Charles River Collaborates with Patient Advocacy Group, FOXG1 Research Foundation to Advance Rare Disease Gene Therapy Development

Clinical trials for AAV9 gene therapy bolstered with plasmid and viral vector CDMO expertise

WILMINGTON, Mass.--(BUSINESS WIRE)--Jul. 30, 2024-- Charles River Laboratories International, Inc. (NYSE: CRL) announced today a collaboration with the FOXG1 Research Foundation (FRF) highlighting the patient advocacy group’s model to independently drive drug development through the clinical phase. The parent-led global organization driving the research to cure FOXG1 syndrome and related neurological disorders will collaborate with Charles River in a comprehensive gene therapy contract development and manufacturing organization (CDMO) agreement.

“Charles River is proud to work with the FOXG1 Research Foundation to advance its gene-therapy through clinical trials,” said Kerstin Dolph, Corporate Senior Vice President, Global Manufacturing, Charles River. “The FOXG1 patient population has an incredible unmet need, and we are looking forward to lending our expertise to FRF as they continue to trailblaze a path toward providing rare disease treatments.”

Through the collaboration, Charles River will provide FRF with access to extensive cell and gene therapy expertise and generate materials for FRF’s Phase I-II adeno-associated viral (AAV) vector-based gene therapy clinical trials at its plasmid DNA and viral vector CDMO centers of excellence (CoE). The established CDMO will supply phase-appropriate High Quality (HQ) plasmid starting materials manufactured at its Alderley Park CoE in addition to good manufacturing practice (GMP) AAV9 viral vector manufactured at its Rockville CoE, leveraging an integrated manufacturing and biologics testing portfolio to streamline their path to the clinic.

“Given the limited investment for rare disease groups like ours, our foundation has created a model that allows us and other patient advocacy groups to operate like a virtual biotech company and independently and efficiently drive drug development,” said Nasha Fitter, FOXG1 Parent, Co-founder and Chief Executive Officer, FOXG1 Research Foundation.

A New Approach to Drive Rare Disease Drug Development

Founded in 2017 and propelled by innovation and an urgency to accelerate the road to therapeutics for FOXG1 syndrome, FRF has created a replicable model for rare disease patient advocacy groups to take control and drive the development of treatments when no options exist. This includes pioneering novel AI platforms for patient data and streamlining preclinical work.

“The success of FRF’s model is not only focused on operating as a highly efficient team, but also partnering with organizations that are equally passionate about bringing treatments to children with the highest unmet need and severe burden of disease. Selecting the right partner is critical and Charles River has demonstrated a deep understanding of our model and commitment to working on our therapies,” continued Fitter.

FOXG1 syndrome is a severe rare neurological genetic disorder that greatly impacts early brain development and typically causes epilepsy and a host of medical complexities and disabilities. There are approximately 1,000 patients diagnosed with FOXG1 syndrome worldwide, with the diagnosis rate climbing steadily year-over-year and no approved treatments. Most children with FOXG1 syndrome cannot walk or talk or take care of their basic needs.

Cell and Gene Therapy CDMO Solutions

In recent years, Charles River has significantly broadened its cell and gene therapy portfolio with several acquisition integrations and expansions to simplify complex supply chains and meet growing demand for plasmid DNA, viral vector, and cell therapy services. Combined with the Company’s legacy testing capabilities, Charles River offers an industry-leading “concept to cure” advanced therapies solution.

Presented live at the Charles River Cell and Gene Therapy Summit, March 19, 2024, in San Francisco, watch Nasha Fitter’s FOXG1 Research Foundation Patient Story session on-demand, and explore the Summit resource hub: https://bit.ly/4bb2uDu

Also, listen to "A Mom’s Mission", a Vital Science Podcast, broadcast July 16, 2024, where Nasha discusses the origins of FOXG1 Research Foundation, how daughter Amara’s life has been shaped by her diagnosis, and how collaboration has helped advance their mission: https://bit.ly /3LuCpog

About Charles River

Charles River provides essential products and services to help pharmaceutical and biotechnology companies, government agencies and leading academic institutions around the globe accelerate their research and drug development efforts. Our dedicated employees are focused on providing clients with exactly what they need to improve and expedite the discovery, early-stage development and safe manufacture of new therapies for the patients who need them. To learn more about our unique portfolio and breadth of services, visit www.criver.com.

