Full Year 2023 Lisata Therapeutics Inc Earnings Call
Operator: Welcome to the Lisata Therapeutics Full Year 2023 Financial Results and Business Update conference call. Currently, all participants are in a listen-only mode.
Welcome to the Lasalle Therapeutics full year 2020 financial results and business update conference call. Currently all participants are in a listen only mode. Following management's prepared remarks, we will hold a Q&A session to ask a question at that time. Please press star one on your telephone you didn't hear it.
Operator: Following management's prepared remarks, we'll hold a Q&A session. To ask a question at that time, please press star 11 on your telephone. You will then hear an automated message advising your hand is raised.
Automated message is largely in your hand as race as a reminder, this call is being recorded today February 29, 2024, I will now turn the call over to John <unk>, Vice President of Investor Relations and corporate Communications at Lossada. Please go ahead Sir.
Operator: As a reminder, this call is being recorded today, February 29, 2024. I will now turn the call over to John Menditto, Vice President of Investment Relations and Corporate Communications at Lisata. Please go ahead, sir.
John D. Menditto: Thank you, operator, and good afternoon, everyone. Welcome to Lisata's full year 2023 conference call to discuss our financial results and provide a business update. Joining me today from our management team are Dr. David Mazzo, President and Chief Executive Officer; Dr. Kristen Buck, Executive Vice President of Research and Development and Chief Medical Officer; and James Nisco, Vice President of Finance and Treasurer. Shortly before this call, we issued a press release announcing our full year 2023 financial results, which is available under the investors and news section of the company website, along with the webcast replay of. If you have not received this news release, or if you'd like to be added to the company's email distribution list, please email me at jmenditto at lisata.com.
Thank you operator, and good afternoon, everyone.
Welcome to the <unk> full year 2023 conference call to discuss our financial results and provide a business update joining me today from our management team are Dr. David Mazzo, President and Chief Executive Officer, Dr. Christian <unk> Executive Vice President of research and development and Chief Medical Officer, and James NIPSCO, Vice President of Fine.
Hansen Treasury.
Shortly before this call we issued a press release announcing our full year 2023 financial results, which is available under the investors and news section of the company's website along with the webcast replay of this call.
If you have not received this news release or if you'd like to be added to the company's email distribution list. Please email me at J D do Atlas side of Dot com.
John D. Menditto: Before we begin, I remind you that comments made by management during this conference call will contain forward-looking statements that involve risks and uncertainties regarding the operations and future results of Lisata. I encourage you to review the company's filings with the Securities and Exchange Commission, including, without limitation, its Forms 10-Q, 8-K, and 10-K, which identify specific risk factors that may cause actual results or events to differ materially from those described in this forward-looking form.
Before we begin I remind you that comments made by management. During this conference call will contain forward looking statements that involve risks and uncertainties regarding the operations and future results of the setup.
I encourage you to review the Companys filings with the Securities and Exchange Commission, including without limitation. Its forms 10-Q, 8-K, and 10-K, which identifies specific risks risk factors that may cause actual results or events to differ materially from those described in the forward looking statements.
John D. Menditto: Furthermore, the content of this conference call contains time-sensitive information that is accurate only as of the date of this live broadcast, Thursday, February 29, 2021. Lisata Therapeutics undertakes no obligation to revise or update any statements to reflect events or circumstances after the date of this conference. With that, I will now turn the call over to Dr. Mazzo. Thank you, John, and good afternoon, everyone.
Furthermore, the content of this conference call contains time sensitive information that is accurate only as of the date of this live broadcast Thursday.
February 29, 2020 for Lasalle of Therapeutics undertakes no obligation to revise or update any statements to reflect events or circumstances.
The date of this conference call.
With that I'll now turn the call over to Dr. Mazzo David.
Thank you John and good afternoon, everyone. Thank you for joining us today as we provide an overview of recent business highlights discuss our full year 2023 financial results and give an update on the progress of our various development programs.
David J. Mazzo: Thank you for joining us today as we provide an overview of recent business highlights, discuss our full year 2023 financial results, and give an update on the progress of our various development programs. During 2023, our first full year as Lisata, we made notable progress in advancing our clinical development programs, targeting several advanced solid tumors using LISTA-1, our lead product candidate, in combination with multiple anti-cancer agents of differing modalities. As we have previously reported, we have both preclinical and early clinical data in humans that we believe demonstrates the potential of LISTA-1 to become an integral part of a revised standard-of-care treatment regimen for many difficult-to-treat cancers. Following the review of the financial results, Lisata's Chief Medical Officer, Dr. Kristen Buck, will provide an update on our ongoing and planned clinical program. With that, I now will turn the call over to James Nisco, our Vice President of Finance and Treasury. James?
In 2023, our first full year as Masada, we made notable progress advancing our clinical development programs targeting several advanced solid tumors using Lister one our lead product candidate in combination with multiple anti cancer agents of different modalities as we have previously reported we have both preclinical.
And early clinical data in humans that we believe demonstrates the potential eclipsed the one to become an integral part of a revised standard of care treatment regimen for many difficult to treat cancers. Following the review of the financial results without as Chief Medical Officer, Dr. Kristi, and Buck will provide an update on our ongoing and planned clinical.
With that I'd now I will turn the call over to James <unk>, Our Vice President Finance and Treasurer Jamie.
James Nisco: Thanks, Steve. Good afternoon, all. I'm pleased to join you today to present a summary of our full year 2023 financial results, starting with operating expenses. For the year ended December 31st, 2023, operating expenses totaled $25.7 million compared to $57.6 million for the year ended December 31st, 2022, representing a decrease of $31.9 million, or 55.4%, excluding the in-process research and development expense of $30.4 million associated with the merger of Operating expenses decreased by $1.5 million, or 5.5%, compared to the year-ended December 31, 2022.
Thanks, Dave Good afternoon, all I am pleased to join you today to present, a summary of our full year 2023 financial results.
