Therapeutics In Development

There are currently no approved therapies exclusively targeting menin. All compounds addressing menin are in clinical development and still need to go through the required trials to apply for approval with the Food and Drug Administration. Most clinical compounds in development inhibit menin using noncovalent binding techniques to connect to the target, menin. They rely exclusively on keeping bloodstream concentrations sufficiently high so that the patient is constantly exposed to the drug while the menin protein is being inhibited. A distinctly different approach is the use of a covalent binding technique when inhibiting the target protein menin. Biomea uses this technique with its covalent menin inhibitor BMF-219.

Covalent binding typically requires much less drug exposure while keeping the protein menin completely inactive. The protein complex is taken out of action quickly, and the only way for the rogue protein to return is through de novo synthesis, the body making a new protein. Covalent binding allows the drug to be dosed at minimal levels, doing its job, and then disappearing, instead of having to be always present.

While perhaps counterintuitive, this approach affords an added degree of selectivity, since “innocent” targets are not exposed to the drug for any longer than necessary. With non covalent drugs currently in development, the patient may be subject to unwanted side effects caused by the drug’s potentially indiscriminate activity against other targets that are not themselves out of equilibrium.  Biomea’s approach specifically employs weak spots in the molecular target that can form a covalent or extremely tight bond with the drug, but in such a way that potentially has less side effects.