About FOXG1 Research Foundation

The FOXG1 Research Foundation (FRF) is the global, parent-led rare disease patient organization dedicated to advancing treatments for FOXG1 syndrome and related disorders, while advocating for and supporting patients and families worldwide. FOXG1 syndrome is a rare neurological developmental disorder linked to Autism Spectrum Disorder, epilepsy, and developmental disabilities. Founded in 2017, FRF has rapidly emerged as a leader and innovator in the rare disease patient advocacy space, developing novel platforms and an efficient blueprint to accelerate drug development for rare diseases. As a Chan Zuckerberg Initiative partner and recognized through its CEO’s presentation at the inaugural White House Rare Disease Forum, FRF is committed to radically improving the landscape for the 300 million patients affected by rare diseases worldwide.

www.foxg1research.org

View source version on businesswire.com: https://www.businesswire.com/news/home/20240730710706/en/

Charles River Investor Contact:

Todd Spencer
Corporate Vice President, Investor Relations 781.222.6455 [email protected]

Charles River Media Contact:

Amy Cianciaruso
Corporate Vice President, Chief Communications Officer 781.222.6168 [email protected]

FOXG1 Research Foundation Media Contact:

Nicole Johnson
Co-Founder and Executive Director [email protected]

Source: Charles River Laboratories International, Inc.

New publication shows groundbreaking results in FOXG1 AAV9 gene therapy studies; rescuing structural brain abnormalities

PRESS RELEASE

Groundbreaking Study Shows Promise in AAV9 Gene Therapy for FOXG1 Syndrome; Rescue of Brain Structure Abnormalities and Deficits.

[Buffalo, New York June 10, 2024] – A landmark study led by Dr. Soo-Kyung Lee, Chief Scientific Officer at the FOXG1 Research Foundation and Empire Innovation Professor and Om P. Bahl Endowed Professor in the Department of Biological Sciences at University at Buffalo, and Dr. Jae Lee, Professor in the Department of Biological Sciences at University at Buffalo, in collaboration with Dr. Kathrin Meyer (responsible for the SMA gene therapy), has been published in Molecular Therapy Methods & Clinical Development.

The paper, titled "The postnatal injection of AAV9-FOXG1 rescues corpus callosum agenesis and other brain deficits in the mouse model of FOXG1 syndrome," presents novel findings that have significant implications for treating FOXG1 syndrome, a severe neurodevelopmental disorder characterized by profound brain structure abnormalities.

The study explores the therapeutic potential of adeno-associated virus 9 (AAV9) mediated delivery of the FOXG1 gene. Remarkably, intracerebroventricular injection of AAV9-FOXG1 in a Foxg1 heterozygous mouse model ‘postnatally’ demonstrated the rescue of a wide range of brain pathologies including the amelioration of corpus callosum deficiencies, restoration of dentate gyrus morphology in the hippocampus, normalization of oligodendrocyte lineage cell numbers, and rectification of myelination anomalies.

"Our findings highlight the efficacy of AAV9-based gene therapy as a viable treatment strategy for FOXG1 syndrome and potentially other neurodevelopmental disorders with similar brain malformations," said Dr. Jae Lee. "This research asserts the therapeutic relevance of our approach in postnatal stages, which is a critical time frame for intervention."

Dr. Soo-Kyung Lee commented, 'We are thrilled by the full rescue of brain structure abnormalities observed in our mouse model through this study. It marks a significant step forward in our research. With these promising results, we are eager to advance this AAV9 gene therapy towards human clinical trials, hopeful that we can extend these breakthroughs to benefit children with FOXG1 syndrome.

This pioneering work provides a solid foundation for advancing this gene therapy towards human clinical trials, aiming to offer a transformative impact on the lives of patients with FOXG1 syndrome.

The FOXG1 Research Foundation continues to lead the way in innovative research for rare neurodevelopmental disorders, emphasizing the urgency and potential of cutting-edge treatments to alter the course of these conditions fundamentally.

Find the Molecular Therapy Methods & Clinical Development FOXG1 Paper HERE

Find FOXG1 Key Papers HERE

Contact: [email protected]

FOXG1 AAV9- Gene Therapy Data from FOXG1 Research Center at UB | Graphic Abstract

Learn more about The FOXG1 Research Center at the University at Buffalo

University at Buffalo launches center to find treatments for FOXG1 syndrome

Research will be led by biologists Soo-Kyung and Jae Lee, whose daughter has the rare neurological disorder, FOXG1 syndrome

FOXG1 Research Center at the University at Buffalo is led by Biologists and FOXG1 parents Dr. Soo-Kyung lee and Dr. Jae Lee

By Tom Dinki

Release Date: January 17, 2024

BUFFALO, N.Y. — University at Buffalo biologists Soo-Kyung and Jae Lee were already studying genetics and brain development when their daughter, Yuna, was born with a rare neurological disorder caused by a mutation of the FOXG1 gene.

