Immunology drug research is looking for better and safer ways to intervene in the inflammation that causes autoimmune diseases. The recent FDA approval of a Bristol Myers Squibb plaque psoriasis medicine made it the first approved product of a new class of drugs targeting a particularly attractive enzyme target. Startup Sudo Biosciences aims to show that its drugs can be the best in this emerging class, and it’s now out of stealth with $37 million in funding.
The enzyme of interest is tyrosine kinase 2, or TYK2. It belongs to a family of proteins called Janus kinases (JAKs). Companies such as Pfizer, Eli Lilly and AbbVie have marketed JAK inhibitors for a range of autoimmune diseases, but their drugs carry the risk of serious side effects. Last year, an FDA investigation into the safety of Pfizer’s JAK drug, Xeljanz, found a higher incidence of cardiovascular problems and cancer, prompting the regulator to update box warnings black for this drug and other JAK class products.
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, knocking out TYK2 should provide a safety advantage over JAK inhibitors. For a drug targeting TYK2 to work, the key is to bind to it without also affecting the other JAK family proteins. Sudo, based in Menlo Park, Calif., now joins a growing group of companies taking a roundabout way to accomplish this task.
Most small molecule drugs work by binding to an active site on a target. Sudo’s drug and other class TYK2 inhibitors are allosteric inhibitors. Rather than binding to one active site, these drugs bind to a different location that may still provide a desired therapeutic effect. According to Sudo CEO Scott Byrd, his company’s core programs target the TYK2 pseudokinase domain. Hitting this target also avoids hitting the JAK proteins which can trigger side effects.
“By allosterically regulating the function of tyk2 kinase by binding to the TYK2 pseudokinase domain (JH2 domain), a significant improvement in selectivity over other JAKs can be achieved,” he said in a E-mail. “Increased selectivity offers the benefit of avoiding safety liabilities for agents known to inhibit JAK2 and/or JAK1.”
The BMS drug deucravacitinib has demonstrated that the pseudokinase domain of TYK2 can be successfully medicinated by a selective allosteric inhibitor. The drug’s September approval in plaque psoriasis came without the black box warning carried by JAK drugs, but its label says cancers have been seen in clinical trials. BMS markets the pill under the name “Sotyktu”.
Investors are gaining confidence in TYK2 as a drug target. Days after Sotyktu’s approval, Nimbus Therapeutics unveiled $125 million to fund mid-stage clinical trials of its TYK2 blocker drug in psoriasis and psoriatic arthritis. Ventyx Biosciences followed with a $177 million private placement to fund the 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 trial last year in ulcerative colitis. A trial in this indication using a higher dose is in progress. BMS is also continuing 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 account 11 TYK2 inhibitors in clinical trials, including three that take the dual approach of blocking both TYK2 and JAK1.
Sudo claims its drugs may be the best in class of TYK2 inhibitors, but the company is not disclosing details. Byrd would only say that each of Sudo’s four programs was designed to meet specific unmet needs not met by known competitors in the market or in development. In hints already addressed by a competitor, Byrd said the goal is to show that Sudo’s programs are better. Sudo’s disease targets also remain undisclosed at this time, but Byrd said one program is an oral pseudokinase drug.
Although Sudo announced its launch last week, it was founded in 2020. The company was formed by the life sciences arm of investment firm Frazier Healthcare Partners. When announcing Sudo’s launch, Dan Estes, general partner at Frazier Life Sciences, said the startup grew out of discussions at Frazier that included scientists and others who saw an opportunity to target pseudokinase as a means of treat a range of autoimmune diseases.
Sudo’s Series A funding 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