Q2 2024 Fulcrum Therapeutics Inc Earnings Call
Good morning and welcome to Fulcrum Therapeutics second quarter 2024 financial results and business update conference call.
Unknown Executive: 2024, Financial Results and Business Update Conference Call. Currently, all participants are in the Sonoma. This call is being webcast live and can be accessed on the investor section of Fulcrum's website at www.fulcrumtx.com. And is being recorded.
Operator: 24, Financial Results and Business Update Conference. Currently, all participants are in a listen-only mode.
Unknown Executive: This call is being webcast live and can be accessed on the investor section of Fulcrum's website at www.fulcrumtx.com and is being recorded. Please be reminded that remarks during this call may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995, including some statements about the company's future expectations and plans, timelines, and financial projections. While these four forward-looking statements represent Fulcrum's views as of today, these should not be relied upon as representative companies' views in the future. Fulcrum may update these statements in the future, but it's not taking on an obligation to do so. Please refer to Fulcrum's most recent filings with the Securities and Exchange Commission for a discussion of certain risks and uncertainties associated with the company's business.
Speaker Change: Currently, all participants are on a listen-only mode. This call is being webcast live and can be accessed on the Investors section of Fulcrum's website at www.fulcrumtx.com and is being recorded.
Mary Marksdorn: Please be reminded that Mary Marksdorn, this call may contain forward-looking statements within the meeting of the Private Securities Litigation Reform Act of 1995. May include statements about the company's future expectations and plans, timelines, and financial projections. While these forward-looking statements represent Fulcrum's views as of today, this should not be relied upon as representing the company's views in the future. Fulcrum may update these statements in the future, but is not taking on an obligation to do so.
Unknown Executive: I think it would be Alan Sapir, CEO and President of Fulcrum. Joining Alex on the call are Alan Musso, Chief Financial Officer; Dr. Pat Horne, Chief Medical Officer; and Dr. Lene Fraser, Senior Vice President of Development. After providing updates on our key programs, there will be a brief Q&A in which Alex, Alan, Pat, and Lane will be available to answer your questions. With that, it's my pleasure to turn the call over to Alex. That's great!
Speaker Change: Please be reminded the remarks during this call may contain forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995.
Speaker Change: made some statements about the company's future expectations and plans, timelines, and financial projections.
Speaker Change: While these four looking statements represent Fulcrum's views as of today.
Speaker Change: This should not be relied upon as representative companies' views in the future.
Speaker Change: Fulcrum may update these statements in the future, but it's not taking on an obligation to do so.
Unknown Executive: Please refer to Fulcrum's most recent filings with the Securities and Exchange Commission for discussion of certain risks and uncertainties of society with the company's principles.
Speaker Change: Please refer to Fulcrum's most recent filings with the Securities and Exchange Commission for discussion of certain risks and uncertainties associated with the company's business.
Unknown Executive: The thing will be Alex Sipir, CEO and President of Fulcrum. Joining Alex on the call are Alan Musso, Chief Financial Officer, Dr. Pat Horn, Chief Medical Officer, and Dr. Lee Faser, Senior Vice President of Development. After providing updates on our key programs, there will be a brief Q&A in which Alex, Alan, Pat, and Mary will be available to answer your questions.
Speaker Change: Speaking today will be Alan Sapir.
Speaker Change: CEO and President of Fulcrum. Joining Alex on the call are Alan Musso, Chief Financial Officer, Dr. Pat Horne, Chief Medical Officer, and Dr. Lene Faser, Senior Vice President of Development.
Speaker Change: After providing updates on our key programs, there will be a brief Q&A in which Alex, Alan, Pat, and Lane will be available to answer your questions. With that, it's my pleasure to turn the call over to Alex.
Alexander Sapir: With that, it's my pleasure to turn the call over to Alex. That's great. Thank you, Lisa, and good morning, everyone, and thanks to all of you for joining us for our second quarter conference call. We've organized today's calls to provide you with updates on recent progress and upcoming milestones for our two clinical stage assets, Los Mappamod and Post-Seredire. And after a brief introduction, we'll segue into our pipeline. I'll then ask Alan to review the financials, and finally, we'll end by taking your questions. I am happy to report that we are on track to report top-line data for the Phase Three REACH trial of Los Mappamod by the end of October, compared to our previous guidance of the fourth quarter.
Alexander C. Sapir: That's great. Thank you, Lisa. And good morning, everyone. And thanks to all of you for joining us on our second quarter conference call. We've organized today's call to provide you with updates on recent progress and upcoming milestones for our two clinical stage assets, Los Mapa Mod and Post-Seer Adair. And after a brief introduction, we'll segue into our pipeline. I'll then ask Alan to review the financials, and finally, we'll end by taking your questions.
Alex: That's great. Thank you, Lisa. And good morning, everyone. And thanks to all of you for joining us for our second quarter conference call.
Alex: We've organized today's call to provide you with updates on recent progress and upcoming milestones for our two clinical stage assets, Los MapaMod and PostSeradare.
Speaker Change: And after a brief introduction, we'll segue into our pipeline, I'll then ask Alan to review the financials, and finally, we'll end by taking your questions.
Alexander C. Sapir: I am happy to report that we are on track to report top-line data for the Phase 3 REACH trial of los mapamad by the end of October, compared to our previous guidance for the fourth quarter. As we advance toward this important inflection point, we continue to build out the team and add talent as we prepare for the potential NDA filing and the U.S. commercial launch of los mapamad. In parallel, we are working with Sanofi in preparation for regulatory filings and the launch of Los Mapa Mods outside of the United States.
Speaker Change: I am happy to report that we are on track to report top-line data for the Phase 3 REACH Trial for Phase 3 REACH. Thank you. Thank you.
Speaker Change: Avlos Maphamad by the end of October compared to our previous guidance of the fourth quarter.
Alexander Sapir: As we advance toward this important inflection point, we continue to build out the team and add talent as we prepare for the potential NDA filing and the US commercial launch of Los Mappamod. In parallel, we are working with Sonofi in preparation for regulatory filings and the launch of Los Mappamod outside of the United States. As a reminder, in May of this year, we announced our collaboration and license agreement with Sonofi for the development and commercialization of Los Mappamod for facioscapulohumeral muscular dystrophy, or FSHD, for sure, for all territories outside of the US. We believe we selected the best possible partner for Los Mappamod, as this collaboration combines Folkram's expertise in FSHD with Sonofi's deep regulatory development and commercial capabilities in neuromuscular markets around the world.
Speaker Change: As we advance toward this important inflection point, we continue to build out the team and add talent as we prepare for the potential NDA filing and the U.S. commercial launch of Los Mapa Mods.
Speaker Change: In parallel, we are working with Sanofi in preparation for regulatory filings and the launch of Los Mapa Mods outside of the United States.
Alexander C. Sapir: As a reminder, in May of this year, we announced our collaboration and license agreement with Sanofi for the development and commercialization of Losmaphimod for fascio-scapulocumaromuscular dystrophy, or FSHD for short, for all territories outside of the U.S. We believe we selected the best possible partner for Los Maffa Mod as this collaboration combines Fulcrum's expertise in FSHD with Sanof Together, we look forward to delivering on our shared commitment to address the high unmet need of patients in the FSHD community.
Speaker Change: As a reminder, in May of this year, we announced our collaboration and license agreement with Sanofi for the development and commercialization of Losmaphimod for fascio-scapulocumaromuscular dystrophy, or FSHD for short, for all territories outside of the U.S.
Speaker Change: We believe we selected the best possible partner for Los Maffa Mod as this collaboration combines Fulcrum's expertise in FSHD with Sanofi's deep regulatory, development, and commercial capabilities in neuromuscular markets around the world.
Alexander Sapir: together we look forward to delivering on our shared commitment to address the high unmet need of patients in the FSHD community.
Speaker Change: Together, we look forward to delivering on our shared commitment to address the high unmet need of patients in the FSHD community.
Alexander Sapir: Let me let me spend a bit more time on Los Mappamond, which, as many of you know, is an oral small molecule, selective P-38 alpha/beta-map kinase inhibitor that inhibits ducts for expression and many of its downstream transcripts and thus prevents muscle cell death in patients with FSHD. An estimated 30,000 patients in the US have FSHD, which is characterized by a slow but relentless loss of muscle function year after year, resulting in significant impairment of upper extremity muscle function and mobility. And while there is a degree of heterogeneity in the onset and disease progression of FSHD, this relentless loss of muscle function means that approximately 20% of patients become wheelchair-bound.
Alexander C. Sapir: Let me spend a bit more time on losmapimod, which, as many of you know, is an oral small molecule selective P38 alpha beta map kinase inhibitor that inhibits ducts for expression and many of its downstream transcripts and thus prevents muscle cell death in patients with FSHD. An estimated 30,000 patients in the U.S. have FSHD, which is characterized by a slow but relentless loss of muscle function year after year, resulting in significant impairment of upper extremity muscle function and mobility. And while there is a degree of heterogeneity in the onset and disease progression of FSHD, this relentless loss of muscle function means that approximately 20% of patients become wheelchair-bound.
Speaker Change: Let me spend a bit more time on losmapimod, which, as many of you know, is an oral small molecule selective P38 alpha-beta map kinase inhibitor that inhibits DUX4 expression and many of its downstream transcripts.
Speaker Change: and thus prevents muscle cell death in patients with FSHD.
Speaker Change: An estimated 30,000 patients in the U.S. have FSHD, which is characterized by a slow but relentless loss of muscle function year after year, resulting in significant impairment of upper extremity muscle function and mobility.