Starting with the operating expenses for the year ended December 31, 2023 operating expenses totaled $25 7 million compared to $57 6 million for the year ended December 31 2022.
Representing a decrease of $31 9 million or 55, 4%.
Excluding the in process research and development expense of $34 million associated with the merger of sand therapeutics, and our predecessor company collateral biosciences, forming Masada therapeutics operating expenses decreased by $1 5 million or five 5%.
Compared to the year ended December 31 2022.
James Nisco: Research and development expenses were approximately $12.7 million for the year ended December 31, 2023, compared to $13.1 million for the year ended December 31, 2022, representing a decrease of approximately 300,000 or 2.5%. This decrease was primarily due to lower costs associated with our LISTA I programs in the current year versus our legacy CD34 cell therapy technology programs in the prior year. Current year expenses were associated with study activities for LISTA-1 Phase 2A of the concept bolster trial and various solid tumors in combination with the corresponding standards of care, and enrollment activities for the LISTA-1 Phase 2B ASCEND study. Chemistry, Manufacturing, and Control, or CMC, activities for LISTA-1 and Study Startup activities for the LISTA-1 Phase 2a Study for the Treatment of Glioblastoma Multivitamins
Research and development expenses were approximately $12 7 million for the year ended December 31, 2023, compared to $13 1 million for the year ended December 31 2022.
Representing a decrease of approximately 300000 or two 5%.
This decrease was primarily due to lower costs associated with our list of one programs in the current year versus our legacy CD 34 cell therapy technology programs in the prior year.
Current year expenses were associated with study activities for list of one phase two proof of concept bolster trial in various solid tumors in combination with the corresponding standards of care.
Enrollment activities for the last the one phase II B ascend study.
Chemistry manufacturing and control or CMC activities for a list of one.
And study startup activities for the list of one phase Iia study for the treatment of Glioblastoma multi form.
James Nisco: General and administrative expenses were approximately $13 million for the year ended December 31st, 2023, compared to $14.1 million for the year ended December 31st, 2022, representing a decrease of approximately 1.2 million or 8.3%. This was primarily due to non-recurring costs associated with the aforementioned merger in the prior year, decrease in equity expense due to prior year performance stock unit best merger option assumption expense and Departing Board Member Restricted Stock Unit Vessel, lower annual stockholder meeting expenses, and a decrease in directors' and officers' insurance premiums, partially offset by severance costs associated with the elimination of the chief business officer position on May 1st, 2023. Overall, net losses were $20.8 million and $54.2 million for the years ended December 31, 2023, and 2022, respectively.
<unk> and administrative expenses were approximately $13 million for the year ended December 31, 2023, compared to $14 1 million for the year ended December 31 2022.
Representing a decrease of approximately $1 2 million or eight 3%.
This was primarily due to nonrecurring costs associated with the aforementioned merger in the prior year.
Decrease in equity expense due to prior year performance stock unit vesting <unk>.
Roger option assumption expense and departing board member restricted stock unit vesting.
Lower annual stockholder meeting expenses and a decrease in directors and officers insurance premiums.
Actually offset by severance costs associated with the elimination of the Chief business officer position on May one 2023.
Overall net losses were $20 8 million and $54 2 million for the years ended December 31, 2023, and 2022, respectively.
James Nisco: Turning now to our balance sheet and cash flow. As of December 31, 2023, Lisata had cash equivalents and marketable securities of approximately $50.5 million. Based on its current expected capital needs, the company believes that its projected capital will fund its current proposed operations into early 2016, encompassing data milestones from all its ongoing and planned clinical trials. This completes my financial overview, and I will now turn the call over to our Chief Medical Officer, Dr. Kristen Buck, for a review of our clinical development pipeline. Kristen?
Turning now to our balance sheet and cash flow.
As of December 31, 2023, Masada had cash cash equivalents and marketable securities of approximately $55 million.
Based on its current expected capital needs. The company believes that its projected capital will fund. Its current proposed operations into early 'twenty six encompassing data milestones from all its ongoing and planned clinical trials.
This completes my financial overview, and I will now turn the call over to our Chief Medical Officer, Dr. Christopher Buck for the review of our clinical development pipeline Kristen.
Kristen K. Buck: Thank you, James, and good afternoon, everyone. As we have previously emphasized, we have designed Lisata's rigorous clinical programs based on sound scientific rationale from a large body of published preclinical and early clinical data. Our platform technology is designed to address major impediments to the successful treatment of advanced solid tumors in an environment of increasing pharmacoeconomic pressure. Generating meaningful clinical data as efficiently as possible is critically important in this field, and I can assure you that our entire organization has this goal top of mind in everything we do. With that in mind, I will now provide an overview of LISTA-1 for the treatment of advanced solid tumors in combination with other anti-cancer agents. Despite advances in cancer therapy today, many solid tumors remain difficult to treat effectively. Cancers such as pancreatic cancer, gastric cancers, and other solid tumors are surrounded by a dense fibrotic tissue known as the stroma, which limits access of most pharmacotherapies to the tumor.
Thank you James and good afternoon, everyone.
As we have previously emphasized we've designed Lasalle is rigorous clinical programs based on sound scientific rationale from a large body of published preclinical and early clinical data.
Our platform technology is designed to address major impediments to the successful treatment of advanced solid tumors in an environment of increasing pharmacopeia economic pressures.
Generating meaningful clinical data as efficiently as possible is critically important in this field and I can assure you that our entire organization has this gold top of mind in everything we do.
With that I will now provide an overview of list of one for the treatment of advanced solid tumors in combination with other anti cancer agents.
Despite advances in cancer therapy today, many solid tumors remain difficult to treat effectively.
Cancers, such as pancreatic cancer gastric cancers, and other solid tumors are surrounded by a dense fibrotic tissue known as the stroma, which limits access of most pharmacotherapy to the tumor.
