Profile

Kymera is working on targeted protein degradation. There is an organelle inside each cell called the Proteasome. This acts like the recycling center of the cell for proteins. When a protein is no longer needed, it gets tagged for degradation. Then it is loaded into the Proteasome where it gets broken down into small fragments that can be used to make new proteins. The targeted protein degraders go into the cell and tag proteins to have them degraded by the Proteasome. This can harness the cell system to create a therapeutic way of removing harmful or unwanted proteins as therapies. Kymera is focused on using this technology to treat inflammation disorders and cancer.

Management

I have been following Kymera and Nello Mainolfi for a while now. So far, I think he is doing a great job. The company is maintaining a good balance sheet while advancing its early clinical trials. They are focused on driving new biology with their assets which means less competition. I think he is driving good innovation which makes this company exciting. They have generated some data so far to show they can work their way through the clinical data process. It will take more time to see how well they do through the whole process of developing a commercial biotech company.

Science

KT-474 targets IRAK4 which is a pathway inside antigen presenting cells that activates the production of inflammatory cytokines like IL-1. The role of these inflammatory pathways in inflammatory diseases is well known. This therapy goes in and degrades the IRAK4 protein so it does not trigger the activation of the cytokines that lead to inflammation. There is early efficacy and safety data that shows it can lower symptoms in patients with skin inflammatory diseases. It has been turned over to their partner Sanofi which will now advance it through phase 2 trials for multiple inflammatory disorders like HS and Atopic Dermatitis.

KT-413 combines the IRAK4 degrader with the IMID degrader to target MyD88 driven tumors. This is an IV infusion every 3 weeks for patients with B cell Non Hodgkin Lymphomas. This is designed to degrade both pathways of IRAK and IMID which are proinflammatory pathways to drive cancer growth. It is currently in the phase 1 dose escalation part of the trial. They are seeing 95% knockdown of IMID and 40% knockdown of IRAK4 in early biomarker data.

KT-333 inhibits the STAT3 pathway by targeting that protein for degradation. This is being developed for STAT3 driven hematologic malignancies. It is in the dose escalation part of phase 1 with them just completing the first dose level. Right now they look to be targeting CTCL and PTCL. They have seen 66% STAT3 knockdown from biomarker data.

KT-253 targets MDM2 which is a protein that inhibits p53. The p53 protein is a key regulator of cell survival and DNA repair. The p53 gene is mutated in about 50% of cancers. This leads to a loss of this tumor suppressor gene. By blocking the inhibitor of p53, they can have higher levels of the p53 protein in these cells. This is designed to increase the level of cell death signals in cancer cells. It is currently in IND enabling studies.

Valuation

Cash $559 million

KT-474 has several indications in which it can show efficacy. I think it could easily do $2 billion in sales if the data continues to do well or improves across all the possible indications for IRAK4. Kymera would get 50% of those sales for $1 billion. I would give this and 1x multiplier as they do have full phase 1 data now. That gives them $1.5 billion in value.

KT-413 has a patient population of about 37,000 patients in DLBCL where it would target MyD88 driven cancers. I think it could do about $1 billion in sales if successful. It would get a .1 multiplier until we see some data from the phase 1 trial. That makes it worth $100 million.

KT-333 could have really big potential if it works out well in oncology with PTCL and CTCL. I would venture a guess of about 20,000 to 25,000 patients for these indications. With a price tag of $100,000, that comes to at least $1 billion in sales. It would depend on the data and market share. I would give this .1 multiplier since it's still early in phase 1 with no data. That makes it worth $100 million.

KT-253 is really hard to predict since I don't have any data on this program yet. I would venture a guess of $1 billion if all goes well. That would be worth $100 million value with being preclinical.

All in, that is a $1.859 billion market cap. Based on the 55.183 million shares outstanding, that comes to $33.68.

Partnerships

Sanofi for IRAK4 in inflammation plus one additional target for world wide outside of oncology. Kymera has the opt in right to any asset for up to 50% of the US. They are entitled to up to $1.7 billion in milestones, and they get royalties in the high single digits to high teens in any areas outside the US.

Vertex partnership for areas outside Kymera's core oncology and inflammation areas. They are entitled to upward of $170 million in milestones per licensed product. They will also get low single digit royalties on these products.

Events

KT-474 Multiple Phase 2 expected to be started by Sanofi in 2023

KT-413 Phase 1 dose escalation in progress

KT-333 Phase 1 dose escalation in progress

KT-253 Sart Phase 1 in early 2023

Announce the next 2 preclinical asset targets this year.

Data Readouts

KT-474 Data in HS and AD

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Events & Presentations

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