Immunology drug research has been casting about for better and safer ways to intervene in the inflammation driving autoimmune disorders. The recent FDA approval of a Bristol Myers Squibb plaque psoriasis drug made it the first approved product in a new class of medicines that address a particularly attractive enzyme target. Startup Sudo Biosciences aims to show that its drugs can be best in this emerging class, and it is now out of stealth with $37 million in funding.
The enzyme of interest is tyrosine kinase 2, or TYK2. It belongs to a protein family called Janus kinases (JAKs). Companies such as Pfizer, Eli Lilly, and AbbVie have commercialized JAK inhibitors for a range of autoimmune diseases, but their drugs come with the risk of severe side effects. Last year, an FDA inquiry into the safety of Pfizer’s commercialized JAK drug, Xeljanz, found a higher incidence of cardiovascular problems and cancer, which prompted the regulator to update black box warnings for that drug and other products in the JAK class.
TYK2 is an attractive drug target because, like its JAK cousins, it is also involved in signaling pathways associated with a wide range of immune-mediated inflammatory conditions. However, hitting TYK2 is hoped to offer a safety edge compared to JAK inhibitors. For a TYK2-targeting drug to work, the key is to bind to it without also hitting the other JAK family proteins. Menlo Park, California-based Sudo is now joining a growing group of companies taking a roundabout way to accomplish that task.
The way most small molecule drugs work is by binding to an active site on a target. Sudo’s drug, and other TYK2 inhibitors in the class, are allosteric inhibitors. Rather than binding to an active site, these drugs binds to a different spot that can still provide a desired therapeutic effect. According to Sudo CEO Scott Byrd, his company’s lead programs target the TYK2 pseudokinase domain. Hitting this target avoids also hitting JAK proteins that can trigger side effects.
“By allosterically regulating TYK2 kinase function through binding to the TYK2 pseudokinase domain (JH2 domain), significant improvement in selectivity versus other JAKs can be achieved,” he said in an email. “Increased selectivity provides the advantage of avoiding safety liabilities of agents known to inhibit JAK2 and/or JAK1.”
BMS drug deucravacitinib demonstrated that TYK2’s pseudokinase domain can be successfully drugged by a selective allosteric inhibitor. The September approval of that drug in plaque psoriasis came without the black box warning carried by JAK drugs, but its label does note that cancers were observed in clinical testing. BMS is marketing the pill under the name “Sotyktu.”
Investors are gaining confidence in TYK2 as a druggable target. Days after Sotyktu’s approval, Nimbus Therapeutics unveiled $125 million to fund mid-stage clinical trials of its TYK2-blocking drug in psoriasis and psoriatic arthritis. Ventyx Biosciences followed with a $177 million private placement to fund clinical development of its drug pipeline, including a TYK2-blocking drug.
Not all TYK2 drug research efforts have been successful. Sotyktu failed a Phase 2 test last year in ulcerative colitis. A test in that indication using a higher dose is ongoing. BMS also continues to test the drug in other immune disorders, such as lupus and psoriatic arthritis. The number of drugs vying to join the class is growing. BioCentury counts 11 TYK2 inhibitors in clinical trials, including three that take the dual approach of blocking both TYK2 and JAK1.
Sudo claims its drugs could be best in the TYK2 inhibitor class, but the company isn’t disclosing specifics. Byrd would only say that each of Sudo’s four programs has been designed to fill specific unmet needs unaddressed by known competitors on the market or in development. In indications already addressed by a competitor, Byrd said the goal is to show Sudo’s programs are better. Sudo’s disease targets also remain undisclosed for now, but Byrd said one program is an oral pseudokinase drug.
Though Sudo announced its launch this past week, it was founded in 2020. The company was formed by the life sciences arm of investment firm Frazier Healthcare Partners. In the announcement of Sudo’s launch, Dan Estes, general partner of Frazier Life Sciences, said that the startup emerged from discussions at Frazier that included scientists and others who saw an opportunity to target pseudokinase as a way to treat a range of autoimmune disorders.
Sudo’s Series A financing was led by Frazier Life Sciences and Velosity Capital. Sudo plans to use its new capital to advance the company’s lead drug candidates into human testing. Byrd declined to offer a timeline for reaching the clinic.
Photo by Sudo Biosciences