- The cystic fibrosis market generated approximately **$11 billion in sales in 2024**, with a **sizable fraction of patients (10-15%)** having unmet needs due to unaddressable mutations or intolerance to current modulators.  **[0001650648_2193959_0]** **[0001650648_2193959_2]** 
- **4D Molecular Therapeutics (FDMT)** is developing **4D-710** for cystic fibrosis, which has demonstrated **great safety** and **high levels of CFTR protein expression (90-95% of cells)** in **16 treated patients**.  **[0001650648_2193959_5]**  The company received an additional **$11 million investment** from the Cystic Fibrosis Foundation, bringing the total to **$32 million**.  **[0001650648_2193959_6]** 
- Advances in gene delivery to the lung include **directed evolution of vectors** to overcome mucus barriers and pre-existing antibodies, **novel capsids** (e.g., Carbon Biosciences' parvoviruses for full-length CFTR delivery), and **small molecule augmenters** (e.g., SphereVant Sciences' SP101 augmenter boosting expression 100x in vitro).  **[0001650648_2193959_1]** **[0001650648_2193959_2]** **[0001650648_2193959_3]** **[0001650648_2193959_4]** 
- Companies are focusing on a panel of efficacy metrics beyond FEV1, such as **lung clearance index**, high-resolution CT scans, and quality of life instruments, to support regulatory approval for smaller patient studies.  **[0001650648_2193959_3]**  Re-dosing strategies are being developed for multi-year durability, which is considered essential for a sustainable market.  **[0001650648_2193959_5]** **[0001650648_2193959_6]**

Gene Therapy in Lung and Cystic Fibrosis Discussed at Chardan Conference

- **4D Molecular Therapeutics (FDMT)** is advancing its lead program, **4D-150**, into **phase three** for **wet AMD** and has a regulatory path for **DME**.  **[0001650648_2193475_0]**  The company aims for **4D-150** to be a **backbone therapy** offering **durability measured in years**.  **[0001650648_2193475_1]** **[0001650648_2193475_5]** 
- **Occugen** plans to file **three BLAs and three market authorization applications** for its gene therapies targeting **retinitis pigmentosa (RP)**, **Stargardt disease**, and **geographic atrophy (GA)**, starting with **RP in 2026**, **Stargardt in 2027**, and **GA in 2028**.  **[0001650648_2193475_0]** 
- **SparingVision** has a lead ocular gene therapy program in **phase two** for **retinitis pigmentosa**, which is **gene-agnostic** and aims to start **phase three in 2027**.  **[0001650648_2193475_0]** **[0001650648_2193475_10]**  **Complement Therapeutics** recently achieved **IND clearance** for its **AAV-based gene therapy** for **geographic atrophy**.  **[0001650648_2193475_0]** 
- The panel highlighted the **significant unmet medical need** in **geographic atrophy (GA)**, noting that the market is **large enough to accommodate multiple entrants** due to its heterogeneity and limitations of existing therapies, including safety concerns like **10% to 12% of patients developing new onset CNV** with current IVT complement inhibitors.  **[0001650648_2193475_2]** **[0001650648_2193475_3]** **[0001650648_2193475_4]** **[0001650648_2193475_5]** 
- Gene therapy companies are focusing on **one-time treatments** that offer **long-term durability** and **functional benefits** to address the high treatment burden and improve patient outcomes in large ophthalmic indications.  **[0001650648_2193475_2]** **[0001650648_2193475_3]**

Chardan's 9th Annual Genetic Medicines Conference Highlights Ophthalmic Gene Therapy Developments

- **4D Molecular Therapeutics (4DMT)** is progressing its lead program, **4D-150**, in **two Phase 3 trials** for **wet AMD**, aiming to offer durability measured in years.  **[0001650648_2193498_0]** **[0001650648_2193498_1]** 
- **Ocugen** plans to file **three Biologics License Applications (BLAs)** and market authorization applications for its gene therapies targeting retinitis pigmentosa (RP) in **2026**, Stargardt disease in **2027**, and geographic atrophy (GA) in **2028**.  **[0001650648_2193498_0]** 
- **Complement Therapeutics** has received **IND clearance** for its lead AAV gene therapy for **geographic atrophy**, preparing to enter the clinic, while **Sparring Vision** has its lead ocular gene therapy in **Phase 2 for RP**.  **[0001650648_2193498_0]** 
- Panelists highlighted that **durability** and the potential for **one-time treatments** are crucial differentiators for gene therapies in large ophthalmic indications, addressing the high treatment burden of current therapies.  **[0001650648_2193498_1]** **[0001650648_2193498_2]** **[0001650648_2193498_3]**