Kristen K. Buck: Many solid tumors also present a hostile tumor microenvironment, or TME, which suppresses the patient's immune system and makes it less effective in fighting cancer. The combination of a dense stroma and a hostile TME prevents many chemotherapies and immunotherapies from being optimally effective in treating these cancers. This, coupled with the fact that most anti-cancer therapies are not efficient in targeting only cancer tissue, defines the major challenge in maximizing effectiveness and safety in the treatment of solid tumors. To combat this, Lisata's approach is to exploit the C-end rule to activate the SEND-R active transport system, a naturally occurring active transport system to selectively deliver anti-cancer drugs through the stroma and into the tumor. Lisata's lead product candidate, Lista-1, is the recipient of multiple orphan drug designations, including for pancreatic cancer in both the United States and Europe, as well as for malignant glioma in the United States.
Many solid tumors are also present, a hostile tumor micro environment.
M E, which suppresses the patient's immune system and makes it less effective in fighting cancer.
The combination of a dense stroma and a hostile tammy prevent many chemotherapies in immunotherapies from being optimally effective in treating these cancers.
This coupled with the fact that most anti cancer therapies are not efficient and targeting only cancer tissue.
The major challenge in maximizing effectiveness and safety in the treatment of solid tumors.
To combat. This <unk> approach is to exploit the C and rule to activate the send our active transport system, a naturally occurring active transport system to selectively deliver anti cancer drugs through the stroma and into the tumor.
We started the lead product candidate list of one is the recipient of multiple orphan drug designation, including for pancreatic cancer in both the United States and Europe as well as for malignant glioma in the United States.
Kristen K. Buck: LISTA-1 selectively activates the SEND-R active transport mechanism on tumor stroma while also having the potential to modify the TME and make it less immunosuppressive. LISTA-1 targets tumor vascular endothelial cells and tumor cells based on its affinity for alpha-B, beta-3, and beta-5 integrins that are selectively upregulated on these cells in comparison to healthy tissue. Lista-1 is a 9-amino acid cyclic internalizing RGD peptide that, once bound to these integrins, is cleaved by proteases expressed in the TME to release a linear peptide fragment called the Ascend-R fragment. The Sendar fragment has high affinity for and then binds to an adjacent receptor called norepilin 1, also upregulated on tumor endothelium and tumor cells.
Lister one selectively actuate loosened our active transport mechanism on tumor stroma, while also having the potential to modify the TMA TMA and make it less immunosuppressive.
Lister, one targets tumor vascular endothelial cells and tumor cells based on its affinity our alpha beta.
Beta three and beta find immigrants and are selectively up regulated on these cells and comparison to healthy tissue.
Listen one of the nine amino acid cyclic internalizing RGB peptide that once bounded these integrations is cleaved by proteases expressed in the TMA to release, a linear peptide framework called ascend our fragrance.
The Sundar fragment has high affinity for and then binds to an adjacent receptor called neuro Pelon, one also up regulated on tumor endothelium and tumor cells.
Kristen K. Buck: This finding activates the C-end rule active transport pathway, which delivers anti-cancer drugs more efficiently into solid tumors. Additionally, LISTA-1 has been shown in a range of preclinical models to modify the tumor microenvironment, making it less hostile to immune cells, reducing tumor resistance to anti-cancer medications, and impeding and or preventing the metastatic cascade. These results come from Lisata-sponsored studies and from collaborators and research groups around the world and have been the subject of more than 350 scientific publications relevant to LISTA-1's mechanism of action. Along with our collaborators, we have also amassed significant non-clinical data demonstrating enhanced delivery of a range of anti-cancer therapy modalities, including immunotherapies and RNA-based therapeutics. To date, LISTA-1 has demonstrated favorable safety, tolerability, and activity to enhance delivery of standard-of-care chemotherapy for patients with metastatic pancreatic cancer. Our development programs are designed to exploit the potential of LISTA-1 to enhance a variety of anti-cancer treatments in a range of solid tumors. Currently, LISTA-1 is the subject of nearly a dozen planned or active clinical trials globally for the treatment of various solid tumors. Let me touch on a few of these individually.
This finding activates the C and rule active transport pathway, which <unk> anti cancer drugs more efficiently into solid tumors.
Additionally, Lister one has been shown any range of preclinical models to modify the tumor microenvironment, making it less hostile to immune cells, reducing tumor resistance to anti cancer medications and impeding <unk>, preventing the metastatic cascade.
These results come from Lasalle sponsored studies and from collaborators and research groups around the world and have been the subject of more than 350 scientific publications relevant to list of one's mechanism of action.
Along with our collaborators we have also amassed significant non clinical data demonstrating enhanced delivery of a range of anti cancer therapy modalities, including Immunotherapies.
RNA based therapeutics.
To date list. The one has demonstrated favorable safety tolerability and activity to enhance delivery of standard of care chemotherapy for patients with metastatic pancreatic cancer.
Our development programs are designed to exploit the potential of list one to enhance a variety of anti cancer treatment and a range of solid tumors.
Currently Lister one is the subject of nearly a dozen planned or active clinical trials globally for the treatment of various solid tumors.
Let me touch on a few of these individually.
Kristen K. Buck: The ASCEND trial is a 158-patient, double-blind, randomized, placebo-controlled clinical trial evaluating Lista-1 in combination with gemcitabine and nabpaclitaxel in patients with metastatic pancreatic ductal adenocarcinoma, also known as MPDAC. This trial is being conducted at 25 sites in Australia and New Zealand, led by the Australian Gastrointestinal Cancer Trials Group, or The study consists of two cohorts.
The ascend trial is a 158 patient double blind randomized placebo controlled clinical trial.
Are you waiting list of one in combination with Gemcitabine and Nab paclitaxel in patients with metastatic pancreatic ductal adenocarcinoma also known as M. P deck.
This trial is being conducted at 25 sites in Australia, and New Zealand led by the Australian gastrointestinal cancer trials group or AG ITG in collaboration with the NIH MRC clinical trial center at the University of Sydney.
The study consists of two cohorts.
