, to ask a question, please press star 1 1 on your telephone and wait for your name to be announced.
Operator: Net loss for the full year 2022 was $395.9 million, or $2.49 per share, compared to a net loss of $342.3 million, or $2.23 per share, for the full year of 2021. Research and development expenses were $80.6 million for the fourth quarter of 2022, an increase of $5 million compared to $75.6 million for the fourth quarter of 2020. Research and development expenses were $294.8 million dollars for the full year of 2022, an increase of $35.8 million compared to $259.10 million dollars for the full year of 2021.
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Please stand by while we compile the Q&A roster.
Our first question comes from the line of Peter Lawson from Barclays.
Great, thanks so much for taking the question. Fred, do you sound confident around the PLA submission by the end of 1Q? Kind of what needs to be done there? What's left? Yeah, Peter, we're really confident that we're gonna get this done. We have essentially a lot of activities we talk about.
relating to the assay works, AMC work, validation work, and stuff like that that we were completing. We talked about it before. It's relatively routine work, but it's very important that the FDA and that's kind of what we're getting done here so we can complete the Rolling Bill A submission.
Operator: The increase in research and development expenses in the fourth quarter and full year 2022 over the prior year periods was primarily attributable to cuts associated with the growth of the internal research and development team, including stock-based compensation expense, as well as facility-related expenses and internal research programs. These increased expenses were partially offset by lower clinical and manufacturing costs, driven by completion of enrollment in pivotal cohorts of a clinical contract. General and administrative expenses were $26.5 million for the fourth quarter of 2022, an increase of $2.7 million compared to $23.8 million for the fourth quarter of 2020.
I know some time's off, but just on the launch of Lufthansa, are you expecting to see a bonus of patients on launch? And kind of any way you can kind of quantify that? Yeah, Jim, do you want to take that one? Sure. Given our experience in dialoguing with the KOLs at many of these sites and even our clinical trials,
And Peter, we do run an EAP program in order to stay in close contact with the site so that we're making sure that we have a good feel for what's out there.
I didn't care for patients as FDA wants you to do.
for patients as FDA wants you to do. Thank you.
Thank you. One moment for our next question. Our next question comes in the line of Mark Breedenbach from Oppenheimer....
Operator: General and administrative expenses were $104.1 million for the full year 2022, an increase of $204 million compared to $83.7 million for the full year 2020. The increase in general and administrative expenses in the fourth quarter and full year 2022, compared to the prior year periods, was primarily attributable to costs associated with the growth of the internal general and administrative and commercial teams, including stock-based compensation expense, the build-out of the new corporate headquarters, as well as pre-commercial. As of December 31st, 2022, 22, there were approximately 187.8 million common shares outstanding. I will now return on the call to the operator to kick off the Q&A session.
Hey, guys. Thanks for taking the question. Two quick ones for me. First, I'm wondering if you can just comment on remaining barriers before you can begin recruitment into the TOVANS 301 study. And then I'm also wondering, aside from the cohort 3A lung data,
That Friedrich mentioned are there plans for traditional clinical data presentations in 2023? Thanks for taking my questions.
Frederick, do you want to talk a little bit about the startup activities for 301? And you can probably talk a little bit about the potential for lung data later this year too if you want.
Sure, happy to. Thanks for the question. So we have spoken about being in startup on TOGANS 301. So that basically means a submission of the protocol.
to two sites reviews at sites, site start-ups, site initiation and then start-up enrollment. There are no specific additional hurdles that would be kind of like one hurdle that would apply to all sites. It's not really activities at individual sites and much of that work is basically going on in parallel and will continue to be a priority for all sites.
Operator: Thank you. As a reminder, to ask a question, please press Star 1-1 on your telephone and wait for your name to be announced.
Operator: To withdraw your question, please press Star 1-again.
Operator: Please stand by when we compile the Q&A roster.
Peter Richard Lawson: Our first question comes from the line of Peter Lawson from Barclays. Great, thanks so much for taking the question.
Frederick G. Vogt: Fred, you sounded confident about the BLA submission by the end of one Q, kind of what needs to be done there. Yeah, Peter, we're really confident that we're going to get this done. We have essentially a lot of activities we talk about relating to the assay work, CMC work, validation work, stuff like that that we have already completed. We've talked about it before.
individual sites. Does that make sense?
I guess I'm trying to get a sense for when you would expect the first patient to be enrolled. We haven't guided to when exactly the first patient will be enrolled. What we have said is we expect enrollment to be well underway at the time of approval of the relapse refractory indication. That's kind of the main point here.
Yeah, Mark, we would certainly advise everyone if when we do randomize the first patient.