Speaker Change: And while there is a degree of heterogeneity in the onset and disease progression of FSHD, this relentless loss of muscle function means that approximately 20% of patients become wheelchair-bound.
Alexander Sapir: Think it's important to remind everyone that there are currently no approved therapies for FSHD and no drugs used off-label to help these patients.
Alexander C. Sapir: I think it's important to remind everyone that there are currently no approved therapies for FSHD and no drugs used off-label to help these patients. Now, let's turn our attention to our Phase 3 Registrational Trial called REACH, which I spoke about earlier. As a reminder, REACH is a 48-week Phase 3 trial intended to be registration-enabling both here in the U.S. and in ex-U.S. geography. In September of last year, we completed enrollment in REACH with a total of 260 patients.
Speaker Change: I think it's important to remind everyone that there are currently no approved therapies for FSHD and no drugs used off-label to help these patients.
Alexander Sapir: Now let's turn our attention to our phase three registrational trial called REACH, which I spoke about earlier. As a reminder, REACH is a 48-week phase three trial intended to be registration enabling both here in the US and in XUS geographies. In September of last year, we completed enrollment in REACH with a total of 260 patients. As presented at the 31st Annual FSHD Society International Research Congress in June of this year, baseline characteristics of the REACH study population are similar to those of our Phase Two Redux IV study population. Building on the encouraging clinical benefit and favorable tolerability observed in our Redux IV trial, the primary endpoint for the REACH study is the change from baseline in the relative surface area or RSA, which is a quantitative assessment of reachable workspace and has been shown to correlate with disease severity and progression.
Speaker Change: Now, let's turn our attention to our Phase 3 Registrational Trial called REACH, which I spoke about earlier. As a reminder, REACH is a 48-week Phase 3 trial intended to be registration-enabling both here in the U.S. and in ex-U.S. geographies.
Speaker Change: In September of last year, we completed enrollment in REACH with a total of 260 patients.
Alexander C. Sapir: As presented at the 31st Annual FSHD Society International Research Congress in June of this year, baseline characteristics of the REACH Study Population are similar to those of our Phase II Redux IV Study Population. Building on the encouraging clinical benefit and favorable tolerability observed in our Redux IV trial, the primary endpoint for the REACH study is the change from baseline in the Relative Surface Area, or RSA, which is a quantitative assessment of reachable workspace and has been shown to correlate with disease severity and progression. RSA is a measure of upper extremity range of motion and muscle function that specifically evaluates shoulder and arm mobility using 3D motion sensor technology and is indicative of the ability to perform activities of daily living.
Speaker Change: As presented at the 31st Annual FSHD Society International Research Congress in June of this year, baseline characteristics of the REACH study population are similar to those of our Phase II Redux IV study population.
Speaker Change: Building on the encouraging clinical benefit and favorable tolerability observed in our Redux IV trial, the primary endpoint for the REACH study is the change from baseline in the Relative Surface Area, or RSA, to a new baseline in the Redux IV trial.
Speaker Change: Which is a quantitative assessment of reachable workspace and has been shown to correlate with disease severity and progression.
Alexander Sapir: RSA is a measure of upper extremity range of motion and muscle function that specifically evaluates shoulder and arm mobility using 3D motion sensor technology and is indicative of the ability to perform activities of daily living. Based on collaborative interactions with the Clinical Outcomes Assessment or COA group at FDA, we are further assessing the extent to which a specific change in the RSA score is meaningful to patients. I'm pleased to report that we are on track to complete the activities agreed upon with the FDA at the time of reporting the REACH top-line data. Additional key secondary endpoints in REACH include muscle fat infiltration or MFI, which is a marker of disease pathology measured by whole body MRI, shoulder dynamometry, and patient global impression of change or PJEC for short.
Speaker Change: RSA is a measure of upper extremity range of motion and muscle function that specifically evaluates shoulder and arm mobility using 3D motion sensor technology and is indicative of the ability to perform activities of daily living.
Alexander C. Sapir: Based on collaborative interactions with the Clinical Outcomes Assessment, or COA, group at FDA, we are further assessing the extent to which a specific change in the RSA score is meaningful to patients. I'm pleased to report that we are on track to complete the activities agreed upon with the FDA at the time of reporting the REACH top-line data. Additional key secondary endpoints in REACH include muscle fat infiltration, or MFI, which is a marker of disease pathology measured by whole body MRI, shoulder dynamometry, and patient global impression of change, or PGIC for short.
Speaker Change: Based on collaborative interactions with the Clinical Outcomes Assessment, or COA, group at FDA, we are further assessing the extent to which a specific change in the RSA score is meaningful to patients.
Speaker Change: I'm pleased to report that we are on track to complete the activities agreed upon with the FDA at the time of reporting the REACH top-line data.
Speaker Change: Additional key secondary endpoints in REACH include muscle fat infiltration or MFI, which is a marker of disease pathology measured by whole body MRI,
Speaker Change: Shoulder Dynamometry, and Patient Global Impression of Change, or PGIC for short.
Alexander Sapir: We believe that the implementation of self-reported quality of life measures and healthcare utilization questionnaires will help inform our payer strategy as we begin preparing for a commercial launch to deliver the first FFSHD treatment for patients. We are now progressing toward the completion of the 48-week treatment phase of the trial for all enrolled patients. As of June 30th, 2024, of the 234 out of the 260 who completed the 48-week treatment phase, 232 of those, or 232 of those patients, or 98% chose to enroll in Part B, the open label extension of the study, in which all patients received drug.
Alexander C. Sapir: We believe that the implementation of self-reported quality-of-life measures and healthcare utilization questionnaires will help inform our payer strategy as we begin preparing for a commercial launch to deliver the first FSHD treatment for patients. We are now progressing toward the completion of the 48-week treatment phase of the trial for all enrolled patients. As of June 30, 2024, of the 234 out of the 260 who completed the 48-week treatment phase, 232 of those patients, or 98%, chose to enroll in Part B, the open-label extension of the study in which all patients received drugs.
Speaker Change: We believe that the implementation of self-reported quality-of-life measures and healthcare utilization questionnaires will help inform our payer strategy as we begin preparing for a commercial launch to deliver the first FSHD treatment for patients.
Speaker Change: We are now progressing toward the completion of the 48-week treatment phase of the trial for all enrolled patients.
Speaker Change: As of June 30, 2024, of the 234 out of the 260 who completed the 48-week treatment phase,
Speaker Change: 232 of those or 232 of those patients or 98% chose to enroll in Part B, the open label extension of the study in which all patients receive drugs.
Alexander Sapir: This very high percentage of patients opting to move into the open label phase is similar to what was observed in our Phase II clinical trial, and we believe is indicative of the high unmet need for patients with FSHD. Again, we are on track to report top-line data by the end of October, which will bring us one step closer to delivering the first-ever FDA-approved therapy for FSHD patients.
Alexander C. Sapir: This very high percentage of patients opting to move into the open-label phase is similar to what was observed in our Phase II clinical trial and we believe is indicative of the high unmet need for patients with FSHD. Again, we are on track to report top-line data by the end of October, which will bring us one step closer to delivering the first-ever FDA-approved therapy for FSHD patients. Now, let's talk a little bit about Posiridir, which is our oral HBF inducer for the potential treatment of patients with sickle cell disease.
Speaker Change: This very high percentage of patients opting to move into the open-label phase is similar to what was observed in our Phase II clinical trial, and we believe is indicative of the high unmet need for patients with FSHD.
Speaker Change: Again, we are on track to report top-line data by the end of October , which will bring us one step closer to delivering the first-ever FDA-approved therapy for FSHD patients.
Alexander Sapir: Now, let's talk a little bit about posterior deer, which is our oral HPF inducer for the potential treatment of patients with sickle cell disease. The elevation of HPF or fetal hemoglobin is a clinically validated therapeutic rationale for sickle cell disease, a lifelong inherited blood disorder that severely impairs quality of life for approximately 100,000 people in the US, and approximately 4.4 million people worldwide. Making sickle cell disease one of the most prevalent non-malignant hematologic diseases. Historically, the standard treatment for sickle cell disease has included blood transfusion, pain medication, and hydroxyurea that focus only on symptom relief.
Speaker Change: Now, let's talk a little bit about Posiridir, which is our oral HPF inducer for the potential treatment of patients with sickle cell disease.
Alexander C. Sapir: The elevation of HBF or fetal hemoglobin is a clinically validated therapeutic rationale for sickle cell disease, a lifelong inherited blood disorder that severely impairs the quality of life for approximately 100,000 people in the US and approximately 4.4 million people worldwide, making sickle cell disease one of the most prevalent nonmalignant hematologic diseases. Historically, the standard treatment for sickle cell disease has included blood transfusions, pain medications, and hydroxyurea that focus only on symptom relief.
Speaker Change: The elevation of HBF, or fetal hemoglobin, is a clinically validated therapeutic rationale for sickle cell disease.
Speaker Change: A lifelong inherited blood disorder that severely impairs quality of life for approximately 100,000 people in the U.S. and approximately 4.4 million people worldwide, making sickle cell disease one of the most prevalent nonmalignant hematologic diseases.
Speaker Change: Historically, the standard treatment for sickle cell disease has included blood transfusion, pain medications, and hydroxyurea that focus only on symptom relief.
