Sorriso Pharmaceuticals, Inc.

Private startup Sorriso Pharmaceuticals laid out Phase 1b data at a medical conference last weekend as part of its effort to bring an oral antibody to market for IBD patients. The results come after Sorriso toplined a readout in December from the small, 22-patient trial in ulcerative colitis that lasted six weeks, but didn’t release specifics. At the time, CEO Ciara Kennedy said the data were strong enough to move into a 200-patient Phase 2 study where researchers could obtain more answers about the drug’s effectiveness. Getting an oral antibody to market would be a significant feat for Sorriso. IBD is a massive patient population and most drugs are systemic treatments, administered through IV infusions or injections, that come with uncomfortable side effects. Previous attempts at developing orals have largely failed due to a focus on monoclonal antibodies. Sorriso’s drug, called SOR102, is an oral bispecific targeting TNF-alpha and IL-23. The compound contains a specialized amino acid linker designed to cleave when exposed to trypsin, which is one of the enzymes that pervades the digestive tract. In Sorriso’s Phase 1b study, six patients received placebo, seven received 810 mg of SOR102 once per day, and nine received 810 mg twice per day. The primary endpoint was safety, but Sorriso looked at a number of efficacy measurements including endoscopic response — part of the traditional primary endpoint in mid- and late-stage UC studies that’s measured by biopsy. “It’s a good proxy for clinical remission, because clinical remission includes endoscopic response,” Kennedy said. Two of the nine individuals in the twice-daily cohort saw an endoscopic response, while none of those in the once-daily arm did. But those figures come with a caveat: Five of the patients taking the drug dropped out of the trial, four of whom were in the twice-daily arm — though only one was due to the treatment itself. Three patients had UC that was too severe to be treated, and the fourth moved shortly after starting the study, Kennedy said. Sorriso assumed none of them responded to SOR102 in their reported data, because they weren’t able to biopsy those patients. All of the patients in the study were recruited in Ukraine and the country of Georgia. As a result, Sorriso was left with two of five patients (40%) responding in the twice-daily “per protocol” population. The entire population’s 22% response rate is “very comparable to monotherapies, and the protocol population, 40%, is much above the response rate that you see in monotherapies,” Kennedy said. The company is still trying to finalize the Phase 2 trial design. Right now, the plan is to enroll 200 patients randomized across four arms: placebo and three twice-daily drug arms. The amount used in the Phase 1b high-dose arm is expected to be the middle “anchor” cohort, Kennedy said. The Phase 2 study will also run on a similar timeframe to most IBD studies, starting patients in a 12-week induction phase and then monitoring them out to a year in a maintenance phase. Sorriso is aiming to improve its manufacturing capabilities to make the drug easier for patients to take. In the Phase 1b study, patients were taking as many as 12 pills per day — six in the morning, and six in the evening. But researchers have already managed to whittle that down to six for Phase 2, with the goal of reducing it even further. “In Phase 1, our drug product was 135 milligrams per capsule. Now we’re in about the 300 milligrams per capsule range,” Kennedy said. “But for Phase 3, we’re looking at formulations where perhaps we move to a single compressed tablet, where we could deliver 800 mg in one tablet.” Kennedy also added that the company is on track to close its Series B round in the middle of this year. “We are in multiple discussions with a lot of different investors,” she said. It raised a $31 million Series A in 2021.