James Ziegler: It's relatively routine work, but it's very important to the FDA, and that's kind of what we're getting done here so we can complete the rolling VLA submission. And then I know some times off, but just on the launch, Lachal, are you expecting to see a bonus? patients on long, kind of any way you can kind of quantify, Yeah, Jim, do you want to take that one? Given our experience in dialogue and with the KOLs at many of these sites and even our clinical child experience, there's a high-end met need, and this translates into a number of patients who are in need of therapy after a checkpoint inhibitor.
Got it. And with respect to other clinical presentations besides the cohort 3A long NBA though.
Yeah, I mean, I can cover that one. We have additional lung studies running right now, including the LEON202 study, which we could potentially read out this year. Plus, we already put out just a few weeks ago the 3A data, and we do want to get to a medical conference and drill into that data a little bit more deeply. So that'll be, I think, a very important presentation for the company when that comes. Okay. But all the presentations will be in longing, is what you're...
James Ziegler: So we are expecting a bolus of patients at launch given that high-end met need. And Peter, we do run an EAP program in order to stay in close contact with the site so that we're making sure that we have a good feel for what's out there, providing care for patients as FDA wants you to do.
Thank you. One moment for our next question.
Our next question comes from the line of Tyler Van Buren from Cowen.
Hi guys, it's Tara Han for Tyler. So I guess staying on the same topic of the long data, so I know that when you just close the few weeks ago or back in January that it was too early to comment on response duration. But what?
Frederick G. Vogt: Thank you. One moment for our next question. The next question comes from the line of Mark Breedembach.
Do you kind of expect to see when the sole results are presented? And then how are your discussions with the FDA going following that positive feedback that you received on study 202? Like is there anything new to report there since January ?
Mark Alan Breidenbach: Mark Breedembach from Oppenheimer. Hey, guys, thanks for taking the question. Two quick ones for me. First, I'm wondering if you can just comment on remaining barriers before you can begin recruitment into the Tivance 301 study. And then, I'm also wondering, aside from the cohort 3A lung data that Friedrich mentioned, are there plans for additional clinical data presentations in 2023? Thanks for taking that question.
I assume you mean the LUN-T02 study? Yes. Yes, that's one where we're engaging with discussions with the FDA. I don't have any updates for you on that right now. On 3a, we are, like we said when we released the data, the durability is something we're going to watch closely and it will certainly be part of our medical meeting presentation on that. I can't really say much more about that ahead of time. That's obviously an important thing to the...
Frederick G. Vogt: Frederick, do you want to talk a little bit about the startup activities for 301? And you can probably talk a little bit about the potential for lung data later this year, too, if you want. Sure, happy to.
Friedrich Graf Finckenstein: Thanks for the question. So we have spoken about being in startup mode on Tidvan 3-1. So that basically means submission of the protocol, to site reviews at sites, site startup, initiation, and then start-up enrollment. There are no specific additional hurdles that would be kind of like one hurdle that would apply to all sites. It's not really activities at individual sites, and much of that work is basically going on in parallel and will continue as we are adding a meaningful number of sites, both in the US and XU. hero and beyond heroes to the site that were more important to this trial.
Thank you. One moment for our next question.
Our next question comes in the line of Michael Yee from Jefferies.
Hi, guys, thanks so much for taking the question. This is Deena on for Michael. Given that you guys are reiterated the submission for Q1, I just kind of wanted to get a better sense on, you know, I know you guys spoke about this slightly, but just if you can add an additional color on the progress you guys made since the last update.
Friedrich Graf Finckenstein: So really, there are no specific hurdles to site startup activities at individual sites. Does that make sense? Sure, I guess I'm trying to get a sense for when you would expect the first patient to be enrolled. Yeah, we haven't been guided as to when exactly the first patient will be enrolled. What we have said, though, is that we expect enrollment to be well underway at the time of approval of the relapse re-factory indication, and I think that's the main thing, Mark, we would certainly advise everyone when we do randomize the first patient. Got it. And with respect to other clinical presentations besides the cohort 3A long media, yeah, I mean, I can cover that one.
and what are just the remaining beating factors to getting that VLA submitted. And also, if you had any further interactions with the FDA since that last update as well, and, you know, based on the commentary that you guys have had with them, you know, is there any color that you can share on a potential ADCOM or priority review? That would be helpful. Thank you.
Now, we haven't had any additional interactions with them. We do expect to have priority review for this and we'll know more about an adcom at some point. We've spoken before about whether an adcom is likely here. It's possible we may not get an adcom because FDA is familiar with T cell therapies at this point. I just talked about that a few times on calls like this.
