Revolutionizing Bone and Cartilage Regeneration

For years, scientists have known what molecules coax the human body to make new bone and cartilage. These molecules hold immense power to heal injuries in servicemembers, athletes and anyone with severe musculoskeletal damage. Here’s the problem: when placed passively at the site where they’re needed, these bone-signaling proteins quickly diffuse away.

Over the last several years, Hertz Fellow Luis Alvarez has developed a new set of similar molecules that stick firmly to orthopedic implants, yielding new bone exactly where it is needed. The molecules can be painted onto implants or injected as a putty. They can help regenerate damaged bone, fuse spinal discs together to treat back pain, or anchor ligaments or dental implants in place with new bone. 

Now, Alvarez’s startup company, Theradaptive, has received a U.S. Department of Defense (DoD) Clinical Trial Award of up to $7.4 million to begin human clinical trials of the proteins. That funding comes on the heels of a successful round of Series A funding that closed in mid-2023. 

“It’s been really exciting and validating that we’ve been able to raise close to $60 million based on our initial data,” says Alvarez. “We are now on the cusp of starting these human clinical trials at seven different sites.”

The first phase I/II trials studies will focus on the use of their OsteoAdapt platform in spinal surgeries and to treat trauma injuries— a cause that feels personal to Alvarez, who began his current line of research after battlefield experiences serving in the U.S. Army in Iraq. 

Alvarez, who graduated from West Point, learned in Iraq how tricky it was for doctors to save soldier’s damaged limbs.  Doctors would place bone void fillers into sites of injury with the goal of stem cells growing inside these fillers, but the fillers could fail. Often, the injuries would never fully heal, leading to amputations months later. 

When Alvarez returned to his graduate studies at the Massachusetts Institute of Technology after his tour in Iraq, he pivoted his chemical engineering research to study tissue regeneration. He thought if certain molecules could attach to the bone fillers, they could better attract and retain stem cells. 

“I feel like science had the ability to solve this long ago but no one had done it,” says Alvarez. “The Hertz Fellowship gave me the freedom to take a risk and explore this concept before I knew whether it would be commercially viable.”

During the remainer of his graduate studies, and then while serving on active duty for the Army, Alvarez developed his idea and began to carry out trials in animals. His new molecule, AMP2 — a sticky, re-engineered version of the natural bone-signaling protein BMP-2 — successfully yielded new bone in numerous early trials.  

When he retired from the military in 2017, Alvarez licensed the technology back from the Army and founded Theradaptive. The company’s platform specializes in re-engineering proteins so they can be targeted to a particular tissue or material but, importantly, without compromising the original function of the protein. While his early work was focused on bone regeneration to prevent amputations after serious trauma, Alvarez quickly began discovering other applications of his “sticky proteins” for Theradaptive to expand to. 

“The broad question is: are there therapeutics out there that are effective but not well-tolerated because of side effects from systemic exposure?” says Alvarez. “There are many.”

For many drugs, being able to “stick” them to one spot in the body can boost their effectiveness and minimize side effects. The company is not only pursuing bone and cartilage regeneration, but also ways to use their technology to target cancer drugs to tumors. They have developed a variant of the immune signaling molecule interleukin 2 (IL2) called IL2X that helps localize key immune cells to tumors without impacting the rest of the body. IL2X has already shown superiority to current standard of care immunotherapies in preclinical studies.

When it works, bone regeneration is relatively fast. So within three to six months of launching their first clinical trials, which will enroll patients both in the U.S. and Australia, Alvarez hopes that Theradaptive will have positive interim data on OsteoAdapt, their lead bone regeneration product. At the same time, they are trying to move their technology to battlefields in Ukraine and Israel under humanitarian use to treat combat trauma. Three “Breakthrough Medical Device” designations from the U.S. Food and Drug Administration (FDA) are helping the technology go through review processes quickly to reach patients. 

Alvarez remains excited about his research and inspired to pursue more ideas in the future. He has also helped mentor Hertz Fellows who are starting companies in the Boston-area. His advice for aspiring entrepreneurs: “Pick a problem that matters to a lot of people, even if it seems very hard. Then have lots of conversations about it with lots of people. This will arm you with the knowledge to act.”