Leveraging Connections & Technology for Rapid Clinical Material Delivery
One Family’s Journey from Diagnosis to Gene Replacement Therapy in 14 Months: Part Three
The Orphan Drug Act defines rare diseases as those that affect less than 200,000 people in the United States. The European Union definition is slightly different, with diseases that affect no more than 1 in 2,000 people considered rare. Those numbers are difficult enough to comprehend, but there are also ultra-rare diseases that affect just 100 to 200 people—or fewer—worldwide. Unfortunately, many young children are experiencing rapid disease progression and limited time and opportunity to receive treatment.
The development of a new drug typically takes many years and billions of dollars. How, then, can parents receiving devastating diagnoses for their children have any chance of finding treatment in time? This blog series outlines the story of one family’s journey from diagnosis to administration of a novel gene replacement therapy 14 months later, and how they were supported by clinicians, researchers, hospitals, universities, and manufacturing organizations to make the seemingly impossible happen for their daughter.
In this series, you can read about one family who refused to take this diagnosis as the end. They managed to bring together the resources and people needed to get an investigational gene replacement therapy manufactured and approved by the Food and Drug Administration (FDA) so that their daughter, Elly Krueger, could be dosed on April 3, 2025, just 14 months from her diagnosis.
In Part ONE, we covered the journey of Michelle and Dan Krueger and their daughter Elly, who was diagnosed with Neurodevelopmental Disorder with Regression, Abnormal Movements, Loss of Speech, and Seizures (NEDAMSS), a recently identified (2018) ultra-rare, progressive, neurodegenerative disease that affects roughly 150 children in the entire world.
In Part TWO we discussed the science of NEDAMSS and highlight the efforts of Dr. Kathrin Meyer, in collaboration with Elly’s Team and a team of researchers, who collectively developed the gene replacement therapy and conducted the preclinical studies necessary for achieving a N=1 drug approval from the FDA.
Here in Part THREE we will cover the work involved in accelerating the process development and manufacture of the novel gene replacement therapy by Andelyn Biosciences, while Part FOUR will summarize the important roles played by the different parties and looks at the next steps for Elly, her family, the other children, and the Elly’s Team foundation.
Part Three:
Of the many important decisions Michelle and Dan Krueger had to make when pursuing the development and production of a novel gene replacement therapy for Neurodevelopmental Disorder with Regression, Abnormal Movements, Loss of Speech, and Seizures (NEDAMSS) was choosing the right contract development and manufacturing organization (CDMO) to manufacture the therapy.
After learning their 8-month-old daughter Elly suffered from a severe form of this ultra-rare neurodegenerative disease, the parents sought out Dr. Kathrin Meyer of Alcyone Therapeutics for her unique knowledge about the cause of NEDAMSS (mutations in the IRF2BPL, or interferon regulatory factor 2 binding protein-like, gene). She encouraged the Kruegers to explore different options and select the CMDO they felt would best meet their needs; there was quite a bit of competition.
Andelyn Biosciences was one of the first CDMOs the Kruegers considered due to the long-term relationship Dr. Meyer has with the company from her time working for Nationwide Children’s Hospital (NCH), from where Andelyn spun out of in 2020. Andelyn was initially formed to produce clinical trial material for physicians conducting gene therapy trials at NCH and today supports many global programs from early to late-stage development and commercial manufacturing.
According to CEO, Wade Macedone, the Andelyn team has much experience working on small projects and does not prioritize Big Pharma clients over emerging biotechs or foundations. In fact, the CDMO reserves a certain percentage of its capacity specifically to support nonprofits, including those involving a single patient and families seeking to access gene therapies for their children.
Mr. Macedone knows that it is not easy for parents like Dan and Michelle to trust an organization they do not know with the production of a novel treatment that will be administered to their child. During his first meeting with Michelle, therefore, he spent time sharing important questions that she should ask of different CDMO contenders, particularly regarding their experience in producing viral vectors used in clinical studies and working with parents focused on saving their children. The latter experience is important because interacting with parents with a severely ill child requires very different skills than those needed when dealing with drug developers.
Dan and Michelle ultimately chose Andelyn Biosciences, largely driven by their expertise, network, and technology. The Andelyn AAV Curator® platform for production of adeno-associated viral (AAV) vectors has been continuously curated over more than 15 years. This adherent platform includes a well-established cell line, well-understood upstream manufacturing and downstream purification processes, and proprietary fit-for-purpose analytical methods for process development and product release. The platform is also available for suspension processes as needed based on afflicted population and dosing required.
