27-28 May 2026
Sanofi Campus Gentilly
3rd Edition
27-28 May 2026
Sanofi Campus Gentilly
3rd Edition
Diseases targeting the liver are life threatening and organ transplantation remains the only treatment for acute liver failure and end-stage chronic liver disease. However, transplantation does not represent an ideal treatment as it entails high risk of surgical complications, indefinite immunosuppression associated with severe side effects, and organ dysfunction. More importantly, the number of organ donors remains constant while the demand for liver transplantation has more than doubled in 10 years. Thus, only a limited number of patients can benefit from this therapy. Cell therapy using hepatocytes represents an alternative for organ transplantation. However, this approach is limited by the difficulty to grow adult primary hepatocytes in vitro. Human induced Pluriptotent Stem Cells (hiPSCs) could provide an alternative source of liver cells for clinical applications. However, several challenges need to be addressed including the development of culture conditions compatible with GMP requirements, large scale production, and protocol of differentiation allowing the generation of cells with mature hepatic functions. Here, we describe our recent progress in addressing these limitations through the development of new methods for in vitro production of hepatocytes with sufficient hepatic function to alleviate life threatening liver diseases.
Ludovic Vallier is Einstein Professor for Stem Cells in Regenerative Therapies at the Berlin Institute of Health (BIH) and Max Planck Fellow at the Max Planck Institute for Molecular Genetics (MPIMG). He received his PhD from Ecole Normale Superieure of Lyon /University Claude Bernard in 2001 where he studied the function of cell cycle regulators in pluripotency. He then joined the group of Prof. Roger Pedersen at the University of Cambridge, Department of Surgery, where he became an independent investigator in 2008 after receiving a MRC non clinical senior fellowship and was named Professor of Regenerative Medicine in 2015. He moved to the BIH in 2022 and his newly created group takes advantage of human pluripotent stem cells and primary organoids to generate liver cells with a clinical interest for disease modelling and cell-based therapy.
GoLiver Therapeutics, a spin-off of INSERM and the University of Nantes (France), is an innovative healthcare biotechnology company specializing in the development of advanced therapy medicinal products that harness the transformative potential of pluripotent stem cells. The company’s ambition is to deliver the world’s first stem cell-based liver therapy, addressing a critical unmet medical need.
Dr Tuan Huy Nguyen is a liver‐directed cell and gene therapy pioneer with more than 30 years spanning basic and translational research. His research at INSERM encompassed a broad spectrum of cutting-edge biological tools, including lentiviral and AAV vectors, CRISPR/Cas and ZFNs, and primary and pluripotent stem cells, applied across both small and large animal models.
From 2012 to 2017, he headed the Liver Cell & Gene Therapy group at INSERM UMR1064 in Nantes and co-led an EU-FP7 project that demonstrated the curative potential of stem-cell-derived hepatocytes in rodent models of Crigler–Najjar syndrome and acute liver failure. This pivotal work laid the groundwork for the 2017 co-founding of GoLiver Therapeutics, where Dr Nguyen now serves as Chief Scientific Officer.
His significant contributions to the scientific community are reflected in his authorship of over 70 peer-reviewed publications, the receipt of three international research awards, and his tenure as Deputy Editor of Current Gene Therapy (2014–2017).
Hematopoietic cell transplantation (HCT) is a crucial therapy for blood disorders like leukemia, sickle cell disease, and autoimmune diseases. Increasing demand for clinical-grade hematopoietic stem cells (HSCs) presents challenges in patient care.
To address this, we propose large-scale HSC production from human induced pluripotent stem cells (hiPSCs) at an Advanced Therapy Medicinal Production (ATMP) core facility and a new large animal model for human HCT. We developed a robust, transgene-free 17-day protocol to differentiate hiPSCs into transplantable HSCs using morphogens and cytokines. Collaborating with Atlantic Bio’s GMP ATMP facility, we scaled up HSC production, ensuring quality control through cytometric validation and transplantation into irradiated NSG mice.
In parallel, we adapted the Aachen mini-pig model for HCT, a suitable pediatric oncology model. Key developments included conditioning regimens using irradiation and immunosuppressive drugs, monitoring, and blood analysis. Overcoming porcine immunity, Cobra Venom Factor was used to protect human cells by inhibiting complement.
With scaled HSC production validated and conditioning protocols established, the large animal HCT study is in process. This marks a critical step towards hiPSC-derived transplants, advancing treatment for hematological and autoimmune diseases.
I am a PhD student under a CIFRE fellowship at the Etablissement Français du Sang (EFS). With a strong foundation in hematology and transfusion science, I’ve dedicated the past five years to research in this field, beginning with a Master’s internship at the Centre de Recherche de Saint Antoine in Paris, where I was inspired by the first laboratory-generated blood transfusions conducted on patients. Our team combines deep expertise in hematopoietic stem cells derived from iPSCs, translational medicine, and a commitment to advancing cell therapies.
Isolated methylmalonic acidemia (MMA) is a severe inherited metabolic disorder primarily caused by mutations in the MMUT gene, leading to toxic accumulation of methylmalonic acid. Clinically, MMA presents in early life with recurrent metabolic crises, growth failure, and progressive multi-organ damage. A promising therapeutic approach involves liver-directed gene therapy using integrative immune-shielded lentiviral vectors (ISLVs). These vectors feature an immune‑evasive design that minimizes immune rejection, supporting long‑term efficacy following a single administration. ISLVs integrate into the host genome, enabling durable gene expression even in dividing hepatocytes, providing stable, lifelong expression of the therapeutic transgene in the liver, a key advantage for treating pediatric patients.
