Profile

Revolution Medicines is focused on the 2 key pathways inside cells that mutate and drive cancer growth. These are the MAPK and mTOR pathways. They are very complex pathways so not everything tested will work. There will be some hit and miss in these pathways to find right combinations to hit the right targets. They are focused on RAS mutations and companion drugs to combine with the RAS drugs to reach the correct inhibition desired. They use an unique approach to blocking the activation of the kinase. They build a binder molecule that takes the activated kinase and binds it to cyclophilin A. This prevents the activation of that kinase and its eventual degradation.

Management

I have followed Revolution Medicines and Mark Goldsmith for over a year now. I think he is doing a good job with this company. They are out there talking about their science and how they are different from others in this space. They have managed the balance sheet well. They recently did a secondary in a really weak biotech market, and it was received well. They even have some early data to show they are working through the drug development process. They have multiple drugs moving into early clinical trials now. It will take more time to see how their science translates into data.

Science

RMC-6236 targets multiple forms of RAS to include multiple KRAS targets. This is designed to be a pan inhibitor. There is a lot of risk in this approach as any hitting of wild type RAS can come with serious side effects. The data shows that upward of 30% of all cancers have a RAS mutation. This could affect well over 100,000 patients across multiple mutations. This is in early phase 1, and they announced some early safety data that shows its being well tolerated so far.

RMC-6291 targets KRAS G12C. This is designed for 2 purposes. The first is it acts as a backup molecule should the multi RAS drug fail. The second is it can be combined with the multi RAS drug in combinations for KRAS G12C cancers. This targets the RAS on form of KRAS. This is different from other KRAS G12C drugs. It does this by binding the KRAS to cyclophilin A. This is early phase 1 with no data yet.

RMC-9805 targets KRAS G12D. This is designed for 2 purposes. The first is it acts as a backup molecule should the multi RAS drug fail. The second is it can be combined with the multi RAS drug in combinations for KRAS G12D cancers. This targets the RAS on form of KRAS. It does this by binding the KRAS to cyclophilin A. This is expected to start dosing in mid 2023.

RMC-4630 is a SHP2 inhibitor. This is the first kinase activated by the growth receptor inside cells. It starts at the top of the MAPK pathway. This is designed to be a companion inhibitor to RAS drugs. This is currently in phase 1b trials in combination with other KRAS G12C inhibitors. The phase 1 data was encouraging, but it needs a dosing regimen to keep tolerability. This program was given back to Revolution from Sanofi. They plan to continue to develop it on their own for key KRAS combinations.

RMC-5552 is a 4EBP1 inhibitor which is downstream of mTOR. This is being designed as another RAS companion drug. The preclinical data was not that compelling so we will have to see how it works in phase 1.

Valuation

Cash $644 million

RMC-6236 is the RAS multi drug with huge potential if the data works out. It could have a market size of 100,000 patients. Even if they get only 30% of that market at a $100,000 price, it comes out to $3 billion in potential. I would give it a .1 multiplier which gives this program $300 million value.

RMC-6291 is a KRAS G12C inhibitor. If RAS multi works, I don't think this gets much market share unless it combines well with the multi RAS inhibitor. That will take a lot of time to prove out if it works at all. I would only give this a small value amount since it requires RAS multi to combo well with it. I would give them $25 million value for a phase 1 asset.

RMC-9805 is a KRAS G12D inhibitor. If RAS multi works, I don't think this gets much market share unless it combines well with the multi RAS inhibitor. That will take a lot of time to prove out if it works at all. I would only give this a small value amount since it requires RAS multi to combo well with it. I would give them $25 million value for a phase 1 asset.

RMC-4630 is a SHP2 inhibitor which can be quite toxic with side effects. That will significantly reduce its market size. I would only give this $250 million in potential unless the data proves otherwise. It has some phase 1 data which gives it a multiplier of .5x. That makes it worth $125 million value.

RMC-5552 is a 4EBP1 inhibitor. I was not impressed with the preclinical data so I will give it no value until I see better data.

All in, that is a $1.119 billion market cap. Based on the 90.49 million shares outstanding, that comes to $12.36.

Partnerships

Sanofi just terminated their partnership and returned RMC-4630 back to Revolution Medicine.

Events

RMC-6236 Single Agent Data mid 2023

RMC-6291 Preliminary Data 2H of 2023

RMC-9805 Phase 1 Start in Mid 2023

RMC-4630 Top Line Data 2H of 2023

RMC-5552 Provide Further Data in 2023

Data Readouts

No Data Yet.

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