Luis Alvarez, founder and CEO of Theradaptive, details his inspiration for change in the field of tissue regeneration and disrupting the orthopedic and protein therapeutics landscape.
Some 20 years ago, the Iraq War ushered in a period that rewrote the rulebook of armed combat. As US servicemembers first set foot in the desert region, it became apparent that medical technology was not sufficiently equipped to deal with the damage that weapons like improvised explosive devices (IEDs) could inflict on the body.
While serving on the ground as a young captain in the United States Army I witnessed first-hand the horrific injuries caused by IEDS on some of my fellow soldiers, particularly on their limbs and extremities. While advances in medicine enabled surgeons to save these soldiers’ limbs in the field in many cases, it was not uncommon to observe long recovery times and acute gaps in the standard of care. Some of these limbs did not heal for weeks or even months after their initial injuries, often leading to veterans facing the painful choice of remaining bedbound or undergoing delayed amputation to regain mobility with prosthetics.
The inability of modern science to provide a regenerative solution for limb salvage inspired me to return to graduate school to pursue a doctorate in biological engineering at the Massachusetts Institute of Technology (MIT). I realized that to solve the problem of slow and ineffective bone regeneration required a molecular biology approach and resulted in my focusing on how therapeutic proteins could be precisely targeted to implant sites. To bring the results of those years of research to as many patients as possible, I spun out Theradaptive.
How to Heal Bones Faster
Patients need better ways to regenerate bone and tissue. Ninety percent of those aged 60 years or older have evidence of spinal disc degeneration, leading to pain and decreased mobility, while 25% of postmenopausal women suffer from debilitating vertebral compression fractures. Current treatments for these conditions involve providing structural stability, but do not provide any regenerative capacity and are often limited in success.
Currently, recombinant therapeutics must usually be administered in high doses to have a beneficial effect, leading to increased safety concerns. The current leading bone regeneration product is based on bone morphogenic protein 2 (BMP2), a core component of the body’s natural bone-healing response that drives the formation and maintenance of bone in the body. However, when BMP-2 is used in bone grafts or as part of medical devices today, it is not well-targeted and quickly diffuses away from where it is needed the most. Simply put, current medical implants are ill-suited to deliver recombinant proteins and conversely recombinant proteins are ill-suited for targeted delivery.
To address this, Theradaptive developed AMP2, a highly osteoinductive engineered variant of BMP2, that permits the targeted delivery of the osteoinductive signal needed to regenerate bone with anatomical precision in specific parts of the body. AMP2 has been designed to bind tightly to materials in bone void filling implants, allowing bone to regrow with anatomical precision at the sites where it is needed. This also leads to accelerated bone healing.
The technology not only benefits the patient, but also results in reduced costs for physicians and insurers, as less of the biologic is needed for successful bone regeneration. The use of AMP2 and related material-binding protein variants promise to usher in improved patient outcomes and provide cost-effective methods of targeting therapeutics for a range of indications. Furthermore, the same approach used to create AMP2 is broadly applicable to engineer almost any biologically active protein to coat almost any device material including wafers, meshes and injectable carriers.
Targeted Therapeutics for the World
Outside of orthopedics, Theradaptive’s technology platform has the potential to improve a patient’s quality of life, or even save it, in a wide variety of clinical indications. One example of this is immuno-oncology where current statistics show only 20-40% of patients respond positively to current treatments. Having the ability to precisely deliver immuno-stimulatory therapeutics with local precision could transform this paradigm. The current standard of immunotherapy care in some renal and melanoma cancer types is Interlukin-2 (IL2) therapy, a cytokine that helps to trigger the patient’s immune system to fight cancerous cells. IL2 is administered by intravenous infusion to activate a systemic immune response.
Like BMP2, IL2 is a powerful therapeutic agent that also has unwanted side effects when administered through traditional methods of systemic delivery. Due to the toxic high doses of IL2 needed to generate the desired immune response, this therapy results in debilitating side effects for patients who are already weakened by their cancer and often results in discontinuation of IL2 followed by progression of the cancer. Theradaptive’s targeted IL2 variants aim to localize IL2 close to the tumor, activating T cells with a much lower dose in the targeted area and limiting IL2’s toxic effects by avoiding systemic exposure.
With an estimated two million Americans diagnosed with cancer each year, our approach seeks to bring new options to the current standard of care for people who have run out of options. By doing so we can hopefully also reduce the suffering, time, and money spent on additional therapies to ease side effects from current treatments.
Theradaptive began as an idea to improve soldiers’ and patients’ lives driven by innovations in targeted protein therapeutics. As Theradaptive initiates human clinical trials later this year, we will be taking steps towards fulfilling that mission, moving us closer to making these therapies available for patients. With the promise that these new regenerative technologies hold, medicine is on the cusp of an exciting new era.