To evaluate the therapeutic potential of this approach, we delivered MMUT-encoding ISLVs to MMA mice. This resulted in rapid and sustained metabolic correction, with improvements in liver histology and mitochondrial structure. High MMUT expression in the liver reduced toxic metabolite levels in extra-hepatic tissues and restored metabolic, lipid, and protein profiles in both liver and blood. Therapeutic benefit was observed across a range of vector doses, with evidence of a selective advantage for corrected hepatocytes. Ongoing studies are focused on advancing ISLV-based gene therapy toward clinical translation as a treatment for MMA.
Julianne Smith is Chief Development Officer at Genespire, where she contributes to the strategic direction, planning, and execution of in vivo liver-directed gene therapy programs, with a particular focus on shaping the nonclinical strategy to advance novel therapies toward the clinic and beyond. She brings over 30 years of experience in scientific research, including 22 years in the biotech industry, with a strong background in cell and gene therapy research, early development, and translational science.
Elena Gaia Banchi1, Nissrine Ballout 2, Rafael Alonso1, Johan Deniaud3, Sylvie Jacquot1, Kevin Fransquin1, Françoise Roux4, Marie Anne Colle3, Jérôme Ausseil2, Françoise Piguet1.
1TIDU GENOV, Paris Brain Institute, Paris, France,
2 Biochemistry, Toulouse University Hospital, Toulouse, France.
3 UMR 703 PAnTher INRAE/Oniris, Ecole Nationale Vétérinaire, Agroalimentaire et de l’Alimentation Nantes-Atlantique
4 ONIRIS Veterinary school of Nantes, Nantes France.
MPSIIIB is an autosomal recessive lysosomal storage disorder, caused by alpha-N-acetylglucosaminidase (NaGlu) enzymatic deficiency leading to accumulation of Heparan Sulfate Oligosaccharides (HSO) in tissues including the central nervous system (CNS). Patients manifest with early developmental delays followed by severe behavioral abnormalities, progressive neurodegeneration, and death before the age of 20 years. To date, there are no curative therapies for MPSIIIB. We have previously conducted a AAV-2/5 phase I/II intracerebral gene therapy trial that has shown promising results in four MPSIIIB patients with best results being obtained in the youngest patient (18 months-old). However, disease progression in tissues as important as meninges, brain capillary walls, and choroid plexus was presumably not stopped. Therefore, treatment of patients younger than 2 years and the delivery of NAGLU both within and outside the brain was concluded.
We recently described and presented last year a novel AAV gene therapy using AAVPHP.eB-CAG-NaGlu vector with intravenous delivery in mouse model and combine intracerebral and intravenous delivery in dog and non-human primates. We demonstrated a good efficacy but some local inflammation at the injection site in the brain.
We thus improved our therapeutic strategy by using last generation AAV with AAVMacPNS1, a serotype able of large Blood brain barrier crossing after intravenous delivery notably in large animals. We demonstrate a large CNS transduction of the vector in mouse and NHP after intravenous delivery as well as supra physiological NAGLU expression and activity and a perfect tolerance of the AAV on all tissues.
Efficacy and safety studies are currently ongoing in the dog model of the pathology and data will be presented.
Dr. Françoise PIGUET is heading the innovation unit GENOV in Paris Brain Institute focused on development of gene therapy approaches for neurodegenerative diseases. Since 2006, she contributed to the field of neurodegenerative diseases and development of AAV based- gene therapy approaches first on leukodystrophies, Huntington, Friedreich Ataxia, ALS and mucopolysaccharidosis. She previously developed a clinical trial on metachromatic leukodystrophy and generated 8 patents for notably a gene therapy approach for Friedreich Ataxia as well as for Rett syndrome, MLD, ALS and MPS as well as cell therapies. More recently, Françoise is working on development of new routes of delivery to efficiently target the central and peripheral nervous system. She is an expert of preclinical studies to fill IND and CTA applications.
Coave Therapeutics is revolutionizing gene therapy with its proprietary ALIGATER™ platform, designed to overcome challenges in tissue specificity, delivery efficiency, and manufacturability. ALIGATER™ enables a one-step chemical conjugation process to attach targeting ligands—such as peptides, small molecules, or antibody fragments—to AAV and non-viral vectors. This approach enhances therapeutic precision while maintaining compatibility with existing manufacturing processes. The platform’s first-generation conjugated AAVs (coAAVs), utilizing sugar-based ligands, have demonstrated superior performance in preclinical studies, achieving enhanced tissue diffusion and distribution in the CNS and retina of mice, rats, and non-human primates. Additionally, peptide-conjugated AAVs have been developed to precisely target human receptors, with targeting efficacy modulated by ligand density. These results highlight the versatility and robustness of the ALIGATER™ platform in enabling advanced gene delivery solutions. By addressing key limitations in gene therapy vector design, ALIGATER™ is paving the way for safer, more effective, and scalable genetic medicines with broad clinical applications.
Dr. Lolita Petit is the Chief Scientific Officer at Coave Therapeutics, a Paris-based biotechnology company developing next-generation gene therapies for CNS, neuromuscular, and ocular diseases. With extensive experience in gene therapy research and development, she has led programs from target discovery to clinical development. Dr. Petit has held key scientific leadership roles at Spark Therapeutics (a Roche company) and Johnson & Johnson, where she contributed to innovative gene delivery platform technologies and advanced therapeutic programs for CNS and ocular indications. She is recognized for building and leading high-performing, cross-functional teams that drive innovation and deliver transformative therapeutic solutions, with a focus on precision AAV engineering.