With respect to the work and a little bit more color on the work, like I said earlier, it's largely validation activities relating to some of the CMC stuff that we do that's part of our filings. I can tell you the bulk of the work for the BLA is done and submitted. So we're on the home stretch now and we're just completing some of these key tasks. It takes a lot of effort from the company. We have a lot of people here working very hard to get this done. And really, it's not the kind of thing where it's extremely technical in nature. It would be very difficult to communicate with the street.
Frederick G. Vogt: We have additional lung studies running right now, including the OUN-2 study, which could potentially read out this year. Plus, we already put out just a few weeks ago the 3A data, and we do want to get to a medical conference and draw into that data a little bit more deeply. So that'll be, I think, a very important presentation for the company when that comes. Okay, but all the presentations will be in longing, is what you're implying. No, not necessarily. I thought you were just asking about how long. I don't know why I'm trying to get him to go for all other indications.
Operator: Thank you. Please take a moment for our next question.
Tyler Martin Van Buren: Our next question comes from the line of Tyler Van Buren from Cowan.
Tara: Hi, it's Tara on for Tyler. So I guess I will go today.
Tara: on the same topic of lung data.
Tara: you know, when you just closed a few weeks ago or back in January, that it was
Can you remind us just how many melanoma treatment centers in the US you have already sort of onboarded, wherein you feel that you've sufficiently trained all the necessary stakeholders at a particular clinical site? So like how many clinical sites have you onboarded as per all of your clinical trial activities to date?
Tara: That it was too early to comment on response duration.
Tara: What do you kind of expect to see when the full results are presented? And then how are your discussions with the FDA going following that positive feedback that you received on study 202? Like, is there anything new to report there since January?
Thanks, Ben. This is- Can we track that? Go ahead, Jim. Great. The onboarding process is exactly that, it's a process. We've engaged a number of key sites across the country to ensure that we have sufficient geographic coverage as well as access. I won't give you the specific numbers, but what we have stated in the past is, based upon our own assessment, looking at analogs like CAR-T's, we know that there's a heavy concentration of care at these top centers.
Frederick G. Vogt: On the the, I assume you mean the L2 study? Yes.
Frederick G. Vogt: Yeah, that's one where we're engaging in discussions with the FDA. I don't have any updates for you on that right now. On 3A, we are, like we said when we released the data, the durability is something we're going to watch closely, and it will certainly be part of our medical meeting presentation on that. I can't really say much more about that ahead of time. That's obviously an important thing to the content of the medical presentation when we do it.
In the CAR T market, about 10 centers drive about 50% of all the treated patients and the top 40 about 80% of all the treated patients. So we're focused on getting the right sites up and are targeted and up ready for launch. We want to
Frederick G. Vogt: But we are very comfortable that what we're seeing should support a potential registrational trial like the one we described in January, and we're doing our best to get back to FDA with that proposal as soon as we can.
Train them in the final phases of launch. You know, if we train them too soon, there could be staff turnover, there could be the recency. So what we're really doing is lining everyone up now, and as soon as we have the BLA acceptance, we'll be able to filing an acceptance.
Frederick G. Vogt: Thank you. One moment for our next question. Our next question comes from the line of Michael Ye from Jeffries.
then we'll start to really accelerate that final onboarding process. Okay, understood that makes sense. And then I want to ask just another question about the timing of data from the CRC program. In particular, the the the the timing of data from the CRC program.
Michael Jonathan Yee: Hi, guys. Thanks so much for seeing the question. This is Dina on for Michael. Given that you guys reiterated the BLA submission for Q1, I just kind of wanted to get a better sense on, you know, I know you guys spoke about this like
The expanded CRC program in the post-Kemo post-Pembro setting. I guess number one, do you have line of sight of when we get data? And then have you said how many additional patients needed to be enrolled there to kind of support a BLA in that setting?
Dina Elmonshed: but just if you can add some additional color on like the progress you guys have made since the last update and what are just the remaining dating factors to getting that BLA submitted and also if you had any further interactions with the FDA since that last update as well, and based on the commentary that you guys have had with them, you know, is there any color that you can share on a potential adcom or priority review that would be helpful, thank you.
I think Ben you're not talking about colorectal, you're talking about non-smol cell lung, right?
I think Ben, you're not talking about colorectal. You're talking about not so long, right? You say, you're seeing.
Yeah, you meant NSCLC, right? So I assume you meant non-tonsil lung, yeah, cut off there. Sorry. We have.
ovarian cancer. My apologies, I said the wrong indication. Yeah we don't have an ovarian indication at IVANS right now, although it's certainly something we're very interested in and we've explored through ISTs. Okay, my bad. I expect that for a different program.
Frederick G. Vogt: That would be helpful. Thank you. No, we haven't asked.
