Immunopharmaceutical research has sought better and safer ways to intervene in the inflammation that causes autoimmune diseases. The recent FDA approval of Bristol-Myers Squibb for the treatment of psoriasis vulgaris makes it the first approved product in a new class of medicines that address a particularly attractive enzymatic target. Startup Sudo Biosciences, which aims to show that its drug can be the best in this emerging class, has now emerged from 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 like Pfizer, Eli Lilly and AbbVie are commercializing his JAK inhibitors for various autoimmune diseases, but those drugs carry the risk of serious side effects. Last year, an FDA investigation into the safety of Pfizer’s commercialized his JAK drug, Xeljanz, found high rates of cardiovascular problems and cancer, prompting regulators to discontinue the drug and his JAK class. now updates black box warnings for other products in .
TYK2, like its JAK cousin, is also involved in signaling pathways associated with a wide range of immune-mediated inflammatory conditions, making it an attractive drug target. However, attacking TYK2 is expected to provide improved safety compared to JAK inhibitors. For drugs that target TYK2 to work, it is critical that they bind to her TYK2 without affecting other her JAK family proteins. Based in Menlo Park, Calif., his Sudo now joins a growing group of companies that are detouring to accomplish that task.
The way most small molecule drugs work is by binding to the active site of their target. Sudo’s drug, and his other TYK2 inhibitors in this class, are allosteric inhibitors. These drugs do not bind to the active site, but to another spot that can provide the desired therapeutic effect. According to Sudo’s CEO, Scott Byrd, his company’s lead his program targets the TYK2 pseudokinase his domain. Hitting this target also avoids hitting the JAK protein, which can cause side effects.
“By allosterically regulating TYK2 kinase function through binding to the TYK2 pseudokinase domain (JH2 domain), we can achieve a significant improvement in selectivity over other JAKs,” he says by email. “The increased selectivity offers the advantage of avoiding safety issues with drugs known to inhibit JAK2 and/or JAK1.”
The BMS drug deucravacitinib showed that the pseudokinase domain of TYK2 can be successfully drugged by selective allosteric inhibitors. His September approval of the drug in psoriasis vulgaris came without a black box warning by the JAK drug, but its label said cancer was observed in clinical trials. BMS markets the tablets under the name ‘Sotyktu’.
Investors have confidence in TYK2 as a draggable target. Days after Sotyktu’s approval, Nimbus Therapeutics announced that it would be funding his $125 million mid-stage clinical trial of his TYK2 blocker in psoriasis and psoriatic arthritis. Ventyx Biosciences has made a $177 million private placement to fund clinical development of a drug pipeline containing a TYK2 inhibitor.
Not all TYK2 drug research efforts have been successful. Sotyktu failed a Phase II trial for ulcerative colitis last year. Trials for that indication using higher doses are ongoing. BMS is also continuing trials of the drug in other immune disorders such as lupus and psoriatic arthritis. A growing number of drugs are vying to join this class. BioCentury counts 11 of his TYK2 inhibitors in clinical trials, including three that take a dual approach that blocks both TYK2 and JAK1.
Sudo claims that the company’s drug may be the best in the TYK2 inhibitor class, but the company has not provided further details. Byrd says only that each of Sudo’s four programs is designed to meet a specific unmet need not addressed by known competitors in the market or in development. As for signs competitors are already addressing, Byrd said the goal is to show that Sudo’s program is superior. , Byrd said one program is an oral pseudokinase drug.
Sudo announced its launch last week, but was founded in 2020. The company was founded by the life science division of investment firm Frazier Healthcare Partners. In announcing the launch of Sudo, Dan Estes, general partner at Frazier Life Sciences, said the startup will help scientists including scientists who see opportunities to target pseudokinases as a way to treat a variety of autoimmune diseases. said it arose out of a discussion in Frazier.
Suto’s Series A funding was led by Frazier Life Sciences and Velosity Capital. Sudo plans to use the new capital to advance the company’s lead drug candidate to human testing. Byrd refused to provide a timeline for reaching the clinic.
Photo courtesy of Sudo Biological Science