The development of biomaterials for orthopedic applications is a crowded space with several large and small companies designing innovative materials. One approach is the use of these materials to deliver therapeutic proteins that enhance healing. Theradaptive has developed a novel method to modify the proteins themselves so that they coat the surface of implants like paint, making them more readily available for cells of the body to interact with. We recently had the opportunity to chat with the CEO of Theradaptive, Dr. Luis Alvarez, about the company’s technology which can be used for several applications with a variety of implant types.
Dr. Rukmani Sridharan, Medgadget: What is your background and how did you start Theradaptive?
Dr. Luis Alvarez, Theradaptive: The origin of Theradaptive is in the Army. I was serving overseas and I noticed that a lot of veterans were undergoing delayed amputation of limbs even though their limbs had originally been salvaged. I realized this was related to tissue repair and regeneration and hence joined MIT’s PhD program to design a solution to repair tissues with precision. Part of my work was spun out to form Theradaptive.
Medgadget: Can you describe your main platform?
Luis Alvarez: Current clinical solutions for healing of bone defects include applying freely-diffusing proteins like BMP2 solution into a defect site, which leads to poor retention of the protein. Moreover, several off-target effects have been reported especially for some proteins used in bone regeneration applications.
Our platform leads to modified recombinant proteins (that are made in other organisms) that make them stick to implant materials with really high affinity. One example is our lead candidate, AMP2 which is targeted towards bone repair, spinal fusion and several other orthopedic applications.
AMP2 is a modified version of bone morphogenic protein (BMP-2), which has been widely used for bone repair. AMP2 maintains the bioactivity of the original protein, with the only change being that it can stick to implants like paint. The main advantage of our platform is the ability of the protein to stick to the implant material, avoiding unnecessary side-effects from freely diffusing proteins while keeping the proteins concentrated at the defect site, where they are needed the most.
Medgadget: What materials do you use to house these proteins?
Luis Alvarez: We have used both in house and external biomaterials. We already have a signed deal with a Japanese company called ORTHOREBIRTH that has a sponge like material used to fill bone voids. We did a goat study together and now have an investment from them to develop a technology called THX-14, which combines our AMP2 technology with their biomaterial ReBOSSIS.
Similarly, we are in talks with several other companies that make materials to which our recombinant proteins will bind with high affinity.
One of the materials we have developed in-house is a product called OrthoTex which is a flexible ceramic – a composite between a medical grade polymer and ceramic. The protein loads very well into the material and we are exploring its use in both bone and cartilage repair applications.
Medgadget: What stage are your pre-clinical studies at?
Luis Alvarez: We have used AMP2 in 5 different pre-clinical studies. Our product has been shown to successfully bridge a 5cm critical size bone defect in large animals such as goats, demonstrating superiority to the current gold standard autograft.
We are currently finishing our GMP manufacturing and the final safety tests that the FDA has requested from us. We expect to start our first human trials (combining Phase I and II) in 18 months which will likely have 40 patients and run for 12-18 months.
Medgadget: Can you talk about other proteins that have been modified by your technology?
Luis Alvarez: We have also developed another protein called TGF that is involved in cartilage repair and have used this in animal studies already. A combination of AMP2 and TGFβ3 has been shown very successful for the repair of osteochondral defects, which are defects in the smooth surface (cartilage) on the end of bones and the underlying bone itself.
Medgadget: Are the doses you use with the implant comparable to what you would use in their absence?
Luis Alvarez: When you put an implant into the body, the cells will migrate from its surroundings into the material and will encounter the protein. Since the protein is stuck to the implant, cells will encounter them with much higher frequency than if it was a liquid dose. So in most cases, we would have to use much less amounts of protein to achieve the same desired effect, which would bring down the cost of the product. However, we could also use the same dose but design a much safer product because we are eliminating off-target effects.
Medgadget: Can you comment on the progress in this space in the coming years?
Luis Alvarez: The field is currently struggling with delivering controlled doses of protein therapeutics locally. Our technology offers a solution to this problem. Another related area is cell therapy, where companies deliver cells to heal defects – the problem of local delivery exists in this field as well. Our platform will allow for cells to be delivered locally into the implant where they can interact directly with the proteins present in it, thereby generating a much more efficacious response. We just completed a study demonstrating this effect and will soon present the use of a new concept called a ‘Bio-device. The FDA currently classifies some protein delivery devices as ‘Class III’ devices, but a cell therapy company can use it as part of their total product packaging to get a better outcome.
Learn more: Theradaptive homepage…