Alexander Sapir: While exciting scientific progress has enabled the advancement, and more recently, the approval of gene editing therapeutic approaches, we believe there remains a high unmet need for an oral therapeutic option that is broadly protective of sickle cell disease symptomatology. As a first-in-class oral small molecule HPF inducer, we believe posterior deer has the potential to address this unmet need. Turning out to our Phase I B clinical trial, the Pioneer trial, we continue to make progress. Given that many of the sites we are newly activating are academic sites here in the US, as well as outside the US, both of which have long site activation lead times.
Alexander C. Sapir: While exciting scientific progress has enabled the advancement and, more recently, the approval of gene-editing therapeutic approaches, we believe there remains a high unmet need for an oral therapeutic option that is broadly protective of sickle cell disease symptomatology. As a first-in-class oral small-molecule HBF inducer, we believe Posteridare has the potential to address this need. Turning now to our Phase 1b clinical trial, the Pioneer Trial, we continue to make progress. However, given that many of the sites we are newly activating are academic sites here in the U.S., as well as outside the U.S., both of which have long site activation lead times, together with our narrower inclusion-exclusion criteria, it is taking longer than initially expected.
Speaker Change: While exciting scientific progress has enabled the advancement, and more recently, the approval of gene editing therapeutic approaches, we believe there remains a high unmet need for an oral therapeutic option that is broadly protective of sickle cell disease symptomatology.
Speaker Change: As a first-in-class oral small molecule HBF inducer, we believe Posteridair has the potential to address this unmet need.
Speaker Change: Turning now to our Phase 1b clinical trial, the Pioneer Trial, we continue to make progress.
Speaker Change: Given that many of the sites we are newly activating are academic sites here in the U.S. as well as outside the U.S.,
Alexander Sapir: Together with our narrower inclusion-exclusion criteria, it is taking longer than initially expected. We expect to have study data to share with everyone in 2025. As a reminder, cohort three of the Phase I B trial will evaluate posterior deer at the 12 milligram once daily dose with a dosing duration of three months, followed by cohort four at the 20 milligram once daily dose also for three months. Both cohorts are expected to enroll approximately 10 patients each. We look forward to building on the encouraging clinical data obtained prior to the clinical hold, which demonstrated that posterior deer increased total fetal hemoglobin of a magnitude that could translate into a meaningful improvement in disease severity.
Speaker Change: Both of which have long site activation lead times, together with our narrower inclusion-exclusion criteria, it is taking longer than initially expected.
Alexander C. Sapir: We expect to have study data to share with everyone in 2025. As a reminder, Cohort 3 of the Phase 1b trial will evaluate posterior at the 12 milligram once daily dose with a dosing duration of three months, followed by Cohort 4 at the 20 milligram once daily dose, also for three months. Both cohorts are expected to enroll approximately 10 patients each. We look forward to building on the encouraging clinical data obtained prior to the clinical hold, which demonstrated that post-serodera increased total fetal hemoglobin of a magnitude that could translate into a meaningful improvement in disease severity.
Speaker Change: We expect to have study data to share with everyone in 2025.
Speaker Change: As a reminder, Cohort 3 of the Phase 1b trial will evaluate posterodear at the 12mg once daily dose with a dosing duration of 3 months, followed by Cohort 4 at the 20mg once daily dose also for 3 months.
Speaker Change: Both cohorts are expected to enroll approximately 10 patients each.
Speaker Change: We look forward to building on the encouraging clinical data obtained prior to the clinical hold, which demonstrated that post-serodera increased total fetal hemoglobin of a magnitude that could translate into a meaningful improvement in disease severity.
Alexander Sapir: These interim results of the Phase I B trial involving 16 patients were recently reported in June at the EHA conference in Madrid and were very well received by the medical community. We believe that posterior deer as an oral HPF inducer has the potential to provide a differentiated therapeutic option for people living with sickle cell disease. And addressing the significant unmet need in the sickle cell disease community remains a key priority for us. Yes.
Alexander C. Sapir: These interim results of the Phase 1b trial involving 16 patients were recently reported in June at the EHA conference in Madrid and were very well received by the medical community. We believe that Posiridir as an oral HPF inducer has the potential to provide a differentiated therapeutic option for people living with sickle cell disease, and addressing the significant unmet need in the sickle cell disease community remains a key priority for us.
Speaker Change: These interim results of the Phase 1b trial involving 16 patients were recently reported in June at the EHA conference in Madrid and were very well received by the medical community.
Speaker Change: We believe that Posiridir, as an oral HBF inducer, has the potential to provide a differentiated therapeutic option for people living with sickle cell disease, and addressing the significant unmet need in the sickle cell disease community remains a key priority for us.
Alan A. Musso: So with that update on the business, let me now turn it over to our Chief Financial Officer, Alan Musso, to run through the financials.
Alan Musso: So, with that update on the business, let me now turn it over to our Chief Financial Officer, Alan Musso, to run through the financials. Alan, over to you.
Alan A. Musso: So, with that update on the business, let me now turn it over to our Chief Financial Officer, Alan Musso, to run through the financials.
Alan Musso: Thanks, Alan.
Alan Musso: I'll now go over our results for the second quarter and the June 30th, 2024. Let me start with our cash position. As of June 30th, 2024, cash, cash equivalent, and $2.2 million as of December 31st, 2023. The increase in our cash position is due to the $80 million upfront payment received from Santa Fe in the second quarter of 2024, partially offset by cash used to fund our operating activities in the first half of the year. Collaboration revenue was $80 million for the second quarter of 2024 compared to $0.9 million for the second quarter of 2023.
Alan A. Musso: I'll now go over our results for the second quarter ended June 30th, 2020. First, let me start with our cash position.
Alan: Alan, over to you.
Alan A. Musso: I thank Alex. I'll now go over our results for the second quarter ended June 30th, 2024.
Alan A. Musso: As of June 30, 2024, cash, cash equivalents, and marketable securities were $273.8 million, as compared to $236.2 million as of December 31, 2023. The increase in our cash position is due to the $80 million upfront payment received from Sanofi in the second quarter of 2024, partially offset by cash used to fund our operating activities in the first half of the year. Collaboration revenue was $80 million for the second quarter of 2024, compared to $0.9 million for the second quarter of 2023.
Alan A. Musso: Let me start with our cash position. As of June 30, 2024, cash, cash equivalents, and marketable securities were $273.8 million, as compared to $236.2 million as of December 31, 2023.
Speaker Change: The increase in our cash position is due to the $80 million upfront payment received from Sanofi in the second quarter of 2024, partially offset by cash used to fund our operating activities in the first half of the year.
Speaker Change: Collaboration revenue was $80 million for the second quarter of 2024, compared to $0.9 million for the second quarter of 2023.
Alan Musso: The increase of $79.1 million was primarily due to recognition of the $80 million upfront payment received from Santa Fe during the second quarter of 2024. Our research and development expenses were $17.3 million for the second quarter of 2024 compared to $17.8 million for the second quarter of 2023. The decrease of $0.5 million was primarily due to the partially offset by increased cash related to the advancements of the reach trial. The general administrative expenses were $10.2 million for the second quarter of 2024 compared to $10.3 million for the second quarter of 2023, and the $1.1 million decrease was primarily due to lower employee compensation costs.
Alan A. Musso: The increase of $79.1 million was primarily due to recognition of the $80 million upfront license payment received from Santa Fe during the second quarter of 2024. Our research and development expenses were $17.3 million for the second quarter of 2024 compared to $17.8 million for the second quarter of 2023. The decrease of $0.5 million was primarily due to the Los Mapa Mod global development cost sharing reimbursement from Sanofi, partially offset by increased costs related to the advancement of the REACH trial.
Speaker Change: The increase of $79.1 million was primarily due to recognition of the $80 million upfront license payment received from Santa Fe.
Alan A. Musso: The general administrative expenses were $10.2 million for the second quarter of 2024, compared to $10.3 million for the second quarter of 2023, and at one point, the 0.1 million decrease was primarily due to lower employee compensation. For the second quarter of 2024, we had a net income of $55.4 million, compared to a net loss of $23.8 million for the second quarter of 2023. For the foreseeable future, excluding the potential for future milestone payments under our Sanofi collaboration.
Speaker Change: during the second quarter of 2024.
Speaker Change: Our research and development expenses were $17.3 million for the second quarter of 2024 compared to $17.8 million for the second quarter of 2023.
Speaker Change: The decrease of $0.5 million was primarily due to the Los Mapa Mod global development cost-sharing reimbursement from Sanofi, partially offset by increased costs related to the advancement of the REACH trial.
Speaker Change: The general administrative expenses were $10.2 million for the second quarter of 2024, compared to $10.3 million for the second quarter of 2023, and the $0.1 million decrease was primarily due to lower employee compensation costs.
Alan Musso: For the second quarter of 2024, we had net income of $55.4 million compared to a net loss of $23.8 million for the second quarter of 2023. For the foreseeable future, excluding the potential for future milestone payments under Santa Fe's collaboration, we expect to be in a loss position, including for the year end is December 31, 2024.
Speaker Change: Transcribed by https://otter.ai
Speaker Change: For the second quarter of 2024, we had net income of $55.4 million compared to a net loss of $23.8 million for the second quarter of 2023.
Speaker Change: For the foreseeable future, excluding the potential for future milestone payments under our Santa Fe collaboration, we expect to be in a lost position, including for the year ended December 31st, 2024.
Alan Musso: And finally, turning to our cash runway guidance based on our current operating plans, we continue to expect that our existing cash, cash prevalence, and marketable securities will be sufficient to fund our operating requirements into 2027.