Kristen K. Buck: Cohort A of the study received a single dose of 3.2 milligrams per kilogram of Lista-1 essentially simultaneously with standard of care therapy, while cohort B is identical to cohort A, but with a second dose of 3.2 milligrams per kilogram of Lista-1 given four hours after the first. As previously reported, a positive outcome from the planned interim futility analysis was announced by the study's Independent Data Safety Monitoring Committee, which recommended the continuation of the study without modification. In addition, we are excited to report that full enrollment in ASCEND has been achieved, and we expect top-line data from the 98 patients assigned to Cohort A to be reported in the fourth quarter of 2024, followed by the complete data set of all 158 patients to be available by mid-2025.
Cohort a of the study received a single dose of $3 two milligram per kilogram list, one essentially simultaneously with standard of care therapy, while cohort b is identical to cohort eight but with a second dose of $3 two milligram per kilogram of lift the one given four hours after the FERC.
As previously reported a positive outcome from the planned interim futility analysis was announced by the study's independent data safety monitoring committee, which recommended continuation of the study without modification.
In addition, we are excited to report that full enrollment of a sudden has been achieved and we expect topline data from the 98 patients assigned to cohort.
To be reported in the fourth quarter of 2024.
Followed by the complete dataset of all 158 patients to be available by mid 2025.
Kristen K. Buck: We plan to use the results of the ASCEND trial to explore possible conditional approvals in several jurisdictions and to design and optimize a phase three program in metastatic pancreatic ductal adenocarcinoma. The BOLSTER trial is our Phase IIa, double-blind, placebo-controlled, multicenter, randomized basket trial with active and planned investigational sites in the United States, Europe, Canada, and Australia, evaluating LISTA1 in combination with standard of care and advanced solid tumors, including second line head and neck squamous cell carcinoma and first line cholangiocarcinoma. This trial will include both cytotoxic and immunotherapy standards of care. Bolster continues to make steady progress, and enrollment completion is expected by the end of 2024. Dendefox
We plan to use the results of the ascend trial to explore possible conditional approvals in several jurisdictions and to design and optimize phase III program in metastatic pancreatic ductal adenocarcinoma.
The bolster trial is our phase II double blind placebo controlled multicenter randomized basket trial with active and planned investigational sites in the United States, Europe, Canada and Australia.
Waiting list of one in combination with standards of care and advanced solid tumors, including second line head and neck squamous cell carcinoma, and first line Cholangiocarcinoma.
This trial will include both cytotoxic and immunotherapy standards of care.
Bolster continues to make steady progress and enrollment completion is expected by the end of 2024.
Turning to Fox the Phase <unk> open label trial in United States of lift the one in combination with new adjuvant <unk> based therapies in pancreatic colon and Appendiceal cancers continues to make steady progress with.
Kristen K. Buck: The Phase 1b, 2a open-label trial in the United States of Lista-1 in combination with neoadjuvant fulviranox-based therapy in pancreatic, colon, and appendiceal cancers continues to make steady progress, with enrollment completion expected by the end of the second quarter of 2024. This trial will provide us with pre- and post-treatment biopsy immunoprofiling data, as well as long-term outcome data. LISTA-1 is also currently being evaluated in combination with gemcitabine and nabpaclitaxel in a phase 1b, 2a open-label trial in China, led by our licensee in that territory, Chilu Pharmaceutical. During the 2023 ASCO annual meeting, Chilo Pharmaceutical presented an abstract sharing preliminary data from the study, which corroborated previously reported findings from the phase 1B2A trial of Lista1 plus gemcitabine and nabpaclitaxel conducted in Australia in patients with MPDAC.
With enrollment completion expected by the end of the second quarter of 2024.
This trial will provide us with pre and post treatment biopsy immuno profiling data as well as long term outcome data.
Lister one is also currently being evaluated in combination with Gemcitabine and Nab Paclitaxel in a phase <unk> open label trial in China led by our licensee in that territory Qi Lu pharmaceutical.
During the 2023 <unk> annual meeting Shilo pharmaceutical presented an abstract sharing preliminary data from this study, which corroborated previously reported findings from the phase <unk> trial of list, the one plus gemcitabine and Nab Paclitaxel conducted in Australia and patients with MPD.
Kristen K. Buck: According to Chilu, final data is expected by the end of the second quarter of 2024, with the initiation of a Phase II trial in China shortly thereafter. In collaboration with our funding partner, WARP9, the iLISTA trial is a phase 1b2a, randomized, single blind, single center, safety, and pharmacodynamic study in Australia evaluating Lista-1 in combination with the checkpoint inhibitor, Dervalumab, plus standard of care chemotherapy, nabpaclitaxel and gemcitabine, versus standard of care alone in patients with locally advanced non-resectable pan Enrollment completion for ILLISTA is expected during the second half of 2024. iGoLista, a Phase 1b, 2a proof of concept safety and early efficacy study evaluating Lista1 in combination with nivolumab and fulfironox as a first-line treatment for locally advanced, non-resectable gastroesophageal adenocarcinoma is pending initiation as The inspiration for this study comes from the findings recently published in Oncology and Cancer Case Reports Journal, which details a patient with metastatic gastroesophageal adenocarcinoma who achieved a complete response when given Lista-1 in combination with standard of care for Firinox and Pembrolizumab. The subject initially underwent months of standard of care treatments and only achieved a partial response.
According to <unk>.
Final data are expected by the end of the second quarter of 2024 with the initiation of a phase two trial in China. Shortly thereafter.
Okay.
Our collaboration with our funding partner Warp nine V I list the trial.
<unk> is a phase <unk> randomized single Blind single Center safety and Pharmacodynamic study in Australia evaluating list. The one in combination with the checkpoint inhibitor <unk> plus standard of care chemotherapy, Nab Paclitaxel and Gemcitabine versus standard of care alone in patients with locally.
<unk> advanced non Resectable pancreatic ductal adenocarcinoma.
Enrollment completion for Elisa is expected during the second half of 2024.
