As senior vice chairman of Discovery Biotherapeutics at Bristol Myers Squibb, Ho Sung Cho leads a group of proficient researchers advancing novel protein and antibody-based therapies with the potential to deal with illness. Cho relies in Bristol Myers Squibb’s San Diego analysis & early improvement web site – a vibrant innovation hub for all times sciences – the place his group is targeted on the exploration of novel biology and goal ideas corresponding to protein degradation and complicated biologics.
In a current 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 area to deliver novel property into the clinic.
Bristol Myers Squibb’s – then Celgene’s – investigation of protein homeostasis started greater than 20 years in the past with the launch of its first protein degrader. Constructing on this deep understanding of earlier discoveries within the protein degradation area, the corporate has introduced six extra protein degraders into the clinic, giving them in depth improvement expertise on this space.
Protein homeostasis is a discipline of examine 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 will accumulate, inflicting most cancers and different illnesses. 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 have been beforehand thought-about “undruggable.”
“Usually once we take into consideration drugging a goal, we take into consideration both antagonizing or agonizing the goal,” stated 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 simply mainly take away it from the mobile biology, versus simply blocking the enzymatic perform of a protein. This enables 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 influence on the remedy of hematologic cancers and sufferers who, till lately, had few remedy choices.
“We have now seen an actual shift when it comes to a number of myeloma remedy, and what meaning when it comes to survival,” stated Cho. “With newer medicines we’ve been capable of shift the most cancers nearer to a power situation that’s extra manageable.”
Based mostly 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 Medication that would probably deal with a broader vary of illnesses, 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 usually be degraded.
“These brokers are being investigated in various kinds of blood cancers corresponding to a number of myeloma and acute myeloid leukemia, in addition to strong tumors and immune-mediated illnesses like lupus,” stated Cho. “In actual fact, a examine on one among our novel protein degraders was lately revealed on the quilt of Blood, which is one thing we’re very happy with,” stated Cho. “BMS can also be evaluating ligand-directed degraders. This strategy is being studied with an androgen receptor degrader presently in a Part 1 examine 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 complete 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.
Photograph: appledesign, Getty Photos