Alan A. Musso: We expect to be in a loss position, including for the year ended December 31st, 2024. And finally, turning to our cash runway guidance, based on our current operating plans, we continue to expect that our existing cash, cash equivalents, and marketable securities will be sufficient to fund our operating requirements into 2025. And with that, let me turn the call back over to Alex.
Speaker Change: And finally, turning to our cash runway guidance, based on our current operating plans, we continue to expect that our existing cash, cash equivalents, and marketable securities will be sufficient to fund our operating requirements into 2027.
Alexander Sapir: And with that, let me turn the call back over to Alex. Great. Thanks so much, Alan.
Alexander C. Sapir: Great. Thanks so much, Alan. So, with that overview of the business and the financials, Lisa, let's go ahead and open it up to questions.
Unknown Executive: So, with that overview of the business and the financials, Lisa, let's go ahead and open it up for questions. Thank you.
Speaker Change: And with that, let me turn the call back over to Alex. Great. Thanks so much, Alan. So with that overview of the business and the financials, Lisa, let's go ahead and open it up for questions.
Operator: Thank you. At this time, if you would like to ask a question, please press star 11 on your telephone. You will then hear a message advising that your hand is raised. If you'd like to remove yourself from the queue, please press star 11 again. We also ask that you wait for your name and company to be announced before proceeding with your question. And our first question will come from Corinne Johnson of Goldman Sachs. Your line is open.
Unknown Executive: At this time, if you would like to ask a question, please press star 11 on your telephone. You will then hear a message advice that your hand is raised. If you'd like to remove yourself from the queue, please press Star 11 again. We also ask that you wait for your name and company to be announced before you proceed with your question.
Lisa: Thank you. At this time, if you would like to ask a question, please press star 11 on your telephone. You will then hear a message advise that your hand is raised. If you'd like to remove yourself from the queue, please press star 11 again.
Speaker Change: We also ask that you wait for your name and company to be announced before you proceed with your question. And our first question will come from Corinne Johnson of Goldman Sachs. Your line is open.
Corinne Jenkins: And our first question will come from Corinne Johnson of Roman Facts. Your line is open. Maybe first, it's for such the work that you're doing to validate original workspace for the agency. It has agency-certified like specific metrics that are most important or the magnitude of change, like the change of the benefit they'd like to see or they're just asking for general proof that they reach a potential. And then, are there more? and I'll see if they requested them to do all sort of have to go in the same direction.
Corinne Jenkins: Maybe first, with respect to the work that you're doing to validate Reachable Workspace for the agency, has the agency specified specific metrics that are most important, or the magnitude of change, like the change or the benefit they'd like to see, or are they just asking for general proof that Reachable Workspace is clinically beneficial? And then, are there multiple analyses that they requested, and do they all have to go in the same direction? And then, my other question would just be, in terms of the cash-run-like items you just provided for 27, what specific clinical milestones and then commercial activities would you like to see?
Corinne Jenkins: Maybe first, with respect to the work that you're doing to validate reachable workspaces for the agency, has the agency specified specific metrics that are most important?
Corinne Jenkins: [inaudible]
Alexander Sapir: And then my other question would just be, in terms of the cash run, my items you just provided into 27, what specific clinical milestones and then commercial activities. Thanks. Yeah, it's great. Thanks, Corinne. Thanks for the question. And if there are any more follow-up questions, maybe just speak up a little bit. You were a little bit difficult to hear. I think in terms of your questions around the workspace and some of the work we're doing to prove out the clinical meeting. I mean, clinical meaningfulness of that work.
Corinne Jenkins: And then my other question would just be in terms of the cash run like items you just provided into 27 What specific like clinical milestones and then commercial activity?
Alexander C. Sapir: Yeah, it's great. Thanks, Corinne. And thanks for the question. And if there are any more follow-up questions, maybe just speak up a little bit. You were a little bit difficult to hear, I think in terms of your questions around Reachable Workspace and some of the work we're doing to prove out the clinical meaningfulness of that work. I'll turn that one over to Iain, and then I'll ask Alan to provide an update on your question around Yes, sure. Thanks.
Speaker Change: Yeah, it's great. Thanks, Corinne, and thanks for the question. And if there are any more follow-up questions, maybe just speak up a little bit. You were a little bit difficult to hear. I think in terms of your questions around Reachable Workspace and some of the work we're doing to prove out the clinical meaningfulness of that work,
Iain Fraser: I'll turn that one over to Ian, and then I'll ask Alan to provide an update on your question around the financial. So Ian. Yeah, sure. Thanks, Corinne. So since the reachable workspace has not previously been used for any approvals, there are no pre-established criteria. And so there, there has not been a numerical criterion put forward by the agencies for this, and the work we are doing is in order to evaluate that across a range of different approaches leading towards an understanding of the meaningful score difference, which is the FDA term for a change within a given patient that is considered meaningful.
Speaker Change: I'll turn that one over to Iain, and then I'll ask Alan to provide an update on your question around the finances.
Iain Fraser: Yeah, sure. Thanks, Corinne.
Iain Fraser: So, since the reachable workspace has not previously been used for any approvals, there are no pre-established criteria. Consequently, there has not been a numerical criterion put forward by the agencies for this. And the work we are doing is in order to evaluate that across a range of different approaches leading towards an understanding of the meaningful score difference, which is the FDA term for a change within a given patient that is considered meaningful. So, as I say, there is no pre-specified numerical value for that, and the results coming out of the work that we are doing will inform.
Ian: Yes, sure. Thanks, Corinne. So since the Reachable Workspace has not previously been used for any approvals, there are no pre-established criteria, and so there has not been a numerical criterion.
Speaker Change: Put forward by by the agencies for this and the work we are doing is in order to evaluate that
Speaker Change: across a range of different approaches leading towards an understanding of the meaningful score difference, which is the FDA term for a change within a given patient that is considered meaningful.
Iain Fraser: So, as I say, there is no pre-specified numerical value for that, and the work coming out of the results coming out of the work that we are doing will inform that.
Speaker Change: So, as I say, there is no pre-specified numerical value for that, and the results coming out of the work that we are doing will inform that.
Alan Musso: And then, Alan, maybe toward the second question that Corinne had? Yeah, sure, Corinne. Good morning. Yeah, the cash runway guidance that we're giving that does anticipate a full sort of success scenario. So it funds the sort of further development of filing and commercialization of Los Mappin Vod. It also funds the completion of the ongoing procedure trial, as well as the follow-up trial that we anticipate, and funds pre-clinical work that we have ongoing, for which we expect it will have new products entering into the clinic from that work. So it's sort of all in what we anticipate with the current portfolio of continued advancement.
Alan A. Musso: And then, Alan, maybe toward the second question that Corinne had. Yeah, sure, Corinne. Good morning.
Alan: And then, Alan, maybe toward the second question that Corinne had. Yeah, sure, Corinne. Good morning. Yeah, the cash runway guidance that we're giving that does anticipate a whole sort of success scenario. So it funds the sort of further development, filing and commercialization of Los Mapa Mods. It also funds the completion of the ongoing posterior trial, as well as the follow up trial that we anticipate.
Alan A. Musso: Yeah, the cash runway guidance that we're giving that does anticipate a whole sort of success scenario, so it funds the sort of further development, filing, and commercialization of Los Mapa Mods. It also funds the completion of the ongoing posterity of the trial, as well as the follow-up trial that we anticipate and funds preclinical work that we have ongoing, for which we expect that we'll have new products entering the clinic from that work. So it's, you know, sort of all in what we anticipate with the current portfolio that we continue to develop.
Alan: and funds preclinical work that we have ongoing for which we expect that we'll have new products entering into the clinic from that work. So it's, you know, sort of all in what we anticipate with the current portfolio of continued advancement.
Corinne Jenkins: Thanks. Sorry for the audio quality. No worries. Thanks, Corinne.
Alexander C. Sapir: Sorry for the audio quality. No worries. Thanks, Corinne. Lisa, next question.
Unknown Executive: Lisa, next question. Thank you.
Alan: Thanks. Sorry for the audio quality. No worries. Thanks, Corinne. Lisa, next question?
Kristen Kluska: And our next question will be coming from the line of Kristen Kruzok of Cantor Fitzgerald. Your line is open. Hi. Good morning, everybody. Thanks for all the transparency and extra guidance today. So, on reasonable workspace, we've been getting a lot of questions just because another company also had data on this. And to your point, given it really is a new end point and hasn't been previously used for approval. Wondering now that we have two data sets supporting the end point, if this helps in your opinion, the risk, this end point for this disease. Yeah, that's great.
Operator: And our next question will be coming from the line of Kristen. Ms. Kluska of Cantor Fitzgerald, your line is open.
Speaker Change: Thank you.
Speaker Change: And our next question will be coming from the line of Kristin.
Speaker Change: Kluska of Cantor Fitzgerald, your line is open.
Kristen Kluska: Hi, good morning, everybody. Thanks for all the transparency and extra guidance today. So on Reachable Workspace, we've been getting a lot of questions just because another company also had data on this. And to your point, given it really is a new endpoint and hasn't been previously used for approvals, I was wondering, now that we have two data sets supporting the endpoint, if this helps, in your opinion, de-risk this end
Kristen: Hi, good morning, everybody. Thanks for all the transparency and extra guidance today.
Speaker Change: So on Reachable Workspace, we've been getting a lot of questions just because another company also had data on this.
Speaker Change: To your point, given it really is a new endpoint and hasn't been previously used for approvals, wondering now that we have two data sets supporting the endpoint, if this helps, in your opinion, de-risk this endpoint for this disease?
Alexander C. Sapir: Yeah, that's great. Hi Kristen, and thanks for the question. I think to answer that, I'll turn it over again to Iain.
