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New TYK2 inhibitors: a growing race to top Bristol Myers

When one drugmaker succeeds, many others try to do better.

That’s one reason why a protein called TYK2 has fast become one of the biotechnology industry’s top targets. At least a half dozen startups have set out to develop drugs that block it to better treat autoimmune diseases.

Conditions like psoriasis and arthritis affect millions of people. For years, they have been treated with injectable drugs like AbbVie’s Humira, which are among the sector’s most lucrative products.

Drugmakers have sought to replace them with more convenient oral medicines, but with mixed results. Pfizer, AbbVie and Eli Lilly, for example, each brought to market pills that target a family of proteins known as Janus kinases, or JAKs, which are involved in the body’s immune response. The drugs have proven effective at treating a wide range of inflammatory diseases, yet their use has been curtailed due to safety concerns.

Enter the TYK2, or tyrosine kinase 2 protein. Though part of the broader JAK family, TYK2 is viewed as a potentially safer target by scientists and drugmakers. That thinking was reinforced in September, when the Food and Drug Administration approved Bristol Myers Squibb’s Sotyktu for moderate-to-severe psoriasis without the safety warnings that have limited its JAK-blocking competitors.

Now the race is on to surpass Sotyktu. At least one startup developing a TYK2 inhibitor has launched since Sotyktu’s approval, while two other companies raised fresh funding to push their drugs further along.

Success could mean significant financial gain. Bristol Myers, which is also testing Sotyktu in psoriatic arthritis, lupus, and Crohn’s disease, forecasts yearly sales of Sotyktu could eventually reach as high as $4 billion.

Here’s where things stand.

What are TYK2 inhibitors and how do they work?

TYK2 inhibitors work by blocking the TYK2 protein and the cellular signals that run through it. Those signals can in turn activate other immune proteins and are associated with inflammation.

Disrupting that signaling by targeting TYK2 is viewed as a promising way to tamp down excessive inflammation brought on by autoimmune diseases such as psoriasis, psoriatic arthritis, Crohn’s disease and lupus.

Another part of the attraction of TYK2 inhibitors is they offer a way to target inflammation without also blocking related JAK proteins, the inhibition of which can cause serious side effects.

Published Oct. 11, 2022

Gwendolyn Wu, Reporter

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