AlfaDAX Online Platform by GreatBay Bio Validates Developability Predictions Across 900+ Public Therapeutic Molecules

▲70 Seconds to Understand AlfaDAX Platform Online System

AlfaDAX Online System Utilizes AI Technology to Comprehensively Evaluate Key Factors Affecting Drug Developability, Including Aggregation and Precipitation, Non-Specificity, Stability, Viscosity, Humanization, etc., for Intelligent Assessment of Drug Molecule Developability.AlfaDAX OnlineThe system conducted a statistical analysis on the drug-likeness prediction evaluation values of more than 900 publicly available drug molecules, and the data shows that the range distribution of various factors is highly consistent with the actual situation.

Aggregates are the most commonly observed product-related impurities, can lead to immunogenicity, and are a key component of developability assessment.

▲AlfaDAX Online System Predicts Over 900 Public Drug Molecules,87.2%No aggregation or precipitation issues

▲28 Groups of Innovative Molecular Aggregation Scoring with Wet Lab Validation, Accuracy Reaches 89.3%

If antibodies have issues with aggregation and precipitation, special process optimization is required, including production processes, purification procedures, formulation design, and storage conditions. Systematic optimization and strict process control are needed to meet the demands of clinical and commercial applications. When these methods fail to solve the problem, it may be necessary to return to antibody engineering design or it could lead to project failure.These methods usually have high process development difficulty and increase production costs. The AlfaDAX online system can eliminate molecules with poor drug-likeness from the molecular discovery stage, reducing the risk in later-stage process development.

The original binding site of a monoclonal antibody contains three (nanobody) or six (conventional monoclonal antibody) CDR regions, which bind to specific antigen epitopes through non-covalent bonds such as hydrogen bonds, hydrophobic interactions, van der Waals forces, and electrostatic forces.

▲AlfaDAX Online System Predicts Over 900 Public Drug Molecules,97.4%No non-specific issues exist.

A well-characterized antibody should possess sharp specificity for a single target, but not all antibodies exhibit this trait. An unbalanced distribution of positive charges or hyperhydrophobicity in the variable regions may lead to non-specific binding, resulting in poor pharmacokinetic (PK) outcomes, reduced biological activity, and severe side effects.

AlfaDAX online system analyzed more than 900 drug molecules that are either already on the market or in clinical stages, and found that 97.4% of the molecules are within a reasonable range.AlfaDAX OnlineThe system has the ability to distinguish non-specific antibody binding.

Stability is a very important factor in the discovery and development stages of therapeutic candidate antibodies, including thermal stability, light sensitivity stability, pH sensitivity stability, physical stress-related stability, and freeze-thaw stability, among others.

▲AlfaDAX Online System Predicts Over 900 Public Drug Molecules,84.1%No stability issues

Proteins undergo unfolding and lose their higher-order structures, thereby losing activity, when exposed to high temperatures or chemical denaturants. Differential scanning calorimetry (DSC) or differential scanning fluorimetry (DSF) is typically used to gradually increase the temperature of protein solutions to detect the thermal denaturation temperature (Tm), reflecting their conformational thermostability.AlfaDAX Online System Analyzed More Than 900 Drug Molecules That Are Either Marketed or in Clinical Stages, Finding That 84.1% of the Molecules Meet the System’s Scoring Criteria.

High-concentration drug products administered through subcutaneous (SC) injection require formulations with controllable viscosity, which is crucial for process and product development to mitigate developability issues.

▲AlfaDAX Online System Predicts Over 900 Public Drug Molecules,70.2%No viscosity issues

Drugs with excessively high viscosity cannot be formulated into high-concentration preparations, requiring frequent high-dose administration, which increases the burden on patients. They may also be unsuitable for intravenous injection due to overly high concentration, while oral formulations face issues of poor absorption and low bioavailability.70.2% of drug molecules that are marketed or in clinical stages meet the AlfaDAX system analysis criteria.

The dawn of recombinant DNA technology has illuminated the path for the modification and production of recombinant monoclonal antibodies.In the 1980s and 1990s, the focus was on humanization and fragmentation of antibodies. Humanized and fully human monoclonal antibodies have now become the mainstream in therapeutic antibody development.

▲AlfaDAX system predicts over 900 publicly available drug molecules,79.0%No humanization issues

Humanized antibodies mainly refer to mouse monoclonal antibodies that are genetically cloned and reformed using DNA recombinant technology to express antibodies again. Most of their amino acid sequences are replaced by human sequences, basically retaining the affinity and specificity of the parent mouse monoclonal antibodies while reducing their heterogeneity, which is beneficial for human application.

▲ Evaluation Results of Humanization for 381 Biopharmaceutical Molecules from Public Experimental Data

During the statistical process, we found that early marketed drugs were derived from murine antibodies without humanization, and their degree of humanization is usually below 0.2, causing significant side effects on the human body. Later marketed drugs and current clinical drugs have higher requirements for humanization, which fully affects whether a drug can be marketed, with their distribution range concentrated between 0.2 and 1.0.79.0% of drug molecules that are marketed or in clinical stages meet the AlfaDAX system analysis criteria.

The AlfaDAX online system learns data on biopharmaceutical sequences and structures from extensive databases, develops trained models, and predicts several key factors influencing drugability. It provides significant guidance for the drugability modification of innovative drug molecules, effectively saving a large amount of wet-lab work and accelerating the process of new drug launches.

▲AlfaDAX Online System Case Evaluation Validation Consistency Data

▲Accuracy of Evaluation Results for Some Customer Projects

The evaluation values of the AlfaDAX online system are highly consistent with experimental results, capable of providing early reminders to users on whether to proceed with subsequent processes or first optimize the molecular sequence. Additionally,Through the innovative solution of the AlfaDAX online system,Enabling the development of drugs for "difficult-to-drug" or "yet-to-be-drugged" targets. Global biopharmaceutical colleagues are welcome to experience and provide feedback.

▲Scan to experience the AlfaDAX online system

[1] Developability assessment at early-stage discovery to enable development of antibody-derived therapeutics. Antib Ther. 2022; 6(1): 13-29.

[2] Machine Learning Applied to Determine the Molecular Descriptors Responsible for the Viscosity Behavior of Concentrated Therapeutic Antibodies. 1167–1175 Publication Date:January 15, 2021

[3] Structure-based charge calculations for predicting isoelectric point, viscosity, clearance, and profiling antibody therapeutics. Published online 2021 Oct 10. doi: 10.1080/19420862.2021.1981805