BMS, Pfizer, Nuocheng Jianhua, BeiGene, etc. are all under development, can it become the next stop for JAK inhibitors?

As a member of the JAK family, TYK2 has now become one of the important research directions in the field of autoimmune diseases

More than a dozen TYK2 inhibitors around the world are expected to achieve a breakthrough of zero in the second half of this year, becoming the world's first TYK2 inhibitor approved for marketing

✦ TYK2: The 4th member of the JAK family ✦

✦ TYK2: The 4th member of the JAK family ✦

The industry's attention to the TYK2 target also begins with the development of the familiar JAK target mechanism

However, because members of the JAK family can mediate signaling pathways for multiple cytokines, currently approved JAK inhibitors (targeting JAK1-3) inevitably have some side effects, which limits their clinical application

Because members of the JAK family can mediate signaling pathways for multiple cytokines, currently approved JAK inhibitors (targeting JAK1-3) inevitably have some side effects, which limit their clinical application

To improve the safety of JAK inhibitors and maximize their efficacy, researchers have set their sights on another member of the JAK family in recent years, TYK2

▲Schematic diagram of TYK2 signal path and JAK1/2/3 signal path (Image source: Reference[1])

▲Schematic diagram of TYK2 signal path and JAK1/2/3 signal path (Image source: Reference[1])

Cytokines are known to play a key role

What's more, studies have shown that when TYK2 regulates cytokines such as IL-23, IL-12, and IFN type 1, other cytokines are not affected

When TYK2 regulates cytokines such as IL-23, IL-12 and IFN, other cytokines will not be affected Inhibition of TYK2 can reduce the side effects of inhibiting other MEMBERS of the JAK family, and is expected to bring a safer and more effective treatment option for the treatment of autoimmune diseases and inflammatory diseases

✦ The first model has been declared for listing, and more than 10 models are in the clinical research stage✦

✦ The first model has been declared for listing, and more than 10 models are in the clinical research stage✦

According to public information, more than ten inhibitors targeting TYK2 worldwide have entered the clinical trial stage, including TYK2 single-target inhibitors, TYK2/JAK1 dual-target inhibitors, and the proposed development indications cover a wide range of autoimmune diseases

These include TYK2 single-target inhibitors, TYK2/JAK1 dual-target inhibitor plaque psoriasis, psoriatic arthritis, systemic lupus erythematosus, lupus nephritis, Crohn's disease, and ulcerative colitis

TYK2 single-target inhibitor

TYK2 single-target inhibitor

In the development of TYK2 single-target inhibitors, the fastest progress was in the deucravacitinib

This unique design allows it to avoid inhibiting other proteins of the JAK family (JAK1-3) And the drug is expected to become the world's first approved TYK2 inhibitor

In addition to Deucravacitinib, several TYK2 inhibitors are under clinical development

Moderate to severe plaque psoriasis Active Psoriatic Arthritis GLPG3667 Proposed indications for the treatment of dermatomyositis include psoriasis, Crohn's disease, and psoriatic arthritis

In China, there are also a number of companies developing TYK2 inhibitors

Two TYK2 inhibitors have entered clinical trials

In addition, BGB-23339 in BeiGene is also being conducted in an international multicentre (including China) Phase 1 clinical trial, which targets the JH2 domain

JAK1/TYK2 dual-target inhibitor

JAK1/TYK2 dual-target inhibitor

At the same time, some companies are exploring the development of TYK2/JAK1 dual-target inhibitors, hoping to achieve better efficacy

Pfizer's development of brepocitinib (PF-06700841) is a TYK2/JAK1 inhibitor, which has completed more than ten Phase 1/2 clinical trials, covering indications including psoriatic arthritis, psoriasis, ulcerative colitis, alopecia areata and purulent sweat glanditis

Indications covered include psoriatic arthritis, psoriasis, ulcerative colitis, alopecia areata and purulent sweat adenitis in Phase 3 clinical trials in patients with dermatomyositis

In China, companies such as Qiyuan Biotech and Gaoguang Pharmaceutical also have JAK1/TYK2 dual-target inhibitors and have entered the clinical trial stage

The drug is also the first new drug under development of Qiyuan Bio to enter the clinical stage

Founded in 2017 to develop small molecule drugs to treat autoimmune diseases and inflammation, another company, Gaoguang Pharmaceuticals, is a TYK2/JAK1 dual inhibitor with high selectivity and activity against JAK1 and TYK2, and is conducting Phase 1 and Phase 2 clinical trials

Its first innovative drug, TLL-018, is a dual inhibitor of TYK2/JAK1

In addition to the above drugs, there are also some TYK2 inhibitors in development worldwide, which are limited by space and will not be introduced

Resources:

Resources:

[1] Gonciarz M, Pawlak-Buś K,et al.
(2021).
TYK2 as a therapeutic target in the treatment of autoimmune and inflammatory diseases.
Immunotherapy.
Immunotherapy.
doi: 10.
2217/imt-2021-0096.

[1] Gonciarz M, Pawlak-Buś K,et al.
(2021).
TYK2 as a therapeutic target in the treatment of autoimmune and inflammatory diseases.
Immunotherapy.
Immunotherapy.
doi: 10.
2217/imt-2021-0096.

[2] He, Xingrui， Chen, Xiabin,et al.
(2019).
Selective Tyk2 inhibitors as potential therapeutic agents: a patent review (2015-2018).
Expert Opinion on Therapeutic Patents, doi:10.
1080/13543776.
2019.
1567713

[2] He, Xingrui， Chen, Xiabin,et al.
(2019).
Selective Tyk2 inhibitors as potential therapeutic agents: a patent review (2015-2018).
Expert Opinion on Therapeutic Patents, doi:10.
1080/13543776.
2019.
1567713

[3] Chang, Y.
, Xu, S.
, & Ding, K.
(2019).
Tyrosine Kinase 2 (TYK2) Allosteric Inhibitors To Treat Autoimmune Diseases.
Journal of Medicinal Chemistry.
doi:10.
1021/acs.
jmedchem.
9b01612

[3] Chang, Y.
, Xu, S.
, & Ding, K.
(2019).
Tyrosine Kinase 2 (TYK2) Allosteric Inhibitors To Treat Autoimmune Diseases.
Journal of Medicinal Chemistry.
doi:10.
1021/acs.
jmedchem.
9b01612

[4] Each company's official website and public information
.

[4] Each company's official website and public information
.