Verastem 3rd Annual Guggenheim Healthcare Innovation Conference

Is that right? That is very good.

I think we are where we wanted to be exactly. I mean, first of all, avutometinib, defactinib, CO-PACK, it is a RAF/MEK inhibitor with a FAK inhibitor. It was the first novel approval we got approved in May of 2025. Now we are at the point where our sales cover the commercial force. That is really great to be break-even for that asset. Then, as you mentioned, the G12D inhibitor, VS-7375, is really exciting, looking best in class, really for any patient with a cancer driven by KRAS G12D. That is really important in pancreatic cancer, colorectal, and lung cancer, which are obviously really large market cancers. So, great point. As you say, the fundraise really lets us drive the clinical development program. We have a couple of trials that Ting will say more about that are gearing toward accelerated approval in the near term.

It is a transition. I think you mentioned Dan Paterson, who has been the CEO since 2011, felt like he has delivered it to this point. As we look toward commercializing the G12D inhibitor now in addition to the RAF/MEK and FAK inhibitor, I think Michael Bailey, the new CEO coming in January 1st, is really well-positioned to do that.

Yeah. Thanks for the question, Michael. I think the data that we have presented on October 14th really highlight that we have the potential to be best in class for G12D space, which means that that allows us to open a lot of opportunities across tumor types. Of course, obviously PDAC, CRC, and also non-small cell lung cancer, and also the recent fundraise allows us to go full steam for all these indications. We are about to fully enroll for our, I would say, PDAC and also CRC study towards the end of this year, non-small cell lung cancer to follow early next year. Then we are starting three phase III confirmatory study in the frontline setting for these indications. So exciting times. I think it validates that we always have a great scientific story about the ON/OFF inhibition, the really good exposure proportional across dose levels, and now it is manifesting in the clinical data that is trending towards best in class.

Of course, this enables a lot across indications.

Yes. Basically, GenFleet did not fully explore 900 mg. I would say in general, they only dosed three patients in total at a 900 mg dose, and they decided to go for speed for 600 mg, given they have seen already favorable benefit-risk. For us, we have fully characterized 900 mg. So a few things, as John probably has already alluded to in several occasions, that we really have a good dose proportional increase in terms of exposure across the 600 and 900 mg. Based on preclinical models, that 900 mg is the more optimal dose that we have hit the optimal exposure. The other thing is about the safety profile or tolerability profile is that 900 mg is identical to 600 mg.

Just a quick reminder that the main AE is GI disorders and predominantly low grade, mostly grade 1, with around 10%-15% grade 2. Other than that, it's a pretty clean safety profile. So that justifies us to go for 900 mg, given no difference in terms of tolerability compared to 600.

Right. For the PDAC data, obviously, I think this is a data set that clearly shows differentiation. First, it is all the patients that we have dosed at 900 mg in a phase I study in a previously treated PDAC setting. We are not hiding any single patients. We are reporting the intended to treat population. Any patient dosed with 900 mg were included in that data set. Also, we are reporting all confirmed response. In terms of data robustness, I think it tells us how rigorous we are about reporting the data. We report intent to treat and also confirm response rate. Also, as you probably noticed that although the sample size is not that large, but I would say it is very consistent in every setting, either in second line or third line beyond.

I think it is very competitive compared to what is available out there, including daraxonrasib currently as standard of care, and also the other G12D inhibitors.