This article was first published in Endpoints News.
Author Contributing Author
Gene therapy is entering a phase of maturation, with dozens of programs advancing across rare, prevalent, and complex indications. As the field has progressed and clinical successes have accumulated, manufacturing has become a central factor in evaluating adeno-associated virus (AAV) based therapeutic candidates. As a result, investor diligence now increasingly extends beyond a therapy’s scientific evidence base and clinical potential to the underlying manufacturing strategy and execution plan. An integrated strategy grounded in early planning across vector design, scalable production approaches, and analytical strategies enables developers to engage investors with greater clarity, confidence, and a stronger foundation for long-term success.
This perspective is reinforced by venture capital investors working closely with emerging biotechnology companies. Gianna Hoffman-Luca, Ph.D., a biotech investor at Perceptive Advisors who supports companies from early development through scale-up, notes that manufacturing strategy has become a central element of investment diligence and a key signal of whether a program can realistically progress beyond early development.
The latest State of the Industry analysis by the Alliance for Regenerative Medicine (ARM) shows that investment in the cell and gene therapy sector remained substantial in 2025, with $11.1B raised across 216 financings. Cell and gene therapies (CGT) accounted for approximately 18% of the value of all biotech venture financing, up from roughly 15% the year prior. The shift suggests that even in a more constrained funding environment, investors continue to prioritize the sector as therapies advance toward clinical and commercial evolution.
“The sector is clearly entering a new phase of disciplined growth,” said Tim Hunt, CEO of the Alliance for Regenerative Medicine. “Investors are increasingly focused not only on breakthrough science, but also on whether companies have a credible path to development, manufacturing scale, and global commercialization.”
For AAV-based gene therapies, manufacturing design decisions are tightly tied to scalability, cost structure, and risk mitigation. Consequently, developers are expected to show not only projected clinical progress, but also technical diligence across vector design, process robustness, scalability considerations, and analytical strategies. The objective is to limit process changes following regulatory filings and support a more predictable trajectory from clinical development through commercial-scale manufacturing.
Across recurring diligence conversations, a consistent theme emerges: investor evaluation of gene therapy programs extends beyond scientific promise to include scientific validity, manufacturing scalability, commercial feasibility, and operational execution. A critical component of this evaluation is Chemistry, Manufacturing, and Controls (CMC) strategy. As illustrated in Figure 1, the manufacturing portion of CMC can span many connected workstreams: drug delivery and vector design, manufacturing design, process and clinical development, and analytical development. Each workstream carries distinct responsibilities and long-term program impact between a developer and manufacturing partner, highlighting that manufacturing is a foundational driver of program value and investor confidence.
Key AAV manufacturing decisions made early in development, such as vector design, production platform, and analytics, often become embedded in regulatory filings and clinical supply chains. Later changes can trigger comparability studies and additional regulatory review, ultimately affecting timelines and cost.
As Dr. Hoffman-Luca notes, investor diligence today often focuses on the realistic alignment between development and manufacturing plans:
“One of the biggest things we look for is whether the development timeline for the drug itself matches with their manufacturing. That’s a key part of diligence to make sure you’re comfortable with the timeline they’ve proposed. The investment has to match how much capital they say they need to raise, and manufacturing needs to be included.”
Consequently, manufacturing architecture increasingly influences investor sentiment well before IND filing. A well-articulated manufacturing strategy signals that a team understands the operational demands of viral vector–based therapies and has considered the long-term implications of early technical decisions.
Investors also look for evidence that developers can communicate manufacturing assumptions clearly and concisely. High-level explanations of dose requirements, expected yield, and scalability help investors determine whether projected development timelines and capital needs are grounded in operational reality.
As Dr. Hoffman-Luca explains, transparency around these assumptions is often more important than excessive technical detail:
“What investors want to see is that the team understands the manufacturing implications of their decisions. You don’t need every technical detail in the pitch, but you do need to show that the assumptions around yield, scale, and timelines are realistic.”
Investors increasingly evaluate whether a developer’s timeline reflects the practical duration required for each stage of development and manufacturing scale-up. Developers who proactively address manufacturing risks while designing scalable processes and analytical strategies are better positioned to reduce diligence friction and uncertainty.
