Aileron Therapeutics is a clinical-stage biopharmaceutical company that is focused on developing and commercializing a novel class of therapeutics called stapled peptides. Our lead product candidate, ALRN-6924, targets the tumor suppressor protein p53 for the treatment of a wide variety of cancers.
We are conducting an ongoing Phase 1 clinical trial of ALRN-6924 in adult patients with advanced solid tumors or lymphomas expressing non-mutated or wild-type p53 that are refractory to or intolerant of standard therapy, or for which no standard therapy exists. ALRN-6924 may reactivate p53-mediated cell death by targeting both of the natural p53 suppressor proteins, MDM2 and MDMX.
By chemically stabilizing — “stapling” — alpha helical peptides and thereby enabling them to engage and modulate targets of interest, we can engage targets that are, for a variety of reasons, too complex or otherwise undruggable by existing drug technologies, such as small molecule chemistry and monoclonal antibodies.
These first-in-class molecules may be able to address historically undruggable targets and complex mechanisms, such as intracellular protein-protein interactions like p53 that underlie many diseases with high unmet medical need.
p53 has long been referred to as “the guardian of the genome” because it is the body’s cellular first line of defense against cancers. p53 is released when DNA damage is detected and is capable of then triggering a cellular self-destruct mechanism, known as apoptosis, which kills the damaged cell before it can become cancerous and replicate. p53 is regulated by MDM2 and MDMX, two suppressor proteins that, in normal cells, bind to and suppress p53 so that its activity remains dormant and cells are able to function as expected.
ALRN-6924 reactivates p53 by disrupting the interactions between p53 and these two suppressor proteins, thereby freeing p53 to transit to its DNA target in the nucleus and initiate apoptosis in cancerous cells. We believe that ALRN-6924 is the first and only product candidate in clinical development that can equipotently bind to and disrupt the binding of both MDM2 and MDMX to p53.