Join us September 16-19, 2019 for TIDES Digital Week, a global 4-day series of live educational webcasts and downloadable resources providing the latest insights for accelerating oligonucleotide and peptide products to commercial success. To sponsor future digital events, contact partners@knect365lifesciences.com or request details.

Day 1: Monday, September 16, 2019



CMC Considerations for Nucleic Acid Based Therapeutics; From Antisense to mRNA
9am EDT / 2pm BST / 3pm CEST

The scope of nucleic acid based therapeutics covers a vast array of types of molecule, ranging in size from approximately 20 nucleotides for antisense oligonucleotides to thousands of nucleotides for mRNA based drug products. Similar analytical techniques can be applied to each type of molecule, for example chromatographic analysis for impurities, but the approach to method design will take into consideration the different types of impurities associated with each type of molecule. Analysis of the associated delivery systems, such as lipid nanoparticles, also forms a key part of drug product testing. This presentation will give an overview and comparison of the analytical considerations for a range of nucleic acid based therapeutics.

Speaker:

Fatma Amari
Scientist
Intertek

View More Details +

Bioanalytical Strategies for the Development of Stereo Pure Oligonucleotide Therapeutics
10pm EDT / 3pm BST / 4pm CEST

Nucleic acid therapeutics have significant potential to address diseases that historically have been challenging to treat with small molecule drugs or biologics. Chromatographic and immunoassay (LC-MS and HELISA) methods are most commonly used to support bioanalysis during preclinical and clinical development of oligonucleotide therapeutics. In this session, a comparison of LCMS bioanalytical methods for quantitation of oligonucleotides with HELISA methods in biological matrices will be drawn to demonstrate that a balance of selectivity and sensitivity for quantitation of nucleic acid can be achieved. Case studies on quantitation of stereopure oligos using different assay in preclinical and clinical studies and its performance will be discussed.

Speaker:


Pallavi Lonkar, Ph.D.
Principal Scientist
WAVE Life Sciences

View More Details +

Day 2: Tuesday, September 17, 2019



NxGen - A novel microfluidic solution for developing a wide range of nanoparticle formulations T
9am EDT / 2pm BST / 3pm CEST

Nanoparticle production using microfluidic mixing has been established as a robust process for developing new formulations. To date, much of this work has been performed on previously published microfluidic structures such as flow focusing and staggered herringbone mixers. We have developed a novel, next-generation mixing structure (NxGen) tailored to the needs of nanomedicine developers. Specifically, this nextgeneration mixer preserves time invariant mixing conditions over a wide range of flow rates, thus enabling the predictable development and manufacture of high quality nanoparticles at throughputs ranging from milliliters per minute to hudards of milliliters per minute. This capability offers a predictable means by which to achieve process scale-up. During this talk, we will present the requirements that led to the development of NxGen and demonstrate its utility in the formulation of liposomes, PLGA micro and nanoparticles and lipid nanoparticles for the delivery of a range of nucleic acids (such as siRNA and pDNA). We will show how these particles compare favorably (size, poly and EE) to those produced on a staggered herringbone mixer and how these formulations can be scaled using the NxGen mixer on the NanoAssemblr(R) platform.

Speaker:


Dr. Euan Ramsay
Chief Commercial Officer and Co-Founder
Precision NanoSystems

View More Details +

Cell Based Production and Selection of PPI-modulating Peptides, and Their Applications in Oncology
10am EDT / 3pm BST / 4pm CEST

At SyntheX, we are discovering and developing peptide-based compounds for targeting intracellular protein-protein interactions (PPIs). Using synthetic biology, we engineered a cell-based ”plug and play” discovery platform, ToRPPIDO, that relies on a simple viability readout for coupling peptide production to a functional selection. The technology allows us to produce and screen intracellular libraries of peptides or macrocycles that can selectively disrupt or bridge PPIs of interest. We have further developed a platform, ToRNeDO, that enables the selection of bivalent peptides that are able to functionally form a ternary complex between an E3 ligase and a target protein of interest, with the degradation of the target being tied to a phenotypic readout. The platforms are broadly applicable, and our first area of focus is oncology.

Target selection in oncology is based on the concepts of synthetic lethality and oncogene addiction. This strategy enables us to achieve cancer cell selectivity and specificity by targeting particular “Achilles’ heel” PPIs that are uniquely essential for the survival and growth of the cancer cells but not healthy tissues. Application of ToRPPIDO towards a crucial PPI within the Homologous Recombination (HR) DNA repair pathway led to the discovery of STX100. Derivatives of STX100 exhibiting low nanomolar affinity to target, cell permeability, and proteolytic stability were tested for activity against various cell lines. Results from a panel of over 30 cancer and primary lines demonstrated acute mono-agent activity of STX100 derivatives selective towards HR-overexpressing cancer cells. Interestingly, STX100-mediated cell killing is independent of canonical cell death mechanisms (apoptosis, necroptosis, pyroptosis, ferroptosis, etc.).

Rather, the elevated abundance of the HR target protein in cancer cells relative to healthy tissues underlies the selective cytotoxicity resulting from an acute calcium surge upon STX100 target engagement. ADME/PK and in-vivo efficacy studies indicate favorable characteristics and further pre-clinical development is currently ongoing.

Speaker:


Maria Soloveychik, Ph.D.
CEO
SyntheX, Inc.

View More Details +

Day 3: Wednesday, September 18 , 2019



Accelerating peptide research and therapeutic peptide development: New automated parallel synthesis tools and methods
9am EDT / 2pm BST / 3pm CEST

Attendees will learn how:

  • increasing the purity, yield, efficiency and speed of peptide synthesis is achieved with automated parallel peptide synthesizers
  • facilitating process optimization is made easier via parallel synthesis under different conditions, including screening of different temperatures, reagents, resins, solvents, and reaction times
  • accessing modified peptides and peptidomimetics is enabled through technologies like controlled induction heating and real-time UV monitoring
  • New automated methods have been developed for the synthesis of challenging peptide sequences and modifications

Speaker:

James Cain, Ph.D. Global Product Manager, Peptide Synthesis
Gyros Protein Technologies

View More Details +

Day 4: Thursday, September 19 , 2019



Second-harmonic generation-based methods to detect and characterize ligand-induced conformational changes in oligonucleotides
9am EDT / 2pm BST / 3pm CEST

Second-harmonic generation (SHG) is a biophysical tool that senses ligand-induced conformational changes in biomolecules. The Biodesy Delta™ has been developed as a high-throughput screening platform to monitor conformational changes in proteins and oligonucleotides by SHG to support drug discovery efforts. This webcast will outline (1) an overview of this technology, (2) practical considerations for developing robust SHG assays for oligonucleotide targets, and (3) a case study that demonstrates the application of these recommendations on an oligonucleotide target.

As a case study, we will focus on assay development for measuring structural changes in an aptamer in response to a ligand. As a first step, we will present the design considerations for the custom oligonucleotide synthesis required to build an SHG assay. Additional considerations include testing for specific tethering of the conjugate to the surface as well as evaluating the stability, reversibility, and concentration-dependence/affinity of ligand-oligonucleotide interactions. A deeper dive into custom synthesis capabilities will also be presented

Speaker:

Mandy Haas Product Manager
Dharmacon

Margaret Butko
Senior Scientist
Biodesy

View More Details +

REGISTER NOW – Please select the webcast(s) you wish to attend and enter your contact details



Day 1 - Monday, September 16, 2019

Day 2 - Tuesday, September 17, 2019

Day 3 - Wednesday, September 18, 2019

Day 4 - Thursday, September 19, 2019