I go Lister a phase one b to a proof of concept safety and early efficacy study evaluating list. The one in combination with <unk> and <unk> as the first line treatment and locally advanced non Resectable gastroesophageal adenocarcinoma.
Is pending initiation as a function of availability of funding by our partner worth nine.
The inspiration for this study comes from the findings recently published in oncology and cancer case reports journal, which details a patient with metastatic gastroesophageal adenocarcinoma, who achieved a complete response.
Given list of one in combination with standard of care for <unk> and Pember lithium atom.
The subject initially underwent months of standard of care treatments and only achieved a partial response.
Kristen K. Buck: Upon subsequent addition of LISTA-1 to such a standard-of-care therapeutic regimen, the subject achieved a complete response, confirmed both radiographically and surgically. We hope to have further updates on timing related to the execution of the study in the coming quarter. A study of Lista-1 in combination with temozolomide and glioblastoma multiforme, or GBM, has been initiated with patients already being treated.
Upon subsequent addition of Lister one to such standard of care therapeutic regimen.
Subject achieved a complete response.
<unk>, both radio graphically and surgically.
We hope to have further update on timing related to the execution of this study in the coming quarters.
A study of list the one in combination with T. Mazola mined in Glioblastoma multi form or GBM has been initiated with patients already being treated.
Kristen K. Buck: This study is designed as a phase 2a, double-blind, placebo-controlled, randomized, proof-of-concept study evaluating Lista-1 when added to standard-of-care temozolomide versus temozolomide and matching Lista-1 placebo in patients with newly diagnosed glioblastoma multiforme. It is being conducted across multiple sites in Estonia and Latvia and is targeted to enroll 30 patients with a randomization Importantly, as recently announced, LISTA-1 has been granted orphan drug designation by the U.S. Food and Drug Administration for malignant glioma. This action by the FDA highlights the unmet medical need but also recognizes the potential of LISTA-1 to benefit patients in this indication. As a reminder, several of these studies are investigator-initiated trials, and although we have great confidence in our investigators running these studies, Lisata has limited control, and thus, timelines and expectations may be subject to change.
This study is designed as a phase two a double blind placebo controlled randomized proof of concept study evaluating list of one.
When added to standard of care team is all online versus team is open mind and matching list. The one placebo in patients with newly diagnosed glioblastoma multi form.
It is being conducted across multiple sites in Estonia, and Latvia and is targeted to enroll 30 patients with a randomization two to one list of <unk> plus standard of care versus placebo plus standard of care.
Importantly, as recently announced list of one has been granted orphan drug designation by the U S food and drug administration for malignant glioma.
This action by the FDA not only highlights the unmet medical need but also recognizes the potential of list of one to benefit patients in this indication.
As a reminder, several of these studies aren't investigator initiated trials and although we have great confidence in our investigators running these studies Lisa <unk> has limited control and thus timelines and expectations may be subject to change that said, we are extremely grateful to our investigators and.
Kristen K. Buck: That said, we are extremely grateful to our investigators and especially to those patients participating in LISTA1 clinical trials around the world. For those who are interested, a more comprehensive description of each of our trials is available in the appendix section of the corporate presentation on our website. Additionally, in the body of the presentation, there are two milestone slides that depict the anticipated timing of key execution milestones and data readouts from our trial. As you will see, there are numerous execution and data milestones projected for our portfolio of clinical trials over the next year and beyond. With that, I will now turn the call back to Dave. Thank you, Kristen.
Especially to those patients participating enlist the one clinical trials around the world.
For those who are interested a more comprehensive description of each of our trials is available in the appendix section of the corporate presentation on our website.
Additionally, in the body of the presentation. There are two milestone slides that depict the anticipated timing of key execution milestones and data readouts from our trials.
As you will see there are numerous execution and data milestones projected for our portfolio of clinical trials over the next year and beyond.
With that I will now turn the call back to Dave.
Thank you Kristen.
To summarize 2023 was a year marked by the holding of our list of one development efforts and keeping with our strategic imperatives of advancing Lister one rapidly toward registration in MP deck as well as demonstrating the broad application of list. The one in combination with a variety of anti cancer agents for the treatment.
David J. Mazzo: To summarize, 2023 was a year marked by the honing of our LISTA-1 development efforts in keeping with our strategic imperatives of advancing LISTA-1 rapidly toward registration in MPDAC, as well as demonstrating the broad application of LISTA-1 in combination with a variety of anti-cancer agents for the treatment of numerous solid tumor types. For 2024, more than ever, we are focused on efficient and timely study execution with the goal of getting to meaningful clinical data readouts as soon as possible. And with that overview, Operator, we're now ready to take questions. Thank you. As a reminder, to ask a question, please press star 1-1 on your telephone. You will then hear an automated message advising that your hand is raised.
Numerous solid tumor types for.
For 2024 more than ever we are focused on efficient and timely study execution with the goal of getting to meaningful clinical data readout as soon as possible and with that overview operator, we're now ready to take your questions.
As a reminder to ask a question. Please press star one on your telephone you will then hear an automated message advising you harness race. Please wait for your name to be announced we ask that you. Please limit your questions to one at a time and return to the queue with any additional questions. One moment for your first question.
And our first question comes from the line of Joe <unk> with H C. Wainwright. Your line is now open.
Operator: Please wait for your name to be announced. We ask that you please limit your questions to one at a time and return to the queue with any additional questions. One moment for our first question. And our first question comes from the line of Joe Pantginis with HC Wainwright. Your line is now open. Hi, good afternoon. This is Sara on behalf of Joe.
Hi, Good afternoon. This is Sarah on for Joe Thanks for taking the question.
Just wanted to gain some insight if you had any further detail on how.
To bolster bolster trial is it rolling and if youre seeing across Europe U S and Canada any region and increased.
Sara Nik: Thanks for taking the question. I was wanting to gain some insight if you had any further detail on how the Bolster trial is enrolling and whether you're seeing across Europe, the U.S., and Canada, any region seeing increased enrollment compared to others. Thank you. Thanks, Sara. I appreciate the question. And say hello to Joe for us as well.