Lipid nanoparticles (LNPs) represent a transformative platform for the precise delivery of therapeutic agents, leveraging their versatile architecture to navigate complex biological landscapes. By tuning core properties such as size, surface charge, and lipid composition, LNPs can preferentially localize within specific tissues, exploiting natural tropisms to enhance drug accumulation where it is most needed. Beyond this passive homing, the integration of targeting ligands—proteins, peptides, or antibodies—onto the nanoparticle surface empowers active recognition of disease-associated markers, dramatically improving cellular uptake and therapeutic efficacy. This dual strategy of combining inherent physicochemical tropism with engineered binding motifs underscores the critical importance of targeting in minimizing off-target effects and maximizing clinical benefit. As LNP technologies continue to evolve, their capacity for bespoke design and precise delivery will be pivotal in advancing next-generation treatments across a spectrum of diseases.
Catalina Bordeianu is a materials chemist with a strong foundation in organic chemistry, earned at the Engineering School of Chemistry in Strasbourg. She completed her PhD in materials chemistry with a focus on engineering novel targeted nanoparticles for magnetic resonance imaging— an achievement that led to the creation of the startup Superbranche.
She subsequently joined Brigham and Women’s Hospital at Harvard Medical School, where she led the development of smart biomaterials designed to prevent lung cancer recurrence. This research has since transitioned into a standalone biotech startup.
In 2020, Catalina joined Sanofi as a Scientist and was appointed Laboratory Head in 2022. She currently leads a multidisciplinary team dedicated to the formulation of innovative lipid nanoparticles for gene therapy applications.
Targeted intracellular delivery of RNA still remains a key requirement. We focus on a bio-inspired chemical evolution strategy. By incorporation of artificial amino acids such as tetraethylene pentamino succinic acid or lipo amino fatty acids (LAF) into xenopeptides (XPs), double pH-responsive carriers have been designed for potent intracellular delivery of RNA in vitro and in vivo. Enhanced endosomal escape turned out to be a key factor for RNA delivery. A pH-dependent polarity of LAF was implemented by a central tertiary amine, which disrupts the hydrophobic character once protonated, resulting in drastic pH-dependent change in the distribution from lipid phase (physiological pH) to lipid/water interface (endosomal pH), as supported by molecular dynamics calculations and SAXS. Activity was maintained in full serum and at very low dosage of only ~2 nanoparticles/cell. Applications include mRNA expression in several organs upon systemic administration, in vivo gene silencing by siRNA-LNPs with superior activity in liver endothelial cells or, when including targeting ligand cRGDfk, in tumor endothelial cells. Potent carriers for CRISPER mediated genome editing, either via Cas9 mRNA/sgRNA or Cas9 protein/sgRNA RNPs, triggering therapeutic genome editing of immune check-point genes in cancer, or in vivo editing of dystrophin.
Prof. Ernst Wagner is Chair of Pharmaceutical Biotechnology, Department Pharmacy, LMU Munich (since 2001). He was Director Cancer Vaccines, Boehringer Ingelheim 1992-2001 (world-wide first polymer-based gene therapy in 1994), 1987-1995 Group Leader at IMP Vienna and Vienna University Biocenter, 1985-1987 postdoc at ETH Zurich, 1985 PhD (TU Vienna). He is Academician of European Academy of Sciences, Controlled Release Society (CRS) College of Fellows, Honorary Professor at U of Sichuan. He authored ≥ 524 publications, with ≥ 54 800 citations, h-index 117 (GS).
Philippe is the Chief Executive Officer of Curapath. He brings over 29 years of experience in the chemical & pharmaceutical industry, with a specific focus on active pharmaceutical ingredient market (CDMO & Generics) and drug delivery solutions from R&D to commercial. Philippe has an extensive track record not only with regards to business development and the creation of trustful partnerships in Europe / US / Japan but also in process development, industrialization, and continuous improvement. Before joining Curapath, Philippe worked for 3 international companies with extensive development and manufacturing capabilities for pharmaceutical markets – Rhodia (now Solvay), Sanofi and Seqens – where he engaged and led global teams towards ambitious roadmaps and through challenging projects. For instance, Philippe was instrumental to
Philippe received two awards from Sanofi for his entrepreneurship and partnership achievements. He graduated from the Engineering School of Physics and Chemistry of Bordeaux (now ENSMAC), and obtained his PhD at University of Bordeaux, funded by EDF and Rhône-Poulenc/Rhodia, for which he was awarded best PhD thesis of French Chemical Society (SFC).
One of the current challenges for the development of novel gene therapies is the prediction of the human dose from preclinical data. In general, the human dose prediction is built on the pharmacokinetics (PK) drug properties informed from preclinical data and allometric scaling principles. For gene therapies no such general allometric scaling principles for PK and human dose prediction have been established.
Here, we present a mechanistic mathematical model for the PK of AVM-022 in monkeys and humans. AVM-022 is a AAV2.7m8 viral vector delivering the aflibercept gene for treating wet age-related macular degeneration via a single intravitreal injection (IVT). The PK model integrated ocular PK of aflibercept with an expression model linking the dose given as vector genome copies (vgc) with the resulting VEGF concentrations in vitreous, retina, aqueous and plasma. The model assumed that the VEGF expression rate per volume of retinal tissue depended on the vgc Cmax in the vitreous with a sigmoid relationship, thus the VEGF expression rate saturated at a high dose levels. Fitting the model to monkey PK data from doses of 3×10¹⁰ – 2×10¹³ vgc/eye a maximal retinal expression rate of 12.7 μg·day-1·cm–³ was estimated. The estimated vitreous concentration for half-maximal expression rate was 1.4×1011 vgc·cm–³ (≙ dose of 0.22×1011 vgc/eye). The data further suggested expression in other ocular tissues at a maximal rate of 0.785 to 4.38 μg·day-1.
