Thread by @Biotech2k1

Profiling $MRTX:

I got interested in $MRTX about 3 years ago while I was an Array Bio investor. They licensed some of the KRAS technology from Array. That got me interested.

1/ $MRTX just replaced their CEO. Chuck moved up to Chairman and they hired David Meek to groom into the new CEO role. He has a history with commercial experience. That is good for taking the company to the next level with approval and sales.

2/ Their original drug is Sitravatinib which hits multiple kinases. This is designed to alter the tumor microenvironment to shift things back toward cellular killing. It had some decent data for patients who developed resistance to PD-1 inhibitors.

3/ They showed about 25% of patient responded to PD-1 again with Sitravatinib. This program has been in a long multi year phase 3 trial as they put it on the back burner to focus on KRAS. I think it could eventually make it to market, but my hopes for sales are low.

4/ They might even drop it someday after they have enough success to soften the blow. I suspect we could see a huge data read out for their next KRAS programs and then an, "oh by the way, we are dropping Sitravatinib to save money on development costs."

5/ Either way, I have not really much expectations for this first program. $MRTX has become all about KRAS G12C and its follow on programs for KRAS G12D.

6/ This makes $MRTX my first company that was focused on the intracellular growth pathways that drive cancer with mutations. These pathways can't be targeted any other way and makes target oncology a powerful weapon.

7/ KRAS is one of the isoforms of RAS and falls into the MAPK pathway. That is one of the main 2 growth pathways. RAS is mutated in up to 50% of all cancer which makes it a huge opportunity.

8/ Different mutations of KRAS are common in NSCLC, Pancreatic and Colorectal Cancers along with some others. They have the best in class data for Adagrasib for KRAS G12C. This could be worth $2 billion in sales.

9/ Their second program is MRTX-1133. This is for KRAS G12D. This could be worth another $1.5 to $2 billion is sales. There are several other KRAS mutations like G12V and Q61 mutations they could go after next.

10/ They just introduced their first program in preclinic that will target Synthetic Lethality around MTAP cancers. I am not a huge fan of MTAP as many companies are focused on it, but I moved $MRTX into my lead spot for my new Synthetic Lethality science category.

11/ I think they are a strong company that could lead the SL space over time. They might even license some tech in this space like they did in KRAS.

12/ My valuation for $MRTX stands around $135 with all the Sitravatinib value. If anything went wrong or it was dropped, that would remove a about half that value. They are in phase 2 with KRAS and could submit for early approval by mid next year if all goes well.

13/ It would take time for KRAS to make up any lost value of a failure or drop of Sitravatinib. That leaves me a bit cautious on $MRTX. Once they are commercial and bringing in cash, then it won't be as bad.

14/ My biggest fear is that they never really developed any really awesome drugs. They have Sitravatinib which is OK, but they licensed their best tech from Array. I have yet to see them develop something on their own that made me excited about their science.

15/ I rest assured that they did know how to go out and license what they needed to make some great blockbuster drugs. They could always do that again.