Andelyn's data-driven approach to process development leverages decades of production data to shorten timelines while still ensuring cost-effective and improved manufacturing processes. The Curator® platform is also highly predictable in terms of yield and quality and eliminates intellectual property concerns because the technology has all been developed internally. Furthermore, review of investigational new drug (IND) applications is streamlined as the referenced Drug Master Files (DMFs) have been reviewed and approved by the FDA previously, removing unnecessary hurdles and delays.
Another important enabler for the accelerated manufacturing of Elly’s gene replacement therapy was the willingness of Michelle and Dan to rely on Andelyn’s expertise, not disrupt progress with any preconceived ideas of what or how things should be done and listen to guidance regarding what they could do to help—and then follow through.
Effective collaboration and coordination with other service providers also made a difference in so rapidly developing a process and producing the gene replacement therapy for Elly. The DNA plasmids, which are critical raw materials for AAV vector production, were rapidly manufactured while Genezen quickly established a stability and compatibility study to ensure the manufactured clinical product was compatible with the materials of intended injection tools.
Collaboration was particularly crucial to successfully getting the plasmids to Andelyn. They were manufactured at an overseas site and were held up at customs when shipped to the United States. The Kruegers worked closely with Andelyn to get them released indicating, “The team moved mountains for us in getting the plasmids released to not miss our manufacturing start date. This was one of the first mountains Andelyn moved for us in our process, with many more to come”.
Providing rapid and cost-effective gene therapy manufacturing services is not the only way Andelyn is committed to helping families like the Kruegers. In addition to educating parents like Dan and Michelle about critical considerations when selecting a contract manufacturer, Andelyn also seeks to raise awareness and funds for the gene therapy and rare disease community. Many families face not only limited treatment options but lack access to necessary financial and other resources.
Andelyn hosts events like the annual FORE One Purpose golf tournament, the first of which was held in September 2024. When planning for this signature event, Mr. Macedone was seeking a family that could benefit from Andelyn Biosciences’ expertise and capabilities to serve as a great example of what courage, fortitude, and commitment can achieve. The Krueger family was the perfect fit. The $50,000 raised from the first tournament went to Elly’s Team, the foundation established by Michelle and Dan to support development of a cure for NEDAMSS. Planning is well underway for the 2025 event, which will take place on August 11th, 2025.
Learn more about the journey to accelerate the production of Elly’s gene replacement therapy in Part ONE and Part TWO. And stay tuned for Part FOUR, where the next steps in the journey are discussed.
Information about the gene therapy development and manufacturing capabilities at Andelyn Biosciences can be found here: https://www.andelynbio.com/. And to stay up to date on the work being accomplished by Elly’s Team, visit https://ellysteam.org/
One Family’s Journey from Diagnosis to Gene Replacement Therapy in 14 Months: Part Three
The Orphan Drug Act defines rare diseases as those that affect less than 200,000 people in the United States. The European Union definition is slightly different, with diseases that affect no more than 1 in 2,000 people considered rare. Those numbers are difficult enough to comprehend, but there are also ultra-rare diseases that affect just 100 to 200 people—or fewer—worldwide. Unfortunately, many young children are experiencing rapid disease progression and limited time and opportunity to receive treatment.
The development of a new drug typically takes many years and billions of dollars. How, then, can parents receiving devastating diagnoses for their children have any chance of finding treatment in time? This blog series outlines the story of one family’s journey from diagnosis to administration of a novel gene replacement therapy 14 months later, and how they were supported by clinicians, researchers, hospitals, universities, and manufacturing organizations to make the seemingly impossible happen for their daughter.
In this series, you can read about one family who refused to take this diagnosis as the end. They managed to bring together the resources and people needed to get an investigational gene replacement therapy manufactured and approved by the Food and Drug Administration (FDA) so that their daughter, Elly Krueger, could be dosed on April 3, 2025, just 14 months from her diagnosis.
In Part ONE, we covered the journey of Michelle and Dan Krueger and their daughter Elly, who was diagnosed with Neurodevelopmental Disorder with Regression, Abnormal Movements, Loss of Speech, and Seizures (NEDAMSS), a recently identified (2018) ultra-rare, progressive, neurodegenerative disease that affects roughly 150 children in the entire world.