The human PK model was derived from the monkey PK model by adjusting all anatomical tissue volumes and surface areas to human. Further it was assumed that the human relationship between vitreal vgc concentration and VEGF expression rate per volume of retina was the same as in monkeys. The extra-retinal expression rate in human was scaled with the human-to-monkey-ciliary body volume ratio assuming that the ciliary body was the main source of VEGF expressed outside the retina.
Predictions of VEGF concentration levels in human aqueous were made for AVM-022 given as a single IVT administration of 2×1011 and 6×1011 vgc/eye and were compared to the observed data from a phase I clinical trial. The predicted median and 90 percentile agreed well with the observed individual concentration time profiles validating the PK modelling approach.
These results demonstrated that a mechanistic PK framework with the assumption that the expression rate per volume tissue is the same between monkey and human provided the correct dose predictions in human. This supports the use of mechanistic PK modelling for dose selection in first-in-human studies and for rational dose adjustments in clinical development, ultimately enabling a more efficient and robust translation of gene therapies from preclinical to clinical settings.
Dr. Matthias Machacek is Managing Director at LYO-X. He is an expert in PK/PD modelling and Quantitative Systems Pharmacology specializing in novel therapeutic formats and has been in the field for over 20 years. His group at LYO-X is supporting biotechnology companies to design efficient preclinical strategies, with robust first in human dose predictions and with clinical dose finding. His particular focus is on establishing and advancing PK/PD modelling and Quantitative Systems Pharmacology approaches for the most recent therapeutic approaches such as T cell engagers, cell-based therapies, oligonucleotides and gene therapies.
Au terme d’une formation scientifique à l’IUT de Montpellier, Nicolas a acquis une double compétence en Biotechnologie et Commerce avec un Master en biologie en 2019 puis un Master en commerce International en 2020.
Après 3 années dans des sociétés de biotechnologie, Nicolas a rejoint RD-Biotech en 2023 en tant qu’ingénieur commercial pour animer et développer notamment le secteur Ile de France, Nord et Europe du Nord.
The development of gene editing technologies, especially CRISPR-Cas9, has revolutionized genomic research and therapy. However, CRISPR and similar methods face limitations, such as off-target effects and challenges in editing large DNA fragments. The GREAT technology, developed by QUIDDITAS S.A., overcomes these challenges by using transposons, natural genetic elements capable of cutting and pasting DNA in the genome. This process, known as tagmentation, was first observed by Barbara McClintock in the 1940s and is responsible for genetic adaptations like antibiotic resistance in bacteria. This powerful yet random mechanism is present in various organisms, from bacteria to humans.
GREAT leverages transposons, specifically Tn5, to facilitate controlled and precise gene editing. Unlike CRISPR, which requires complex molecular designs and can result in off-target effects, transposons like Tn5 can insert larger DNA sequences with higher efficiency. The challenge has been controlling their activity, as transposons act in dimers and require structural rearrangements to function. The fusion of a transposon with guiding proteins typically inactivates the dimer, leading to loss of control. Recent advances have led to the development of CRISPR-controlled transposon systems, but these designs remain large and are not easily transposable for therapeutic applications.
The GREAT technology addresses this by designing a system where transposon dimers are loaded with a guiding DNA sequence, which restrains their activity until they encounter the target genomic location. Upon reaching the target, the guiding sequence « frees » the transposon, allowing it to perform its natural cutting and pasting action. This system allows for precise insertion of neo-synthesized DNA or the recombination of larger DNA fragments at specific genomic sites. By controlling the transposon dimer itself, GREAT enables efficient and targeted genetic rearrangements that were previously difficult to achieve.
The key innovation of GREAT technology lies in its ability to recombine large DNA fragments, enabling precise manipulation of large genomic regions. This advancement opens new opportunities in research and therapeutic applications, particularly for treating genetic disorders caused by large-scale mutations, such as certain neurodegenerative diseases and inherited diseases.
From a scientific and technical perspective, GREAT offers several advantages over existing methods. It is highly versatile, efficient, and precise with different types of genetic material. The system can be transferred using expression plasmids or RNA expression, making it scalable and compatible with a wide range of applications. From a medical point of view, the technology holds potential for safe and effective treatments for genetic diseases, as it is could base on well-established transposases like Sleeping Beauty and PiggyBac, which have been clinically validated for gene therapy.
Economically, GREAT could lower the cost of gene therapies, making them more accessible for clinical applications. By reducing the need for large, complex molecular designs, it simplifies the gene-editing process and improves scalability.
GREAT technology represents an advance in the field of gene therapy and genome editing. By enabling the recombination of large DNA fragments with precision, it expands the therapeutic possibilities beyond the limitations of current technologies like CRISPR. This innovation opens new possibilities for treating genetic diseases and advancing therapeutic gene editing.
I hold a PhD from a transatlantic co-thesis program between the University of Paris and Massachusetts General Hospital/Harvard Medical School, with a focus on BioTherapies and Genetics. I also hold a Master’s degree in Bioengineering from the EBI School and have further developed my management skills through the HEC Paris Business School Challenge+ program. In December 2022, I co-founded QUIDDITAS in Belgium.
Background: CAR-regulatory T cells (Treg) therapy holds promises for inducing long-term transplant tolerance while getting rid of immunosuppressive drugs. Our strategy aims to enhance the proportion of donor-specific CAR-Tregs and selectively deplete alloreactive T cells. We hypothesize that TCR-deficient (TCR-) CAR-Tregs will act synergistically with anti-CD3 therapy to achieve these goals.