So the Lees are well positioned — and motivated — to lead a research center dedicated to FOXG1.

UB’s new FOXG1 Research Center (FRC), set to launch in the coming months, aims to translate new discoveries from the lab to clinical trials and, ultimately, develop a cure for FOXG1 syndrome, as well as related autism spectrum disorder.

The FRC will be supported by the FOXG1 Research Foundation (FRF), as well as UB's College of Arts and Sciences and Office of the Vice President for Research and Economic Development. 

“This center will make UB the home of the world’s premier research center devoted to the studies of FOXG1 syndrome, as well as provide our campus with a new neurodevelopmental biology training program and numerous research funding opportunities,” says Soo-Kyung Lee, PhD, Empire Innovation Professor and Om P. Bahl Endowed Professor in the UB Department of Biological Sciences, who is currently FRF’s chief scientific officer and will serve as the FRC’s inaugural director. “The FRC will harness the expertise of our faculty to unravel the remaining mysteries of FOXG1 syndrome and, hopefully, help Yuna and the other children impacted by this disorder.”

The FOXG1 gene is one of the most important genes for early brain development. A master regulator gene, FOXG1 carries the instructions for making a protein called forkhead box G1 that regulates the activity of other genes, many of which are crucial for cellular connectivity and communication. Impairment of FOXG1 causes cognitive and physical disabilities as well as life-threatening seizures. 

There are only about 1,000 known patients diagnosed with FOXG1 syndrome worldwide, according to the FOXG1 Research Foundation. However, the FOXG1 gene has been linked to autism, Alzheimer’s disease and schizophrenia, suggesting that therapy development may be transferable to more common disorders.

There has also been a national push to better study and raise awareness for rare diseases, like FOXG1 syndrome. Last year, the Biden administration established the Advanced Research Projects Agency for Health (ARPA-H) within the National Institutes of Health, whose mission includes treating rare disorders.

The Lees, who joined UB in 2019, have established themselves as leading experts on FOXG1 syndrome since Yuna, now 14, was diagnosed with the disease at the age of 2. Their research has found that the FOXG1 gene and protein remain active in mice after birth, providing hope that some symptoms can be alleviated.

“Although we cannot go back and undo the damage to people who have FOXG1 syndrome, we may be able to modify the effects of the disease and increase their quality of life,” says Jae Lee, PhD, professor of biological sciences. 

They’ve recently had success in this area. Mice who began receiving the Lees’ viral gene therapy a day after their birth saw some functions restored. Soo-Kyung Lee received a $1.5 million grant from the Simons Foundation Autism Research Initiative earlier this year to continue the research.

Planned research topics for the FRC include drug discovery, sensory issues like sleep disturbance and mood changes, and the role of mitochondria in neurodevelopmental disorders.

Joining the Lees at the FRC will be an interdisciplinary team of UB faculty, including expected new hires. Collaborators already in place include:  

• Denise Ferkey, PhD, associate professor and associate chair of the Department of Biological Sciences;

• Michael Yu, PhD, associate professor of biological sciences; 

• Wei Sun, PhD, associate professor and director of undergraduate studies of the Department of Communicative Disorders and Sciences; 

• Priya Banerjee, PhD, associate professor of physics; 

• Yungki Park, PhD, associate professor of biochemistry; 

• Edward Kwon, DDS and PhD, assistant professor of oral biology.  

Graduate students are also expected to conduct research in FRC labs.

“The FRC will harness the expertise of our faculty to unravel the remaining mysteries of FOXG1 syndrome and, hopefully, help Yuna and the other children impacted by this disorder. ”

Soo-Kyung Lee, Empire Innovation Professor and Om P. Bahl Endowed Professor of Biological Sciences

University at Buffalo

Media Contact Information

Tom Dinki
News Content Manager
Physical sciences, economic development
Tel: 716-645-4584
[email protected]

The FOXG1 Research Center at the University at Buffalo led by FOXG1 parents Dr. Soo-Kyung Lee and Dr. Jae Lee, along with FOXG1 Research Foundation, co-founder Nicole Johnson, Chief Drug Development Officer Dr. Gai Ayalon, and FOXG1 grandparents Tom and Janet Horton

2023 Impact Report

2023 marked six years of the FOXG1 Research Foundation. We are a parent-driven, global foundation with the mission to help improve the lives of every person affected by FOXG1 syndrome worldwide. We are immensely proud of the organization we have built and the resources we have made available to our community since 2017.

