Oral 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. In 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. Thirty-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. An 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.