Orthopedics R&D Program

Executive Summary

  1. Platform technology with multiple applications – a powerful addition to “heal with steel”
  2. Clinical proof of concept from Phase 2 trial
  3. Fast Track review granted by the US FDA
  4. Twenty one (21) issued patents provide protection until 2031
  5. Multi-billion market opportunity in fracture healing, joint health, dental, sports injuries and spinal health.

 

Carmell’s BioActive Material: Advantages over Autologous PRP:

  1. Off-the-shelf: Autologous PRP requires specialized training for extraction, procurement of capital equipment and waiting time for patient
  2. Quality assurance/lot consistency: Autologous PRP can be highly variable depending on the health of the patient. Carmell’s product utilizes pooled allogeneic PRP to ensure consistent bioactivity.
  3. Duration of exposure: Autologous PRP is metabolized within 24 hours. However, Carmell’s product has significantly longer bio-availability due to proprietary processing, including crosslinking.

Our Innovative Science

Note: When activated, platelets release PGF and adhesion molecules to mediate a variety of cellular interactions: chemotaxis, cell adhesion, migration, cell differentiation, and immunomodulatory activities. These platelet cell-cell interactions contribute to angiogenesis and inflammatory activities, ultimately to stimulate tissue repair processes. Carmell’s product utilizes platelet extracts following activation with calcium chloride. 

Human Platelet Derived Growth Factors

Autologous Platelet Rich Plasma (PRP) has been widely used to treat a variety of orthopedic issues ranging from sports injuries to degenerative bone disorders.

Platelet & Plasma Mechanism of Action

The underlying scientific rationale for PRP therapy is that an injection of concentrated platelets at sites of injury may support and accelerate tissue repair via the release of many biologically active factors (growth factors, cytokines, lysosomes) and adhesion proteins that are responsible for initiating the hemostatic cascade, synthesis of new connective tissue, and revascularization.

Additionally, plasma proteins (e.g., fibrinogen, prothrombin, and fibronectin) are present in the platelet-poor plasma fraction (PPP). PRP concentrates can stimulate the supraphysiological release of growth factors to jump-start healing in chronic injuries and accelerate the acute injury repair process.

At all stages of the tissue repair process, a wide variety of growth factors, cytokines, and locally acting regulators contribute to most basic cell functions via endocrine, paracrine, autocrine, and intracrine mechanisms.

Source: Everts P, Onishi K, Jayaram P, Lana JF, Mautner K. Platelet-Rich Plasma: New Performance Understandings and Therapeutic Considerations in 2020. Int J Mol Sci. 2020 Oct 21;21(20):7794. doi: 10.3390/ijms21207794. PMID: 33096812; PMCID: PMC7589810

In addition to the healing benefits provided by platelet and plasma-derived factors, Carmell’s orthopedic formulation includes beta tricalcium phosphate, a proven osteoconductive scaffolding material to support bone growth and regeneration.

Carmell Clinical and Preclinical Studies

Preclinical Studies: Safety & Efficacy

  1. Tibia healing, rodent study, Dr. Jason Smith
  2.  Mechanism of action, rabbit study, Dr. William Walsh
  3. Skin flap healing model, rodent study, Dr. Stephen Badylak
  4. Pacemaker infected pocket model, rabbit study, Dr. David Schwartzmann
  5. Mouse cutaneous radiation burn model, rodent study, Dr. Eric Miller
  6. ISO 10993-6 bone implantation, rabbit model, WuXi AppTec
  7. Heterotropic bone model, rodent, Dr. Phil Campbell
  8. Spine fusion model, rabbit, Charles River

Phase 2 Human Trial: Safety & Efficacy

Study design (HEAL I):

  • Prospective, double arm, randomized, multi-center
  • Treatment arm: 20. Control arm: 10

 

Recruitment criteria:

  • Open tibia fractures – defined as fractures which communicate with the outside environment through a soft tissue wound. The majority of open fractures are those of the long bones, while most occur in the lower extremity and particularly the tibia. Open tibial fractures have always been a challenge to manage, as historically they often resulted in amputation, sepsis or even death.
  • Highly co-morbid patients (e.g. 70% smokers)
  • Very severe injuries – Gustilo Open Fracture Grade IIIA/B Classification 

Adverse Events:

  • No AEs associated with drug product

 

Study Outcomes:

  • 2x faster bone healing at 6 months
  • 4x more wounds healed at 1 month
  • 4x fewer infections through 12-month follow-up

 

Next Steps:

  • FDA approved IND for launching clinical trial (HEAL II)
  • CMC package ready