In Part TWO we discussed the science of NEDAMSS and highlight the efforts of Dr. Kathrin Meyer, in collaboration with Elly’s Team and a team of researchers, who collectively developed the gene replacement therapy and conducted the preclinical studies necessary for achieving a N=1 drug approval from the FDA.
Here in Part THREE we will cover the work involved in accelerating the process development and manufacture of the novel gene replacement therapy by Andelyn Biosciences, while Part FOUR will summarize the important roles played by the different parties and looks at the next steps for Elly, her family, the other children, and the Elly’s Team foundation.
Part Three:
Of the many important decisions Michelle and Dan Krueger had to make when pursuing the development and production of a novel gene replacement therapy for Neurodevelopmental Disorder with Regression, Abnormal Movements, Loss of Speech, and Seizures (NEDAMSS) was choosing the right contract development and manufacturing organization (CDMO) to manufacture the therapy.
After learning their 8-month-old daughter Elly suffered from a severe form of this ultra-rare neurodegenerative disease, the parents sought out Dr. Kathrin Meyer of Alcyone Therapeutics for her unique knowledge about the cause of NEDAMSS (mutations in the IRF2BPL, or interferon regulatory factor 2 binding protein-like, gene). She encouraged the Kruegers to explore different options and select the CMDO they felt would best meet their needs; there was quite a bit of competition.
Andelyn Biosciences was one of the first CDMOs the Kruegers considered due to the long-term relationship Dr. Meyer has with the company from her time working for Nationwide Children’s Hospital (NCH), from where Andelyn spun out of in 2020. Andelyn was initially formed to produce clinical trial material for physicians conducting gene therapy trials at NCH and today supports many global programs from early to late-stage development and commercial manufacturing.
According to CEO, Wade Macedone, the Andelyn team has much experience working on small projects and does not prioritize Big Pharma clients over emerging biotechs or foundations. In fact, the CDMO reserves a certain percentage of its capacity specifically to support nonprofits, including those involving a single patient and families seeking to access gene therapies for their children.
Mr. Macedone knows that it is not easy for parents like Dan and Michelle to trust an organization they do not know with the production of a novel treatment that will be administered to their child. During his first meeting with Michelle, therefore, he spent time sharing important questions that she should ask of different CDMO contenders, particularly regarding their experience in producing viral vectors used in clinical studies and working with parents focused on saving their children. The latter experience is important because interacting with parents with a severely ill child requires very different skills than those needed when dealing with drug developers.
Dan and Michelle ultimately chose Andelyn Biosciences, largely driven by their expertise, network, and technology. The Andelyn AAV Curator® platform for production of adeno-associated viral (AAV) vectors has been continuously curated over more than 15 years. This adherent platform includes a well-established cell line, well-understood upstream manufacturing and downstream purification processes, and proprietary fit-for-purpose analytical methods for process development and product release. The platform is also available for suspension processes as needed based on afflicted population and dosing required.
Andelyn's data-driven approach to process development leverages decades of production data to shorten timelines while still ensuring cost-effective and improved manufacturing processes. The Curator® platform is also highly predictable in terms of yield and quality and eliminates intellectual property concerns because the technology has all been developed internally. Furthermore, review of investigational new drug (IND) applications is streamlined as the referenced Drug Master Files (DMFs) have been reviewed and approved by the FDA previously, removing unnecessary hurdles and delays.
Another important enabler for the accelerated manufacturing of Elly’s gene replacement therapy was the willingness of Michelle and Dan to rely on Andelyn’s expertise, not disrupt progress with any preconceived ideas of what or how things should be done and listen to guidance regarding what they could do to help—and then follow through.
Effective collaboration and coordination with other service providers also made a difference in so rapidly developing a process and producing the gene replacement therapy for Elly. The DNA plasmids, which are critical raw materials for AAV vector production, were rapidly manufactured while Genezen quickly established a stability and compatibility study to ensure the manufactured clinical product was compatible with the materials of intended injection tools.
Collaboration was particularly crucial to successfully getting the plasmids to Andelyn. They were manufactured at an overseas site and were held up at customs when shipped to the United States. The Kruegers worked closely with Andelyn to get them released indicating, “The team moved mountains for us in getting the plasmids released to not miss our manufacturing start date. This was one of the first mountains Andelyn moved for us in our process, with many more to come”.