We are known in the industry as innovators focused on three equally critical areas: FOXG1 science, FOXG1 patient data, and FOXG1 patients and community. From advancing our gene therapy program, to building our own bioinformatics platform, to helping guide parents through the rare disease medical caregiver journey, this year has been a year of upward progress in all three areas.

Our community is mourning the loss of 8 children in 2023 alone. We must stop this from happening. We are grateful for this incredible team working collectively to advance this goal, and most importantly, to our donors who enable this work.

Here are some of the FOXG1 Research Foundation highlights from 2023:

• Raised >$1.5M ($7.5M to date)

• Concluded our gene therapy preclinical work to upregulate the FOXG1 gene, rescue symptoms, and pass preliminary safety measures 

• Finalized characterization of key FOXG1 animal models, which are critical for drug screening

• Hired Chief Drug Development Officer, Dr. Gai Ayalon from Neumora Therapeutics to lead us successfully to a gene therapy clinical trial with the FDA and other international regulatory agencies

• Named Dr. Soo-Kyung Lee our Chief Scientific Officer, a FOXG1 mother and esteemed neuroscientist  who leads the FOXG1 Research Center of Excellence at the University at Buffalo with a team of >20 members focused solely on FOXG1 syndrome

• Built FOXG1 bioinformatics platform where all raw scientific, genetic and clinical data is normalized and cleansed enabling drug discovery and data for accelerated drug development from novel AI tools 

• Published paper on FOXG1 syndrome from our FOXG1 patient registry; 3 more publications underway

• Submitted paper to Journal of Neurology on epidemiology of FOXG1 syndrome meta-analysis results 

• Joined pharmaceutical-funded Biomarker studies with CombinedBrain

• Implemented FOXG1 Parent Support Team with monthly support zooms and resourceful webinars

• Connect newly diagnosed families to resources, medical professionals, and other families

• Announced the first FOXG1 patient to our advisory board, bringing a FOXG1 patient’s voice to our community

• Remain sought-after thought leaders/ speaker on podcasts and conferences

Here are some of the things the FOXG1 Research Foundation is working on in 2024:

• Moving our gene therapy program from preclinical to clinical stages with a focus on GMP manufacturing of product and toxicology studies 

• The 2024 FOXG1 Science Symposium and Parents Conference in November in Florida, USA

• Continue preclinical projects around small molecule, RNA and antisense oligonucleotide (ASO) drug screenings while continue studying the FOXG1 gene’s impact on the brain 

• Undertaking a large body of pre-work for clinical trials: deciding clinical trial endpoints, publishing a Disease Concept Model, meetings with clinical trial sites, meetings with the FDA and international agencies 

• Collaborations with biopharma companies as potential partners for our drug development programs 

• Exciting new resources for families to help assist managing their medical journeys, which includes new parent support webinars, virtual support meetings, and more

• Publication on FOXG1 Natural History Study data and FOXG1 Epidemiology papers in peer-reviewed medical journals  

• FOXG1 Research Center of Excellence at the University at Buffalo official ribbon cutting

• Growing FOXG1 clinicians network towards Standard of Care Guide for FOXG1 syndrome

• Establishment of expanded biobank with Coriell

• Continuing to expand our toolkit of assets to evaluate current and future therapeutic approaches
  

2023 FOXG1 Research Foundation Media 

*CARETALK Podcast: Why Rare Disease Research is SO Important with FOXG1 Research Foundation CEO, Nasha Fitter: Rare Disease Research and Its Potential To Unlock Medical Mysteries

*Ranked #9 Top Podcast Episode on Apple Health!

