The pre-clinical company Oncolyze has recently been granted Orphan Drug Designation (ODD) for its lead compound OM-301 for the potential future treatment of multiple myeloma that forces myeloma cells to pop open and die.

This compound previously received Orphan Drug Designation for the treatment of Acute Myeloid Leukemia (AML) in January 2022. Please note that Orphan Drug Designation is very different from receiving FDA approval, as has been pointed out in HealthTree posts on several occasions in the past. In a nutshell,

“The FDA has authority to grant orphan drug designation to a drug or biological product to prevent, diagnose or treat a rare disease or condition. Orphan drug designation qualifies sponsors for incentives including: 

• Tax credits for qualified clinical trials
• Exemption from user fees 
• Potential seven years of market exclusivity after approval.”

Those interested in learning more about FDA’s Orphan Drug program may wish to go to the orphan drug part of the FDA website. A “rare disease” is a condition with a US pool of less than 200,000 patients. The products/treatments that we are familiar with in our myeloma treatment have all qualified as “orphan drugs” in the past.

But let’s focus on the compound OM-301, that has a unique method of action compared to the compounds/treatments that have been discussed by HealthTree for Multiple Myeloma so far.

OM-301 targets the protein HDM2 (human minute-binding protein-2) that regulates cell growth. HDM2 is not only present in high concentrations inside a cancerous cell, but also outside on the cell's surface, whereas normal cells have hardly any HDM2 on the cell's surface.

“The unique expression of extracellular HDM2 on cancer cells makes it an excellent, selective target for an anti-cancer therapeutic agent.”

OM-301 is called a “fusion peptide”, a small protein that has two parts with different properties. The first part is designed to bind with HDM2 on the cell surface, the second part is a group of amino acids some of which have “water liking” properties and some of which have “water hating” properties.

“When one end of OM-301 attaches to the cell surface HDM2, the other end wants to burrow its way into the cell membrane. Ideally, that part of OM-301 would probably prefer to go through the membrane and into the cell, but because the other end is attached to HDM2, it is forced to stay there [on the outside of the cell] . There is likely tension because some parts like to stay in the membrane, some parts like the extracellular water. What happens next is outstanding. This tension causes pores or holes to be made in the cell membrane. The OM-301 almost acts as a ‘molecular icepick’. The overwhelming presence of holes causes the extracellular fluid to rapidly enter the cell via an osmotic mechanism. The cell rapidly enlarges, resulting in even greater tension on the stretched cell membrane, until it pops open.

The cancer cell dies, not through the classical mechanism leveraged by most cancer therapeutics, known as apoptosis, rather a cell membrane mediated, biophysical mechanism for which we have coined the term ‘pop-tosis’.”

Remember that Oncolyze is a pre-clinical company. The company has promising laboratory results on 8 different myeloma cell lines and on mice, but still has a long way to go through the full regulatory process with the associated development risks at each of the steps. Fingers crossed, this unique approach to treating cancer will give us patients another treatment option some years from now.