When we published our 2024 report, children suffering from Leber Congenital Amaurosis 4 (LCA4) – a severe inherited retinal dystrophy – had only hope that one day they might see the world. Today, thanks to an investigational gene therapy, we know that the 11 kids who participated in the trials can, for the first time in their lives, discern a toy, recognize a human face, and even spot a grain of sand. The biotech behind this achievement is MeiraGTx, which has now filed its therapy for approval under exceptional circumstances in the UK, which would expedite the process.
Stories like that of MeiraGTx illustrate the transformative power of gene therapies on patients. More broadly, they highlight the potential for rare diseases R&D to emerge as the principal driver of therapeutic innovation. ‘Rare diseases have become a critical area for exploring new treatment modalities because, in many cases, there is no existing therapy, or even a model. For patients who have no options, innovative approaches are important,’ shares Marc Dunoyer, the CEO of Alexion, the rare diseases subsidiary of AstraZeneca. Ironically, the very severity and uncommonness of these illnesses can also be a blessing, as it allows for bolder approaches by both researchers and regulators. Moreover, rare disease drugs have historically had higher approval success rates compared to other drugs. The Tufts Center for the Study of Drug Development found that orphan-designated drugs had a Phase 1-to-approval success rate of 17%, compared to 7.9% for non-orphan drugs. Benefiting from faster approval pathways and enhanced regulatory incentives, entrepreneurs in the field face better odds of innovating successfully.
And when they do, the implications of their therapies go far beyond their original target. ‘Many of the advances seen today, such as gene editing and RNA-based therapies, originated in rare disease research before moving into larger indications,’ says Dunoyer. Arcturus Therapeutics, for instance, is addressing cystic fibrosis via a new delivery mechanism. ‘Our cystic fibrosis program is a prime example, where the ability to inhale mRNA safely could have a huge impact on the pharmaceutical industry. The rare disease field offers a shorter regulatory pathway to approval and a higher likelihood of success. This makes it an attractive space for evaluating next-generation technologies like mRNA therapeutics,’ shares Arcturus’ CEO, Joseph Payne, as the company is expecting results from their Phase 2 trials in 2025.
Similarly, the CEO of MeiraGTx, Alexandria Forbes, believes the biotech’s delivery approach will have broad effects: ‘Our strategy involves local delivery with small doses, which has shown effectiveness in diseases beyond retinal disorders, including conditions like Parkinson’s.’ We find the same pattern in the story of Ultragenyx, which, with its four approved therapies to date, is a reference in the field. ‘Rare diseases serve as unique biological models, providing a deeper understanding of the biological processes that underlie a wide range of conditions. For instance, our work with galactosialidosis led to an interesting finding: the protease involved in this condition also affects amyloid buildup, which is central to Alzheimer’s disease. This discovery has the potential to lead to a gene therapy approach for Alzheimer’s, providing a new avenue for treatment,’ tells us Emil Kakkis, Ultragenyx’s CEO and Founder. This year, his company is anticipating its first gene therapy approval. Those who anticipate it even more, no doubt, are all the kids who suffer from Sanfilippo syndrome—an inherited metabolic disorder that causes progressive neurological degeneration and developmental delays due to the body's inability to break down certain sugars. ‘It is typically diagnosed in children between two and six years old, and by the age of ten or twelve, they often become bedridden and may pass away as early as the second decade of life,’ Kakkis says. Ultragenyx’s gene therapy is potentially life-changing.
Incyte, with a market cap of over $11 billion at the time of writing, can easily be considered a biotech that ‘made it’. We asked their CEO, Hervé Hoppenot, what is behind their achievements: ‘Our primary focus has always been on innovative science. Not all science is innovative; the true challenge lies in exploring uncharted territories to uncover the unknown,’ he tells us. Mr. Hoppenot is genuine about the company’s culture of venturing into ‘the unknown’. Incyte has consistently pioneered new treatments, such as the first FDA-approved products for myelofibrosis and polycythemia vera. Presently, Incyte is working on addressing unmet needs in oncology and inflammation and autoimmunity (IAI).
Another European company, argenx, with its stock up by more than 20 times since their IPO in 2017, has equally been walking on untrodden paths. The biotech’s name comes from the Greek myth of the Argonauts—an ambitious team on a bold journey. ‘In biotech, many companies push new technologies onto existing disease targets, but we believe in discovering new biology,’ argenx’s CEO Tim van Hauwermeiren tells us. Their work is centered on finding novel ways to modulate the immune system to address autoimmunity. The success of argenx has so far been driven by Vyvgart, a medication approved in 2021 for generalized myasthenia gravis (gMG). ‘About 40% of gMG patients in our trials became completely symptom free, while 80% experienced a clinically meaningful improvement in muscle strength. Importantly, there were no significant safety concerns. In real-world use, more than 50% of patients report living symptom-free, essentially regaining the life they had before diagnosis.’ Vyvgart has since been approved for two other diseases (in the U.S. and in Japan). But the potential for broader effects is enormous: ‘This opens the door to treating over 100 autoimmune diseases, with three indications already approved and many more in development,’ concludes van Hauwermeiren. When asked what message he has for other European biotech leaders, argenx’s CEO is clear: ‘Ambition is key. Too often, European biotech companies sell their assets or exit early instead of going all the way. In the U.S., we have seen more companies push through to build long-term value’.
Often, the best way for insights from rare diseases to be passed on to a broader range of therapeutics is via mergers&acquisitions orother forms of collaboration with bigger pharmaceutical companies. Novo Nordisk, which recently acquired Dicerna Therapeutics, a rare diseases biotech that developed RNAi therapies, demonstrates the value of a healthy biotech- pharma ecosystem. ‘Since integrating Dicerna, we have expanded our focus beyond rare diseases to include more prevalent conditions such as diabetes, obesity, and cardiovascular diseases. These are major global health challenges where RNAi has the potential to provide transformative treatments,’ says Novo Nordisk’s SVP, Jacob Petersen. To our question about his definition of success, Petersen replies: ‘Success, to me, means that we can bring these groundbreaking therapies to patients at scale, making their lives easier and improving disease management. With RNA technologies, some treatments could even become one-time therapies with lifelong effects.’
Last year at the Biocom California Global Life Science Partnering & Investor Conference in San Diego it was not clear whether SMSbiotech’s new type of stem cell therapy would ever see human clinical trials. As we reached back to Abdulkader Rahmo, the Co-Founder & President, we were pleased to find out that, after more than a decade of work, the company’s therapy for chronic obstructive pulmonary disease (COPD) is commencing Phase 1 clinical trials in Australia. ‘The approval [to begin clinical trials] itself is a significant achievement because the cells we are working with are largely unknown to the scientific community and regulators,’ Rahmo tells us. Small Mobile Stem (SMS) cells, the backbone of this therapy, stimulate the body’s own stem cells instead of building foreign tissue. One of the expected benefits is an increased safety profile compared to traditional stem cell therapies. The first safety data is to be announced about four months into the trial.