Methods: Human TCR-deficient HLA-A2-targeted CAR-Tregs were generated via lentiviral transduction and CRISPR-Cas9 gene editing. In the first in vivo model, NSG mice received HLA-A2+ PBMC along with either TCR+ or TCR- CAR-Tregs. In the second model, a mix of TCR+ CAR-T and TCR- CAR-Tregs, expressing CBG or Firefly luciferase, respectively, was adoptively transferred into murine hosts with HLA-A2+ skin grafts. The selective depletion of TCR+ cells via anti-CD3 therapy was assessed by in vivo bioluminescence imaging and flow cytometry.
Results: TCR-deficient CAR-Tregs, despite the absence of the TCR/CD3 complex, could still be activated in a HLA A2-specific manner. These cells retained key phenotypic and epigenetic Treg markers. Transcriptomic analysis revealed that gene editing predominantly affected TRAC-related genes, with minimal impact on other pathways. TCR+ CAR-Tregs, in contrast to their TCR- counterparts, were selectively eliminated from blood and lymphoid organs following anti-CD3 treatment. Similarly, anti-CD3 therapy induced selective depletion of TCR+ CAR-T infiltrating HLA-A2+ skin allografts, while TCR-deficient CAR-Tregs were preserved and persisted within the allografts. Ongoing transcriptomic profiling and imaging mass cytometry analysis of skin allografts are being conducted to further evaluate the effectiveness of this combination strategy and to map the location of graft-resident CAR-Tregs.
Conclusions: Our data demonstrate that antiCD3 therapy can selectively advantage TCR-deficient CAR-Treg cells over resident TCR+ T cells in vivo. This approach enhances the therapeutic potential of CAR-Tregs, while reducing the number of cells required, thereby improving the clinical applicability of CAR-Treg-based therapies.
Tifanie BLEIN is a PhD student specializing in immunology and cell therapy. After graduating from Polytech Marseille in 2019, she joined Institut Imagine as an Engineer in Dr. Isabelle André’s team, working under Pr. Julien Zuber on developing CAR regulatory T cells (CAR-Tregs) to promote transplant tolerance. In 2022, she began a Ph.D. focusing on the synergy between anti-CD3 therapy and CAR-Tregs to enhance immune tolerance in transplantation. Her research aims to advance innovative immunotherapies, contributing to the development of safer and more effective treatments for transplant patients and autoimmune disorders.
Background: In developed countries, retinal degenerative diseases that affect the Retinal Pigmented Epithelium (RPE), such as Age-related Macular Degeneration (AMD) and inherited conditions like Retinitis Pigmentosa (RP), are leading causes of blindness. Despite significant scientific progress in recent years, no cure currently exists for these debilitating diseases.
Project description: We have successfully developed a novel cell therapy medicinal product, utilizing advanced tissue engineering and pluripotent stem cell techniques. This innovative cell therapy consists of RPE cells derived from clinical-grade human embryonic stem cells, cultured on a biocompatible substrate to create a 3D functional sheet suitable for transplantation. After functional validation in a rodent model of RP (Ben M’Barek et al., 2017), we assessed the safety of the surgical procedure and local tissue tolerance in non-human primates (NHP; Ben M’Barek et al., 2020). The encouraging results laid the foundation for the initiation of a Phase I/II clinical trial in 2019 (NCT03963154), which is currently ongoing. Seven patients have undergone transplantation thus far, with initial results showing no major adverse events, and in some cases, stabilization of nystagmus and fixation.
Innovative strength and applications: Our team has developed several patented medical devices for the production and preparation of the cell-based tissue-engineered product. Additionally, we have established proprietary protocols for the industrial-scale production of specialized retinal cells from human pluripotent stem cells. Through these innovations, we have demonstrated that tissue engineering significantly enhances therapeutic outcomes compared to traditional cell suspension injections. To protect this cutting-edge technology, three patents have been filed or granted. This approach holds promise for treating RP caused by gene mutations affecting RPE cells, as well as AMD patients. We are also advancing the technology to incorporate additional cell types into the engineered tissue, such as photoreceptors, to address all forms of RP and advanced stages of AMD.
Conclusion: We have developed a unique tissue-engineered product aimed at treating both AMD and RP. Looking ahead, our focus will be on advancing the product through the next stages of clinical development and refining industrial processes to scale up treatment for more prevalent conditions like AMD. To accelerate this progress, we are actively seeking industrial partners and investors to support the continued development and commercialization of this innovative therapy.
For over 12 years, I have been dedicated to developing stem cell-based therapies aimed at treating retinal dystrophies, including Retinitis Pigmentosa and Age-related Macular Degeneration. My work involves the use of human pluripotent stem cells (hiPSCs/hESCs) and tissue bioengineering to create innovative solutions. Additionally, I have developed various surgical techniques and medical devices designed to successfully engraft complex retinal tissue into the eye, advancing the field of regenerative medicine for eye conditions.
Cell and gene therapies are biopharmaceuticals whose development has accelerated in recent years due to their efficacy. Both genetically modified cell and gene therapies use a vector to deliver a genetic payload. This vector is typically a 30 to 150 nm large nanoparticle that contains DNA or RNA and delivers it to the targeted cell. Due to fabrication limitations, only a fraction of the vectors are correctly loaded while some of them are totally or partially empty. The latter reduces the efficiency of the drug and may be toxic.