San Francisco Business Times: How two mothers are finding hope in searching for their children’s cures

Video Recap: The 2022 FOXG1 Science Symposium and Parents Conference

SFARI News: Dr. Soo-Kyung Lee, FOXG1 Research Foundation Scientist, Earns Grant from Simon Foundation Autism Research Initiative (SFARI) for Genomics of ASD: Pathways to Genetic Therapies 

Cafe Mom: 'Power of Moms': This Mom Quit Her Job To Find a Cure for Her Daughter’s Rare Disease

Press Release: New Children's Book "Joyfully Josie" Aims to Spark Conversations Around Disabilities, Rare Diseases, and Inclusion

Enable Magazine: Disability Pride Month: Educating the next generation to create an inclusive future

FRF Appoints Chief Drug Development Officer, Dr. Gai Ayalon

We’re thrilled to announce the appointment of Dr. Gai Ayalon as the Chief Drug Development Officer of the FOXG1 Research Foundation (FRF).

Dr. Ayalon is a distinguished neuroscientist and drug developer, who over many years led teams and spearheaded drug development programs for neurological diseases including rare neurodevelopmental disorders, spanning the discovery, translation and clinical phases. He joins our foundation at a critical and pivotal juncture as we enter Phase Four on our Path to a Cure, taking programs through safety studies and clinical trials. 

We have successfully accomplished Phase One through Three on our Path to a Cure: building disease models, studying these models, and testing gene therapies, ASO's, CRISPRa and saRNA therapies on our models. These early experiments have shown that we can upregulate FOXG1 gene and protein levels, we can do so safely, and we can rescue key symptoms in animals such as motor function, cognition and corpus callosum degeneration. Dr. Ayalon will now lead this next phase by taking our therapeutic programs, one by one, to clinical trials. In order to do this we will be performing activities such as vector optimization, exploratory toxicology, GLP manufacturing and toxicology, and completing regulatory filings. 

Dr. Ayalon previously worked at Ultragenyx Pharmaceutical, where he was the Project Team Leader of programs for pediatric neurodevelopmental disorders such as Angelman syndrome. Prior to Ultragenyx, Dr. Ayalon was a scientist at Genentech, in the neuroscience department. At Genentech he led drug discovery programs and teams focused on immunotherapeutic approaches to neurodegenerative diseases. 

Most recently, Dr. Ayalon was Vice President, Head of the Portfolio and Program Management group at Neumora Therapeutics, where he also led clinical stage programs for neuropsychiatric disorders. Dr. Ayalon received his Ph.D. from the Hebrew University Medical School in Jerusalem, Israel, and conducted his postdoctoral research at the Howard Hughes Medical Institute at the Duke University Medical Center.  

In his new role as Chief Drug Development Officer, Dr. Ayalon will navigate the FOXG1 Research Foundation through clinical drug development, working closely with Dr. Soo-Kyung Lee’s lab at the University at Buffalo, as well as the FOXG1 Scientific Consortium of labs, and our global biopharma and clinical partners.  

We cannot be more optimistic about joining hands with Dr. Ayalon for this next chapter in our journey to greatly improve the lives of every patient and the families affected by FOXG1 syndrome. 

Dr. Soo-Kyung Lee Named FOXG1 Research Foundation Chief Scientific Officer

Dr. Soo-Kyung Lee and the Lee Lab at the FOXG1 Center of Excellence University at Buffalo

Buffalo, New York August 10, 2023: The FOXG1 Research Foundation (FRF), a parent-led rare disease patient organization focused on driving therapeutics for FOXG1 syndrome, an Autism-related neurological condition, announced today the appointment of Dr. Soo-Kyung Lee as the new Chief Scientific Officer of the FOXG1 Research Foundation (FRF). Dr. Lee is an Empire Innovation Professor and Om P. Bahl Endowed Professor at University at Buffalo Department of Biological Sciences. 

Since joining the FRF in 2017, Dr. Lee has elevated the FOXG1 research center at the University at Buffalo to a global leader in the field. Her exceptional work has garnered around $3M annually from federal agencies, FRF, UB, and the Simon Foundation Autism Research Initiative (SFARI), notably receiving SFARI's 2022 Genomics of ASD: Pathways to Genetic Therapies award.

Dr. Lee’s dedication to curing FOXG1 syndrome is deeply personal as a mother to Yuna, diagnosed with FOXG1 syndrome in 2009.

Her passion and commitment have inspired everyone fortunate enough to work with her. It's a rare and special circumstance to have FOXG1 parents leading the scientific journey towards effective therapeutics for all FOXG1 children globally.

Watch Dr. Soo-Kyung Lee's incredible story in this New York Times video.

