I have been in Kymera for about 9 months now. I think Nello Mainolfi has done a good job so far. Its still early stages so don't know how well he will navigate the regulatory and commercial aspects of the business.
2/ Science:
Kymera is working on Targeted Protein Degradation. This uses the Proteasome of the cell to target and breakdown unwanted proteins. This can be harnessed to target proteins that can be therapeutic to inhibit.
3/ They are working on targets for immunology and oncology. Their first 2 drugs focus on IRAK4 which is part of the pathway for activation of Toll Like Receptors in immune cells. This blocks the production of key inflammatory cytokines like IL-1b.
4/ This has the potential to be the next great anti inflammatory drug like Humira. They are testing IRAK4 in HS, AD and RA. They are testing IRAK4 in combo with IMID in oncology indications for cancer driven by MyD88 driver mutations.
5/ Their third drug targets STAT3 which is part of the famous JAK/STAT pathway. They are focused on STAT3 for oncology and immunology indications like fibrosis. Their last drug is for MDM2 which inhibits p53. This is a potential target for p53 mutant cancers.
6/ Potential:
I think Kymera has a ton of potential depending how well these targets work in the possible indications. The IRAK4 alone in inflammation could do $3 billion to $5 billion in sales if it works well.
7/ It could go much higher if it turns out to be a powerful anti inflammatory drug. It can also do up to $1 billion in the MyD88 driven cancers.
8/ Its hard to estimate what STAT3 might do in revenues, but I would speculate upward of a few billion if it works as well as I think it could.
9/ Value:
Kymera seems cheap at just under $2 billion market cap for all the potential it has. They have $567 million in cash and burned $100 million in 2021. They have a good 2 years of cash as they move these programs into the clinic.
10/ It is still very early, and a lot depends on the first efficacy data from the IRAK4 indications in HS and AD. If these programs are successful, this could prove to be a very cheap company at this valuation.
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I have been in C4 Therapeutic for about 8 months now. I don't know the CEO Andrew Hirsch all that well. He seems to be doing good so far. The biggest issue I have is with the high level of risk in their strategy.
2/ They are highly focused on using Protein Degraders in already very proven indications and targets. This means they will have to show strong superiority over current therapies on efficacy or safety to really stand of chance of capturing any market share.
I have been in Arvinas about 9 months, and I am still undecided about John Houston. I don't like the idea they started in ER and AR which are highly competitive spaces.
2/ Their best programs have been sitting in the preclinic for years going nowhere. They fall further and further behind in those best indications like tau or KRAS. I am still hopeful they will impress me someday.
I don't know Mark Goldsmith very well. I have only been in Revolution Medicine about a year. That isn't a lot time to really know a management team. So far, I think he has done and excellent job.
2/ All their programs are still very early so it is hard to see how well they will navigate the regulatory and commercial parts of the business at this stage.
Mirati is one of my older holdings along with Blueprint. They were lead by founder and scientist Charles Baum. I think he did a really good job developing the company up to this point.
2/ He created Sitravatinib and in-licensed Adagrasib for KRAS G12C. Recently, they changed management by moving Baum to Chief of Research. They brought in David Meek as the new CEO to take them into the commercial phase of development.
Blueprint is one of my oldest holdings. They have an outstanding CEO with Jeff Albers. Recently, they announced the CEO transition to Kate Haviland. Jeff will move to the Chairman role.
2/ Any time there is a CEO transition, there is reason for concern. I have been in companies before that were very successful under one CEO and then it was all down hill after the CEO changed.
I have been a bit cautious on the management of Schrodinger. I think Ramy Farid is a software guy and doing a good job with the software business. I don't own the company because of the software as I don't believe it will be that big of a business.
2/ I do see what the software could do for the company with its own drug discovery business. I think Karen Akinsanya is doing an excellent job on the biotech side of things.