Moderna, Inc. announced recent updates to several of its immuno-oncology and rare disease programs. Moderna has 21 mRNA development candidates in its pipeline, with 11 programs now in clinical development. OX40L (mRNA-2416): Based on previously reported clinical observations in two patients with advanced ovarian carcinoma in its Phase 1 study, Moderna has submitted an Investigational New Drug (IND) amendment to the U.S. Food and Drug Administration (FDA) and to the study’s clinical research sites to commence a Phase 2 cohort of mRNA-2416 as a monotherapy in advanced ovarian carcinoma within its current Phase 1 study. Thus far, 28 patients have been dosed in the ongoing Phase 1 trial for mRNA-2416, an open-label, multicenter study of repeated intratumoral injections of mRNA-2416 in patients with advanced relapsed/refractory solid tumor malignancies and lymphomas. Initial data from the Phase 1 study were presented in a poster session at the Annual Meeting of the Society for Immunotherapyof Cancer in November 2018. OX40L + IL23 + IL36? (Triplet) (mRNA-2752):Moderna has dosed the first patient in the Phase 1 study of mRNA-2752, an intratumoral injection comprising three mRNAs encoding for OX40L + IL23 + IL36? for the treatment of advanced or metastatic solid tumor malignancies or lymphoma. The open label, multi-center study is evaluating the safety and tolerability of mRNA-2752 as a single agent and in combination either with AstraZeneca’s durvalumab or tremelimumab, and will assess anti-tumor activity, protein expression in tumors and pharmacokinetics, and exploratory endpoints that include assessment of immunological response. Personalized Cancer Vaccine (PCV) (mRNA-4157): Moderna and Merck areplanning a randomized Phase 2 study comparing PCV and KEYTRUDA® against KEYTRUDA alone. To date, interim Phase 1 PCV study data from 24 patients showed no dose limiting toxicities up to 0.39 mg (the third of four dose levels). Interim Phase 1 immunogenicity data have also been collected in certain patients dosed with mRNA-4157 as a monotherapy, and potential antigen-specific T cell responses have been detected. The Phase 1 study continues in the dose-escalation phase of the protocol. KRAS vaccine (mRNA-5671): Merck will lead an open-label, multi-center, dose-escalation and dose-expansion Phase 1 study to evaluate the safety and tolerability of mRNA-5671 administered as an intramuscular injection both as a monotherapy and in combination with KEYTRUDA. KRAS is a frequently mutated oncogene in epithelial cancers, primarily in non-small cell lung, colorectal and pancreatic cancers. The IND for a KRAS vaccine was originally submitted by Moderna and included an mRNA for the membrane protein STimulator of INterferon Gene (STING) to help promote antitumor activity. That IND was transferred to Merck which now will move the program forward under the same IND with KRAS as the sole mRNA. Merck may choose to include STING mRNA in later clinical development of the KRAS vaccine. Methylmalonic Acidemia (MMA) (mRNA-3704): An IND application has been submitted to the FDA for mRNA-3704, Moderna’s development candidate for MMA. If approved, this will be Moderna’s first rare disease program to advance into clinical trials. The Company plans to conduct an open-label, multi-center, dose escalation Phase 1/2 study of multiple ascending doses of mRNA-3704 in pediatric patients with isolated MMA due to MUT enzyme deficiency. The objectives of the study are to evaluate safety and tolerability. mRNA-3704 has received Rare Pediatric Disease Designation by the FDA and Orphan Drug Designation by both the FDA and the European Medicines Agency. Propionic Acidemia (PA) (mRNA-3927): mRNA-3927 was granted Orphan Drug Designation by the FDA in December 2018 and Rare Pediatric Disease Designation by the FDA in January 2019. PA is a rare, life-threatening, inherited metabolic disorder due to a defect in the mitochondrial enzyme propionyl-CoA carboxylase, or PCC. It primarily affects the pediatric population and there is no approved therapy. Moderna is continuing to advance mRNA-3927 in pre-clinical studies. Moderna also continues to enroll patients in a global natural history study of MMA and PA (MaP Study) designed to identify and correlate clinical and biomarker endpoints for these disorders. This is a global, multi-center, non-interventional study for patients with confirmed diagnosis of MMA due to methylmalonyl-CoA mutase (MUT) deficiency or PA.