BackgroundOral immunotherapy (OIT) is an increasingly acceptable therapeutic option for peanut‐allergic (PA) children, despite significant side effects. Major peanut allergenic proteins are heat‐resistant and are not rendered hypoallergenic after baking or cooking. Lyophilized peanut protein—MH (LPP‐MH) is a novel composition from developing peanuts, enabling cooking‐induced reduction in allergenicity. We aimed to explore the safety and efficacy of OIT, with extensively heated and baked (EHEB) LPP‐MH in PA children.MethodsIn a single‐arm, single‐center, pilot study, PA children with a single highest tolerated dose of <100 mg peanut protein were placed on a 40‐week OIT protocol with 300 mg daily of heat‐treated LPP‐MH. A repeat open peanut food challenge was performed after 40 weeks of treatment and at a 6–12 months of follow‐up visit.ResultsThirty‐three children with PA were enrolled, with a mean cumulative tolerated dose (MCTD) of 71.2 mg PP (95% CI 45–100 mg). After 40 weeks, 32/33 patients were able to consume more than 300 mg of natural PP, with MCTD of 1709 mg (CI 365–3675 mg). There were no severe allergic reactions requiring epinephrine, during any of the observed LPP‐MH challenges or any treatment related doses at home. After 6–12 months on daily maintenance, the MCTD was 8821 mg (95% CI 1930–13,500 mg). This enabled most children age‐appropriate dietary inclusion of peanuts.ConclusionAn OIT protocol with heat‐treated LPP‐MH, a novel composition from developing peanuts, seems a potentially safe and efficacious OIT modality for PA children, enabling the introduction of dietary levels of peanut proteins in highly allergic PA children. Validation in randomized controlled studies is mandated.