The transitioning of named patient products (NPPs) of therapy allergens is regulated under the German therapy allergen ordinance (TAO) since 2008. The establishment of a sound dose–response relationship constitutes a pivotal aspect in clinical development programs of drugs in general. Up to now, there are only few comprehensive studies dedicated to the determination of a dose–response relationship in allergen immunotherapy (AIT) because of various challenges. Among these aggravating factors are high placebo effects, variability of trial endpoints and especially for native allergens a narrow therapeutic window and safety profile. The phase II trials of the modified allergen tyrosine associated—monophosphoryl lipid A (MATA MPL) platform for birch and grasses established convincing and significant dose–response relationships decisive for AIT product optimization. The significant dose–response relationship for birch and grass allergoids reached an efficacy plateau and allowed the definition of critical milestones in drug development such as the median effective dose (ED50) for the MATA MPL platform combining modified allergens (allergoids) with microcrystalline tyrosine (MCT) and MPL in an adjuvant system. This marked a pivotal milestone in AIT drug development allowing the definition of the “optimal dose” (optimal risk–benefit ratio) to be taken forward to phase III trial. The MATA MPL platform is characterized by a scientifically sound dose–response relationship across allergens which underlines the pivotal role of a well-defined optimal dose as a success factor for phase III.