Ep.2 with Jonathan Tobin: Behind-the-scenes of a $1.5 billion acquisition

Okay, Jonathan, so I think you've introduced quite a few concepts which

may not be familiar to all of our

audience.

Let's just go through them.

I'd love to unpeel the science a little bit.

So first of all, antibody drug conjugates, ADCs.

I mean, they are really a triple construct that starts with an antibody, which targets a specific marker in a cell.

Then there's a payload, which is not always, but typically a small molecule.

And then there's a linker, which links the two together, and you can get cleavable and non-cleavable linkers.

And ADCs, they've been a hot and a crowded space for some time now.

So before we go on and talk about NMT biology, tell me what was it that you think made you decide to convert this company that was originally focused on monochemistry into an ADC? And what gave you the confidence that you'd be able to differentiate versus all of the other ADCs in the field?

Yeah, I guess there were push and pull factors.

So the first was that it was a way of solving a toxicity problem and to create a molecule that was more potent and more efficacious.

The second

thing commercially was that in 2023, the ADC field was getting very crowded with molecules that had basically one of two classes of payloads.

So either microtubule inhibitors, which basically stop cancer cells dividing by disrupting their mitotic spindle, or topoisomerase inhibitors, which essentially prevent DNA replication.

And despite having lots of different targets, they were all working on the same payload.

And there was research coming out which was showing that if a patient had become resistant to that payload class, if you dosed them with another ADC with the same payload mechanism, they'd be very unlikely to respond to that.

And so our bet three and a half years ago was that the field would demand novel mechanisms of payload which were completely orthogonal to one of those two classes.

And NMT was really in this Goldilocks zone between broad cytotoxic molecules like microtubule inhibitors, which just kill any cell that's dividing, and targeted therapy, which is much more specific for the mutation in the cancer cell, but much more niche.

So you have to have that specific mutation for it to work.

and they tend to develop resistance patients will often have a short duration of response to those drugs as biologically sit somewhere between those two extremes so we saw it as a way of having quite large breadth of activity

without inducing resistance rapidly

The other thing that was super interesting to me is that NMT doesn't just kill dividing cancer cells.

It also kills senescent cancer cells, which have been somewhat overlooked because often chemotherapy actually induces cancer cells to exit the cell cycle and become senescent, where they really just sit there and lie dormant and then potentially drive a later relapse.