Assessing if the vector is empty or loaded is currently a challenge. Available techniques are too slow, too complex, or too specific to be used routinely. Analytical ultra centrifugation takes hours to perform a single measurement, transmission electron microscopy requires a trained specialist to operate the instrument, and high performance anion exchange chromatography only works with specific vectors.
To address this challenge, we introduce a new technique called Digital Holography NanoTracking Analysis (DH-NTA). It is based on an interferometry scattering (iSCAT) microscope optimized for the detection and analysis of biological nanoparticles in the 30–300 nm size range. Its sensitivity enables label free detection of cowpea chlorotic mottle virus of 4MDa and a diameter of 30 nm in a few minutes demonstrating sufficient sensitivity to detect the smallest vector used in cell and gene therapy. The instrument provides three key parameters of the detected vectors at the single-particle level: hydrodynamic diameter (via diffusion tracking), scattering cross-section (proportional to mass via the amount of light scattered), and particle concentration. We use mass measurement to discriminate full and empty vectors, thanks to the fact that the latter are lighter than the former. We demonstrate mass measurements with a relative standard deviation of 3%, well below the typical mass difference between a full and empty vector.
Matthieu Greffet is an engineer specializing in physics applied to biology. He worked for 4 years as the first engineer of the start-up Myriade, developing an instrument for characterizing nanoparticles in the 80-400 nm range. For the last 3 years, he has been working at the Charles Fabry laboratory from the Institut d’Optique Graduate School on optical techniques for characterizing 5 nm nanoparticles, such as monoclonal antibodies, and 20 to 300 nm nanoparticles, such as viral vectors/LNP/EVs used as biopharmaceutical. He is currently President of the start-up UNVEIL, which develops instrumentation for biotech companies.
Background
Gene therapy for inherited retinal diseases (IRDs) has made significant strides, with adeno-associated virus (AAV) vectors emerging as the primary delivery system for therapeutic genes. However, assessing vector efficiency and specificity in human retinal cells remains a challenge due to the complexity of the retina and species differences in preclinical animal models. Human induced pluripotent stem cell (iPSC)-derived retinal organoids provide a physiologically relevant in vitro model, closely mimicking the structural and functional properties of the human retina. Optimizing AAV transduction in this system is critical for advancing gene therapy research and translation to clinical applications.
Project Description
Newcells’ human iPSC-derived retinal organoid model offers a cutting-edge platform for evaluating AAV gene therapy vectors. Retinal organoids are generated from iPSCs through a directed differentiation protocol, leading to the formation of laminated structures containing photoreceptors, Müller glia, and other retinal cell types. This model was utilized to assess the transduction efficiency of various AAV capsid variants (AAV5, AAV2 7m8, AAV2 quad mutant, AAV2 Y444F, and AAV8 Y733F) carrying fluorescent reporter genes under different promoters (CAG, GRK1, and EFS). After transduction, organoids were analyzed for reporter expression, cellular specificity, and viability. The study identified AAV2 quad mutant and AAV2 7m8 as the most effective serotypes for photoreceptor transduction, while GRK1-driven transgenes demonstrated selective targeting of photoreceptors.
Innovative Strength & Applications
Newcells’ retinal organoid model represents a transformative tool for preclinical gene therapy research:
Conclusion
Newcells’ human iPSC-derived retinal organoid model offers a robust, innovative platform for AAV gene therapy development. By optimizing transduction parameters and enabling targeted gene expression, this model enhances the predictive power of preclinical assessments, bridging the gap between in vitro studies and clinical applications. Its ability to replicate human retinal structure and function makes it an invaluable tool for advancing gene therapies for IRDs and beyond, contributing significantly to the field of in vitro cell and gene therapy (ICGT).
Amy is a Business Development Manager at Newcells Biotech. After earning a PhD from Newcastle University, she worked as a Research Associate in diagnostics before joining Newcells in 2022 as a Product Manager. She later transitioned into Business Development, where she focuses on fostering strong client relationships and supporting the design of customized projects to address key business challenges. She is particularly passionate about reducing reliance on animal models by utilizing advanced in vitro systems to promote more ethical research. At Newcells, she helps clients leverage innovative in vitro tools to gain insights into drug interactions with different tissues.
Background: Cardiac fibrosis is a key driver of heart failure, a leading cause of mortality worldwide. Excessive extracellular matrix (ECM) accumulation stiffens heart tissue, impairing function and leading to failure. Despite efforts to counteract disease progression, effective treatments capable of preventing or reverting fibrosis remain limited. Developing advanced preclinical models that accurately replicate human fibrosis to boost the test of innovative therapeutic strategies remain an urgent need.
Project description: In this context, we developed uScar, a 3D in vitro Organs-on-Chip (OoC) model of human cardiac fibrosis designed to simulate fibrotic remodelling under mechanical stress. By integrating dynamic mechanical stimulation in a 3D environment, uScar recreates key aspects of fibrosis progression. The uScar model consists of human atrial cardiac fibroblasts (AHCFs) cultured in 3D within a beating heart-on-chip system, allowing for the application of a cyclic uniaxial strain to microtissues – 10% at 1 Hz – which mimics the mechanical forces experienced by cardiac cells in vivo. This mechanical stimulation demonstrated to be sufficient to induce fibrotic traits in the human model, characterized by high fibroblast-to-myofibroblast transition and by an increased expression of ECM proteins such as collagen and fibronectin.