Enrollment compared to other thank you.
Thanks I appreciate the question.
Saint Laurent shelf for us as well as it relates to bolster bolster is actually on track to reach the enrollment goal of completion by the end of 2024, and we are quite pleased with that says most people know enrollment in clinical trials is not linear it actually has.
David J. Mazzo: As it relates to Bolster, Bolster is actually on track to reach the enrollment goal of completion by the end of 2024, and we're quite pleased with that. As most people know, enrollment in clinical trials is not linear. It actually has more of the shape of a hockey stick.
The shape of the hockey stick and were finally on the up slope of that curve and moving things very very nicely as it relates to regional contributions so far the U S has been the greatest.
David J. Mazzo: And we're finally on the upslope of that curve and moving things very, very nicely. As it relates to regional contributions, so far, the U.S. has been the greatest contributor to enrollment, but that's mostly because many of our European sites will only really be coming online in the month of March. And so we expect to see a significant contribution from the European theater starting in the second quarter of this year. Okay, that's helpful. Thank you. Thank you. One moment for our next question, please. And the next question comes from the line of Pete Enderlin with Moz Partners. Your line is now open. Hi Pete, go ahead. It's Dave. Pete, you may be muted.
<unk> two enrollment, but that's mostly because many of our European sites will only really be coming on line in the month of March and so we expect to see a significant contribution from the European theater, starting in the second quarter of this year.
Okay. That's helpful. Thank you.
Thank you one moment for our next question. Please.
Our next question comes from the line of Pete Enderlin with MAZ Partners. Your line is now open.
I think go ahead Steve.
Okay.
Pete you may be muted.
Peter J. Enderlin: Yeah, I... Can you hear me now? Yes, go ahead. Okay, sorry. Thanks for taking the questions. First, we're maybe a little bit different. Did you get a milestone for enrolling the cohorts for the ASCEND trial? And if so, by whom? I don't even know who it would be.
Yes.
Can you hear me now yes, okay sorry.
Thanks for taking the questions.
First one maybe a little.
Not even way did you get a milestone for enrolling.
Cohorts for the ascend trial, and if so by whom I.
Uh huh.
No it would be.
David J. Mazzo: No, that's a trial that's funded by us. So, okay. No, there are no milestones associated with that, no milestone payments associated with that, and... You mentioned Warp 9 as a source of funding for a couple of the programs. That's a three-year-old company or organization. Do you have any sense of what their financial resources would be?
No.
The trial is funded by US so okay out there no milestones associated with the milestone payments associated with that.
And.
You mentioned <unk> nine as a source of funding for a couple of the programs.
The three year old company or organization.
Do you have any sense of what their financial resources would be I know that they get corporate.
David J. Mazzo: I know they get corporate funding, I think, but I'm not sure how big a company it is or how robust their financial resources are. Well, WARP9 is a philanthropic foundation in Australia dedicated to the improvement and the rapid accessibility of patients to novel treatments for gastrointestinal cancers of all types. So far, I mean, we don't really monitor their finances per se.
Funding I think but I'm not sure how big a company that is or how robust their financial resources are.
Well worth nine.
<unk> philanthropic foundation.
Australia dedicated to the improvement in the rapid accessibility of patients to novel treatments for gastrointestinal cancers of all types. So far I mean, we don't really monitor their finances per se. So far they've met all their commitments to us, though is it related to financing.
David J. Mazzo: So far, they've met all their commitments to us, though, as it related to the financing of the trials associated with LISTA1. Okay.
The trials associated with Mr. Webb.
Okay.
Those.
David J. Mazzo: AGITG typically takes a financial interest in anything that they help you with, or the way some universities do here, or is that not the way they do it? I don't know what they typically do, but as it relates to our associations with AGI-TG for Ascend and any other work we may do, there is no financial interest from them. They're purely clinicians operating at the site level, so we don't give up any commercial rights to them, and they don't take any commercial or financial interest in the product. Okay, fair enough. And then on Ascend Cohort B. I'm just curious, from a naive perspective, what's the significance of a four-hour delay in the second dose versus, say, a 24-hour delay, which, you know, it sort of seems like it would be more normal to go through a normal metabolic cycle for the patient. So, what's four hours versus a longer period of time? Well, I'll describe the sort of, you know, sort of top line.
Agi TG typically take a financial interest in anything that they help you with or.
The way some universities two here is that not the way they do it.
I don't know what they typically do but as it relates to our associations with AG ITG for ascend and any other work. We may do there is no financial interest from from them, they're purely clinicians executing at the site level. So we don't give up any commercial rights to them.
And they don't take into commercial or financial interest in the product.
Fair enough.
Cohort b.
I'm just curious from a naive perspective, what's the significance of a four hour delay and the second dose versus say a 24 hour delay.
Sort of seems like it would be more normal to go through our normal metabolic cycle for the patient.
Four hours versus a longer period of time.
Well ill describe the sort of top line.
David J. Mazzo: And if we, if you want to have a more detailed conversation, we could always take that offline with Dr. Buck. But, generally speaking, it's a, the choice of four hours is a combination of both knowledge of the pharmacokinetic and pharmacodynamics of LISDA-1 in humans and also simply practicality for patients. So without getting too technical, LISTA-1 has a half-life in humans of about 90 minutes. So, you know, and so after one or two half-lives, you can expect that the concentration of Lista-1 would be significantly decreased in the bloodstream. What we are doing is re-initiating administration at four hours to bring that concentration back up to the earlier peaks in order to see if the concentrations of the co-administered chemotherapeutic agents, gemcitabine and napaxlitaxel, both of which have active components that have very long half-lives, might actually see another increase in activity due to that second dose. The reason, you know, it's four hours and not five, six, or something else is that most patients do not want to spend an overnight in a hospital or do not want to have to return to the hospital or clinic for treatment a second day after receiving chemotherapy.
Want to have a more detailed conversation could always take that offline with Dr. Buck, but generally speaking.
