Bede Portz: “Targeting MYC condensates in the fight against ovarian cancer”

[Transcript]

We are going after one of the holy grail targets in oncology, this is a protein called MYC. MYC regulates the expression of genes that in turn drive cancer proliferation. And MYC mediates this function through a condensate, which you can think of as an integrating node of disease. It’s the inflection point between stimulus and response. So the cell is receiving signals and it’s deciding via MYC condensate, to proliferate. Nearly all cells need MYC, but it’s dysregulated in some 70% of cancers, some various types.

So why ovarian cancer? Well, it’s frequently amplified in ovarian cancer, meaning there are more copies of the MYC gene than there should be, and this happens in some 30% of ovarian cancers, which is a very high rate. So we started with ovarian cancer. And of course, the unmet need in ovarian cancer is sky high, the survival rates are not good. It is often not detected until the disease is advanced. The existing treatment options are limited. They involve chemotherapies that are really tough on patients. Often ovarian cancer develops resistance to these treatments, and they stop working effectively. And so other treatment options exist, but they’re not really used with curative intent, so there’s a real urgency. MYC is a very well-known driver of cancer. Broadly, it’s frequently dysregulated in ovarian cancer specifically. And there’s a high unmet need in ovarian cancer. And so that’s the first indication where we started to look.

When MYC is dysregulated, it’s not dysregulated in isolation. There are other genetic abnormalities that also impact MYC condensates and their function. And so what we’re trying to do in our program is broadly capture mechanisms that impact MYC condensates directly, as well as the regulators of those condensates more indirectly.

There are many cancers, solid tumors, high unmet need that have MYC dysregulation, and MYC genetic amplification. And some of those are pancreatic cancer, esophageal cancer, and so on. When MYC is dysregulated, other genetic abnormalities that occur coincidently with MYC dysregulation are also shared amongst certain cancer types, and indications.