Implementation
Project Implementation
How do we move forward?
1. Overview
LACMA is a synthetic biology solution targeting lactate accumulation in the tumor microenvironment (TME). It has completed closed-loop validation of the "lactate sensing - signaling - sLOx expression" pathway and core functional verification of sLOx-mediated lactate degradation. Moving forward, it will follow the cancer immunotherapy development pathway—"research and development, regulatory approval, commercialization"—to overcome common challenges such as "in vitro efficacy but in vivo translation difficulties" and " Safety and Specificity Balance." With the core objective of "precisely regulating TME lactate to enhance immunotherapy efficacy," the project will advance through three phases: laboratory validation, preclinical and clinical trials, and market access with scaling. Throughout, intellectual property protection will be prioritized, building a patent portfolio covering module design, target mechanisms, and application scenarios. This will refine technology transfer processes and establish a foundation for commercialization.
2. Laboratory Validation
This phase focuses on providing data support for preclinical research, concentrating on three key areas: First, expanding in vitro functional validation by integrating LACMA into clinically common therapeutic immune cells and verifying its function across multiple high-lactic acid TME tumor models; Second, optimizing delivery systems by testing and improving two mainstream delivery methods—lentiviral vectors and red blood cell exosomes—to enhance targeting and safety; Third, establishing a closed-loop dry-wet experimental system by predicting module response thresholds through modeling and validating them experimentally. Concurrently, implementing a standardized in vitro quality control system ensures LACMA-related cell products meet standards for module integrity, functional activity, and safety.
3. Preclinical and Clinical Trials
This phase focuses on the safe transition of LACMA from the laboratory to patients, advancing work in accordance with international cancer immunotherapy regulatory requirements. Preclinical studies evaluate the efficacy (e.g., tumor suppression, survival extension) and safety (systemic toxicity, organ damage, risk of metastasis) of LACMA-related cell products using two clinically relevant animal tumor models. Clinical trials follow a "dose escalation - efficacy validation - large-scale validation" logic: Phase I determines maximum tolerated dose and safety; Phase II validates efficacy and explores combination effects with PD-1 inhibitors; Phase III confirms key metrics like overall survival through multicenter controlled trials. Ultimately, data will support submissions for biologics license applications to multiple national regulatory authorities, seeking priority review status.
4. Market Entry
This phase centers on the Chinese market as the primary entry point, focusing on regulatory compliance, localized manufacturing, strategic partnerships, pricing/reimbursement strategies, and scaling initiatives. On the manufacturing front, costs are reduced through hiring specialized talent, collaborating with universities to cultivate skills, and establishing localized supply chains. For partnerships, prioritize collaborations with leading domestic biopharmaceutical companies to leverage their resources for accelerated implementation. In the competitive landscape, capitalize on the differentiated advantage of "TME lactic acid-targeted degradation" to fill market gaps. Adopt a hybrid business model combining "technology licensing + internal development," with pricing strategies integrated with healthcare reimbursement negotiations to enhance patient access. Exit pathways focus on M&A or IPO, while addressing regional disparities in healthcare resources. The goal is to expand market penetration through healthcare coverage expansion.
5. Quality Control and Safety
This phase establishes a comprehensive quality and safety system spanning the entire LACMA lifecycle, centered on "gene fidelity, cellular stability, functional controllability, and clinical safety." During the gene construction stage, sequence integrity and activity specificity are validated. The immune cell adaptation phase controls integration rates, off-target risks, and cellular activity. The GMP production phase adheres to high-cleanliness standards to ensure vector quality and final product functionality. The clinical phase rigorously screens patients, controls initial dosing, and continuously monitors toxicity and proliferation risks post-treatment. Concurrently, a bidirectional "batch-to-patient" traceability system is established, anonymizing patient data. Third-party verification aligned with NMPA standards ensures data retention meets regulatory requirements, comprehensively mitigating module malfunction and cell therapy-related safety risks.