Providing rapid and cost-effective gene therapy manufacturing services is not the only way Andelyn is committed to helping families like the Kruegers. In addition to educating parents like Dan and Michelle about critical considerations when selecting a contract manufacturer, Andelyn also seeks to raise awareness and funds for the gene therapy and rare disease community. Many families face not only limited treatment options but lack access to necessary financial and other resources.
Andelyn hosts events like the annual FORE One Purpose golf tournament, the first of which was held in September 2024. When planning for this signature event, Mr. Macedone was seeking a family that could benefit from Andelyn Biosciences’ expertise and capabilities to serve as a great example of what courage, fortitude, and commitment can achieve. The Krueger family was the perfect fit. The $50,000 raised from the first tournament went to Elly’s Team, the foundation established by Michelle and Dan to support development of a cure for NEDAMSS. Planning is well underway for the 2025 event, which will take place on August 11th, 2025.
Learn more about the journey to accelerate the production of Elly’s gene replacement therapy in Part ONE and Part TWO. And stay tuned for Part FOUR, where the next steps in the journey are discussed.
Information about the gene therapy development and manufacturing capabilities at Andelyn Biosciences can be found here: https://www.andelynbio.com/. And to stay up to date on the work being accomplished by Elly’s Team, visit https://ellysteam.org/
One Family’s Journey from Diagnosis to Gene Replacement Therapy in 14 Months: Part Three
The Orphan Drug Act defines rare diseases as those that affect less than 200,000 people in the United States. The European Union definition is slightly different, with diseases that affect no more than 1 in 2,000 people considered rare. Those numbers are difficult enough to comprehend, but there are also ultra-rare diseases that affect just 100 to 200 people—or fewer—worldwide. Unfortunately, many young children are experiencing rapid disease progression and limited time and opportunity to receive treatment.
The development of a new drug typically takes many years and billions of dollars. How, then, can parents receiving devastating diagnoses for their children have any chance of finding treatment in time? This blog series outlines the story of one family’s journey from diagnosis to administration of a novel gene replacement therapy 14 months later, and how they were supported by clinicians, researchers, hospitals, universities, and manufacturing organizations to make the seemingly impossible happen for their daughter.
In this series, you can read about one family who refused to take this diagnosis as the end. They managed to bring together the resources and people needed to get an investigational gene replacement therapy manufactured and approved by the Food and Drug Administration (FDA) so that their daughter, Elly Krueger, could be dosed on April 3, 2025, just 14 months from her diagnosis.
In Part ONE, we covered the journey of Michelle and Dan Krueger and their daughter Elly, who was diagnosed with Neurodevelopmental Disorder with Regression, Abnormal Movements, Loss of Speech, and Seizures (NEDAMSS), a recently identified (2018) ultra-rare, progressive, neurodegenerative disease that affects roughly 150 children in the entire world.
In Part TWO we discussed the science of NEDAMSS and highlight the efforts of Dr. Kathrin Meyer, in collaboration with Elly’s Team and a team of researchers, who collectively developed the gene replacement therapy and conducted the preclinical studies necessary for achieving a N=1 drug approval from the FDA.
Here in Part THREE we will cover the work involved in accelerating the process development and manufacture of the novel gene replacement therapy by Andelyn Biosciences, while Part FOUR will summarize the important roles played by the different parties and looks at the next steps for Elly, her family, the other children, and the Elly’s Team foundation.
Part Three:
Of the many important decisions Michelle and Dan Krueger had to make when pursuing the development and production of a novel gene replacement therapy for Neurodevelopmental Disorder with Regression, Abnormal Movements, Loss of Speech, and Seizures (NEDAMSS) was choosing the right contract development and manufacturing organization (CDMO) to manufacture the therapy.
After learning their 8-month-old daughter Elly suffered from a severe form of this ultra-rare neurodegenerative disease, the parents sought out Dr. Kathrin Meyer of Alcyone Therapeutics for her unique knowledge about the cause of NEDAMSS (mutations in the IRF2BPL, or interferon regulatory factor 2 binding protein-like, gene). She encouraged the Kruegers to explore different options and select the CMDO they felt would best meet their needs; there was quite a bit of competition.
