January 2024: Antibody-Drug Conjugates - Emerging into 2024
Biointron2024-02-02Read time: 7 mins
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Entering into the new year, the popularity of antibody-drug conjugates (ADCs) in the biopharma industry shows no signs of slowing down. In 2023, there were a record number of licensing partnerships in the ADC space, particularly Merck’s $22 billion deal with Daiichi Sankyo, Inc.
New deals this month:
Jan 23: Celltrion Inc and WuXi XDC sign partnership deal. WuXi XDC will provide process development through manufacturing services to support Celltrion’s ADC and other bioconjugates pipeline.
Jan 8: Johnson & Johnson acquires Ambrx for $2 billion. J&J will now handle ARX517, an ADC aimed to treat prostate cancer which showed success in early-stage trials.
Jan 2: MediLink Therapeutics enters into collaboration and license agreement worth potentially $1 billion with Roche to develop YL211, an ADC targeting c-Met against solid tumors.
Dec 26: LegoChem Biosciences inks $1.7 billion ADC deal with Janssen Inc. The license agreement is for LCB84, a Trop2-targeted ADC with the aim of treating solid tumors and shows promising preclinical data.
Global ADC Market. Source: market.us
Similarly, the research space into ADCs is also growing. ADCs comprise of an antibody, payload (toxic pharmaceutical molecules with high efficiency), and linker connecting them both. Because of this structure, ADCs can be highly valuable targeted chemotherapeutic drugs by the specific recognition of target antigens and release of payloads to eliminate target cells.
Last week, a paper by Guo et al. developed a strategy for ADC discovery with highly efficient bystander-killing effects, through the use of rational optimization strategy based on a graph attention network (GAT)-driven scoring model. They then constructed novel ADCs with improved approaches to combating tumor heterogeneity.
The target antigen of ADCs are what lead the direction of their pharmacological properties. Currently, the majority of targets are specific proteins which are overexpressed in typical tumor cells, including HER2, TROP2, CD19, and CD22. Over 150 clinical trials for ADCs are underway.
While there are many successes, there are many more failures during development. This month, the failed HER2-directed ADC DHES0815A Phase I trial results published. Meanwhile, the HER2-directed ADC SHR-A1201 revealed positive results from the development and validation of its pharmacokinetics assays. Also last week, Gilead’s Trodelvy (Trop2-directed ADC) failed to meet its Phase III study endpoints. On the other hand, OBI Pharma’s OBI-992 (TROP2 ADC) was approved for an FDA investigational new drug (IND) clearance to conduct a Phase 1/2 study.
Strategies for ADC structural innovation and treatment optimization. Source DOI: 10.1002/cac2.12517
In news for the future, ADCs have several more years to advance its development, including the design of new antibody delivery tools, formats like bispecific ADCs, linker developments, conjugation methods, and payload optimization.
Furthermore, Wang et al. described peptide-drug conjugates (PDCs) as the new paradigm for targeted cancer therapy. PDCs are made up of the cell-targeting peptide, linker, and cytotoxic payload. While they appear similar in concept, the structure and nature of PDCs and ADCs are very different. PDCs are much smaller and flexible, thus achieving stronger tumor penetration and less immunogenicity, in addition to being metabolized by the kidney instead of the liver.
Mechanism of action of peptide-drug conjugates. Source DOI: 10.1016/j.ejmech.2023.116119
This report aims to explore the events and trends of the biopharmaceutical industry in Q2 (April, May, June). Besides crovalimab and Vyloy, two more novel antibody drugs have been approved this year
These past few weeks, several antibody drug startups have progressed from the pre-seed stage to final funding rounds. In the pre-seed stage, the focus is on early research, often funded by founders, grants, or angel investors. As the company progresses to the seed stage, it seeks additional funding to validate its scientific concept and develop initial prototypes, attracting early-stage venture capital.
In August, the US FDA approved Galderma’s Nemluvio (nemolizumab) for adult patients living with prurigo nodularis (PN). Nemluvio is the first approved monoclonal antibody specifically inhibiting the signaling of IL-31, a neuroimmune cytokine that drives multiple disease mechanisms in (PN). Prurigo nodularis is a chronic skin condition that affects approximately 181,000 patients in the United States
Anti-drug antibodies (ADAs) are immune system proteins that can develop in response to therapeutic drugs, particularly biologics like monoclonal antibodies. These biopharmaceuticals have significantly advanced therapies for cancer and autoimmune diseases, but their long-term use can elicit immunogenicity due to repeated administration. The host immune system may recognize epitopes in the biologic drug as foreign, triggering the production of ADAs. This can lead to the formation of drug–ADA immune complexes, which accelerate drug clearance and potentially neutralize the drug's efficacy.