Innovative Strength & Application: By recapitulating these fundamental aspects of fibrosis, uScar demonstrated to be suitable to serve as a valuable tool for evaluating the efficacy of both existing and novel anti-fibrotic therapies. For a preliminary efficacy qualification, standard-of-care drugs, including Pirfenidone and Tranilast, have been tested in this model and were confirmed to effectively prevent the onset of fibrotic characteristics, validating uScar as a relevant and reliable preclinical platform. Beyond standard drug testing, the uScar model resulted pivotal to provide critical insights into the limitations of certain emerging therapies. Specifically, a promising miRNA-based therapy (i.e. miRs-1, 133, 208 and 499 – named « miRcombo »), developed to counteract fibrosis by promoting cardiomyocytes (CMs) differentiation in situ, was tested. miRcombo was previously shown to effectively reprogram fibroblasts into CMs in 2D cultures and it displayed similar efficiency when tested in static 3D culture (i.e. static uScar). However, it showed a reduced reprogramming efficacy when tested in the mechanically stimulated uScar model. Additionally, when tested for its ability to revert fibrotic traits, this novel miRNA-based therapy resulted able only to limit fibrotic-related characteristics (i.e. it effectively reduced the transition of fibroblasts into myofibroblasts as well as reducing matrix deposition) but failed to reprogram the CMs.
Conclusion: These findings underscore the crucial role of mechanical forces in cellular responses, highlighting the need for 3D in vitro models with in vivo-like stimulation for more predictive results. By closely replicating the physiological environment, uScar improves the assessment of therapies before clinical translation. Overall, uScar enables more accurate drug screening, reducing the reliance on animal models and increasing the likelihood of successful clinical outcomes as well as opening the path for testing advanced therapeutics specific targeting human genes. As research advances, integrating mechanical and biochemical cues will be crucial for refining disease models and accelerating anti-fibrotic treatment development.
I got my PhD in Biomedical Engineering in 2022. In BiomimX, I’m involved in strategic collaborations with Hospitals, Universities, CRO and Pharma in the context of organs-on-chip. As main activities, I lead the commercial and marketing team while also contributing to the composition of research grants. I represent BiomimX at relevant business and scientific events where I network with potential clients, industry professionals, and stakeholders to establish synergistic partnerships. I also collaborate closely with our R&D team, serving as a liaison between customers and engineers and communicating client needs, feedback, and product enhancements.
CAR-T therapies have demonstrated remarkable success in oncology and autoimmune diseases. However, their widespread adoption is hindered by high costs, significant adverse events, and the necessity for patient conditioning. In-vivo CAR-T reprogramming of the immune system offers compelling advantages over classical CAR-T approaches, including the elimination of pre-conditioning, controlled transient exposure, and improved dosage management. Despite generating significant interest in the field, this novel modality’s recent emergence and unique characteristics necessitate a case-by-case approach to drug development.
This presentation will elucidate the key aspects of nonclinical drug development for LNP-based in vivo CAR-T therapies. It will navigate the complex and evolving regulatory landscape, highlighting the challenges and opportunities inherent in this innovative approach. Ultimately, we will propose a blueprint for successfully advancing these promising therapies through the development pipeline and into the hands of patients who need them most.
Franck Chanut received his Doctor in Veterinary Medicine degree in 2002 from the Veterinary School of Nantes (France). He received a master’s degree in biotechnology from the University of Nantes in 2005 and obtained the same year his specialist degree in anatomic pathology. He successfully passed the examination to be a diplomate of the European College of Veterinary Pathologist in 2006. After experiences in the agrochemical industry, contract research organization, and pharmaceutical industry abroad working in non-clinical drug development mainly in the discovery pathology field, and with special interests in gene therapy. In 2015 he joined Sanofi, first as a pathologist and then as the head of the Techniques in Pathology group. He successfully passed the exam to be a diplomate of the American Board of Toxicology in 2016 and after being Head of Global Preclinical Safety Operations for the Paris area, he is now the Head of Preclinical Safety Projects for the French area, supporting all therapeutic areas globally. He is the author of several articles, posters, lectures and book chapters
This presentation outlines the development, qualification, and validation of DNA- and RNA-based analytical methodologies for quality control in the manufacturing and release of cell and gene therapy products. Emphasis is placed on alignment with the drug development lifecycle, analytical suitability, and regulatory compliance. We illustrate our approach with representative cases, such as AAV genome sequence identity verification via Oxford Nanopore sequencing and the quantitative assessment of chromosomal translocations in CRISPR/Cas9-edited CAR-T cells. For those interested in further technical detail, we invite you to visit our accompanying poster.
Sergey Yakushev studied protein biochemistry and molecular biology at Moscow State University and University of Zürich and obtained his PhD title in Integrative Molecular Medicine. During his postdoctoral research in prion disease at University Hospital Zürich he additionally finished the advanced studies in Pharmaceuticals at Swiss Federal Institute of Technology Zürich (ETH).
In 2015 he joined Microsynth AG, a leading company in nucleic acid synthesis & analysis. As head of the genetic analysis business unit his focus is on developing, validating, and applying various analytical procedures, utilizing state-of-the-art technologies such as digital PCR, NGS, and ONT-sequencing. Goal is to support biotech/pharma industry from R&D phase to the market authorization and routine release tests and to act as a reliable partner for the academy, enabling the collection of critical research data.
This presentation will describe how researchers have integrated patient engagement and co-design in the PragmaTIL trial, an ongoing Phase II clinical trial comparing safety, QoL, and efficacy of two IL-2 regimens (high-dose IL-2 vs. ANV419) in TILs therapy. This presentation will demonstrate how conducting iterative focus groups with patients and other key stakeholders from the project outset resulted in changes and improvements to the clinical trial, including addition of the patient-reported CTCAE as a co-primary trial endpoint, adaptation of the informed consent form into more accessible terms and creation of a supportive care tool and a patient information booklet. The experience of the PragmaTIL project demonstrates the value of patient engagement in the design and conduct of an early phase TILs therapy trial in capturing patient experience and symptom burden and in building a clinical trial pathway that is well adapted to patient needs.