Andelyn Biosciences was one of the first CDMOs the Kruegers considered due to the long-term relationship Dr. Meyer has with the company from her time working for Nationwide Children’s Hospital (NCH), from where Andelyn spun out of in 2020. Andelyn was initially formed to produce clinical trial material for physicians conducting gene therapy trials at NCH and today supports many global programs from early to late-stage development and commercial manufacturing.
According to CEO, Wade Macedone, the Andelyn team has much experience working on small projects and does not prioritize Big Pharma clients over emerging biotechs or foundations. In fact, the CDMO reserves a certain percentage of its capacity specifically to support nonprofits, including those involving a single patient and families seeking to access gene therapies for their children.
Mr. Macedone knows that it is not easy for parents like Dan and Michelle to trust an organization they do not know with the production of a novel treatment that will be administered to their child. During his first meeting with Michelle, therefore, he spent time sharing important questions that she should ask of different CDMO contenders, particularly regarding their experience in producing viral vectors used in clinical studies and working with parents focused on saving their children. The latter experience is important because interacting with parents with a severely ill child requires very different skills than those needed when dealing with drug developers.
Dan and Michelle ultimately chose Andelyn Biosciences, largely driven by their expertise, network, and technology. The Andelyn AAV Curator® platform for production of adeno-associated viral (AAV) vectors has been continuously curated over more than 15 years. This adherent platform includes a well-established cell line, well-understood upstream manufacturing and downstream purification processes, and proprietary fit-for-purpose analytical methods for process development and product release. The platform is also available for suspension processes as needed based on afflicted population and dosing required.
Andelyn's data-driven approach to process development leverages decades of production data to shorten timelines while still ensuring cost-effective and improved manufacturing processes. The Curator® platform is also highly predictable in terms of yield and quality and eliminates intellectual property concerns because the technology has all been developed internally. Furthermore, review of investigational new drug (IND) applications is streamlined as the referenced Drug Master Files (DMFs) have been reviewed and approved by the FDA previously, removing unnecessary hurdles and delays.
Another important enabler for the accelerated manufacturing of Elly’s gene replacement therapy was the willingness of Michelle and Dan to rely on Andelyn’s expertise, not disrupt progress with any preconceived ideas of what or how things should be done and listen to guidance regarding what they could do to help—and then follow through.
Effective collaboration and coordination with other service providers also made a difference in so rapidly developing a process and producing the gene replacement therapy for Elly. The DNA plasmids, which are critical raw materials for AAV vector production, were rapidly manufactured while Genezen quickly established a stability and compatibility study to ensure the manufactured clinical product was compatible with the materials of intended injection tools.
Collaboration was particularly crucial to successfully getting the plasmids to Andelyn. They were manufactured at an overseas site and were held up at customs when shipped to the United States. The Kruegers worked closely with Andelyn to get them released indicating, “The team moved mountains for us in getting the plasmids released to not miss our manufacturing start date. This was one of the first mountains Andelyn moved for us in our process, with many more to come”.
Providing rapid and cost-effective gene therapy manufacturing services is not the only way Andelyn is committed to helping families like the Kruegers. In addition to educating parents like Dan and Michelle about critical considerations when selecting a contract manufacturer, Andelyn also seeks to raise awareness and funds for the gene therapy and rare disease community. Many families face not only limited treatment options but lack access to necessary financial and other resources.
Andelyn hosts events like the annual FORE One Purpose golf tournament, the first of which was held in September 2024. When planning for this signature event, Mr. Macedone was seeking a family that could benefit from Andelyn Biosciences’ expertise and capabilities to serve as a great example of what courage, fortitude, and commitment can achieve. The Krueger family was the perfect fit. The $50,000 raised from the first tournament went to Elly’s Team, the foundation established by Michelle and Dan to support development of a cure for NEDAMSS. Planning is well underway for the 2025 event, which will take place on August 11th, 2025.
Learn more about the journey to accelerate the production of Elly’s gene replacement therapy in Part ONE and Part TWO. And stay tuned for Part FOUR, where the next steps in the journey are discussed.
Information about the gene therapy development and manufacturing capabilities at Andelyn Biosciences can be found here: https://www.andelynbio.com/. And to stay up to date on the work being accomplished by Elly’s Team, visit https://ellysteam.org/