Gene Therapy R&D Has a Business Problem, Not a Science Problem

Cell and gene therapy research has made important strides in recent years. In gene therapy alone, there are now clinical research programs testing 50 potential treatments. Still, that number is low compared to other treatment types. Surprisingly, the bottleneck to cell and gene therapy growth is not in the science, but in the research and development business model.

As reported in The New York Times, gene therapy research’s largest roadblock is a virus shortage. Cell and gene therapy is delivered through a deactivated virus that targets specific cells, a method that is called a viral vector. Put in simpler terms, a viral vector is the delivery truck, and the gene therapy is the ‘drug’ that can be put in the delivery truck to reach the right cells.

From The New York Times:

Few gene-therapy companies have the factories or expertise to make the viruses for use in clinical trials, where standards are exacting and comprehensive. The firms that can do it are swamped with orders and requests.

When we learned this at Applico, we realized gene therapy research can be improved with business model innovation.

Why the current cell and gene therapy development model is slow

Currently, gene therapy clinical trials are conducted largely by pharmaceutical companies who own a viral vector. Take for example Avexis, a Novartis company. Avexis focuses on developing gene therapy to treat rare neurological diseases. Currently Avexis is working on a drug to treat SMA (spinal muscular atrophy), a disease linked to ALS that affects motor neurons. They have drugs in the preclinical stage being tested to treat ALS and Rett Syndrome, a rare neurological disease that almost exclusively affects young girls.

Avexis is able to test its therapy for SMA in clinical trials through its viral vector AAV9. What’s remarkable about AAV9 is that is has proven to be safe and effective in delivering gene therapy in multiple diseases. However, the development of gene therapies delivered through AAV9 is slowed by Avexis’s ability to research and develop drugs.

Meanwhile, a recent study by CRA discovered that

In many cases, researchers cannot determine the final mode of drug delivery until late in the development program, which presents significant risk. … Very few biotechnology companies have the expertise and capability to produce vectors on site, and demand for vector production from a limited range of third-party suppliers can result in multiyear wait lists and extremely high costs.

Thus for scientists researching gene therapies, the bottleneck occurs when the researchers try to find a viral vector that isn’t exclusively owned by companies like Avexis. And Avexis isn’t alone. Orchard Therapeutics and Moderna Therapeutics also own viral vector methods and research new therapeutics. Other companies like Sirion Biotech and Vigene Biosciences develop viral vectors for researchers, but can be costly or have long wait lines.

Thus we have two groups of people who have a common business need – researchers need vectors, vector owners would benefit from faster research. A third group, viral vector developers, can be tapped to supplement the supply of vectors. That’s exactly the type of business challenge that can be solved with a platform business.

Platform can accelerate development of gene therapies by solving one key bottleneck

Imagine a platform wherein researchers can pitch their therapies to the owners of viral vectors. Conversely the owners of vectors can search for therapies that would in theory perform well with their delivery method. By including vector developers, large pharmaceutical companies can invest in specific viral vector research to expand its vector supply by type.

In an ideal world, the platform is truly open to all researchers, vector owners and developers, pharmaceutical companies, and investors. By opening up the platform, the research is most effective in identifying the best therapeutic-vector fit.

However, in practice, the platform would likely have some gatekeeping as the industry adapts to this new business model.

For example, in a platform co-owned by pharmaceutical companies conducting genetic therapies for different diseases, the platform may be divided into different areas of focus such as neurological disease, cancer, gastrointestinal diseases, and so on. This would prevent pharmaceutical companies from easily leaping across areas of focus (e.g., the pharmaceutical companies focused on neurological diseases won’t be able to easily leap to cancer research vis-a-vis the platform).

Even less efficient, but also a possibility is the idea of granting the owner (or owners) right of first refusal. A pharmaceutical company may pass on a therapeutic for a variety of reasons. Perhaps their vector isn’t a good fit for the gene therapy, or the therapeutic is too far afield from the pharmaceutical company’s area or focus or still too early-stages to adopt. Whenever the platform owner chooses not to invest in a therapeutic, the therapy passes on to the platform for other pharmaceutical companies and investors to appraise.

Additional benefits of a gene therapy research and development platform

We believe the primary benefit of this platform is in connecting gene therapy research with capital. However, there are other benefits and uses of this platform that can make cell and gene therapy R&D more efficient, such as:

bringing rare disease therapies to market through new investment models,
creating a marketplace for gene therapy research data and software, and
Improving clinical trial patient sampling and data gathering

Incentivize investment in rare disease therapies

Because the platform connects multiple investors there is an opportunity for co-investment in therapies for rare diseases. In the United States, a rare disease is defined as a condition that affects fewer than 200,000 people. Currently, pharmaceutical companies resist investing in drugs that affect too few patients for many reasons that range from poor patient sampling for clinical trials to bad business economics.

A platform could help highly motivated investors, who are passionate about curing a specific rare disease, find a gene therapy for that disease. Or could help a group of investors co-invest in a drug that otherwise may not have come to market.

Accelerate data sharing and software discovery for preclinical research

The platform also has uses in the preclinical phase of research. Scientists working on a specific disease, especially rare diseases, are often working remotely from each other. They are reliant on journals and databases to share research information. This platform could centralize research data across diseases to improve the flow and discovery of information.

In addition, gene therapy research and supply chain tracking requires specific software. The platform could include a marketplace for buying or licensing gene therapy-related software and tools. Doing so could also improve software feedback and improve research tools considerably.

Improve clinical trials

Lastly, clinical trials for rare and uncommon diseases could be improved through a platform as well. We’ve written before about how platforms can save clinical trials. A platform could incorporate remote data gathering and patient discovery, thereby improving study quality and outcomes. We highly recommend our article on clinical trials, because it covers how a platform makes clinical trial research more efficient at just about every stage.

FDA regulations would need to adapt

One issue with our vision for platformized cell and gene therapy development is purely regulatory. When we’ve discussed this idea with pharmaceutical company leaders, the idea is appealing but for one problem. Consider a viral vector that is used to deliver therapies A, B, and C. A and B perform well and are brought to market. Later, during the clinical trial of therapy C, a fatal incident occurs. It’s feasible that therapies A and B are then also at risk, because they share the same viral vector, which may or may not be the cause of the incident, but nonetheless is an underlying component of all three treatments.

We believe the FDA would need to be included in the design of this platform to address regulatory concerns and find common sense solutions. The benefits to human health and quality of living make a platform like this an imperative, and the FDA should be an enthusiastic partner in its creation.

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