Kristen Kluska: Hi, Kristen. And thanks for the question.
Iain Fraser: I think to answer that, I'll turn it over again to Ian. Yeah, thanks. Thanks, Kristen. I think it is encouraging for us to see that others are using this particular end point in FHC. We certainly have hints from the agency that that's the case; that they're hearing about this as we engage with them around our discussions around reachable work. Space, and I think it also reinforces the point that we've made previously that we haven't been suggested an alternative primary endpoint in Office HD. So I think we're overall encouraged by those reports that have been coming out.
Speaker Change: Yeah, that's great. Hi, Kristen, and thanks for the question. I think to answer that, I'll turn it over again to Iain.
Iain Fraser: Yeah, thanks. Thanks, Kristen.
Ian: Yeah, thanks. Thanks, Kristen. I think it is encouraging for us to see that others are using this particular endpoint in FSHD. We've certainly had hints from the agency that that's the case that they're hearing about this as we engage with them around our discussions around reachable workspace.
Iain Fraser: I think it is encouraging for us to see that others are using this particular endpoint in FSHD. We've certainly had hints from the agency that that's the case that they're hearing about this as we engage with them in our discussions around reachable workspace. And I think it also reinforces the point that we've made previously that we haven't been suggested an alternative primary endpoint in FSHD. So I think we're overall encouraged by those reports that have Yes, and
Speaker Change: And I think it also reinforces the point that we've made previously that we haven't been suggested an alternative primary end point in AFIS-HD. So I think we're overall encouraged by...
Alexander C. Sapir: Yeah, and the thing I would add, Kristen, this is Alex. And you mentioned some other data that had recently been published or reported out. I assume you're referring to the AVIDITY data. I think what the AVIDITY data does is it certainly validates not only the DUX4 pathway, but more specifically to your question, reachable workspace as the clinical endpoint. We believe that many of the registrational trials that will come after us will have this as part of their primary endpoint.
Speaker Change: by those those reports that have been coming out.
Alexander Sapir: Yeah, and the thing I would add, Kristen, this is Alex, and you had mentioned some other data that he has recently been published or reported out. I assume you're referring to the Ovidity data. I think what the Ovidity Data does is it's certainly validates not only the ducts for pathway, but more specifically to your question, reachable workspace. As the clinical endpoint, we believe that many of the regional trials that will come after us will be required as part of their primary endpoint. Okay, appreciate that.
Alex: Yeah, and the thing I would add, Kristen, this is Alex, is, and you had mentioned some other data that had recently been published or reported out, I assume you're referring to the AVIDITY data. I think what the AVIDITY data does is it certainly...
Kristen: validates not only the DUX4 pathway but more specifically to your question.
Speaker Change: Reachable Workspace as the clinical endpoint, we believe that many of the registrational trials that will come after us will be required as part of their primary endpoint.
Kristen Kluska: Okay, appreciate that. And then, assuming that the trial is successful, when you plan to meet with the FDA, can you just remind us first what the safety data set is, including from the previous company that had studies in other indications? And then second, how much open-label extension data you're going to have from phase two at that point to add to the pool of evidence?
Alexander Sapir: And then, assuming that the trial is successful, when you plan to be with the FDA, can you just remind us first what the safety data set is, including from the previous company that had studies in other indications. And then second, how much open label extension data you're going to have from phase two at that point to add on to the pool of evidence. Thanks so much again. Yeah, thanks, Kristen. Maybe I'll take the first question. I'll turn the second question over to you. Yeah, I think that is really one of the truly unique things about Loach Mavimut.
Kristen: Okay, appreciate that. And then, assuming that the trial is successful, when you plan to meet with the FDA, can you just remind us first what the safety data set is, including from the previous
Kristen Kluska: Thanks so much again. Yeah.
Ian: company that had studies in other indications. And then second, how much open label extension data you're going to have from phase two at that point to add on to the pool of evidence. Thanks so much again. Yeah, thanks, Kristen. Maybe I'll take the first question. I'll turn the second question over to Ian. Yeah, I think that is really one of the truly unique things about Lodz-Mavimat. I don't know if this is unprecedented, but we will be filing our new drug application with a patient safety database that includes over 3,600 patients. So I think for a rare disease such as FSHD with a prevalence of 30,000 to have 3,600 patients in the patient safety database is quite remarkable.
Alexander C. Sapir: Yeah, thanks, Kristen. Maybe I'll take the first question. I'll turn the second question over to Ian.
Alexander C. Sapir: Yeah, I think that is really one of the truly unique things about Lodz-Mahabimad. I don't know if this is unprecedented, but we will be filing our new drug application with a patient safety database that includes over 3,600 patients. So I think for a rare disease such as FSHD with a prevalence of 30,000, to have 3,600 patients in the patient safety database is quite remarkable. And I think one of the encouraging signs is that the drug does have a fairly sort of unremarkable AE profile, and we've demonstrated that in our Redux 4 study and expect to replicate that in our REACH study. And then, Alan, sorry, Ian, maybe to Kristen's second question. Yeah, so,
Alexander Sapir: I don't know if this is unprecedented, but we will be filing our new drug application with a patient safety database that includes over 3,600 patients. So I think for rare disease, such as FSHD with a prevalence of 30,000, to have 3,600 patients in the patient safety database is quite remarkable. And I think one of the encouraging signs is the drug does have a fairly sort of unremarkable AE profile. We demonstrated that in our in our in our Redux IV study and expect to replicate that in our in our reach study.
Ian: I think one of the encouraging signs is the drug does have a fairly sort of unremarkable AE profile, and we've demonstrated that in our Redux 4 study and expect to replicate that in our REACH study. And then Alan, sorry, Iain, maybe to Kristen's second question.
Alan Musso: And then Alan, sorry, maybe to Kristen's second question. Yeah, so we'll have data from the Redux IV Phase Two study. Remember that enrolled 80 patients, and there's been a high rate of retention in the open label extension of that study, now up to exceeding three years of exposure in some of those patients, the ones that were enrolled at the very earliest in that study. We have about 11 patients in a separate open-label study in Europe that also has a prolonged duration of treatment. And then in the reach study itself, there are 260 patients. And as Alex mentioned in the original remarks, a very high proportion of those are electing to roll over into the open label extension.
Iain Fraser: Yeah, so we'll have data from the Redux 4 Phase 2 study. Remember that it enrolled 80 patients, and there was a high rate of retention in the open-label extension of that study, now up to exceeding three years of exposure in some of those patients, the ones that were enrolled at the very earliest in that study. We have about 11 patients in a separate open-label study in Europe that also has a prolonged duration of treatment.
Ian: Yeah, so we'll have...
Ian: Data from the Redux.
Ian: for Phase 2 study. Remember that enrolled
Ian: 80 patients and there's been a high rate of retention in the open label extension of that study.
Speaker Change: are now up to exceeding three years of exposure in some of those patients, the ones that were enrolled at the very earliest in that study. We have about
Alex: 11 patients in a separate open-label study in Europe that also has a prolonged duration of treatment and then in the REACH study itself there are 260 patients and as Alex mentioned in the original remarks
Iain Fraser: And then in the REACH study itself, there are 260 patients, and as Alex mentioned in the original remarks, a very high proportion of those are electing to roll over into the open label extension. And so they will continue to experience exposure to LASMAP-MOD as we move towards filing. Thus, there is not only a large safety database from other indications that preceded the work that we had done but also a large and growing safety database for this relatively rare disease.
Alex: A very high proportion of those are electing to roll over into the open-label extension, and so they will continue to experience exposure to
Alan Musso: And so they will continue to experience exposure to the last map a month as we move towards filing. So there there there is not only a large safety database from other indications that preceded the work that we had done, but also a large and growing safety database for this relatively erect.
Alex: to Last Map of Mark as we move towards filing.
Speaker Change: So, there is not only a large safety database from other indications that preceded the work that we had done, but also a large and growing safety database for this relatively rare disease.
Unknown Executive: and Edward Tenthoff.
Unknown Executive: Thank you. That's great.
Operator: Thank you. That's great. Thanks, Kristen. Lisa, next question.
Unknown Executive: Thanks, Kristen. Lisa, next question?
Unknown Executive: Thank you.
Alex: Thank you. That's great. Thanks, Kristen. Lisa, next question. Thank you.
Joseph Schwartz: And our next question will be coming from the line of Joseph Schwartz of Leverick Partners.
Joseph Patrick Schwartz: And our next question will be coming from the line of Joseph Schwartz, of Leverett Partners.
Alex: And our next question will be coming from the line of Joseph Schwartz.
Joseph Schwartz: All right. Thanks for the update. Sorry.
Joseph Patrick Schwartz: Hi, thanks for the updates. Sorry.
Joseph Patrick Schwartz: of Leverett Partners. All right, thanks for the...
Alexander Sapir: So I was wondering a couple of things on our procedure there first and then Los Mappamod. Can you talk a little bit more about why it's taking longer to proceed with the cohort three group of patients for procedures just at the IRB level? Is it enrollment? Can you give us any clearer progress update and maybe talk about what initiatives you have to accelerate things? And then I have a question on Los Mappamod. Sure. That's great, Jo. Thanks for the question. This is Alex.
Joseph Patrick Schwartz: Hi, thanks for the updates. Sorry. So I was wondering a couple things on Posiridaire first and then Los Mapa Mod. Can you talk a little bit more about why it's taking longer?
