NEW YORK – A new public benefit corporation founded by a patient advocacy group is on its way to developing treatments for familial dysautonomia (FD), a debilitating genetic disease.
Tikun Therapeutics, based in New York City, was launched last year by the Familial Dysautonomia Foundation, a nonprofit formed by parents of children with this inherited disorder to support research, medical care, and awareness of the conditions. The startup remains wholly owned by the FD Foundation.
There aren't any disease-modifying treatments for FD, a rare and progressive disease characterized by sensory issues, such as limited pain and temperature sensation, and, by adulthood, dysfunction of typically involuntary functions like heart rate, swallowing, balance, and vision. The disease is caused by a mutation in the ELP1 gene that disrupts mRNA splicing, resulting in a lack of the eponymous protein, which is needed to develop and maintain nerve cells.
The FD Foundation opted to launch Tikun as a separate company that would lead promising drug development efforts, so that the foundation could continue to function as an FD patient support and research advocacy organization, said Adam Sachs, president and CEO of Tikun and member of the FD Foundation's board of directors. Tikun's mission is entirely focused on advancing treatments for FD, alleviating symptoms, and hopefully slowing disease progression, said Sachs, who's also the father of an FD patient.
"It's very focused," Sachs said of the startup's mission. The company doesn't have any employees, as it's a volunteer-run endeavor.
There are only 350 people in the world known to have FD, an extremely rare disease that's almost exclusively seen in children with Ashkenazi Jewish ancestry. The company's name, Tikun Therapeutics, comes from the Hebrew word "Tikun," which means "restore," aligning with its goal to advance treatments that restore protein function for these patients, Sachs said.
Like many rare diseases, FD patients don't have a lot of treatment options. Pharmaceutical companies are often hesitant to devote resources to making treatments for rare diseases, because drug development is expensive, and there are limited opportunities to recoup the costs if the therapy is for a very small group of patients. Even in cases where an experimental drug shows early promise at treating a rare disease, a drugmaker may drop it from its pipeline, pause development, or sell it to a different company to preserve resources for an asset with bigger commercial potential. Additionally, companies must evaluate these treatments in clinical trials with small study populations and may still exhaust the known patient population before they're able to commercialize it.
"Where are we going to get therapeutics for those diseases?" said Tikun CSO Frances Lefcort. "Big Pharma's not going to develop therapeutics for these rare diseases."
Nonprofits and patient advocacy organizations in the rare disease community are filling the void and trying to figure out how to create and fund drug development for many conditions that Big Pharma may pass on, she noted. The FD Foundation's decision to launch Tikun as a separate biotech startup represents one potential strategy being tried to advance rare disease therapies.
As another example, just last year, the US Food and Drug Administration selected companies to participate in a pilot program to accelerate development of gene and cell therapies for rare diseases. Separately, a public-private consortium led by the Foundation for the National Institutes of Health in 2024 published a "playbook" for drugmakers to help shepherd developers of rare disease gene therapies through preclinical research and into clinical trials.
Tikun, for its part, is supporting R&D for three FD treatment candidates being developed at various research institutions: an antisense oligonucleotide (ASO), a gene therapy, and a small molecule splicing modulator. These therapeutic candidates were previously supported by the FD Foundation through grants and donations.
However, after speaking with people involved in other rare disease patient advocacy groups about what to expect as these candidates continued to advance, the FD Foundation realized it would need significantly more capital to get them into clinical trials and make them accessible to as many patients as possible.
"We were kind of overwhelmed by the zeros that were involved [in the cost]," said Lanie Etkind, executive director of the FD Foundation. She credited Sachs with "pounding the pavement" and investigating how to raise that money, eventually determining that, as a public benefit corporation, Tikun could be eligible for funding sources that the FD Foundation can't access as a nonprofit.
While there are treatments available to address symptoms of FD, such as using a continuous positive airway pressure (CPAP) machine during sleep to help with breathing, feeding tubes to support nutrition, and physical and occupational therapy, without disease-modifying therapies patients will continue to get worse.