Frederick G. Vogt: No, we haven't had any additional interactions with them. We do expect to have priority for review for this, and we'll know more about an adcom at some point. We've spoken before about whether an adcom is likely here; it's possible. We may not get an adcom because FD is familiar with T-SEL therapies at this point. Raj, Raj, we just talked about that a few times on calls
Too many earnings calls today. All right, I appreciate that. Thanks, guys. Thanks, everybody. Thanks, everybody.
Thank you. One moment for our next question. Our next question comes from the line of Renny Benjeman from JMP Securities. Hey good afternoon guys, thanks for taking the questions. I guess just to start off, maybe for free, Greg. You know, the PD1 selected till studies the PBL therapy and the PD1 in action.
Frederick G. Vogt: With respect to the work and a little bit more color on the work, it's like I said earlier, it's largely validation activities relating to some of the CMC stuff that we do that's part of our filings. I can tell you the bulk of the work for the BLA is done and we will submit it. So we're in the home stretch now, and we're just completing some of these key tasks. It takes a lot of effort from the company.
the I think near term or imminent right way once the deal is done. Can you just, I think you've talked about in the past, but can you just remind us what sort of near term revenues you expect from ProLuken this year? Why don't I take the first one and I'll have Jean-Marc.
Frederick G. Vogt: We have a lot of people here working very hard to get this done. And really, it's not the kind of thing where it's extremely technical in nature. It's not very difficult to communicate with the street on this, but it's basically a lot of additional CMC validation activities like we've spoken about before.
cover the revenues. We can't give you guidance on revenues, Renny, but we can tell you historically what revenues have been for that product and, you know, you can figure out how to look when they, particularly upon launch of LIFO-LUSOL.
Operator: Thank you. One moment for our next question. Our next question comes from the line of Ben Burnett from Steefell.
For the PD-1 selected and PD-1 knockout, the PD-1 selected program, both of those programs are running and we could be putting data on those this year at some point. PD-1 knockout in particular is of high interest to us. That's why it's on the highlights of our portfolio because that.
Benjamin Jay Burnett: Great, thank you. I just want to ask about the launch preparations for Lyplucell. Can you remind us just how many melanoma treatment centers in the U.S. you have already sort of onboarded, where you feel that you've sufficiently trained all the necessary stakeholders at a particular clinical site? So, like, how many clinical sites have you onboarded as part of all of your clinical trial activities to date? Thanks, Ben. This is... Go ahead, Jim.
particularly in Long and in melanoma should we think give us additional efficacy. So we're very excited about that. That's one that when we have data, we'll be putting it out pretty quickly. PD1 Select is something we've been running for a while and at some point we'll discuss that further. Jean-Marc, do you want to cover the revenue? Yeah. Thank you, Fred, and thank you, Remi, for the question. I mean, as Fred mentioned, we're not giving any kind of revenue guidance.
James Ziegler: Great. So the onboarding process is exactly that: a process. We've engaged a number of key sites across the country to ensure that we have sufficient geographic coverage as well as access. I won't give you the specific numbers, but what we have stated in the past is, based upon our own assessment looking at analogs like CAR-T, we know that there's a heavy concentration of care at these top centers. In the CAR-T market, about 10 centers treat about 50% of all the treated patients, and the top 40 treat about 80% of all the treated patients.
First of all, we need to go the deal first and then we can't talk about the potential in the future. What we have publicly communicated is the revenue that was generated by a clinch, and which followed came in the past, and we were mentioning 2021 was that...
close to 30 million pounds or $35 million. So that's the only indication that we're giving in terms of past revenue. Got it, okay. And just one final one, really just has to do with mainly the CEO search. Is that still going, Fred, are you dying to move your interim status to something more permanent?
James Ziegler: So we're focused on getting the right sites up and targeted and ready for launch. We want to train them in the final phases of launch. You know, if we train them too soon, there could be staff turnover, there could be incompetence.
You know, and I'll throw it out there. Kristy Shaw's left Kite Gilliad. Is someone close to that name joining anytime soon? That's it for us. Thank you. I can't say specifics like that, but the search is ongoing and no, it won't be me. So at some point we'll be able to talk more about that and the board is definitely interested in finding somebody who knows.
James Ziegler: So what we're really doing is lining everyone up now, and as soon as we have the BLA acceptance, well, BLA filing and acceptance, then we'll start to really accelerate that final onboarding. Okay, that makes sense. And then I want to ask just another question about the timing of data from the C or C program. In particular, the expanded CRC program in the post-chemo, post-Pembro setting, I guess number one, do you have a line of sight as to when we get data? And then have you said how many additional patients needed to be enrolled there to kind of support a BLA in that setting?
Thanks, Fred. Thank you. One moment for our next question. Our next question comes from the line of Mara Goldstein from the ZUHO Group. Great. Thanks so much for taking the question. I did have a quick follow-up on the...
