Cystic Fibrosis Foundation (CFF) Therapeutics Lab
The Cystic Fibrosis Foundation (CFF) Therapeutics Lab in Lexington, Massachusetts, has dramatically expanded in size. Credit: CFF

While there’s still no cure for cystic fibrosis (CF), patients with the disease are living longer than ever, says the Cystic Fibrosis Foundation (CFF), which is dramatically expanding its CF Therapeutics Laboratory in Lexington, Massachusetts.

Some 105,000 people in 94 countries now have CF, including nearly 40,000 in the United States, according to the foundation’s latest statistics—up sharply from 70,000 globally and 30,000 in the United States only 10 years ago.

Meanwhile, the median predicted age of survival for a child born with CF today is 53 years, up from 38 a decade ago. Thanks to advances in multidisciplinary care, treatments, nutrition, and universal newborn screening, more adults than children now have CF—and they’re attending college, getting married, and starting families of their own.

“The improvements in research and care in CF in the past 20 years have been nothing short of extraordinary, and today’s announcement of the increase in population of people living with CF is a testament to that,” said Bruce Marshall, MD, the CFF’s executive vice president and chief medical officer, in a July 28, 2022, press release.

“We must learn what challenges adults with CF face when living longer with a chronic disease,” Dr. Marshall added. “This generation of adults with CF will help us better understand what it means to live a long life with CF. Through evolving our care model, clinical care guidelines, and adding clinical expertise, such as pharmacists, gastroenterologists, and endocrinologists, we are working to ensure that adults with CF get the care they need.”

To that end, the foundation has enlarged the size of its lab by around 30% to nearly 27,000 square feet. This expansion allows the lab to add new staff members while working alongside industry partners—beginning with Carbon Biosciences. In June, the CFF announced its investment of $6 million in that company to support its preclinical research into an innovative gene therapy approach for CF.

This collaboration marks the first time the foundation is hosting scientists from a startup company. Carbon’s president and CEO is Joel Schneider, PhD, the former chief operating officer of Solid Biosciences, which is developing a gene therapy for Duchenne muscular dystrophy.

Accelerating ‘Tech Transfer From Academia to Industry’

Martin Mense, PhD, the CFF’s senior vice president of drug discovery as well as head of its Therapeutics Lab, said Carbon hopes to use a new approach that may potentially treat all people with CF—regardless of their mutation—by delivering a functional cystic fibrosis transmembrane conductance regulator (CFTR) gene directly into their lung cells.

The idea is to prevent the immune response of the lungs while allowing the possibility of redosing patients.

Dr. Mense, a German biophysicist who earned his PhD at Yale University, New Haven, Connecticut, has overseen the CFF Therapeutics Lab for 11 years.

“We conceived the lab because we wanted to be a middleman that basically accelerates technology transfer from academia to industry,” said Dr. Mense, whose lab employs 40 staffers at a 4-story, standalone building in suburban Boston. “At the same time, we always felt more research could be done. We were looking to complementary work that wasn’t being done by industry or academia . . . to develop into a research hub for cystic fibrosis.”

Equipment in the Cystic Fibrosis Foundation (CFF) Therapeutics Lab in Lexington, Massachusetts. Credit: CFF

Carbon Biosciences, for example, has found a viral vector that can be used to deliver the CFTR gene in gene transfer therapy.

“In contrast to the standard AAV or adeno‑associated virus that most of the industry uses for these types of purposes, the virus that Carbon Bio’s looking to develop—which stems from the parvovirus family—has a larger capacity to deliver the full CFTR gene, which cannot fit into AAV. That’s one major advantage,” he told Rare Disease Advisor in a recent phone interview.

“The second major advantage is that this virus actually seems to be able to be redosed without the immune response that would neutralize it,” Dr. Mense said. “With most standard AAV approaches, if one has to redose within a relatively short amount of time, let’s say months, antibodies basically neutralize the viral vector, and so the second or at least the third delivery becomes pretty inefficient. We expect that will not be the case with the Carbon Bio product.”

Other CFF Incubator Ventures

Carbon Biosciences is the first company to publicly launch from the CFF’s $20 million incubator collaboration with Longwood Fund, an early-stage venture capital firm that invests in science-based companies. But it’s not the only startup that’s recently received funding from the CFF.

In mid-2022, the foundation provided $15.9 million in additional funds for Eloxx Pharmaceuticals of Watertown, Massachusetts, to expand clinical studies of ELX-02, a potential therapy for people who have CF and nonsense mutations. The new funding will let Eloxx expand its studies to determine whether the combination of ELX-02 with a CFTR modulator results in increased effectiveness over ELX-02 alone.

“Eloxx has been working on this for over 10 years, with some of the original research coming out of Israel,” Dr. Mense said. “They’re now in clinical trials. As a foundation, we’re supporting them. We’re excited to see what this can really do for the patients with these type of mutations.”

Materials at the Cystic Fibrosis Foundation (CFF) Therapeutics Lab in Lexington, Massachusetts, where foundation staff members work alongside industry researchers. Credit: CFF

The CFF has also invested in SalioGen Therapeutics of Cambridge, Massachusetts, to support the company’s preclinical research into a novel genetic therapy for CF that seeks to insert a large piece of healthy CFTR DNA at a precise location within the CFTR gene.

“By putting in a large piece of healthy DNA, we hope to basically address all the mutations that would otherwise occur behind this healthy piece inserted, so that at the end of the day, it is successful. This therapy that SalioGen is working on could potentially be a cure for 99.9% to 100% of patients,” he said.

“That’s of course a little bit more science fiction right now compared to Eloxx, but we are excited,” Dr. Mense said. “This is a kind of approach that we have internally been discussing and dreaming of for a long time. SalioGen’s technology promises to possibly deliver on that.”

He added: “With available therapies which are not cures, 92-93% of CF patients can be treated and will see clinical benefit. The remaining 7% will require a type of therapy that we currently do not have. Ultimately, we think that the 7% can and need to be addressed through genetic therapies.”