The choice of four hours is a combination of both.
Knowledge of the.
Pharmacodynamic factory, the pharmacokinetic and pharmacodynamics of Lister one in humans and also simply practicality for patients so without getting too technical Lister one has a half life in humans of about 90 minutes.
So.
And so after one or two half life you can expect that the concentration of list. The one would be significantly decreased in the blood stream.
We are doing is re initiating administration at four hours to bring that concentration back up to the earlier peaks in order to see if the concentrations of the co administered chemotherapeutic agents Gemcitabine and Nab Paclitaxel.
Both of which have active components that have very long half life might actually see another increase of.
Activity due to that second dose the reason, it's four hours and not five or six or something else is that most patients do not want to spend an overnight in a hospital or do not want to have to return to the hospital or clinic for treatments second day after receiving chemotherapy.
Peter J. Enderlin: So four hours is a convenient time for patients who come in in the morning, receive their chemo, wait four hours at the center, receive their second dose, and then can go home. And so, as I said, it's a combination of scientific design and practicality for patients. That's very interesting, and it makes a lot of sense.
So four hours is a convenient time for patients who come in in the morning received their chemo wait for hours up to center receive their second dose and that can go home and so as I said, it's a combination of scientific design and practicality for patients.
That's very interesting and it makes a lot of sense. Thanks, and then one more if I might.
David J. Mazzo: And then one more, if I might, and this is sort of a premature question, which a lot of them typically are from people like me, but what would be the optimum business model? You know, once these drugs are approved and, you know, you have different co-administrations of other modalities and so on, what would be the typical business model for that kind of a co-administered program, in terms of who pays and how we divide the funding and all that. Well, who pays is typically insurance companies and sometimes government entities. That's standard. How it's divided up is actually quite simple.
Sort of a premature question, which a lot of them typically are for <unk>.
Like me, but.
What would be the optimal business model.
What these drugs are approved and you have.
Different.
Co administration of other modalities and so on what would be the typical business model for that kind of a co administered.
Program.
In terms of <unk>.
Who pays and divides the funding at all that well, who pays a typically insurance companies and at <unk>.
Sometimes government entities that standard right.
How it's divided up it's actually quite simple even though these products are co administered they're not sold as a bundled product necessarily so we will sell or somebody will sell list one and they will get paid for that and somebody will sell gemcitabine and Nab paclitaxel and they'll get paid from that now.
David J. Mazzo: Even though these products are co-administered, they're not sold as a bundled product necessarily. So we will sell, or somebody will sell, this to one, and they'll get paid for that. And somebody will sell gemcitabine and napaclitaxel, and they'll get paid for that. Now, at some point, there could be arrangements that allow for bundling, so you buy a single package for convenience, or even some sort of combination product that could be developed, which would involve a new product and new regulatory pathways, et cetera. And all of those things are possible. I would suggest that if someone is looking for a metaphor, an analog here to something like this, I would suggest that you go back and look at the case.
Some point.
There could be arrangements that allowed for bundling. So you buy a single package for convenience or even some sort of combination product that could be of ultimately developed which would involve.
Our new product and new regulatory pathways et cetera, and all of those things are possible I would suggest that.
Someone is looking for it.
Metaphor an analog here.
Like this I would suggest that you go back and look at the case its not in oncology, but the business case would be with the similar look at the business case for <unk>, which was sharing plasma cholesterol absorption inhibitor, which was approved as.
David J. Mazzo: It's not an oncology drug, but the business case would be similar. Look at the business case for ezetimibe, which was Schering-Plau's cholesterol absorption inhibitor, which was approved as Zetia, and how that product was used in combination with almost all of the then-approved statins. And then, ultimately, a new product was developed, which is now called Phytorin, which is actually the combination of Simvastatin, Merck's second-generation statin, plus ezetimibe in a single product sold as Phytorin and ultimately became one of the reasons why Merck purchased Chering Plow.
<unk>.
And how that product was used in combination with almost all of the debt approved status.
And then ultimately a new product was developed which is now core cytori, which is actually the combination of simvastatin Merck's second generation statin plus <unk>.
And a single product so thats why tour and ultimately became one of the reasons why Merck purchased Schering plough, but you can see the model there.
Brian Kemp Dolliver: But you can see the model there of how a product that could be used in combination with a variety of other products can be marketed in a variety of different ways and can achieve great commercial success. Thanks, that's very helpful. Thanks, Dave. Thank you, AP. Thank you. One moment for our next question, please. Our next question comes from the line of Kim Dolliver with Brookline Capital Markets. Your line is now open.
Product that can be used in combination with a variety of other products can be marketed in a variety of different ways. It can achieve great commercial success.
Thanks, that's very helpful. Thanks, Dave.
Thank you one moment for our next question. Please.
Our next question comes from the line of Oliver with Brookline Capital markets. Your line is now open.
Brian Kemp Dolliver: Thank you. Thank you. Hi, thanks. And good afternoon. Two or three questions.
Hi, guys. Thanks, Hi, Thanks, and good afternoon.
I have two or three questions.
Brian Kemp Dolliver: Just to close the loop with WARP 9, how long do they have to raise the adequate amount of money to run the trials before you can just contractually walk away and find another entity? There's really, there's nothing contractually in that about a timeline, so it's really something that, again, we approach pragmatically. To the best of our knowledge, they are very close to having all the funding necessary to supply for iGoLista, and they've already, of course, fully funded iLista alone, so we, they're actually pretty efficient at getting to full funding, and it's because they tap a network of, you know, philanthropic organizations and individuals within their region of the world, mostly Australia and New Zealand, who are very interested in supporting the cause.
Just to close the loop with warp nine how long do they have to raise.
Adequate amount of money to run the trials before you can just contractually walk away and find another entity.
There's really there's nothing contractually in that about a timeline. So its really something that again, we approach pragmatically to the best of our knowledge. They are very close to having all of the funding necessary to supply for Iqos.
