A summary of the assets of 42 public companies, segmented by approach & vector. Some takeaways and thoughts on the space:

• This analysis is not exhaustive: there are >350 gene therapies in development across >115 companies
• The space remains early in development - ~62% of assets are preclinical or IND-enabling. Of the remaining ~38%, the majority (~31%) are in Phase 1/2
• We'll better understand the commercial potential as a few recently approved assets ramp towards an inflection point (i.e. Novartis' Zolgensma, Roche's Luxturna, bluebird's Zynteglo / Skysona and CSL / Uniqure's Hemgenix). A few things to watch for:
• Payor dynamics & the use of value-based agreements
• Patient receptivity
• Hospital readiness
• Sales trajectory
• Scalable manufacturing
• The first generation of therapies were primarily for genetic diseases with no standard of care. Emerging assets are targeting more prevalent conditions & competing with established drugs. Reimbursement & prescribing trends in this environment will be interesting to monitor
• The number of FDA approved assets might double this year:
• Krystal Biotech's Vyjuvek
• BioMarin's Roctavian (approved in EU)
• Sarepta's SRP-9001
• PTC Therapeutic's Upstaza (approved in EU)
• Bluebird's LentiGlobin
• Taysha's TSHA-120
• While the challenging market environment reduced IPOs, follow-ons and fundraising, 2022 saw a comparable amount of deal flow to 2021. A few highlights included Lilly's ~$610M acquisition of Akouos and Astellas' $50M investment into Taysha. 2023 is off to a good start with Voyager / Neurocrine (~$1.6B) and Astellas / Selecta (~$350M)
• The space is dominated by in vivo AAV gene therapies in part due to the well-characterized tissue selectivity of different serotypes. However, these tend to use large doses of viral particles, which is associated with poor safety outcomes & manufacturing concerns. Non-viral therapies (i.e. LNPs) are less widely used right now but may overcome limitations with AAVs such as payload restrictions, immunogenicity and manufacturing
• Safety has been a key barrier to adoption - clinical holds due to SAEs / patient deaths have slowed development pace & dampened enthusiasm. Better vector design & broader thinking about virus tropism and virus-cell interaction would go a long way to advance the field. All ex vivo work could potentially disappear with better vectors or delivery vehicles. Multiple developers are rising to meet the field's challenges
• Lastly, CMC / manufacturing is critical. Choosing whether to develop in-house expertise vs. leverage CDMOs is a major decision, with most opting for a hybrid approach to protect against capacity bottlenecks. For both, scalability to clinical / commercial level is a key challenge

Note: public companies only, not exhaustive; data as of Feb'23