Immorna Biotherapeutics, Inc. (Immorna), a clinical stage biotechnology company developing both self-replicating and conventional mRNA-based therapeutics and vaccines, announced that the U.S. Food and Drug Administration (FDA) has cleared its investigational new drug (IND) application for JCXH-211 intravenous (IV), a novel, first-in-class self-replicating mRNA (srRNA) encoding the engineered human interleukin (IL)-12 protein.

The IND clearance allows Immorna to initiate a Phase 1/2, multi-center, open-label, dose escalation and expansion study of JCXH-211 administered intravenously in patients with malignant solid tumors. The goal of the study is to assess safety and tolerability, determine the recommended Phase 2 dose (RP2D) for JCXH-211 IV in combination with checkpoint inhibitor (CPI), and assess preliminary efficacy of the combination at the RP2D.

"We are excited to have achieved this important milestone for one of our key assets," said NgocDiep Le, M.D., Ph.D., President and Global Chief Medical Officer of Immorna. Based on data from our preclinical studies, clinical data from our JCXH-211 intratumoral administration (IT) trial, and the candidate drug's mechanism of action, we believe JCXH-211 IV in combination with CPI has the potential to work synergistically to enhance anti-tumor effect. We look forward to working with the investigators and patients to bring this potential novel therapy to patients who are in dire need of new and effective treatments."

JCXH-211 is a first-in-class lipid nanoparticle (LNP) encapsulated srRNA, using Immorna's proprietary technology, encoding the engineered human IL-12 protein. In multiple preclinical animal and patient-derived xenograft (PDX) models, the anti-viral innate response triggered by RNA replicon together with the potent anti-cancer immunity stimulated by IL-12 conferred JCXH-211 superior tumor-eradicating potency, which was better than similar preclinical candidates employing conventional (non-replicating) mRNA. Interim data from a Phase 1 trial of JCXH-211 IT monotherapy has demonstrated excellent safety, tolerability and significant anti-tumor biological activities, including abscopal effect.

IL-12 is a naturally occurring cytokine that plays a key role in the body's immune response against cancer. Despite consistently showing potent antitumor activity in preclinical studies, recombinant IL-12 protein treatment at tolerable doses in humans failed to provide clinical benefit. One key challenge for IL-12 protein treatment is the non-overlap of tolerability window and therapeutic window. Recombinant IL-12 is unstable in vivo and have a very short half-life, and frequent intravenous administration of recombinant human IL-12 protein was challenging due to unacceptable toxicities. Thanks to the intrinsic feature of our srRNA technology, JCXH-211 IV enables a prolonged expression of IL-12 preferentially in tumor tissues rather than normal tissues, leading to modulation of tumor microenvironment and activation of antitumor immune responses, while minimizing systemic toxicity. JCXH-211-IV demonstrated excellent safety profile in nonclinical studies using rodents and non-human primates. If successful, JCXH-211 IV may become another lifesaving yet easily accessible therapy for cancer patients who have progressed on or are resistant to currently available treatments.