Frederick G. Vogt: I think, Ben, you're not talking about colonrect, you're talking about non-small so long, right? You said CRC. Yeah, you meant NSC, right?
Frederick G. Vogt: So I assume you meant not so long, yeah, cut off there. Sorry. But yeah, we have ovarian cancer.
in terms of the Delta improvement looking for, given the number of patients in the trial? And secondarily, the presence of the crossover arm, how do you account for pressure on the OS secondary endpoint there?
Frederick G. Vogt: My apologies. I said the wrong indication. Yeah, we don't have an ovarian indication Ivance right now, although it's certainly something we're very interested in. And we've explored it through ISTs. Okay, my bet. Are you thinking? I was like that for a different program. Too many earnings calls today. All right, I appreciate the help. Thanks, guys.
Yeah, maybe Jean-Marc, do you want to take the first part of that and Frederic get the second part? Yeah, sure. Yeah, I'm trying to think about the best way to answer your question. So I think our goal is to integrate polluting in a way that we will keep it as a profitable activity. I mean it will be separate in a way.
Operator: Thank you. One moment for our next question. Our next question comes from the line of Reni Benjamin from JMP Securities.
Reni John Benjamin: Hey, good afternoon, guys, thanks for taking the questions. I guess just to start off, maybe for Friedrich, you know, the PD1 selected TIL studies, the PBL therapy, and the PD1 inactivated. Can you give us a sense as to how those studies are progressing, and kind of on Mark's question? Do you think this is something that we might see some initial data for at the end of this year? I guess that would be question number one.
in capital as itself because again we're not talking about large amount. We will not carry a lot of amount of inventory and everything should be pretty much managed correctly. So no concern on that. ATM related I mean we've commented about the activity with that we just done and I think what's the most important there is to
Keep in mind we have enough cash, including the acquisition of Proloqing, into the second half of 2024.
Reni John Benjamin: Question number two would be, you know, the pro-lucan revenues are supposed to be, I think near-term or imminent, right, like once the deal is done. Can you just, I think you've talked about in the past, but can you just remind us what sort of near-term revenues you expect? pro-lucans Yeah, why don't I take the first one, then I'll have Jean Mark cover the revenues.
Okay. Thank you for that. And then the till lands question. Yeah, sure. Thanks for the question for you here. So I think that was was a two-part question. What do we think about deltas that we're trying to achieve in the context of study design and sample size and the question and second question was about.
Frederick G. Vogt: We can't give you guidance on revenues, Rennie, but we can tell you historically what revenues have been for that product. And, you know, you can figure out how they will look when they, particularly upon the launch of Leuyl, For the PD1 selected and PD1 knockout, the PD1 select program, both of those programs are running, and we could be putting data out on those this year at some point. PD1 knockout in particular is of high interest to us.
or I have that ratio between the two arms. What you usually do when you design a study like as you do look at the best available information might be expecting in your control arm, and then you're powering in order to be able to get the difference or the hazard ratio. So it's a little different from how we would have done this.
Frederick G. Vogt: That's why it's in the highlights of our portfolio because, particularly in the lung and in melanoma, it should give us additional efficacy, so we're very excited about that. That's one that when we have data, we'll be putting it out pretty quickly. PD1 Select is something we've been running for a while, and at some point, we'll discuss that further. John Mark, do you want to cover the revenue? Yeah.
information is available in the USPI for PEMBRO or in publication.
So that's probably as much as I can say here. The confidence here comes from our knowledge of what we are currently seeing in our COM 202 cohort 1a, where the response rate is...
John Mark Bellamyne: Yeah, thank you, Fred, and thank you, Remi, for the question. I mean, as Fred mentioned, we're not giving any kind of revenue guidance. First of all, we need to close the deal first, and then we can talk and be more specific about the potential in the future. What we have, you know, publicly communicated is the revenue that was generated by a clean gene, which probably came in the past, and we were mentioning 2021 was close to 30 million pounds or 35 million dollars. So that's the only in the that we were giving in terms of past revenue. Got it, okay.
is 66.7% with our last update, and that would compare to something up in the low 30% for pembrolism of monotherapy.
So that gives you an idea around the ORR. The crossover, so yes, obviously the crossovers are something that you have to keep in mind as you are thinking about an overall survival endpoint, but that is exactly the reason why overall survival is not a primary endpoint yet.
It's very typical to in that situation then go with a non-overall survival endpoint and we are particularly happy about having that in agreement of being able to use ORR and PFS as dual endpoint in our discussion with the FDA. And that's exactly the reason for it. The value of the crossover arm in this case is outweighing...
