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.
3/ This is a high risk strategy vs other companies that are focused on pioneering new science with little competition.
4/ Science:
They are using Targeted Protein Degradation. They are using both mono functional and heterobifunctional degraders. This does give them some versatility in how they go after each target.
5/ They are focused with their lead drug for IKZF1/3 which is very much the same as original IMIDs like Pomalidomide. The early data does seem to have much more potency at much lower doses.
6/ We will have to see the data to see what kind of difference that makes. Their other indications are BRAF and EFGR. There is room here if they can hit the same or better efficacy with lower levels of toxicity as many kinase inhibitors do have side effects.
7/ It will all come down to the data. I have to say there is a concern here at TPD can surpass TKI for safety and efficacy. That has yet to be established, but I know Blueprint just announced a partnership to get access to TPD for their discovery programs.
8/ Potential:
They have a lot of potential if they can capture a decent level of market share vs some of these current block buster drugs. The IKZF1/3 program could have effects in many of the blood cancers like NHL or even Multiple Myeloma.
9/ That could be worth $2 billion or more if they can surpass some of the other therapies in this space. The BRAF space has been very successful in Melanoma which could be worth over $1 billion in potential should it do as well as some of the other BRAF inhibitors.
10/ The EFGR indications are very big with Osimertinib doing upward of $5 billion a year in revenues.
11/ Value:
The company looks cheap at just over $1.1 billion market cap. They have $451 million in cash and burned $84 million in 2021. They have plenty of cash to last them a few years as they start to move programs into clinical trials.
12/ The big value driver here will be data. Any data that suggests superiority over current therapies could really drive the value. This is a higher risk, higher reward play.
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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 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.
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.