In Vivo CAR-T Technology Route Investment Value Analysis

Based on my in-depth research on the In Vivo CAR-T technology route, I will provide you with a comprehensive investment value analysis.

In Vivo CAR-T technology represents a major breakthrough in the field of cell therapy. By directly generating CAR-T cells in the patient’s body, it completely changes the complex process of traditional CAR-T therapy that requires ex vivo cell manufacturing. This technical route has revolutionary advantages:

1. Significantly Reduced Manufacturing Costs
   : Eliminates complex ex vivo operations such as cell separation, modification, and expansion
2. Improved Treatment Accessibility
   : Shift from “personalized customization” to “off-the-shelf products”
3. Shorter Treatment Time
   : From the 2-4 week preparation cycle of traditional CAR-T to a few days

• Rapid Transfection
  : The LNP platform enables rapid T-cell targeting and transfection [1]
• Repeatable Administration
  : LNP formulations have better safety and repeatable administration characteristics [2]
• Targeting Precision
  : T-LNP (T-cell targeting lipid nanoparticle) technology achieves highly selective T-cell targeting

Vivacta Bio’s GT801 released encouraging first-in-human trial data at the 2025 ASH Annual Meeting [1]:

• Uses T-LNP to deliver mRNA encoding anti-CD19 CAR
• Both patients showed high CAR expression in circulating T cells
• Well-tolerated with no obvious off-target effects
• Supports the feasibility of repeat administration

CREATE Medicines’ MT-303 also initiated clinical trials in first-line treatment of hepatocellular carcinoma [3], demonstrating the application potential of LNP technology in solid tumors.

• Stable Integration
  : Lentiviral vectors enable stable integration of genes, providing long-lasting therapeutic effects
• High Transduction Efficiency
  : Significant advantage in transducing T cells in vivo

Kelonia Therapeutics’ KLN-1010 achieved breakthrough progress in BCMA multiple myeloma treatment [4]:

• 100% MRD-negative response rate (4 patients)
• Longest follow-up of 5 months, all patients maintained response
• No grade 3 or higher cytokine release syndrome (CRS) or immune effector cell-associated neurotoxicity syndrome (ICANS)
• Excellent safety profile

1. BMS Acquires Orbital Therapeutics - $1.5 Billion
   [5]
   • Acquisition Core: OTX-201 (next-generation in vivo CAR-T therapy)
   • Strategic Significance: Strengthens CAR-T layout in the field of autoimmune diseases

2. Gilead Acquires Interius BioTherapeutics - $350 Million
   [6]
   • Acquisition Core: Lentivirus-mediated in vivo CAR-T platform
   • Strategic Significance: Deepens cell therapy layout through the Kite division

3. Other M&A Activities with Undisclosed Amounts

1. Technical Complementation Needs
   : Large pharmaceutical companies need to quickly acquire emerging technology platforms through acquisitions
2. Market Access Barriers
   : High threshold for in vivo CAR-T technology, high risk of independent R&D
3. Urgency of Patent Layout
   : Early patent layout is crucial for future market position
4. Cost-Effectiveness Considerations
   : Acquiring mature platforms is more cost-effective than R&D from scratch

1. Clinical Data Catalysts
   • Pay attention to key clinical trial data readout time points of various companies
   • Data releases at important academic conferences such as ASH and ASCO
   • Regulatory milestone events

2. Technology Platform Companies
   • LNP delivery technology platform companies (e.g., Acuitas Therapeutics)
   • Targeting ligand technology providers
   • CDMO service providers

1. Commercial Breakthroughs
   • First in vivo CAR-T product approved for marketing
   • Indication expansion (from hematological tumors to solid tumors)
   • Cost reduction due to mature manufacturing processes

2. Platform Licensing Opportunities
   • Licensing cooperation of technology platforms to large pharmaceutical companies
   • Commercial cooperation in regional markets

1. Technology Integration and Innovation
   • Combination of in vivo CAR-T and gene editing technology
   • Application of artificial intelligence in drug design
   • Development of personalized medicine

2. Market Pattern Reshaping
   • Traditional CAR-T companies transitioning to in vivo technology
   • IPO opportunities for emerging technology companies
   • Accelerated industry integration

1. Technical Risks
   • In vivo delivery efficiency and specificity still need optimization
   • Long-term safety and immunogenicity issues
   • Solid tumor treatment faces greater challenges

2. Regulatory Risks
   • Regulatory path for new technology routes is not yet clear
   • Potential impact of safety events

3. Market Risks
   • Pricing and medical insurance access challenges
   • Continuous improvement of traditional CAR-T technology forms competition

: In vivo CAR-T technology represents the future development direction of cell therapy. The LNP and lentivirus technical paths each have their advantages; it is recommended to adopt a “dual-wheel drive” investment strategy.

1. Key Investment Directions
   :
   • Companies with differentiated technology platforms
   • Projects in clinical data validation phase with good safety
   • Mid-to-late stage projects with potential for cooperation with large pharmaceutical companies

2. Timing of Investment
   :
   • Pay attention to clinical data catalyst events
   • Use market fluctuations to invest at low points
   • Attach importance to the scalability of technology platforms

3. Risk Control Strategies
   :
   • Diversify investment in technical routes
   • Pay attention to regulatory progress and safety data
   • Set clear exit mechanisms

[1] BioSpace - “Vivacta Bio Announces Promising First-in-Human Results for GT801, an In Vivo CAR-T Therapy, in Non-Hodgkin’s Lymphoma at the 2025 ASH Annual Meeting” (https://www.biospace.com/press-releases/vivacta-bio-announces-promising-first-in-human-results-for-gt801-an-in-vivo-car-t-therapy-in-non-hodgkins-lymphoma-at-the-2025-ash-annual-meeting)

[2] BioSpace - “Acuitas Therapeutics Showcases Collaboration with Children’s Hospital of Philadelphia for Personalized CRISPR Therapy and New LNP Research at ASGCT 2025” (https://www.biospace.com/press-releases/acuitas-therapeutics-showcases-collaboration-with-childrens-hospital-of-philadelphia-for-personalized-crispr-therapy-and-new-lnp-research-at-asgct-2025)

[3] BioSpace - “CREATE Medicines Doses First Patient in Frontline HCC Trial Evaluating MT-303, an In Vivo CAR Therapy” (https://www.biospace.com/press-releases/create-medicines-doses-first-patient-in-frontline-hcc-trial-evaluating-mt-303-an-in-vivo-car-therapy-in-combination-with-standard-of-care-immunotherapy)

[4] BioSpace - “Kelonia Therapeutics Presents First-in-Human Data From Phase 1 inMMyCAR Study of KLN-1010 in vivo BCMA CAR-T Therapy at the 2025 ASH Annual Meeting” (https://www.biospace.com/press-releases/kelonia-therapeutics-presents-first-in-human-data-from-phase-1-inmmycar-study-of-kln-1010-in-vivo-bcma-car-t-therapy-at-the-american-society-of-hematology-ash-2025-annual-meeting)

[5] Yahoo Finance - “Bristol Myers buys Orbital Therapeutics for $1.5 billion” (https://finance.yahoo.com/news/bristol-myers-buys-orbital-therapeutics-111651114.html)

[6] Yahoo Finance - “Gilead’s Kite scoops in vivo CAR-T specialist Interius for $350m” (https://finance.yahoo.com/news/gilead-kite-scoops-vivo-car-105336605.html)