Frederick G. Vogt: Got it, okay. And just one, one final one, you know, this, uh, It really just has to do with mainly the CEO search. Is that still going, Fred, are you dying to move your interim, you know, status to something more permanent? You know, and I'll throw it out there. Christy Shaw's left, Kite Gilead, someone, you know, close to that name, joining anytime soon?
Frederick G. Vogt: Thank you. I can't say specifics like that, but the search is ongoing, and no, it won't be me. So at some point, we'll be able to talk more about that, and the board is definitely interested in finding somebody. Who knows?
So I guess first regarding manufacturing, I guess how do you think about kind of initial launch capacity and then the timing for step ups if we're kind of thinking about it similarly to what we've been seeing with the autologous CAR T therapies, maybe just a bit more granular than kind of the phase one, phase two that you lay out for the ICTC.
Operator: Thank you. Please take a moment for our next question. Our next question comes from the line of Mara Goldstein from Missouho Group. Great, thanks so much for taking the question. I did have a quick follow-up on Prolucan, and I respect you're not giving guidance, but I'm just curious about your expectations about working capital and how the ATM figures into that as you onboard that product. And then secondarily, can you speak to the Tilvan trial and how we should think about the primary endpoint in terms of the delta improvement looking for, given the number of patients in the trial? And secondarily, the presence of the court. Crossover arm, how do you account for pressure on the OS secondary endpoint there?
And then secondly, maybe just a quick one. Are you able to provide any more color on your plans for potentially expanding into Europe for melanoma? Great. Thank you so much. Yeah, let me take the last one and then Igor can give you some more color on the manufacturing. Yes, Europe is something we're very interested in. We haven't publicly spoken much about Europe .
the world where we have a high incidence rate of melanoma.
Mara Goldstein: Yeah, John Mark. Do you want to take the first part of that, and Frederick will get the second part? Yeah, sure.
Igor, do you want to answer the manufacturing question? Happy to, Kelsey. Thanks for the question. So, as I mentioned earlier, we have built the capacity, the facility is built and support more than 2,000 patients per year. And we're now hiring the manufacturing team to meet the demand that we anticipate at launch.
John Mark Bellamyne: Yeah, sure. Yeah, I'm trying to think about the back way to answer your question. So I think our goal is to integrate polluting in a way that we will keep it as a profitable activity. Again, it will be separate in a way from life goals, so we will still sell it for looking outside of our own usage. So currently, I would say polluting is profitable, and we want to do the same in the future after integration.
We're not sharing the exact demand numbers, but as Jim mentioned, actually in response to an earlier question, we expect to maybe evolve so we're taking that into consideration as we're planning, planning the initial launch capacity. Beyond that, we can continue hiring the staff as needed and then also build out the shell space that we have within the existing.
John Mark Bellamyne: I'm not too much concerned around working capital as such because again, we're not talking about large amounts, we will not carry a lot of inventory, and everything should be pretty much managed correctly. So no concern on that. E.m related, I mean, we've commented on the activity that we just did, and I think what's the most important thing there is to keep in mind we have enough cash, including the acquisition of production into the second half of 2020.
those as well.
Okay, great. Thank you so much.
Okay, great. Thank you so much.
Thank you. One moment for our next question. Our next question comes from the line of Azteca Goonwarden from Truist.
John Mark Bellamyne: Yeah, sure, thanks for the question, Frederick here. So I think that was a two-part question, all of them were about how do we think about deltas that we're trying to achieve in the context of the study design and sample size? And the question, the second question was about the class of one. So the first question, I mean, I'm just stating the obvious here, the design of the study is a randomized comparative study, right?
Hi, this is Karina for ASTECA. My question is for children's 301 study. How long do you anticipate it will take for you to finish recruitment? And given that the study is open label, do you plan to report interim data?
Hi, this is Karina for ASTICA. My question is for Tillman's 301 study. How long do you anticipate it will take for you to finish recruitment? And given that the study is open-label, do you plan to report interim data? And if so, at what point? Thank you. On sleeping time, right after C
Frederick, do you want to take that? Yeah, so the projection of accomplishing the analysis is hard, particularly when you are in the early phases of startup. I think we'll better understand that once we're in and make progress on enrollment and site activation.
John Mark Bellamyne: So we're not shooting for specific deltas to an existing benchmark. Instead, we're shooting for a difference or a hazard ratio between the two arms. What you usually do when you design a study like that is look at the best available information about what you might be expecting in your control arm, and then you power in order to be able to get the difference or the hazard ratio. So it's a little different from how we would have done this or are doing it in our single-arm design.
Also, keep in mind that ultimately the endpoints, particularly the PFS endpoint, are event-driven and a true and exact projection is never really truly possible because of that. So stay posted on that. Repeat the second question about the study phase for me. says 4. Sorry!