Together with her neuroscientist husband, Dr. Jae Lee, Dr. Soo-Kyung Lee has created a suite of comprehensive models to understand the full spectrum of FOXG1 syndrome. With a team of more than 20 scientists (and growing) dedicated to FOXG1 syndrome, the Lee Lab is spearheading cutting-edge translational therapeutic strategies, notably the AAV9-dependent viral gene therapy. As parents gearing up to apply this gene therapy to their own daughter, they uphold unparalleled safety, efficacy, and urgency standards.

In her new role as Chief Scientific Officer, Dr. Lee will be responsible for leading the  scientific initiatives of the FOXG1 Research Foundation, which includes the FOXG1 Scientific Consortium of labs along our roadmap to successful therapeutics. With Dr. Lee at the helm, and in collaboration with the global partners, the FRF will operate with the agility and focus of a world-class organization, maintaining their mission-driven ethos to advance multiple therapies into clinical trials as soon as possible.

“The FOXG1 community is privileged to have Dr. Lee spearheading our therapeutic efforts for FOXG1 syndrome. Her unparalleled dedication, acumen, and urgency have consistently shone through her work, with biopharma leaders, the NIH and other global agencies tapping her knowledge in the field of FOXG1 research. We eagerly anticipate the continued groundbreaking accomplishments her leadership will usher, and therapies for all children suffering from FOXG1 syndrome,”expressed FOXG1 Research Foundation CEO and co-founder, Nasha Fitter.

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2022 Impact Report

2022 marked five years of the FOXG1 Research Foundation.

Our work brings us closer to successful therapeutics for every child, while supporting families along this difficult journey. We continue to be one of the most innovative foundations in the rare disease space, focused on three equally critical areas: FOXG1 science, FOXG1 patient data, and FOXG1 patients and community. From gene therapy to rescuing a FOXG1 family in the Ukraine, this year marks our biggest breakthroughs in all three areas.

Our greatest purpose is to end the suffering of children with this terrible disease. Our community is mourning the loss of 11 children in 2022/23 alone. We must stop this from happening. We are grateful for this incredible team working collectively to advance this goal, and to our donors who enable this work.

2022 Research Highlights (see details below)

• Breakthrough gene therapy results showing rescue of FOXG1 brain structure, behavior, memory and cognition symptoms in animal models

• Positive results on initial compound drug screens to identify molecules to increase FOXG1 levels; now moving forward to larger screens

• Never-before understanding of FOXG1 biology uncovered from six FOXG1 patient human cell lines and mouse models 

• Successful testing of guide RNAs to increase FOXG1 expression with a CRISPRa Cas-9 system

• Discovered ASO sequences (antisense gene therapy) to modulate FOXG1 expression; testing initiated with Creyon Bio  

• FOXG1 data package presented to several biotech companies with high interest

2022 Foundation Highlights

• Hosted first-ever FOXG1 Syndrome Parents Conference (in-person and virtual) with parents, families, clinicians, scientists from all over the world

• Hosted third FOXG1 Syndrome Science Symposium (in-person and virtual) with a consortium of global scientists collaborating on the path to a cure 

• Publishing first 100 patient natural history study of FOXG1 syndrome patients 

• Launched successful rescue operation of FOXG1 family trapped in the Ukraine; created fundraising campaign to help rebuild their lives in Poland

• Asked to speak on multiple podcasts and industry events, continued to be called “innovators” and “leaders,” assisting many other rare disease foundations 

• Launched FOXG1 Research Foundation España

• Raised over $1,000,000 globally in 2022 ($6M to-date)

2022 Funding and Research Details (View Research Projects)

Gene Therapy:

• Breakthrough AAV9 gene therapy preclinical trial results with two promoters that successfully rescue FOXG1 brain structure, behavior, memory and cognition symptoms in animal models. Next step is toxicology studies as we begin an IND application. If successful, we will be in clinical trials within two years

• Further testing of additional promoters at the Lee Lab - FOXG1 Center of Excellence that may more-effectively drive FOXG1 in specific cells

• Funding Dr. Goichi Miyoshi at Gunma University Graduate School of Medicine to identify cells and circuits responsible for the manifestation of FOXG1 Syndrome in the brain and test a specialized rescue strategy  

• Initiated the development of a “rescue” mouse model to be used to determine the cell types and timelines that are key to restoration of FOXG1 symptoms