"It's a devastating disease," said Sachs, who has been involved in the FD Foundation for most of his son's life, who's now 30. But last year, he felt the need to dive deeper into the drug development space, as he saw there were multiple promising treatments undergoing preclinical testing. Sachs has experience in the life sciences industry, having held leadership roles at companies including AstraZeneca, Thermo Fisher Scientific, and several biotech startups.
While the FD Foundation has supported development of the three therapeutic programs in Tikun's pipeline, Tikun now is exploring non-dilutive funding opportunities for itself among investors and looking into small business grants, which it can use to advance these candidates, Sachs said. "We're driving [the three assets] simultaneously right now, in the hopes that one, two, or all three will benefit the FD population," he added.
The candidate that's the furthest along is an ASO designed to correct the splicing defect at the root of FD. So far, one patient has received the ASO as part of a clinical trial supported by the N-Lorem Foundation, a nonprofit founded by former Ionis Pharmaceuticals CEO Stanley Crooke to create ASOs for patients with extremely rare monogenic disorders. N-Lorem, which is funded by philanthropy, primarily from biotech companies, designs these drugs and provides them to patients for free.
It took about three years after getting connected to N-Lorem to get the go-ahead from the FDA to begin clinical testing the ASO in a single patient, said Horacio Kaufmann, a professor at New York University's Grossman School of Medicine and director of the dysautonomia center at NYU Langone Health, who's one of the study's investigators. He noted that N-Lorem conducted the toxicology and pharmacology studies in animal models needed to secure FDA clearance of an investigational new drug (IND) application.
The first patient, a 15-year-old, received the ASO through a spinal injection last June and will continue to receive subsequent doses every four months for two years as part of the study, Kaufmann said. Investigators will monitor outcomes related to vision and balance, such as changes in retinal thickness, visual function tests, and gait analysis. After the experience with the initial patient, Kaufmann said the research team is seeking authorization from the FDA to treat three more patients.
The ASO is based on preclinical research by Adrian Krainer, a professor at Cold Spring Harbor Laboratory. Krainer's research also underpinned Biogen and Ionis Pharmaceuticals' Spinraza (nusinersen), an ASO for spinal muscular atrophy that became the first drug approved by the FDA for that condition in 2016.
The NYU Langone Health's dysautonomia center is where Tikun anticipates it will run most of its therapy trials. The FD Foundation is the main funder of the dysautonomia center, which it helped establish in the 1970s and which it says remains the only specialized FD treatment center in the world. The FD Foundation also collaborates with clinics treating FD in Israel, where there's a large population of people with Ashkenazi Jewish ancestry.
In January, Tikun received orphan drug designation from the FDA for the two other preclinical therapeutic programs it's supporting. These designations provide incentives such as tax credits for clinical trials and exemption from user fees for sponsors of certain rare disease therapies.
Tikun's other two assets include BPN-36964, an oral, small molecule splicing modulator developed in a lab at Massachusetts General Hospital that's designed to correct ELP1 mRNA splicing, and rAAV2-U1a-hELP1, a gene therapy developed in a lab at Montana State University that's designed to express the ELP1 gene to try to prevent progressive optic neuropathy and vision loss in FD.
The gene therapy was developed by Tikun's Lefcort when she was a professor of cell biology and neuroscience at Montana State. Lefcort, who has since retired, was inspired to focus on this area after one of her cousins, who was diagnosed with FD, lost his vision. Losing the ability to see as an adult had an enormously negative impact on his life, Lefcort recalled.
If multiple candidates in Tikun's pipeline prove effective, she noted that leaves open the possibility of a combination regimen. "Each approach has its advantages," Lefcort said. "You could imagine, one day, a cocktail of all three."
Tikun intends to keep supporting all three programs, which Sachs acknowledged will be expensive. He's open to working with industry partners interested in Tikun's candidates, particularly if these treatments are found to have applications beyond FD.
Still, even if these treatments end up having broader uses, he emphasized that Tikun will stay focused on FD. For now, Tikun's priorities are proving safety, efficacy, and getting one or more of the therapeutics to patients as quickly as possible.
"We have three opportunities — three different modes of action," Sachs said. "That makes us very optimistic."