Friedrich Graf Finckenstein: The information that we're pulling in for that is pretty straightforward. It's available information on what you're seeing in a frontline population of patients treated with temporalism monotherapy and use, and the information is available in the USPI or in publication.
Oh yeah, you were saying that this is an open label study. It's actually not. It's a blinded study. So meaning we are blinded to the treatment assignments as you would in any other study design. The assessments are done by a blind.
Friedrich Graf Finckenstein: So that's probably as much as I can say here. The confidence here comes from our knowledge of what we are currently seeing in our Com 2-02 cohort 1A, where the response rate is 66.7% with our last update, and that would compare to something that's in the low 30% for Pembrozism of Monocle, so that gives you an idea of the OR. The crossover, so yes, obviously the crossovers are something that you have to keep in mind as you are thinking about overall survival as the end point, but that is exactly the reason why overall survival is not a primary goal.
Okay. And also, I have another question. You said that you did not expect to get a REMS. Is that still the case?
Yeah, that's the, we don't see any reason why we will get a REMS. The TIL treatment regimen, CyFlu and IL-2 don't have a REMS today, so, and TILs don't really…
Friedrich Graf Finckenstein: It's very typical to in that situation and go with a non-overall survival endpoint, and we are particularly happy about having gotten agreement to use OR and PFS as dual endpoints in our discussion with the SBA, and that's exactly the reason for it. The value of the crossover arm in this case is outweighing potential impact on the overall survival of the secondary, Okay.
carry any safety issues themselves. So we don't see, we don't have the issues that you see with some of the CAR-Ts that triggered the REMS in those cases.
issues themselves, so we don't have the issues that you see with some of the CARTs that triggered the runs in those cases. Okay, thank you.
Thank you. One moment for our next question. Our next question comes from the line of Madhu Kumar from Goldman Sachs. Hi guys, this is Rob on Simmerdoo. Thanks for taking our question.
Just how should we think about the timing of data from the cervical cancer cohort? And then on the genetically edited till project products, what are you guys thinking in terms of efficacy? I were like, where do you expect to be better?
Friedrich Graf Finckenstein: Okay, thank you very much. Thank you. One moment for our next question.
Operator: Our next question comes from the line of Kelsey Goodwin from Guggenheim Partners.
Kelsey Beatrice Goodwin: Hey, guys, thanks for taking my questions. I guess, regarding manufacturing, how do you think about kind of initial launch capacity and then the timing for step-ups, if we're kind of thinking about it similarly to what we've been seeing with the Autologist Carty therapies, maybe just a bit more granular than kind of the phase one, phase two that you lay out for the ICTC?
Yeah, the genetically-aided TIL product, to take that one first, that combines a PD-1 cocktail with a TIL product. So we're hoping to get something that would look like additive efficacy between the two modes, the TIL response and then the blockade of the inhibitory mechanism directly within the…
Igor P. Bilinsky: And then secondly, maybe just a quick one. Are you able to provide any more color on your plans for potentially expanding into Europe for melanoma? Great. Thank you.
people developing bi-specific antibodies right now that blockade PD-1 and something else. I mean, this is the kind of thing that we want to do within the cell. And so the first, the PD-1 knockout is the first one that's in humans right now. We'll have more updates on that for you later on this year. Cervical, we just restarted enrollment in that study and that's a pivotal study. We intend that to be a pivotal study. And so we don't have an update for you today on that. The post PD-1 cervical population.
Frederick G. Vogt: Yeah, let me take the last one, and then Igor can give you some more color on the manufacturing. Yes, Europe is something we're very interested in. We haven't publicly spoken much about Europe, but we are active there. Obviously, our trials have been run there, and we continue to run them there until Vance 301 is going to have a significant European presence. We are engaged with European regulators, and I think you'll hear more from us in 2023 on that. But that is an important market we think for melanoma as well as other markets around the world where we have a high and sense. Creative melanoma.
Igor P. Bilinsky: You already want to answer the manufacturing question? Happy to, Kelsey. Thanks for the question. So as I mentioned earlier, we have the capacity because the facility is built to support more than 2,000 patients per year, and we're now hiring the manufacturing team to meet the demand that we anticipate at launch. We're not sharing the exact demand numbers, but as Jim mentioned, actually, in response to an earlier question, we expect maybe Ebola, so we're taking that into consideration as we plan the initial launch. Beyond that, we can continue hiring the staff as There's a process that's similar to cross-tel therapy, similar to KARTE, that requires capacity demo submissions to the agency, and we're planning those.
Thank you again for joining the I-Advanced Biotherapeutics fourth quarter and full year 2022 Financial Results Conference call.