Emma Gillanders is a Project Manager in the Cancer Survivorship Research Group at Gustave Roussy. Primarily working on international European projects, Emma has experience implementing co-design of research projects and studies with patients and other key stakeholders and ensuring collection of patient quality of life in diverse clinical trial settings. Through this work, Emma hopes to help design and conduct innovative, patient-centric and clinically relevant clinical research projects with the goal of building a cancer survivorship care model that is proactive, personalized and participatory.
For more than 15 years, EFS has been supporting therapeutic innovation projects’ holders. This has resulted in the production of over 300 ATMP clinical batches. These therapeutic innovators work in cell therapy, so innovation covers a wide range of cell models.
In cell therapy, the process is key, as it defines the drug product: this is why it is necessary to accompany project leaders step by step, and to ensure a high degree of transferability between the R&D stages and the production of clinical batches.
We will use 2 examples, involving different cell models, to illustrate how EFS helps therapeutic innovators to successfully optimize their processes and produce batches for clinical trials.
With a scientific background in biochemistry/biotechnology (MSc) at UPMC and Université de Technologie de Compiègne, Célia Mercier completed her training at NEOMA Business School, enabling her to support a wide variety of biotech, pharma and academic projects, mainly in Europe.
With over 20 years of experience, she currently serves as Business Development Manager at the French Blood Establishment (EFS) for Bioproduction of ATMPs, in collaboration with the four GMP bioproduction sites. Previously, she led various Business Development positions at CDMOs and CROs, from early pre-clinical stages to clinical manufacturing supply, at a European level. She also served at the French Foundation for Rare Diseases as regional manager for the scouting of innovations from academics and support to researchers in establishing relationship with pharma and biotech companies.
The traditional method of CAR-T cell production involves lengthy ex vivo culture times, reducing crucial naïve T cell subsets and prolonging time-to-patient, contributing to disease progression. This study describes an innovative 24-hour CAR-T manufacturing process involving one-step isolation and activation of T cells, followed by a 20-hour lentiviral transduction. By minimizing T cell activation to less than 24 hours, we maintained a higher percentage of naive/stem-cell like T cells, accelerated production, and reduced costs through automation. This approach provided quicker access to CAR-T therapy with enhanced efficacy and demonstrated feasibility in the clinic.
Drug discovery and development is a lengthy, costly, and high-risk process, often exceeding $2 billion per drug. Thermo Fisher Scientific offers end-to-end support through Accelerator™ Drug Development, a full-service CDMO and CRO solution that simplifies the journey, reduces risk, and speeds up market entry.
We partner with you from pre-IND to commercialization across all major modalities and therapeutic areas. Our global network includes drug manufacturing, clinical supplies, clinical sites, patient recruitment, and regulatory expertise. Over 120 biotech companies advance over 350 protocols with us, with 78% starting in Phase I or II and growing through commercialization.
Pr Makoto MIYARA, MD, PhD is a full professor in immunology. He is the coordinator of the Reference Laboratory for SLE and Antiphospholipid syndrome at the APHP.Sorbonne-Université, Pitié-Salpêtrière hospital. His hospital time is dedicated to the development of innovative diagnostic techniques including the implementation of AI in pattern recognition and of gene editing for the detection of autoantibodies. He is also the President of the Ethics Committee of APHP.Sorbonne-Université and the head of the Pitié-Salpêtrière Biobank. He has completed his clinical training at the Pitié-Salpêtrière hospital, in Paris, as an internist and was awarded the gold medal of Internat de Paris. He is the head of a research team that is focused on the manipulation of tolerance mechanisms, mainly regulatory T cells, to provide innovative therapeutic strategies to promote tolerance to allografts in transplantation, restore immune homeostasis in autoimmune diseases, to promote tissue regeneration or to enhance antitumor immune responses. His main papers have been cited more than 1500 times. His is the PI of 3 ongoing phase I clinical trials evaluating Treg cell therapy in liver, kidney and lung transplantation.
Prime editing (PE) is a double-strand break-free method that edits DNA using a Cas9 nickase fused with reverse transcriptase, and a modified guide RNA with a 3’ extension (pegRNA). However, PE efficiency depends on the target, cell type and edit size, with inefficient long insertions or replacements (>50bp). In addition, the scaffold sequence from the pegRNA can be incorporated into the genome. Our goal is to develop safer and more efficient PE tools. We created a DNA Polymerase-based method called POLYPRIME. We replaced the reverse transcriptase moiety with DNA polymerases, which could help to install long edits and reduce scaffold incorporation. POLYPRIME uses a hybrid RNA-DNA molecule, pegDNA, which we produce by ligating a standard gRNA to a DNA extension. POLYPRIME activity was tested in in vitro assays, cultured cells and zebrafish and was found to be a promising alternative to the original prime editing method.
Dr. Jean-Paul Concordet, PhD, is co-head of the “Genome Editing and DNA repair” team with Dr. Carine Giovannangeli at the “Structure et Instabilité des Génomes” laboratory (INSERM U1154, CNRS UMR7196, Muséum national d’Histoire naturelle, Paris, France). Their team develops novel genome editing tools and strategies for basic research and therapeutics development. Main goals are to increase the efficiency of precise genome editing, using either Cas9 nuclease or prime editing, and optimize delivery of genome editing reagents for different therapeutic applications.