They've already of course fully funded Idyllist alone. So we they're actually pretty efficient at getting to full funding and it's because they tap a network of philanthropic organizations and individuals within.
Their region of the World, mostly Australia, and New Zealand, who are very interested in supporting the cost.
David J. Mazzo: Okay, that's helpful, thank you. When do you expect you will get your rebates for your Australian activity for this year? It looks like you were paid about $2 million last year in the second quarter.
Okay. That's helpful. Thank you.
And.
When do you expect you will get your.
Rebates for your Australian activity for this year it looks like.
You were paid about $2 million last year in the second quarter.
Brian Kemp Dolliver: Is that a good ballpark, number one? And then, number two, are these... R&D credits included in the runway guidance. So the R&D credits are included in the runway guidance. James, if you're still available, and your connection is working.
Is that a good ballpark number one and number two are these.
R&D credits included in the runway guidance.
So the R&D credits are included in our runway guidance James If you are still available in Europe.
Connection is working could you just jump in please.
James Nisco: Could you just jump in, please? Yes. So, in September, we received $600,000 from the Australian Taxation Office related to the 2022 tax year. And at the end of this year, we did have a million dollars recorded as an income tax receivable. So we typically file our returns in the June-July time frame and then receive the refund around September.
So in September we received 600000 from the Australian tax taxation office that was related to the 2022 tax year.
And at the end of this year, we did have.
Million recorded as an income tax receivable, so we typically see.
While our returns in the June July timeframe, and then receive the refund around the September timeframe.
James Nisco: And that'll be the expectation of about a million in 2024 based on the 2023 tax year. And yes, that is included in our projected capital runway. That's great.
And that'll be the expectation of about a $1 million in.
In 2024 based on the 2023 tax year and yes that is included in our projected capital runway.
Okay.
Brian Kemp Dolliver: And then with regard to Chilu, you know, it looks like you've had some recent communication with them because there was verbiage out versus last quarter regarding the timing of them advancing the program once they have data. And So, I think in the past you said the next milestone from them would be in 2025. Is that still the case? And I think the estimate could be that it would be as much as $10 million.
That's great. Thank you and then with regard to Chile.
It looks like you've had some recent communication with them because there was some.
Verbiage added versus last quarter regarding the timing of them advancing.
The program once they have data.
And.
So.
I think in the past you've said the next milestone from them would be in 2025.
Is that still the case and I think the estimate could be.
As much as $10 million.
David J. Mazzo: So the estimate is correct. Actually, it's not an estimate; it's contractual. At the beginning of phase, when they dose the first patient in phase three or in a registration trial, it's typically a phase three trial in the region. They are contractually obliged to pass a milestone of 10 million U.S. dollars. To the best of our knowledge, they'll be starting phase two at the end of this quarter or early next quarter. And while we don't know the projection of a phase two timeline in China, one could guesstimate that a typical phase two program takes between 18 and 24 months.
So the estimate is correct.
It's not an estimate its contractual set at the beginning phase when they dosed the first patient in phase III or in a registration trial, which is typically a phase III trial in the region.
Okay.
Our contractually obliged to passing a milestone of 10 million U S.
Dollars.
As to the best of our knowledge there'll be starting phase III at the end of this quarter.
Or early next quarter and while we don't know the projection of the phase III.
Timeline in China, but one could guesstimate that a typical phase II program takes between 18 to 24 months. So we're starting now roughly two years from now one might expect that the milestone might be come due but it's all dependent on energy.
David J. Mazzo: So if we're starting now, roughly two years from now, one might expect that the milestone might become due. But it's all dependent on enrollment rate and progression of the development program by Chiru in China. Okay, thank you. And I'll just press on this a little more in case you, Sure. They've indicated anything, but the CFDA has done a pretty good job of replicating many of the accelerated pathways of USDA and
Right and progression.
The development program by Chile, and China.
Okay. Thank you and.
Just press on this a little more in case.
Sure.
The indicated anything but.
The see FDA has done a pretty good job of replicating.
Many of the accelerated pathways of USDA FDA and so.
Brian Kemp Dolliver: And so. Have you heard from Shilu whether or not the CFDA has indicated some eligibility for and Accelerated Pathway if the data hold up? To our knowledge, they have had, that is, Chiluv has had discussions with the Chinese regulatory authorities, and I believe that their program is designed to take maximum advantage of the possibility of an accelerated approval pathway. But we have not been privy to any written, well, we don't read Chinese anyway, but any translated written communications between them that might actually codify that.
Have you heard from Sheila whether or not <unk>.
FDA has indicated some eligibility for.
An accelerated pathway if the data hold up.
To our knowledge. They have that is Chile has had discussions with the Chinese regulatory authorities and I believe that their.
<unk> is designed to take maximum advantage of the possibility of an accelerated approval pathway, but we have not been privy to any written while we don't read Chinese anyway, but any translated the written communications between them.
David J. Mazzo: But that's what we've been told, but they're developing the drug with achieving accelerated approval in mind. Okay, that's reasonable. Thank you so much. Thanks, Kevin. Thank you. This concludes the Q&A portion. I will now turn the call back to Dr. Mazzo for closing remarks. Thank you, Operator, and again, thank you all for participating in today's call. We look forward to speaking with you again during our next quarterly conference call and to continuing to provide updates on our achievements and progress. We remain grateful for your continued interest and support. Stay well and have a good evening. This concludes today's conference call. Thank you for your participation. You may now disconnect. Everyone have a wonderful day.
Actually codify that but that's what we've been told that they're developing with achieving accelerated approval in mind.
Alright, Okay. That's a reasonable thank you so much.
Kevin.
Thank you this.
This concludes the Q&A portion I will now turn the call back to Dr. Zhao for closing remarks.
Thank you operator and again, thank you all for participating in today's call. We look forward to speaking with you again during our next quarterly conference call and to continuing to provide updates on our achievements and progress we remain grateful for your continued interest and support stay well and have a good evening.
This concludes today's conference call. Thank you for your participation you may now disconnect everyone have a wonderful day.
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