Cancer drug research continues to provide patients with targeted therapies for tumors that express specific genetic or biological signatures. This precision oncology approach means a clinician can tailor treatment to a patient’s disease. Such precision medicine strategies are beginning to find their place in immunology.
Martin Babler, CEO of Alumis, said his company’s research into the genomics of autoimmune diseases allows it to better understand what’s happening in the body. This understanding could help inform a clinician which patients may respond to a particular medication. Some of these drugs could come from Alumis.
“Ultimately, our goal is to have a precise treatment, so that patients feel like if I take this drug, I will really benefit from it,” Babler said in an interview at the JP Morgan Healthcare conference in January. “As a company, we are fundamentally founded on the principle of precision immunology: how can we find the right drug for the right patient, at the right time, with a narrow enough set of targets to hit so that the patient actually gets the main benefit and doesn’t have to suffer a lot of side effects.”
Alumis’ lead program, envudeucitinib, is in late-stage clinical development for plaque psoriasis. The drug is an oral small molecule designed to block TYK2, a protein that plays a role in inflammation. After announcing positive preliminary phase 3 results earlier this year, Alumis was able to raise more than $345 million as part of a share offering. Clinicians and investors have been waiting for more detailed data. These results are included in the form of last minute presentation scheduled for this Saturday at the annual meeting of the American Academy of Dermatology in Denver. Alumis will hold a conference call on Sunday to discuss the data.
Emergence of oral medications for psoriasis
When patients needed something stronger than a topical medication to treat plaque psoriasis, the next line of therapy was injectable biologic medications. Bristol Myers Squibb offered patients an oral alternative with Sotyktu, which became the first TYK2 inhibitor to reach the market following its launch. FDA approval in 2022.
While the psoriasis drug market is crowded between topical and injectable products, companies are trying to fill the space between them with oral medications, a formulation favored by many patients. Last week, Johnson & Johnson received FDA approval for Icotyde, an oral peptide that targets the IL-23 receptor to treat plaque psoriasis. J&J predicts that this pill could reach peak sales of $5 billion in several indications. As for Sotyktu, the BMS drug has not become a big seller, with sales of $291 million in 2025. Alumis is part of a group of biopharmaceutical companies developing TYK2 inhibitors intended to offer better safety and effectiveness than BMS’s once-daily pill.
Alumis’ genetic studies showed that a drug must hit TYK2 very hard, meaning that over the course of a day the molecule must cover more than 90 percent of the target, Babler said. TYK2 is found throughout the body, so there must be sufficient levels of the drug circulating to block enough of these proteins. Without TYK2 coverage greater than 90%, proteins that are not blocked still send signals that trigger inflammation, so a drug does not achieve the desired therapeutic effect.
“Where we are different from all other TYK2 inhibitors is that we have found a way to get greater than 90% TYK2 coverage for 24 hours in patients,” Babler said. “At the same time, though, you don’t want to push it too high, because if you push it too high you get side effects.”
In January, Alumis reported that envudeucitinib had reached statistically significant skin clearance in two phase 3 studies. Results at 24 weeks showed that approximately 65% of patients achieved clearance of 90% or more on a scale used to assess the severity of psoriasis. More than 40% of them achieved complete skin clearance – a functional cure. This, Babler said, has not been accomplished by any other plaque psoriasis medication. Babler said the results go beyond skin clearing. One of the manifestations of plaque psoriasis is severe itching. Babler said envudeucitinib results showed a strong reduction in itch and improvement in quality of life that Alumis believes will differentiate it from other products in its class.
Takeda Pharmaceutical’s zasocitinib is one such drug. At the end of last year, Takeda released preliminary phase 3 results showing that more than half of patients achieved clear or near-clear skin. at week 16 and these responses increased through week 24. Andy Plump, Takeda’s president of research and development, previously told MedCity News that the advantage of zasocitinib is achieving almost complete TYK2 inhibition over a 24-hour period with a once-daily pill.
Twice-daily dosing of Alumis’ medication is a little less convenient for patients. Babler said the two pills per day are needed to cover more than 90 percent of TYK2 receptors for 24 hours. Alumis is also developing a once-daily version of its drug, but this formulation is still being optimized.
“Other people have optimized for convenience, but maybe they haven’t optimized for safety and efficiency to the same level as us,” Babler said. “This is really the element that we believe will differentiate our molecules from others. We will optimize later for convenience with a separate formulation. Our first goal was to optimize safety and effectiveness.”
Next step for Alumis: Lupus
The role that TYK2 plays in inflammation is associated with many autoimmune diseases. Lupus is the second target of envudeucitinib; results from a phase 2b study are expected this summer. Babler said envudeucitinib could treat about 20 different indications, but Alumis won’t address them all. For some disorders, it may make more sense to work with a partner. Babler added that the recent funding gives the company time to wait at least after reading the lupus study before making any partnership decisions.
Leerink Partners considers envudeucitinib best in class. In a recent research note, Leerink analyst Thomas Smith said the properties of Alumis’ drug make it superior in blocking TYK2 with better inhibitory coverage. He added that the positive phase 3 results in plaque psoriasis partially reduce the risk of the upcoming mid-stage reading of lupus.
Research has also shown that TYK2 plays a role in neurological disorders. Alumis therefore developed a second TYK2 inhibitor capable of penetrating the brain. The drug has potential applications in Alzheimer’s and Parkinson’s diseases, but its first neurological test will be a proof-of-concept clinical trial in multiple sclerosis.
For the indications Alumis is pursuing, Babler said the company is taking a precision immunology approach. In some diseases, such as psoriasis, the main driver of the disorder is defined. But for others, like lupus, there are several factors. In other diseases, it is not clear what the main determining factor(s) is. Babler said the goal is to be able to characterize patients to assess whether a particular therapy would be appropriate for the cause of their disease. The idea is to determine what would be the most effective therapy for a given patient or group of patients.
“Right now, a lot of these patients are on medication and it works for maybe half of the patients or two-thirds,” Babler said of lupus medications. “The others still have to take the medicine, [but] do not necessarily gain an advantage. If we could improve that ratio, that’s really the goal of accuracy.
Photo by Flickr user FutUndBeidl via Creative Commons license
