Dyne Eyes IPO for R&D of Genetic Medicines for Rare Muscle Diseases

Xconomy Boston — 

Not long ago, having early data about how an experimental drug worked in humans was expected of biotechs considering IPOs. Dyne Therapeutics may not reach human testing until 2022, but, like many of its preclinical peers this year, the company is choosing to jump into public markets now while investor interest in the biotech sector is riding high.

In paperwork filed with securities regulators late Tuesday, Dyne set a preliminary $100 million target for its IPO. The company has applied for a Nasdaq listing under the stock symbol “DYN.”

Waltham, MA-based Dyne is developing treatments for rare, inherited muscle disorders. The company’s drug candidates employ oligonucleotides, nucleic acids intended to correct the function of a disease-causing gene. While there are already FDA-approved oligonucleotide drugs, one of the challenges for these therapies is getting enough medicine into the target tissue, the company says in its filing. Dyne overcomes this hurdle by linking its oligonucleotides to an antibody that targets a protein found in abundance on the surface of muscle cells. The target protein, transferrin receptor 1 or TfR1, is needed for transporting iron into muscle cells. By binding to TfR1, Dyne says its drugs can deliver its nucleic acid payload to muscle cells without interfering with the protein’s role transporting iron.

Dyne calls its proprietary drug technology platform “Force.” The company says its drugs have the potential to overcome limitations associated with today’s gene therapies, such as the antibodies that patients have or can develop against the engineered adeno-associated virus (AAV) used to deliver gene many such therapies. These viruses are also tied to side effect risks throughout the body, which is a problem when higher doses of a gene therapy are needed to deliver a treatment to muscle tissues. Also, while AAV can carry genes up to a certain size, Dyne says its technology has flexibility to deploy different types of therapeutic payloads, including ones too big for those viruses to ferry.

The first muscle disease target on Dyne’s radar is myotonic dystrophy type 1 (DM1), a type of muscular dystrophy in which mutant RNA leads to muscle weakness, muscle wasting, difficulty breathing, and early death. It’s caused by a mutation to the DMPK gene and the disorder has no FDA-approved therapies. Dyne designed its DM1 drug candidate to reduce levels of mutant pre-cursor RNA in the nucleus. The company says this approach allows the cell to make proteins normally and potentially stop or even reverse the progression of DM1.

The DM1 program is one of three preclinical programs in Dyne’s pipeline; the others are for Duchenne muscular dystrophy and facioscapulohumeral dystrophy. The company says its Force technology also could potentially be applied to the development of treatments for rare skeletal diseases, cardiac disorders, and metabolic conditions.

Dyne isn’t the only biotech that has latched onto the concept of using an antibody to deliver a genetic medicine into muscles. Avidity Biosciences is also developing oligonucleotide drugs that use antibodies to target muscle tissue. The San Diego-based biotech, which raised $260 million in its June IPO, is developing potential treatments for the same diseases that Dyne is targeting. It expects to start a Phase 1/2 study testing its DM1 drug candidate, AOC 1001, by the end of next year. Other companies developing DM1 treatments include AMO Pharma, Astellas Pharma subsidiary Audentes Therapeutics, and Vertex Pharmaceuticals (NASDAQ: VRTX).

Dyne was formed in 2017 by venture capital firm Atlas Venture, which provided seed funding and incubated the startup. Last year, Dyne came out of stealth backed by $50 million in Series A financing. Romesh Subramanian, Dyne’s founder and CEO at the time, told Xconomy last year that in preclinical research, the company’s drugs successfully reached skeletal, smooth, and cardiac muscle tissue. Subramanian has since shifted to the chief scientific officer role. The company is now led by president and CEO Joshua Brumm, the former chief financial officer of Kaleido Biosciences (NASDAQ: KLDO). Dyne’s chief operating officer is Susanna High, who joined recently from gene therapies developer Bluebird Bio (NASDAQ: BLUE).

According to its prospectus, Dyne has raised more than $167.7 million, most recently a $115 million Series B round of financing that closed earlier this month. Atlas Venture is Dyne’s largest shareholder owning 31.1 percent of the company, the filing shows. Dutch venture capital firm Forbion owns a 19.6 percent stake; MPM Bioventures, which has offices in Cambridge, MA, and Brisbane, CA, owns 15.8 percent.

Dyne plans to apply the IPO proceeds toward research and development, including studies that would support an application to test its drugs in humans. A filing seeking FDA permission to start a clinical trial for its DM1 candidate is one of three such applications the company says it expects to submit between the fourth quarter of next year and the fourth quarter of 2022. The company will also set aside some cash for further development of its Force technology.

Image: iStock/Amiak


Want more Xconomy content? Subscribe today for free newsletters, event and webinar alerts, whitepapers, podcasts, and more.