We've had an exciting start to 2023 with the Pro-Lukin Agreement and new clinical data, and we look forward to completing the BLA this quarter and delivering on our regulatory, commercial, manufacturing, pipeline activities and milestones throughout the year.
for their support. Please feel free to reach out at any time to our Investor Relations team for any follow-up. Thank you. This concludes today's conference call. Thank you for participating. You may now disconnect.
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Igor P. Bilinsky: Okay, great. Thank you so much. Of course.
Operator: Thank you. Please take a moment for our next question.
Asthika Sarith Goonewardene: Our next question comes from the line of Askika Gunwarden from Truis.
Karina Rabayeva: Hi, this is Karina from Ostica. My question is about the TILN3-1 study.
Karina Rabayeva: How long do you is this?
Karina Rabayeva: study, how long do you estimate it will take for free to finish recruitment? And given that the study's open label, do you plan to print out to report interim data? And if so, at what point?
Friedrich Graf Finckenstein: Thank you. Frederick, do you want to take this? Yeah, so the projection of accomplishing the analysis is hard, particularly when you are in the early phases of startup. I think we'll better understand that once we're in and make progress on enrollment and site activations. Also keep in mind that ultimately, the end points, particularly about the PFs and points, are event driven. And a true and exact projection is never really, truly, truly possible because of that.
Oh.
Friedrich Graf Finckenstein: So stay posted on that. Then repeat the second question about the study phase. Oh, yeah, you were saying that this is an open-label study, it's blinded, so meaning we are blinded to the treatment assignments, as you would in any other study design. The assessments are done by a blinded independent radiology committee. So there's probably probably no update in between, other than if the final decision is being made by the DMC.
You can dial star 11.
Karina Rabayeva: Okay, and also, I have another question. You said that you do not expect to get a rems. If that's still the case, thank you.
Frederick G. Vogt: Yeah, that's the, we don't see any reason why we will get a REMS. The toll treatment regimen, Cy flu, and IL2, don't have a REMS today, so untils don't really carry any safety issues themselves. So we don't have the issues that you see with some of the Cartes that triggered the REMs in those cases.
Operator: Thank you. Please take a moment for our next question.
Madhu Sudhan Kumar: Our next question comes from the line of Madhu Kumar from Goldman Sachs.
Rob: Hi guys, this is Rob. I'm going to do it. Thanks for taking our just how should cervical cancer code. And then on the genetically edited Till Project products, what do you guys think? Or, like, where do you expect to be better?
Frederick G. Vogt: Yeah, the genetically edited TIL product, to take that one first, that combines a PEDA with the TIL product, so we're hoping to get something that would look like additive efficacy between the two modes, the TIL response, and then the blockade of the inhibitory mechanism directly within the cell now. And then as we add additional immune checkpoint targets to our gene editing, we can hopefully add on top of that, too. So that's the basic theory behind it. We're testing that now in humans, and we'll, we'll. know more about how that works.
Frederick G. Vogt: It's similar in many respects to how you see a lot of people developing bispecific antibodies right now that blockade PD1 and something else. I mean, this is the kind of thing that we want to do within the cell. And so the first, the PD1 knockout, is the first one that's in humans right now. We'll have more updates on that for you later this year. Cervical, we just restarted enrollment in that study, and that's a pivotal study.
Frederick G. Vogt: We intend that to be a pivotal study, and so we don't have an update for you today on that. The post-PD1 cervical population is large enough that we think we can enroll it reasonably well, but we'll know more later this year on that.
Frederick G. Vogt: Thank you. At this time, I would now like to turn the conference back to Fred Vote for closing remarks.
Frederick G. Vogt: Thank you again for joining the IAvance Biotherapeutics fourth quarter and full year 2022 Financial Results Conference call. We've had an exciting start to 2023 with the ProLUcan Agreement and new clinical data, and we look forward to completing the BLA this quarter and delivering on our regulatory commercial manufacturing pipeline activities and milestones throughout the year. I am grateful for the patients, physicians, and regulators as well as our employees and cross-functional teams who have worked in close collaboration to advance our mission to be the global leader in pill therapy.
Frederick G. Vogt: I would also like to thank our shareholders and covering analysts for their support. Please feel free to reach you at any time or our investor relations team for any follow-up. Thank you. This concludes today's conference call.
Operator: This concludes today's conference calls. Thank you for participating. You may now disconnect. The conference will begin shortly. To raise and lower your hand during TUNA, you can dial star 1-1. Thank you.
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Operator: Thank you. Thank you. Thank you. The conference will begin shortly. To raise and lower your hand during Q&A, you can dial star 1-1. I'm going to be.
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Operator: Thank you. Thank you. Thank you. Thank you. Thank you. Thank you, Thank you Bhopi.