RNA Therapies

• RNAi/a therapies - Identified multiple sequences and conducted experiments that both upregulate and downregulate FOXG1 gene expression via RNAa and RNA mechanisms in human neurons. Now stabilizing sequences and testing for efficacy and toxicity in additional patient derived human stem cells and animal models. If successful, we are within 3 years of clinical trials

• ASO therapies - Identified a group of ASO molecules that upregulate FOXG1 gene expression. Using a proprietary platform, we are testing these ASO’s to find the most optimal ones. If successful, we could be in clinical trials in 2024 

Drug Repurposing and Label Expansion

• Screening of 4,000 compounds to increase FOXG1 expression led to 40 FDA-approved drug candidates found through Rarebase neuroscience platform 

• Screened ~150 small molecules on our zebrafish platform

• Created neuronal assets and investigated several neuronal platforms, screens to start within next few months

• Initiating c-elegans genetic screen in FOXG1 worm models to identify pathways that can compensate for the loss of FOXG1 

CRISPRa Therapy

• Identified a number of lead sgRNA and dCas9-effector combinations for upregulating FOXG1 expression in HEK293 cells, healthy NSC, and in patient iPSC-derived NSC

• Next steps are to check for potential off-target effects and ability to rescue neuronal phenotypes before embarking on toxicity studies to assess if this is an effective modality for FOXG1

Genetic Model Characterization Work

• Analyzed brain structure and behavioral deficits in three mouse models, developed insight into impact of DNA binding affinity; continuing to research additional models and publication underway

• Confirmed the presence of FOXG1 mutations and otherwise normal chromosomal composition in six patient iPSC lines; seeing protein expression changes

• Funded Dr. Jeanne Paz at Gladstone Institute to characterize the electrophysiology and seizures in our mouse models. This will identify where in the brain seizures are forming as well as identify any unique brain signatures

• Confirmed the formation of smaller brain organoids from two patient lines compared to healthy controls

FOXG1 Patient Data

• Enrolled >100 children and adults with FOXG1 syndrome into our natural history study, hosted on the Ciitizen platform, the most comprehensive and innovative natural history study for FOXG1 syndrome patients 

• Longitudinal medical record collection for all participants, averaging ~1200 pages of data from ~5 institutions, per participant - this totals 618 years of data reviewed

• Uncovered information on demographics, comorbidities, common medications, exam findings, therapeutic procedures, developmental milestones; data will assist in identifying primary and secondary endpoints in clinical trials

• Two years of FDA validated surveys completed by the first 50 participants, evaluating developmental milestones, behavior, and sleep

• Three breakthrough manuscripts in preparation that include clinical data about FOXG1 syndrome

• Continued to build global FOXG1 Patient Registry encompassing ~500 unique patient mutations

FOXG1 Research Models / Assets Created

• 6 human stem cell lines and 16 patient fibroblasts containing unique mutations available in FOXG1 Coriell global repository

• Five CRISPR corrected patient stem cells stored in FOXG1 In-House Cellular lab 

• Inducible rescue mouse line underway at Lee Lab - FOXG1 Center of Excellence

• 5+ patient mouse models being characterized and stored at Lee Lab - FOXG1 Center of Excellence; publication underway 

• Accessible raw patient survey and natural history data available at FOXG1 Data Center and Ciitizen

2023 Goal: Drive the science to clinical drug development

• Continue progress towards clinical trials for gene therapies

• Accelerate each project by funding additional post-docs; continue funding scientific team 

• Fund further understanding of FOXG1 symptoms, such as electrophysiology characterization in mouse models

• Compile arsenal of repurposed drugs that can be prescribed by individual physicians 

• Continue to expand upon patient registry and natural history study work

• Raise reserves for clinical drug development

• Partner with biopharma to include FOXG1 syndrome in their pipelines

• Host continued parent and science conferences 

• Be there for our community through resources, encouragement and love

Funding:

FOXG1 Research Foundation 2022 Source of Funds

Media

The Lee Lab in Spectrum News | Global Genes Rare Leader Interview | I AM BIO Podcast | Port Washington Living | Rare Mama Rising Podcast | Female Founders Paving the Way for Innovation - BIO International Convention | Women’s Entrepreneur Day (WEDO) Conference at the UN |

THANK YOU

This work to improve countless lives is truly a global collective and collaborative effort. We can not thank every person who is a part of this journey with us enough. On behalf of the worldwide FOXG1 community, thank you for believing is us, guiding, and supporting us.

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The Johnson Family - Changing the World Right Here in Port Washington