Distinctive Group

Partnerships between small biotechs and Big Pharma could unlock faster drug development for rare diseases, says Dan Williams, PhD, CEO of SynaptixBio.

In an increasingly interconnected and competitive world, collaboration has become an essential tool for organisations of all sizes. Forming partnerships to address complex challenges that the individual organisation can’t readily meet is now the norm in many industries.

In the world of rare disease drug development, collaboration between smaller biotech companies and Big Pharma may be the perfect model for bringing new therapies more quickly to market, improving the life-chances of millions.

The extraordinary number of rare diseases, combined with the lack of knowledge about many of them, creates enormous challenges for drug developers; according to the European Commission, there are between 5,000 and 8,000 known rare diseases, with new conditions being discovered regularly.

The global rare disease treatment market reached more than $195 billion in 2022, according to a report from GMI Insights that also predicts double-digit growth over the next decade.

And it’s largely untapped; with up to 400 million people worldwide affected, and about 90% with no treatment, it’s a big field.

So how might collaboration work in practice? What are the obstacles, and what are the incentives for companies on both sides? What more could be done could help speed up drug discovery and development?

Small is beautiful

Smaller biotech companies, indeed smaller companies generally, are more flexible and agile than their bigger counterparts; they have a faster decision-making process and can more readily change direction as new scientific advances emerge. Big Pharma, by contrast, has more complex decision-making processes, linked to heavier bureaucratic structures and a more conservative disposition

Agility bestows several important advantages; smaller biotechs can more readily adopt new technologies, such as gene sequencing or AI, and can more readily convert (or repurpose) existing drugs for new, perhaps related, conditions. This is because they typically have deep knowledge of the pathology and mechanisms of action of specific rare diseases, and teams are simply much more closely knit (there is very little silo effect as seen in larger organisations) so are better placed to share ideas – in other words, collaborate.

Big Pharma has the resources and infrastructure to develop many drugs, of course, but they are more driven by shareholder demands for rapid financial returns, so naturally focus on the mass-market; rare diseases therapies are simply less economically attractive. As a result, much rare disease drug research and development is carried out by smaller biotechs.

In calculating this financial case, a Big Pharma company will also take into account sales and marketing costs, which can be enormous; smaller biotechs targeting a single disease have no need for mass-market advertising.

After identifying and developing a promising candidate, the smaller biotech has options; for example, it could seek further investment to carry out clinical trials on its own, or perhaps it could go public to raise funds. But forming a partnership with Big Pharma may be the best option, as their different strengths (navigating regulatory approvals, negotiating with governments and health services, and manufacturing) are almost perfectly complementary to those of the smaller biotech.

On a more prosaic level, the smaller biotech can make a bigger name for itself by becoming the recognised leader in the search for a specific rare disease therapy.

Renewed purpose

Repurposing common drugs for the treatment of rare diseases is a potentially efficient way of getting more treatments more quickly into the market; development timescales are reduced, costs are lower and toxicology and other safety tests have already been carried out.

There are examples too of rare disease drugs having application for more common conditions, but this presents problems that almost mirror the benefits listed above; for example, the need for clinical validation and regulatory approval prior to mass market use.

An important consideration for Big Pharma is its ability to use drugs developed for rare diseases to address a cluster of related conditions, usually ones that affect a specific part of the body; this can move the dial in terms of the financial case, so it’s not surprising that some Big Pharma companies have units dedicated to finding such applications.

Wider collaboration

Patient advocacy groups have historically played a vital role in lobbying for change; in the US in the 1980’s it was advocacy by the National Organization for Rare Disorders (NORD) that resulted in the passage of the Orphan Drug Act (ODA) in 1983, a seminal moment in the history of rare disease drug development.

The ODA included provisions for 7‐year market exclusivity for orphan drugs, tax credits, development grants, fast‐track approval, and the waiving of some fees. These incentives help offset the high costs and risks associated with developing therapies for diseases with small patient populations, making it more feasible for smaller biotech companies to undertake such projects.

In the UK, to take one example, the H-ABC Foundation supports patients and families affected by the disease, advocates on their behalf, and raises money to help fund vital research.

These patient groups have, perhaps, the greatest incentive to progress knowledge and disseminate best practice, as they typically consist of, or represent, parents with children affected by a rare disease. They could be used more formally within the system as a focal point for sharing research and other medical knowledge.

The early bird

The most dramatic change in our diagnostic capability is in the field of genetic and molecular diagnostics. Gene sequencing technology has revolutionised the identification of genetic mutations and abnormalities.

Testing newborns is the ideal. Blood spot tests are offered typically five days after birth, and can reveal a range of rare diseases including cystic fibrosis and sickle cell disease.

Once technology allows, it would seem a natural step to expand this scheme to try to identify as many rare diseases as possible, which would dramatically improve the life-chances of those affected – and save money by avoiding those long ‘diagnostic odysseys’.


Developing drugs for rare diseases is a major challenge for drug developers, but there are several ways in which it can be accelerated; collaboration between smaller biotechs, who typically develop drugs for one or perhaps two conditions, and Big Pharma, is one way. Repurposing is another, and clustering is a third.

Smaller biotech companies often collaborate with patient advocacy groups, who can advocate for funding and legislative change, all of which (ultimately) helps.

Once a smaller biotech’s candidate orphan drug has passed toxicology tests and gone through clinical trials, Big Pharma’s strengths in navigating regulatory approvals, making deals with Governments and health services, and manufacturing, could then prove vital.

Expanded early bloodspot testing could identify many more rare conditions, and whilst this doesn’t directly speed up drug development it does improve patients’ lives – something we mustn’t overlook.

In a world controlled by economic mantras, rare disease drugs would likely never be developed; so, government intervention has, in this case, proved vital to the life-chances of millions of patients worldwide.

By leveraging their agility, flexibility, and strategic collaborations, smaller biotechs can bring life-changing therapies more quickly to market, improving quality of life for the many millions of rare disease patients worldwide.

Collaboration is the key.


About SynaptixBio

Formed in early 2021, SynaptixBio has a formidable heritage; the founders are all recognised biotech leaders.

SynaptixBio is the first and only company developing a therapy to treat a rare, deadly and currently incurable disease – TUBB4A related leukodystrophy. It is hoped that in-human clinical trials can begin in late 2024. In 2022 the company signed a worldwide exclusive license to intellectual property from CHOP, enabling commercialisation of treatment​.