Conference Day Two
Wednesday, December 11, 2024
8:25 am Chair’s Opening Remarks
Unveiling the Next-Generation LNPs to Pioneer Engineering & Boost Safety
8:30 am Case Study: Building Next-Generation LNPs with Gangliosides Instead of PEG to Reinvent Safety & Mitigate Immunogenicity
Synopsis
- Cytodigm successfully developed CytofinityTM LNP by replacing the PEG-lipid with a ganglioside in the LNP formulation
- The Cytofinity LNP can load various nucleic acid cargos and exhibited good colloidal stability, high encapsulation efficiency, and excellent safety profile
- The Cytofinity LNP possesses all the benefits of traditional LNPs while also offering additional advantages and capabilities
9:00 am Next Generation LNPs for Multiple Therapeutic Applications
Synopsis
- Efficacy of the next generation LNPs in cancer models
- Efficacy of the next generation LNPs for infectious diseases
- Innate and adaptive immune responses for efficacy and safety
Overcoming Solutions Controlling & Monitoring PEG-Mediated Immunogenicity & Toxicity
9:30 am Overcoming Anti-PEG Antibody Responses – a Novel PEOZ-lipid That Fails to Elicit an Immune Response to the Polymer-lipid in mRNA-LNP Formulations
Synopsis
- Overcoming toxicity challenges associated with PEG lipids by altering nanoparticle formulation and design employing a novel poly (2-ethyl-2-oxazoline) PEOZ-lipid
- Absence of an IgM or IgG response to PEOZ-lipid
- Substitution of PEG-lipid with PEOZ-lipid does not alter payload properties following in vitro and in vivo transfection
10:00 am Replacing PEG Lipids with Safer Components while Maintaining Stability & Targeting Efficiency to Prevent Toxicity
Synopsis
- Discussing molecules that can be used to replace PEG to reduce toxicity
- Leveraging conjugates to achieve organ-specific targeting while preventing off-target effects
- Harnessing natural lipids or un-pegylated lipids to mitigate anti-PEG responses in vivo
10:30 am Morning Break & Networking
11:30 am Roundtable: Discussing the Impact of PEG on Safety & Immunogenicity Studies to Indicate Potential Solutions
Synopsis
- Reviewing how PEG impacts preclinical and clinical safety studies for vaccines, gene and cell therapies
- Discussing solutions and approaches to minimize this impact and generate robust safety data
- Understanding and minimizing unwanted infusion associated reactions stimulated by PEG lipids
- How will PEG lipids impact multi-dosing strategies?
12:30 pm Lunch Break & Networking
1:30 pm Determining Effective PEG-Antibody Controls to Enhance Monitoring of Anti-PEG Responses in Patients
Synopsis
- Measuring and monitoring anti-PEG antibody levels in patients to indicate degree of reaction
- Determining anti-PEG antibodies at baseline compared with the rate following an infusion associated reaction
- Harnessing statistical analysis of healthy samples to determine a median control to measure anti-PEG levels
- Utilizing this control to influence set points for anti-PEG assay development to measure and predict response
Reforming Clinical Delivery Strategy to Reduce Immunogenicity
2:00 pm Mastermind: Benchmarking Dosing Strategy & Route of Administration to Turbocharge Clinical Delivery
Synopsis
- Reviewing safety concerns with multi-dosing to prevent unwanted toxicity
- Discussing best practice to determine dose frequency, size and scaling to mitigate adverse reactions in the clinic
- Evaluating best route of administration for LNP systems by reviewing potential safety concerns for various delivery routes to optimize persistence and mitigate off-target effects
3:00 pm Formulation Technologies for Delivery of RNA by LNPs & Other Nanoparticles
Synopsis
- Nanoparticles for RNA delivery need to be tailored for a given therapeutic intervention
- Parameters to be optimized comprise molecular characteristics, structure, size, immunogenicity and (surface) functionalization
- Novel LNPs and other nanoparticle formats can be eligible for such purposes
3:30 pm Benchmarking Delivery to Novel Organs Without Compromising Safety
Synopsis
- Building and engineering surface modifications to LNPs to target new organize while evading the immune system
- Harnessing antibody conjugates to guide LNPs to target organ site while mitigating accumulation in off-target organs
- Developing natural conjugates to prevent chemical residues and resultant toxicity