Data from Dual-Acting Oral Biologic Show Promising Safety and Efficacy Profile Topline Clinical Data Demonstrates Activity of SOR102 Across Multiple Clinical Endpoints Supporting Advancement to Phase 2 Development SALT LAKE CITY, UT, USA I December 19, 2024 I Sorriso Pharmaceuticals, a biopharmaceutical company developing novel orally dosed antibodies for immune-mediated disease, today announced positive results from its Phase 1b clinical trial evaluating SOR102, an oral, dual-acting biologic targeting TNFα and IL-23, in patients with ulcerative colitis (UC). The study met its primary objectives, demonstrating a favorable safety and tolerability profile. Additionally, key exploratory efficacy endpoints showed promising activity of SOR102 across multiple clinical endpoints. This is the first successful demonstration of an orally dosed antibody delivering clinical efficacy. “Our Phase 1b results with SOR102 mark a significant milestone for Sorriso Pharmaceuticals and the field of autoimmune therapeutics,” said Ciara Kennedy, Chief Executive Officer of Sorriso Pharmaceuticals. “We believe SOR102, a first-in-class, oral biologic that inhibits TNFα and IL-23, two validated pathways in inflammatory bowel disease, will be a game changer. These clinical data for SOR102 provide strong evidence for its potential to provide an effective and convenient oral treatment option for patients living with ulcerative colitis. We are excited to advance SOR102 into Phase 2 development.” The randomized, double-blind, placebo-controlled trial enrolled 22 patients across 2 sites. Patients were randomized to receive one of two SOR102 doses or placebo for 6 weeks. The study assessed safety, tolerability, pharmacokinetics, pharmacodynamics, immunogenicity and preliminary efficacy. Among patients who completed the study, those in the high-dose SOR102 group achieved statistically significant separation from placebo across multiple clinical endpoints, including Mayo Score clinical response, modified Mayo Score clinical response, symptomatic remission, and mean decreases from baseline in Mayo Score, modified Mayo Score, and UC-100 score. Based on these results, Sorriso Pharmaceuticals plans to initiate a Phase 2 clinical trial in 2025, further evaluating SOR102 in a larger patient population. “Ulcerative colitis remains a challenging condition, but we have seen promising rates of clinical remission from dual inhibition of TNFα and IL-23 using systemically delivered antibodies,” said Carlos Sattler, Chief Medical Officer of Sorriso Pharmaceuticals. “These results, observed after just six weeks of treatment, compare favorably to approved treatments and underscore SOR102’s potential to redefine the treatment paradigm by targeting these two critical inflammatory pathways with a convenient oral therapeutic.” Dr. Vipul Jairath, Professor of Medicine at Western University, Canada and Chair of Sorriso Pharmaceuticals’ Scientific Advisory Board, added, “As a clinician and researcher, I’m thrilled to see the progress SOR102 is making in addressing the complex pathophysiology of ulcerative colitis. The dual inhibition of TNFα and IL-23 with an orally administered product is a bold and innovative approach that holds great promise for transforming patient care. These Phase 1b results provide a strong foundation for further development and underscore the potential of Sorriso’s platform to deliver groundbreaking oral therapies.” The detailed study results will be presented at the upcoming 20 th Congress of ECCO, to be held in Berlin, Germany from February 19 to 22, 2025. About SOR102 SOR102, an oral biologic, simultaneously inhibits TNF⍺ and IL-23(p19), two clinically validated drivers of inflammatory bowel disease (IBD), providing combination therapy locally within inflamed tissue with minimal systemic exposure. This dual targeting approach may increase efficacy through simultaneous blockade of different mechanisms of IBD. About Sorriso Pharmaceuticals Sorriso Pharmaceuticals is a biopharmaceutical company advancing a pipeline of disease-modifying antibodies for the treatment of immune-mediated diseases, including ulcerative colitis and Crohn’s disease. The Sorriso platform generates potent antibodies that can be delivered orally and are designed to maintain activity throughout human intestinal tissue. For more information, please visit www.sorrisopharma.com SOURCE: Sorriso Pharmaceuticals

A private startup from Salt Lake City aiming to develop oral antibodies says it has succeeded in an early trial, a potentially significant scientific advancement in a world where systemic treatments are the norm. The company, Sorriso Pharmaceuticals, said an oral bispecific antibody targeting TNF-alpha and IL-23 hit its safety and efficacy benchmarks in a 22-patient, Phase 1b trial in ulcerative colitis. Specific data aren’t being disclosed until February’s European Crohn’s and Colitis Organisation conference in Berlin, but the results are apparently good enough for Sorriso to move into a Phase 2 trial next year and to seek a Series B round, CEO Ciara Kennedy told Endpoints News . “We will be launching a Series B fundraising on the basis of this data,” Kennedy said, “pretty soon.” The size of the round is still being worked out, she added. Some of the best-selling drugs of all-time — mostly monoclonal antibodies — get big chunks of their revenue from the immunology space such as inflammatory bowel disease, like Humira and Remicade. But those are administered through IV infusions or injections. The systemic nature of the therapies can lead to sometimes serious side effects, and are generally uncomfortable for patients. Oral antibodies, however, have the opportunity to deliver targeted treatment directly to the affected areas in the stomach. There have been earlier attempts to develop such drugs, though they have largely focused on monoclonal antibody approaches, which are large proteins, Kennedy said. Larger proteins delivered orally typically fail in the intestines because of how harsh the environment is. But where Sorriso thinks it’s found a recipe for success lies in the chemistry of its program, known as SOR102. The antibodies are about one-tenth the size of monoclonal antibodies, and are engineered to be resistant to much of the proteases that make things difficult for bigger compounds. Researchers are also using a specialized amino acid linker connecting the TNF-alpha and IL-23 antibodies designed to cleave when exposed to trypsin — one of the enzymes that pervades the digestive tract. “They work together when they’re bound together, but they also work just as well when they’re separated from each other,” Kennedy said. “It just means that they can engage with their target independently at the location of the other part of the drug.” All told, it makes for a more stable drug. Sorriso’s platform comes from an acquisition of a UK biotech called VHsquared, which had been working on oral gut-restricted antibodies. Sorriso went after ulcerative colitis first, because patients typically respond to their treatments faster than those with Crohn’s disease, Kennedy said. Also, VHsquared had tested the program in Crohn’s but at too short an interval for the active and placebo arms to separate, she added. But Sorriso has plans to expand into Crohn’s at a later date. And given the oral administration, SOR102 will probably stick to IBD rather than expand into other immunological areas like rheumatoid arthritis or psoriasis. “We’re not necessarily looking to increase systemic circulation,” Kennedy said. The upcoming Phase 2 in UC is expected to run for 12 weeks and enroll about 200 patients, and patients will have the option to continue therapy in an extension trial out to one year. Sorriso’s other efforts include a preclinical anti-IL-7-alpha and anti-TSLP combo, as well as a way to tamp down on colitis that emerges as a side effect from cancer treatments.