NIA-Funded Small Business Spotlight: Juvena Therapeutics Unlocking the Secrets of Tissue Regeneration

As we age, our muscles and other tissues break down in much the same way as degenerative diseases progress. What we learn from studying degenerative diseases such as muscular dystrophy could help researchers develop new interventions to fight common age-related ailments and chronic illnesses.

With help from NIA, biotechnology company Juvena Therapeutics has begun unlocking the secrets of proteins for regenerative medicine. Juvena scientists are using a form of muscular dystrophy — myotonic dystrophy type 1 (DM-1) — as a model to sift through proteins that are produced by the body’s stem cells. These cells have the potential to become any type of cell in the body, from liver tissue to skin cells. The goal is to find proteins that encourage tissue growth and repair, ultimately designing new drugs to prevent and treat degenerative diseases like DM-1.

As part of this process, Juvena hopes to learn more about how to reduce the effects of aging on muscles and other tissues, too.

“We want a whole pipeline of therapeutics that don’t just rejuvenate tissue but rejuvenate lives,” said Juvena CEO Hanadie Yousef, Ph.D. NIA has supported several key steps on Yousef’s path to realizing that vision, from support for research training to small business research and development funding.

Aging healthier with dignity

Yousef has been interested in drug discovery since she was 16 years old. She first knew she wanted to be an entrepreneur in high school, when she interned at a pharmaceutical company developing cancer treatments.

In graduate school at the University of California, Berkeley, Yousef showed that human embryonic stem cells produce proteins that promote regeneration of many adult tissue types. Stem cells do this by producing or “secreting” proteins into blood and tissue.

Secreted proteins from all kinds of cells are involved in many biological processes. Some of the most well-known drugs — like insulin— are secreted proteins, part of a class of therapeutics known as “biologics.” Yousef thought that therapeutics based on stem cell-secreted proteins might combat typical diseases that come along with age, such as metabolic, heart, or neurological disorders.

Using stem cell proteins to rejuvenate aging bodies dovetailed with Yousef’s personal experience of seeing her father age.

“My father began suffering from metabolic and cardiovascular disease, and I saw an opportunity to develop therapies that could help us age in a healthier manner,” Yousef said, “one that enables us to retain our dignity and mobility so we have that health, energy, and vitality that enables us to live life to the fullest.”

From 2016 to 2018, Yousef garnered more than $130,000 in NIA funding as an F32 postdoctoral fellow at Stanford University. Her research with Tony Wyss-Coray, Ph.D., explored how secreted proteins carried through the blood promote brain aging and degeneration. These secreted proteins, which she found by analyzing human plasma and mouse models, aren’t from stem cells but instead part of normal human aging. They break things down.

Through this award, Yousef also cultivated a network of mentors,

scientists, venture capitalists, angel investors, and corporate attorneys who encouraged her and provided seed funding and support to establish Juvena. After her fellowship ended, NIA awarded Yousef a Small Business Innovation Research (SBIR) grant, which helped Juvena develop its lead drug candidate, JUV-161, raise nearly $56 million in investments, and secure more than $4.2 million in grant funding to date.

Not your basic biologic

At its start, Juvena set its sights on the promise of biologics. Unlike a chemical compound such as aspirin, which was discovered in tree bark, many biologics are based on human proteins that have normal functions, such as insulin. Stem cells naturally use secreted proteins to guide and stimulate muscle growth throughout the body. With time, this normal process of building and rebuilding gives way to aging and muscle decline, which is where biologics could play a new role.

“It’s the aging process itself that leads to failing tissues and the onset of degenerative symptoms for chronic, debilitating diseases,” Yousef said. “Unfortunately, most of these diseases have no cure.”

Biologics is a complex, growing area of interest in drug development, and Juvena was ready to explore whether biologics might hold promise for future therapies targeted at degenerative diseases. Established in 2017 by Yousef and systems biologist Jeremy O’Connell, Ph.D., the company developed an advanced computational platform to narrow down and select proteins that could address the effects of DM-1, resulting in JUV-161.

In what Yousef calls a “marriage between biology and technology,” Juvena’s platform searches for disease-related proteins within stem cell “secretomes.” These are collections of secreted proteins, sometimes thousands, and most of them are not well-studied or -understood. Juvena uses artificial intelligence, human multi-omics, and high-content image analysis to select promising proteins for testing. In DM-1’s case, if proteins could stimulate old or diseased muscle cells to fuse into fibers like young ones do, Juvena researchers moved the proteins on to the next step.

Juvena’s Phase 1 SBIR grant helped the team optimize JUV-161’s desired characteristics and develop a mouse model of DM-1. This work demonstrated the platform’s ability to find promising drug candidates and develop them into engineered biologics. In addition to tissue repair and regeneration, Juvena scientists are searching for proteins that maintain healthy stem cell function, reduce inflammation and tissue scarring, and generally improve cell energy metabolism and tissue health.

“With every round of screening, we get more information about what the proteins in our library are doing,” Yousef said. “That information gets added to our algorithms to better predict the next round of candidates that could target a given tissue.”

Support from the ground up

A new biotech trying to establish itself can feel isolated from the larger scientific community. For example, Juvena is unable to submit findings for publication before taking care of intellectual property protections. But NIH’s peer-review process offered confidential, scientifically rigorous feedback to fill that critical gap, and the NIA Small Business Programs staff offered helpful advice.

“We can get the input, guidance, and advice that we need to really better the work,” Yousef said.

Five years in, the company has now raised about $60 million. But Yousef said that NIA funding is more than just financial support and feedback. It gives the company no-strings-attached freedom to explore the scientific potential of their ideas as well as the capital needed to pursue preclinical development of new leads, unlike loans or business obligations that come with venture capital.

Juvena’s JUV-161 has shown potential to improve muscle regeneration and strength in multiple models. Next steps include taking JUV-161 through the Investigational New Drug process required by the Food and Drug Administration before a therapy can be tested on humans.

“I hope to continue building our relationship and working with NIA to succeed in developing therapeutics for age-related diseases,” Yousef said.

Juvena’s ultimate mission is to make injectable drugs such as insulin for many age-related and chronic diseases. The company has plans to explore secretomes from more types of adult stem cells, enabling exploration of other human systems. The team knows it will be a long journey, but with crucial seed investments from NIA and other funders, Juvena is on track to make the secretome spill its secrets.

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