Aanastra Unveils Breakthrough Preclinical Data for In Vivo CAR-T and P53 Restoration Therapies
核心洞察
Aanastra (搜索)'s AAN-14x (搜索) achieved greater than 90% B cell depletion within 12 hours of a single dose, demonstrating rapid efficacy in preclinical studies.
The company's AAN-53x (搜索) therapy showed remarkable tumor regressions across a broad range of P53 mutated tumors, addressing a significant unmet medical need.
Multiple redosing of AAN-14x (搜索) showed no evidence of hepatic or other toxicity, highlighting the safety profile of the PEP-NP™ delivery system.
Aanastra (搜索) Inc. has announced compelling preclinical data for its lead RNA therapeutic programs, showcasing the potential of its proprietary PEP-NP™ peptide delivery technology to address critical unmet needs in cancer treatment. The biotechnology company will present data on two breakthrough programs: AAN-14x (搜索) for in vivo CAR-T therapy and AAN-53x (搜索) for P53 tumor suppressor restoration.
Rapid B Cell Depletion with In Vivo CAR-T
The company's AAN-14x (搜索) program demonstrated remarkable efficacy in preclinical studies, achieving greater than 90% depletion of B cells within 12 hours of a single dose. This rapid onset of action represents a significant advancement in in vivo CAR-T therapy, which engineers a patient's T cells inside the body to target and destroy cancer cells.
"Among the broad applications of the PEP-NP™ technology, we are particularly excited by the preclinical data in our in vivo CAR-T program as well as our ability to target wide-ranging P53 driver mutations in our P53 program for which no therapy exists today," said Neil Desai Ph.D., Founder and CEO at Aanastra (搜索).
The technology addresses key limitations of current approaches. Traditional ex vivo CAR-T processes are available to less than 20% of eligible patients in the US due to their costly and complex nature. Current lentiviral methods for in vivo CAR-T allow only single treatments due to immune responses against viral components, while lipid nanoparticle-based mRNA delivery is limited by liver toxicity and immune-related side effects.
Safety Profile Enables Repeat Dosing
A critical advantage of Aanastra (搜索)'s approach is the ability to perform multiple redosing of AAN-14x (搜索) at desired intervals with no evidence of hepatic or other toxicity. This safety profile could enable sustained treatment effects that are currently restricted by dosing challenges in existing systems.
The PEP-NP™ system efficiently targets CAR RNA to T cells for safe, repeat dosing without the toxicities associated with current methods, potentially expanding access for hematological cancers and autoimmune diseases.
P53 Restoration Shows Broad Tumor Activity
Aanastra (搜索)'s AAN-53x (搜索) program demonstrated remarkable tumor regressions across a broad range of P53 mutated tumors. P53, known as the "Guardian of the Genome," is a crucial tumor suppressor that preserves DNA integrity by regulating DNA repair and cell division. It is mutated or inactivated in over 50% of cancers, affecting 400,000 new U.S. patients annually and over 10 million globally.
The significance of this target cannot be overstated. Mutations span hundreds of variants, making broad therapies difficult, and these mutations are markers of poor prognosis and key cancer drivers. No existing treatments restore p53 function across this spectrum, leaving a significant unmet need.
Novel Delivery Technology Overcomes Current Limitations
The PEP-NP™ technology is based on short, amphipathic peptides that form stable nanoparticles with RNA for efficient delivery. These peptides are designed with distinct hydrophobic and hydrophilic regions, adopting α-helical conformations facilitating membrane interaction and cellular entry.
Importantly, PEP-NP™ peptides can include specific receptor-targeting domains, enabling precise cell and tissue targeting without using antibodies or other large proteins. This antibody-free targeting allows rapid design flexibility and avoids immunogenicity associated with protein-based ligands.
The system can completely bypass the liver, without immunogenicity or safety issues upon repeat administration, and uses no lipid, viral or protein components. PEP-NP™ nanoparticles can enter cells through a non-endosomal mechanism, enhancing RNA release into the cytoplasm for effective therapeutic action.
Conference Presentations Showcase Technology
Aanastra (搜索) will present its findings at multiple upcoming conferences, including the Advancing Cell and Gene Therapies for Cancer Conference in Philadelphia on October 15-16, 2025, and the mRNA Vaccines and Therapeutics Summit in Barcelona on October 23-24, 2025.
The presentations will be delivered by Gilles Divita, Ph.D., covering both the in vivo CAR-T generation using CAR mRNA delivered with the PEP-NP peptide-based delivery system and the P53 mutant tumor regression data with AAN-53x (搜索).
These preclinical results highlight the versatility of the PEP-NP™ platform, demonstrating its potential to address multiple therapeutic areas through precise RNA delivery, from immune cell reprogramming to direct tumor suppressor restoration.