Alexander C. Sapir: So, I was wondering a couple of things about posterior deer first and then los mapimod. Can you talk a little bit more about why it's taking longer to proceed with the cohort three group of patients for posterior deer? Is this at the IRB level? Is it enrollment? Can you give us any clearer progress update and maybe talk about what initiatives you have to accelerate things? And then I have a question about Los Mapimod. Sure.
Joseph Patrick Schwartz: to proceed with the Cohort 3.
Joseph Patrick Schwartz: Group of Patients for Perseidere. Is this at the IRB level? Is it enrollment? Can you give us any clearer progress update and maybe talk about
Joseph Patrick Schwartz: What initiatives you have to accelerate things? And then I have a question on Los Mapamon.
Alexander C. Sapir: Sure, that's great, Joe. Thanks for the question. This is Alex.
Alexander Sapir: I'll take the first one, and then depending on what the second question is, we'll figure out who we can to tree on that one too. Yeah. So as I mentioned, and maybe I'll give a little bit more color, the seven or eight sites that were involved in the pioneer trial prior to the initiation, prior to the initiation of the clinical hole, which happened I think in February of 2023. Most of those sites tended to treat younger patients that didn't have the disease severity that was matching our new inclusion exclusion criteria that we reached agreement on with the agency in order to get off, in order to get off clinical hold.
Joseph Patrick Schwartz: Sure, that's great, Joe. Thanks for the question. This is Alex. I'll take the first one and then depending on what the second question is, we'll figure out who we can triage that one too. Yeah, so as I mentioned, and maybe I'll give a little bit more color
Alexander C. Sapir: I'll take the first one, and then, depending on what the second question is, we'll figure out who we can triage that one, too. Yeah, so as I mentioned, and maybe I'll give a little bit more color, the seven or eight sites that were involved in the Pioneer trial prior to the initiation of the clinical hold, which happened, I think, in February of 2023, most of those sites tended to treat younger patients that didn't have the disease severity that was matching our new inclusion-exclusion criteria that we reached agreement on with the agency in order to get off clinical hold.
Joseph Patrick Schwartz: The seven or eight sites that were involved in the Pioneer trial prior to the initiation of the clinical hold, which happened, I think, in February of 2023,
Speaker Change: Most of those sites tended to treat younger patients that didn't have the disease severity that was matching our new inclusion-exclusion criteria that we reached agreement on with the agency in order to get off
Alexander Sapir: So many of those existing sites would have been terrific to reactivate; it would have taken several months to get the new protocol through the IRB. All the contracting had been done. But because what we were hearing from those PIs is that they did not have those patients, essentially we had to activate all new sites both in the US as well as in countries outside of the US, specifically in Africa. Our goal is still to activate about 15 to call it 17, 18 sites in the US and a handful of sites outside of the US. So we should have 20 sites, which should be more than adequate to enroll these 20 patients in the next, you know, in these next two cohorts.
Alexander C. Sapir: So many of those existing sites would have been terrific to reactivate, but it would have taken several months to get the new protocol through the IRB. All the contracting had been done, but because what we were hearing from those PIs was that they did not have those patients, essentially, we had to activate all new sites, both in the US as well as in countries outside of the US, specifically in Africa. Our goal is still to...
Speaker Change: In order to get off clinical hold. So many of those existing sites
Speaker Change: It would have been terrific to reactivate it, it would have taken several months to get the new protocol through the IRB, all the contracting had been done, but because what we were hearing from those PIs is that they did not have those patients.
Speaker Change: Essentially, we had to activate all new sites, both in the U.S. as well as in countries outside of the U.S., specifically in Africa. Our goal is still to... Our goal is still to...
Speaker Change: activate about 15 to call it 17, 18 sites in the U.S.
Speaker Change: and a handful of sites outside of the U.S. So we should have 20 sites, which should be more than adequate to enroll these.
Alexander Sapir: So I think it's really just, it's this long lead time of activating these sites, many of which are academic sites, and as many of you know, it can take, you know, up to nine months from contracting the IRB approval, all of the back and forth with the sites to get these sites activated again at these major academic institutions.
Speaker Change: 20 patients in the next you know in these next two in these next two cohorts I think it's really just it's this long lead time of activating
Speaker Change: These sites, many of which are academic sites, and as many of you know, it can take, you know, up to nine months from
Speaker Change: contracting, the IRB approval, all of the back and forth at the sites to get these to get these sites activated again at these at these major academic institutions. In terms of what we're doing to try to
Alexander Sapir: In terms of what we're doing to try to speed that up, I think we're trying to do, I think we're doing a couple of things. Number one, when a contract provision comes in, we're typically returning that around in about 24 to 48 hours. So the people in our legal group knows that pioneers, the top priority, and anything that comes in from pioneer gets put to the top of the pile. Unfortunately, we're sort of at the whim of, you know, the large institutional bureaucracy, and unfortunately, things just take time. But I will say that, you know, of the sites that we have activated and we have activated the number of sites, they continue to be very encouraged of the, you know, transformational potential that posterior could bring to their, to their patient population.
Speaker Change: speed that up. I think we're trying to do, I think we're doing a couple of things. Number one, when a contract provision comes in, we're typically returning that around in about 24 to 48 hours. So the people in our legal group knows that
Speaker Change: Pioneer is the top priority, and anything that comes in from Pioneer gets put to the top of the pile. Unfortunately, we're sort of at the whim of...
Speaker Change: You know, the large institutional bureaucracy, and unfortunately, things just take time. But I will say that, you know, of the sites that we have.
Speaker Change: activated, and we have activated a number of sites.
Speaker Change: They continue to be very encouraged of the, you know, transformational potential that Posterior Adhera could bring to their to their patient population.
Alexander Sapir: There is a relatively, you know, small number of patients somewhere between seven and a half to 10% of that 100,000 that I mentioned that do meet our inclusion exclusion criteria. So call it, you know, about 10,000 patients. But we believe that's more than an adequate number to be able to recruit these 20 patients.
Speaker Change: There is a relatively, you know, small number of patients, somewhere between seven and a half to ten percent of that hundred thousand that I mentioned, that do meet our inclusion-exclusion criteria, so call it
Speaker Change: You know, about 10,000 patients, but we believe that's more than an adequate number to be able to recruit these 20 patients. And as I mentioned, we will expect to have data that we can share with everybody sometime in 2025. And maybe turning to your Los Mapamon question,
Alexander Sapir: And as I mentioned, we will expect to have data that we can share with everybody sometime in 2025.
Unknown Executive: And it may be turning to your most map of my question.
Unknown Executive: Yeah, thanks. That was helpful color on procedure here.
Joan Park: So, as far as Los Mammog goes, I was wondering if you could talk about the output that will emerge from the work to define the minimally clinically relevant difference on the RWS. Is this just one single number? Is it a range which might provide more context? And how do you feel about the ability of Los Mammog to provide a benefit which exceeds whatever you define as the MCD?
Speaker Change: Yeah, thanks. That was helpful, Collar on Paseer Deer. So, as far as LISMAPMOD goes, I was wondering if you could talk about the output that will emerge from the work to define the minimally clinically relevant difference on the RWS.
Joseph Patrick Schwartz: Is this just one single number? Or is it a range that might provide more context? And how do you feel about the ability of Los Matamad to provide a benefit which exceeds whatever you define as the MCD?
Speaker Change: Is this just one single number? Is it a range which might provide more context? And how do you feel about the ability of Los Mapumad to provide a benefit which exceeds whatever you define as the MCD?
Iain Fraser: Sure, thanks, Jo. I think to answer that, let me turn that one over to Ian as well. Yeah, thanks, Jo. And just to clarify, I think that the number that in the FDA terminologies, the meaningful score difference, and I think the important thing to emphasize about that is that that's not a mean score for the overall population that needs to be exceeded, but that's the score for a within-patient change. So that's understanding what a change in the reachable workspace score is for an individual patient. And so what that's most likely to be reflected in looking at the clinical trial data is proportions of patients, individual patients that exceed that meaningful score difference.
Speaker Change: Sure. Thanks, Joe. I think to answer that, let me turn that one over to Iain as well.
Iain: Yeah, thanks, Joe. And just to clarify, I think that the number that in the FDA terminology is the meaningful score difference.
Alexander C. Sapir: Yeah, thanks, Joe. And just to clarify, I think that the number that, in FDA terminology, is the meaningful score difference.
Speaker Change: And I think the important...
Iain: I think to emphasize about that is that that's not a mean score for the overall population that needs to be exceeded, but that's the score for within patient change. So that's understanding what a change in the reachable workspace score is.
Iain: for an individual patient. And so what that's most likely to be reflected in looking at the clinical trial data is proportions of patients, individual patients, that exceed that meaningful score difference.
Iain Fraser: So I think that's just conceptually a way of thinking about it. That's an important piece of it. And that's really the focus of this.
Iain: So I think that's just conceptually a way of thinking about it, that's an important piece of it. And that's really the focus of this. There might well be a range of these depending on the outputs of that work, and we'll report that at the time of the top-line data.
Joan Park: There might well be a range of these depending on the outputs of that work, and we'll report that at the time of the top line data. Very helpful. Thank you.
Joseph Patrick Schwartz: Very helpful. Thank you.
Unknown Executive: Thanks, Jo. Leigh, next question.
Iain: Very helpful. Thank you. Thanks, Joe.
Dae Ha: And our next question. We'll be coming from the line of Daegonha, of Stiefel. Your line is open. Hey, great. Good morning. Thanks for taking our questions.
Lee: Leigh, next question?
Speaker Change: And our next question will be coming from the line of Daegon Ha of Stiefel. Your line is open.