Investors assess manufacturing strategy, the experience of the leadership team and execution partners, and whether the manufacturing partner offers capabilities beyond capacity, such as platform technologies, established processes, and in-house analytics. The starting point of a program also shapes investor perception. Programs originating at a vector core or academic facility offer a practical, cost-effective path to early material, particularly when speed to proof-of-concept is the priority. At the same time, material produced in these settings may require additional alignment as programs transition, including facility fit activities and process familiarization. Integrating prior data with results generated at a new site can also influence the pace toward key milestones. By contrast, programs that begin and remain with a single manufacturing partner benefit from process continuity, accumulated run history, and a tighter feedback loop between development and manufacturing decisions. As illustrated in Figure 2, these two paths carry different timeline implications, differences that investors can identify and weigh. Together, these factors highlight the importance of clearly communicating manufacturing strategy and decision-making.
As Dr. Hoffman-Luca explains:
“If whoever is responsible for articulating the manufacturing decisions can’t really talk about the process they’ve implemented, that’s a red flag. Investors need to trust that the person or team making those detailed decisions understands the manufacturing strategy and can explain why those choices were made. At the same time, the development plan has to be realistic. You’re not going to set clinical milestones that aren’t feasible from a manufacturing perspective.”
When evaluating a manufacturing plan, investors expect a clear outline of key technical considerations, including:
Vector design
Production platform
Scale strategy
These core assumptions should demonstrate how manufacturing supports both near-term clinical supply and long-term commercial readiness.
Investors also evaluate whether the manufacturing strategy reflects disciplined risk management. Credible plans acknowledge the inherent challenges of AAV production—including analytical complexity, supply chain dependencies, and scale transitions—while explaining how process design choices, platform technologies, or CDMO partnerships mitigate these risks over time.
Highlighting platform advantages or strategic manufacturing partnerships can further strengthen investor confidence by demonstrating operational reliability and reduced execution risk.
Three technical areas strongly influence whether a gene therapy program can translate efficiently from development to clinical manufacturing.
Vector design affects manufacturability from the outset. Decisions around capsid, promoter configuration, codon optimization, and genome size influence transfection efficiency, genome packaging, and purification performance. Designing with manufacturability in mind helps minimize variability and reduce scale-up challenges (see Design It Right: Evaluating AAV Manufacturability Through Molecular and Upstream Optimization).
Analytical strategy must mature alongside the program. AAV characterization presents challenges such as heterogeneous capsid populations and evolving potency assays. Investors typically look for a staged analytical roadmap that expands as regulatory expectations increase (see 3 Tiers for AAV Potency Assay Development Success and Where Do I Start? And Will It Work?).
Together, these elements signal manufacturing readiness and a program’s ability to scale toward clinical and commercial production.
Investors also expect analytical strategies to evolve alongside manufacturing development. Rather than relying on a fixed early-phase testing panel, teams should present a staged analytical roadmap that expands as regulatory expectations increase, and manufacturing processes mature.
Additionally, investors look for evidence of risk identification and mitigation. A credible manufacturing strategy acknowledges challenges such as analytical complexity, supply chain dependencies, and process scalability while presenting achievable timelines grounded in practical manufacturing considerations. Rather than exhaustive technical detail, investors rely on transparency and strategic thinking regarding risk management.
To structure these discussions, a practical diligence checklist can help organize key considerations for gene therapy manufacturing programs. This framework enables development teams to communicate manufacturing strategy clearly during early fundraising, board discussions, or later financing rounds while demonstrating disciplined decision-making and operational foresight. Figure 3 illustrates a representative set of diligence areas investors frequently evaluate when assessing gene therapy manufacturing readiness.
As AAV gene therapy programs mature, investors are placing significant weight on the technical realism of a developer’s manufacturing strategy. Manufacturing readiness, analytical capabilities, and process robustness have shifted from downstream considerations to central determinants of program feasibility and capital requirements.
Teams that demonstrate clear alignment between vector design, process development, analytical planning, and regulatory strategy signal a deep understanding of the operational demands required to scale beyond the laboratory.
Ultimately, manufacturing strategy has become a discipline of thoughtful decision-making under real-world constraints. Developers who can clearly articulate how early choices translate into predictable timelines and reduced comparability risk are better positioned to win investor confidence. By positioning manufacturing as a strategic driver rather than a supporting function, teams can present a more credible, investor-aligned narrative—one that highlights a derisked manufacturing supply chain and lays the foundation for sustainable clinical and commercial success.
Learn more about manufacturing your gene therapy at Forge Biologics. Connect with our team here.