As senior vp of Discovery Biotherapeutics at Bristol Myers Squibb, Ho Sung Cho leads a crew of gifted researchers advancing novel protein and antibody-based therapies with the potential to deal with illness. Cho is predicated in Bristol Myers Squibb’s San Diego analysis & early growth web site – a vibrant innovation hub for all times sciences – the place his crew is concentrated on the exploration of novel biology and goal ideas similar to protein degradation and sophisticated biologics.
In a latest MedCity Pivot Podcast, Cho shared insights into his strategy to drug discovery and the way Bristol Myers Squibb is constructing on many years of expertise within the protein degradation house to convey novel property into the clinic.
Bristol Myers Squibb’s – then Celgene’s – investigation of protein homeostasis started greater than twenty years in the past with the launch of its first protein degrader. Constructing on this deep understanding of earlier discoveries within the protein degradation house, the corporate has introduced six further protein degraders into the clinic, giving them in depth growth expertise on this space.
Protein homeostasis is a discipline of research devoted to sustaining the equilibrium of proteins within the human physique. Cells have a built-in system for disposing of and recycling proteins and sustaining protein homeostasis. When a cell is unable to get rid of sure proteins, they’ll accumulate, inflicting most cancers and different ailments. Protein degradation is the method by which proteins are destroyed in a cell. With focused protein degradation, researchers are harnessing the cell’s personal equipment to degrade a number of proteins that had been beforehand thought-about “undruggable.”
“Usually after we take into consideration drugging a goal, we take into consideration both antagonizing or agonizing the goal,” mentioned Cho. “What we do with the protein homeostasis drug is we goal the protein or goal of curiosity to be degraded by the proteasome so that you just mainly take away it from the mobile biology, versus simply blocking the enzymatic operate of a protein. This permits us to go after targets that may be usually considered as undruggable or troublesome to drug.”
Cho noticed that protein degraders have made a major affect on the remedy of hematologic cancers and sufferers who, till just lately, had few remedy choices.
“We have now seen an actual shift by way of a number of myeloma remedy, and what meaning by way of survival,” mentioned Cho. “With newer medicines we’ve been in a position to shift the most cancers nearer to a power situation that’s extra manageable.”
Primarily based on learnings from the corporate’s early analysis in focused protein degradation, Bristol Myers Squibb is now targeted on learning a number of novel Cereblon E3 Ligase Modulation Medicine that would probably tackle a broader vary of ailments, alone or together with different brokers. These compounds act as a “molecular glue” to change the protein-binding properties of cereblon to advertise interplay with disease-causing proteins that may not sometimes be degraded.
“These brokers are being investigated in several types of blood cancers similar to a number of myeloma and acute myeloid leukemia, in addition to strong tumors and immune-mediated ailments like lupus,” mentioned Cho. “The truth is, a research on one in all our novel protein degraders was just lately revealed on the quilt of Blood, which is one thing we’re very pleased with,” mentioned Cho. “BMS can be evaluating ligand-directed degraders. This strategy is being studied with an androgen receptor degrader at the moment in a Part 1 research for castration resistant prostate most cancers.”
With the regular progress being made within the protein degradation discipline, Bristol Myers Squibb is working to determine which proteins have therapeutic utility to offer sufferers as a lot time and hope as potential.
To entry the total podcast interview with Cho, the place he discusses his strategy to drug discovery, views on coping with failure, and a few of the work his groups are doing within the protein degradation and COVID-19 areas, click on right here.
Picture: appledesign, Getty Photos