Unknown Caller: Hey, great, good morning. Thanks for taking our questions. I'll stick with my two questions on the Los Matamotos side of things, specifically on powering. So maybe a question for Iain.
Dae Ha: All stick my two questions with the last map and what side of things. Specifically on powering, so maybe a question for Ian. So the first question is you previously talked about powering for reach as having benefited from the over-enrollment. I think it was 96% to show 10% placebo-adjusted RSA. Just to clarify, was this just for the FSHE type 1 or inclusive of type 2? And now that you do have the type 2 baseline characteristics disclosed, like what would that powering be if any different from the original one.
Dae Gon Ha: Hey, great. Good morning. Thanks for taking our questions. I'll stick my two questions with the Los Matamotos side of things, specifically on empowering. So maybe a question for Iain.
Unknown Caller: So the first question is, you previously talked about powering for REACH as having benefited from the over-enrollment. I think it was 96% to show 10% placebo-adjusted RSA. Just to clarify, was this just for FSHC Type 1 or inclusive of Type 2? And now that you do have the Type 2 baseline characteristics disclosed, what would that powering be, if any, different from the original one? And then, second question on powering as well. Just curious, have you guys done additional sensitivity analysis around sort of the evolving RESOLVE natural history data, and what might that mean for the powering of REACH? Thanks so much.
Dae Gon Ha: So, the first question is, you previously talked about powering for REACH as having benefited from the over-enrollment.
Speaker Change: I think it was 96% to show 10% placebo-adjusted RSA.
Speaker Change: Just to clarify, was this just for the FSHC Type 1 or inclusive of Type 2? And now that you do have the Type 2 baseline characteristics disclosed, what would that powering be, if any, different from the original one? And then second question on powering as well,
Iain Fraser: And then second question on powering as well. Just curious, have you guys done additional sensitivity analysis around sort of the evolving resolve, natural history data? And what might that mean for the powering of reach? Thanks so much. That's great. Thanks, Daegonha. And thanks for the question. Yeah, Ian, you want to take that one? Yeah, I think we've articulated before that the powering for reach was based on specifically the FSHE 1 patient population. And that's because the data that we used for the powering was from Redox 4, and that study enrolled only FSHE type 1s. And so that was the approach that was taken even though the primary endpoint for the REACH trial will include not only the type 1s but also the type 2s.
Speaker Change: Just curious, have you guys done additional sensitivity analysis around sort of the evolving resolve natural history data and what might that mean for the powering of REACH? Thanks so much.
Alexander C. Sapir: That's great. Thanks, Dagon, and thanks for the question. Yeah, Iain, you want to take that one? Yeah. Hi, Dagon. As I think we've
Ian: That's great. Thanks, Dagon, and thanks for the question. Yeah, Iain, you want to take that one? Yeah. Hi, Dagon. As I think we've articulated before, the powering for reach
Ian: was based on specifically the FSHD1 patient population, and that's because the data that we used for the powering.
Ian: was from Redox 4, and that study enrolled only FSHD type 1s. And so that was the approach that was taken, even though the primary endpoint for the REACH trial will include not only the type 1s, but also.
Iain Fraser: And so the powering initially the powering was based on 210 FSHE type 1 patients, and that was the powering at 93%, and the expectation was that we would in addition have 20 FSHE type 2 patients, so push the total up to 230. The over enrollment pushed the total enrollment from 230 to 260. And the type 1s went from 210 to 242. And so that's really the comparison for the powering was the 210 to 242 type 1s, moving it from 93 to 96%. As you've indicated, we have the baseline characteristics; we know they're 18 FSHE type 2 patients, and we also know that the randomization is stratified for that.
Speaker Change: like to his
Speaker Change: And so the powering, initially the powering.
Speaker Change: was based on 210 FSHD type 1.
Speaker Change: Patients, and that was the powering up at 93%.
Speaker Change: And the expectation was that we would, in addition, have 20.
Speaker Change: FSHD type 2 patients, so push the total up to 230.
Speaker Change: The over-enrollment pushed the total enrollment from 230 to...
Speaker Change: to 60.
Speaker Change: And the Type 1's went from 210 to 242, and so that's really the comparison for the powering was the 210 to 242 Type 1's, moving it from 93 to 96%.
Speaker Change: As you've indicated, we have the baseline characteristics. We know there are 18 FSHD type 2 patients, and we also know that the randomization is stratified for that. So the expectation is that there'll be nine and nine in each of the groups.
Dae Ha: So the expectation is that there'll be 9 and 9 in each of the groups placebo. and I. Great, thanks again for the question, Dae Gaun, Lisa.
Speaker Change: Placebo and Acton.
Unknown Executive: Thank you.
Iain Fraser: Thank you.
Gregory Renza: And our next question will be coming from the line of Gregory Renza.
Speaker Change: Great. Thanks again for the question, Dagon. Lisa?
Operator: will be coming from the line of
Lisa: Thank you.
Speaker Change: And our next question.
Speaker Change: We'll be coming from the line of...
Gregory Renza: Yes, hey, good morning, Alex and team. Congrats on the progress; we're looking forward to the data in October. Alex, just on that, let's map them out. As you touched a bit upon pair engagement, maybe just give us a glimpse of what that engagement will and has been looking like. What do you see as the potential tailwinds from the potential data package and let's map them out profile? Maybe what do you foresee as some of the greatest challenges when it comes to establishing the value proposition, assuming that the data cards flip as you foresee? Yeah, great, great question, and thanks for that.
Speaker Change: Yes. Hey, good morning, Alex and team. Congrats on the progress. We're looking forward to the data in October .
Speaker Change: [inaudible]
Speaker Change: Just on ListMapMod, as you touched a bit upon pair engagement, maybe just give us a glimpse of what that engagement will and has been looking like. What do you see as the potential tailwinds from the potential data package and ListMapMod's profile? And maybe what do you foresee as some of the greatest challenges when it comes to establishing the value proposition, assuming that the data cards flip as you foresee?
Alexander Sapir: Yeah, I think so. We've done some pair research following the results of the Redux for study results. And what we heard from the pair community, and again, we probably went out and talked at the time to about 15 or so pairs; the majority of those were US-based pairs. And I think what we heard across the board is it'll be difficult to restrict access to this drug when approved for patients, given the fact that there are clearly nothing available and nothing used off label to help these patients with FSHD. I think the other thing that we heard from that pair research when probing a bit on what they expected the pricing to look like for the drug.
Speaker Change: Yeah, great, great question and thanks for that. Yeah, I think so. We've done some pair research following the results of the Redux for
Speaker Change: study results. And what we heard from the payer community, and again we probably went out and talked at the time to about 15 or so payers, the majority of those were U.S. based payers, and you know I think what we heard across the board is you know it'll be difficult
Speaker Change: to restrict access to this drug when approved for patients, given the fact that there are clearly nothing available and nothing used off-label to help these patients with.
Speaker Change: with FSHD. I think the other thing that we heard from that payer research when probing a bit on what they expected
Alexander Sapir: And we have not given any specific guidance around pricing. But what we clearly heard back from the payers is they would expect this to look very similar to other rare disease drugs that have been priced in the, call it hundreds of thousands of dollars every year per patient. I think it's also important to remind people that patients that will start on this drug, we assume, will more than likely stay on this drug for very, very long periods of time. And we've been seeing that now greater than 85% of patients in the Redux for study are still on drug after a three-year period of time.
Speaker Change: the pricing to look like for the drug. And we have not given any specific guidance around pricing. But what we clearly heard back from the payers is they would expect this to look very similar to other, you know.
Speaker Change: Rare disease drugs that have been priced in the call it hundreds of thousands of dollars every year per patient I think it's also important to remind people that
Speaker Change: You know, patients that will start on this drug, we assume will more than likely stay on this drug for very, very long periods of time. And we've been seeing that now, you know, greater than 85% of patients in the Redux 4 study are still on drug after a three-year period of time.
Alexander Sapir: So once we get the REACH trial results, Greg, we'll go ahead and do more significant payer research. But to your question around the tailwind, and we spend a lot of time thinking about this, I think that one of the biggest tailwinds will have with payers is the requirement for a confirmed genetic test at the time or prior to the approval of the drug. And what we know right now from the work that we've done is only about 20 to 30% of patients are actually receiving a confirmed genetic test. So if every payer, we're operating under the assumption that payers will require that confirmed genetic test before approving the drug.
Speaker Change: So, if every payer, we're operating under the assumption that payers will require that confirmed genetic test.
Alexander Sapir: And so we're doing a lot of work now. And there's a lot of examples out there of other rare diseases in which payers have required genetic tests. So this is not a, you know, this is not a new concept. We're essentially sort of replicating the playbook of many other rare disease products that have come before us. But we will make sure at the time of launch that a lack of a or we will make sure that genetic testing does not become an impediment to access. And whether that's through, you know, a partnership that we do with the MSHD Society or whether we do it directly and provide genetic testing free of charge to patient.
Speaker Change: Before approving the drug and so we're doing a lot of work now And there's there's a lot of examples out there of other rare diseases in which pairs have required genetic tests So this is not a you know, this is not a new concept We're essentially sort of replicating
Speaker Change: and the playbook of many other rare disease products that have come before us. But we will make sure at the time of launch that
Alexander Sapir: We're working through that right now to make sure that, at the time of launch, that does not become the tailwind that you mentioned.
Alexander Sapir: Richard. That supplement may be related, and Alan has provided some detail on your runway. How are you coordinating the urgency, but the planning for building a commercial organization when it comes to the leadership in such a capability, and slotting that with respect to the data coming? Yeah, great question, Greg, and thanks for asking it. Yeah, so we have begun building out our commercial organization. I would expect it sometime in the third quarter of this year; we will announce the appointment of our Chief Commercial Officer, and one of the things that I said to this individual while I was interviewing with them is we will make sure that we properly resource this launch.
Speaker Change: in such a capability and slotting that with respect to the data coming.
Speaker Change: Yeah, great question, Greg, and thanks for asking it. Yeah, so we are, we have begun building out our commercial organization. I would expect that sometime in the third quarter.
Speaker Change: of this year, we will announce the appointment of our Chief Commercial Officer, and one of the things that I said to this individual while I was interviewing with them is we will make sure that we properly resource this launch. We will make sure that if it's a question of do we fund it or do we not fund it, we will always err on we should fund it instead of not funding it, because we have to make sure that this is properly resourced, and as Alan mentioned in one of the earlier questions, the runway guidance that we have provided assumes a launch that we have very properly resourced beginning in
Alan Musso: We will make sure that if it's a question of do we fund it or do not fund it, we will always err on we should fund it instead of not funding, because we have to make sure that this is properly resourced. And as Alan mentioned in one of the earlier questions, the runway guidance that we have provided assumes a launch that we have very properly resourced, beginning in 2026. Is that fair, Alan? Okay. Got it. Thanks, as always, for the caller. Yeah, thanks so much, Greg. Thank you.
Alan: 2026. Is that fair, Alan? Okay.
Speaker Change: Got it. Thanks, as always, for the call. Yeah, thanks so much, Greg.
Matthew Biegler: One moment for the next question. And our next question will be coming from Matthew Beagler of Optical. Your line is open. Thank you, guys. Good morning.
Speaker Change: Thank you. One moment for the next question.
Operator: And our next question will be coming from Matthew Biegler.
Speaker Change: And our next question will be coming from Matthew Biegler of OPCO. Your line is open.
Matthew Biegler: We were curious if, in your discussions with the FDA, they'd ever asked for more data around the map of the mechanism of action. You know, as you mentioned, Divinity had some biomarker data on ducks for reduction clinically. I know preclinically you showed that you hadn't been able to clinically.
Matthew Cornell Biegler: You know, as you mentioned, Avidity had some biomarker data on DUX4 reduction clinically. I know preclinically you showed that, but you hadn't been able to clinically.
Matthew Biegler: So I'm just kind of curious if, you know, you'd be open to rerunning archive biopsies from Redux using maybe a more sensitive assay if the FDA wanted you to. Or if not, if you think, you know, really at this point, the FDA is only concerned with, you know, validating the RWS tool. Thanks. Yeah, thanks, Matt. Great question.
Speaker Change: So I'm just kind of
Matthew Cornell Biegler: I'm curious if, you know, you'd be open to rerunning archived biopsies from Redux using maybe a more sensitive assay if the FDA wanted.
Speaker Change: You too, or if not, if you think.
Speaker Change: You know, really, at this point, the FDA is only concerned with
Speaker Change: You know, validating the RWS tool. Thanks.
Iain Fraser: And let me turn that over to Ian as well. Thanks. The issue of going back to biomarker says not being something that's come up in any of the any of the discussions with the agency. The focus, I think, is very much been on the endpoints given that it's a functional end point in the secondary end point. Similarly, our functional or related to muscle health. So we haven't up to this point received any specific requests around that. So, we don't have any specific plans to do so. The evidence that we have both in the original discovery of the last map mod, as well as in the characterization of it, was done in muscle cells derived from patients with FSH, and you can perform the characterizations of the effects on ducks for all the downstream transcripts pretty, pretty convincingly in that in vitro system where you don't have competition from other cell types.
Matthew Cornell Biegler: Hey Matt, thanks. The issue of going back to biomarkers has not been something that's come up in any of the discussions with the agency. The focus, I think, has very much been specific requests around that.
Ian: Yeah, thanks, Matt. Great question. And let me turn that over to Iain as well. Hey, Matt, thanks. The issue of going back to biomarkers has not been something that's come up in any of the discussions with the agency. The focus, I think, has very much been on biomarkers.
Ian: On the endpoints, given that it's a functional endpoint and the secondary endpoints similarly are functional or related to muscle health.
Speaker Change: So we haven't, up to this point, received any.
Speaker Change: specific requests around that, so we don't have any specific plans to do so.
Iain: The evidence that we have, both in the original discovery of Les Mapumat, as well as in the characterization of it.
Iain: was done in
Speaker Change: pretty convincingly in that in vitro system where you don't have competition from other cell types and issues related to the biopsy and so on and and I think those data are very robust and show the mechanism of action.
Iain Fraser: And issues related to the biopsy and so on, and I think those data are very robust and show the mechanism. Action on a Fluss Mathemat on the reductions of ducts for in the downstream transcripts. Okay, that makes sense. Thanks for that.
Speaker Change: of Los Matamoros on the reductions of DUX4 and the downstream transcripts.
Alexander Sapir: In maybe just one on the reach three guidance. Is this a revision or just more fine-tuning from the prior guidance, which was year-end? And if it's a revision, kind of what are some of the factors driving that faster cadence going from year-end to now end of October? Thanks again. Yeah, Matt. This is Alex. Yeah, no, it's nothing more than simply fine-tuning. We, you know, as we, as we're getting closer and we're seeing, you know, the, the last handful of patients having their last visit, we feel very confident in terms of our ability to report out the top line results by the end of October.
Speaker Change: Okay, that makes sense. Thanks for that, Iain. Maybe just squeeze one on the Reach 3 guidance. Is this a revision or just more fine-tuning from the prior guidance, which was...
Matthew Cornell Biegler: Year End. And if it's a revision kind of thing, what are some of the factors driving that faster cadence going from year end to now end of October? Thanks again. Yeah, Matt.
Speaker Change: year end. And if it's a revision, kind of what are some of the factors driving that that faster cadence going from year end to now end of October ? Thanks again.
Speaker Change: Yeah, Matt, this is Alex. Yeah, no, it's nothing more than simply fine-tuning. We, you know, as we, as we're getting closer and we're seeing, you know, the last handful of patients having their last visit, we feel very confident in terms of our ability to report out the topline results by the end of October .
Unknown Executive: Appreciate it. Looking forward to it. Great. Thanks so much, Matt. Thank you. At this time, if you would like to ask a question, please press star one on your telephone.
Matthew Cornell Biegler: Appreciate it, looking forward to it.
Operator: Great. Thanks so much, Matt. Thank you at this time.
Speaker Change: Appreciate it, looking forward to it. Great, thanks so much Matt.
Speaker Change: Thank you. At this time, if you would like to ask a question, please press star 1-1 on your telephone.
Unknown Executive: There are no more questions in the queue.
Alexander Sapir: I would like to turn the call back to Alex for close remarks. Please go ahead. That's great. Thanks so much, Lisa. And again, thanks to everybody for joining. Thanks to everyone for your interest in all the great things we're doing here at Fulcrum.
Speaker Change: There are no more questions in the queue. I would like to turn the call back to Alex for closing remarks. Please go ahead. That's great. Thanks so much, Lisa. And again, thanks to everybody for joining. Thanks to everyone for your interest in all the great things we're doing here at Fulcrum. And I guess before we conclude, I want to remind everyone that we continue to make progress with our phase one pioneer trial of Posiridir and are on track to report top line data for the phase three REACH trial by the end of October of this year. In parallel, we continue to prepare for the potential NDA filing and commercial launch of Los Maffiamad in the U.S.
Alexander Sapir: And I guess before we conclude, I want to remind everyone that we continue to make progress with our phase one pioneer trial of posterior and are on track to report top line data for the phase three reach trial by the end of October of this year. In parallel, we continue to prepare for the potential NDA filing and commercial launch of those. Map them out in the US with our cash runway into 2027. We believe we are well positioned to execute on our corporate objectives and look forward to building on this momentum in the months and years ahead.
Speaker Change: With our cash runway into 2027, we believe we are well positioned to execute on our corporate objectives and look forward to building on this momentum in the months and years ahead.
Alexander Sapir: And as I always like to do before we jump off the call, I would be remiss if I did not extend my sincere appreciation and gratitude to my fellow Fulcrum teammates, to the positions we work with to advance our clinical studies. For our partners at the FHD Society and finally, and most importantly, to the patients and their families around the world: without you and your commitment to become involved in clinical trials, none of what we do would be possible. Thanks again to everyone who joined the call this morning. Please stay safe and healthy. Thanks so much.
Speaker Change: And as I always like to do before we jump off the call, I would be remiss if I did not extend my sincere appreciation and gratitude to my fellow Fulcrum teammates.
Speaker Change: to the physicians we work with to advance our clinical studies, to our partners at the FSHD Society, and finally and most importantly to the patients and their families around the world. Without you and your commitment to become involved in clinical trials, none of what we do would be possible.
Speaker Change: Thanks again to everyone who joined the call this morning. Please stay safe and healthy. Thanks so much.
Unknown Executive: Thank you for today's conference call. You all made this connect. Thank you very much.
Speaker Change: Thank you for today's conference call. You all may disconnect.
Speaker Change: [inaudible]
Speaker Change: [inaudible] Relaxing acoustic guitar music
Speaker Change: [inaudible]
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Speaker Change: In an Wright book by Richard Randall Crane in Ledbrook, the equivalent of Joan Greene For more information on the Medical Xbox, go to www.amt.gov
Speaker Change: [inaudible]