SBIR-STTR Award

Direct to Phase II

According to the United States Centers for Disease Control, 34 million Americans have diabetes. One of themost prevalent complications of diabetes is the diabetic foot ulcer (DFU). Approximately 25% of diabetics willdevelop a non-healing foot ulcer in their lifetime. DFUs are highly susceptible to infection and tissue necrosisthat require extreme surgical interventions to remove extensive dead tissue and preserve the limb. Unfortunately,tissue damage is often so extensive that these surgical procedures leave behind complex wounds withexposed bone, tendon, and or fascia - which are notoriously difficult to heal and where current bioengineeredskin products do not have benefit. Indeed, foot ulceration is the most common single precursor of lower extremityamputations among persons with diabetes and is a precursor to approximately 85% of the lower extremityamputations within this population - exceeding 100K every year in the US alone. Furthermore, reported mortalityrates for DFU patients range from 55 to 74% after 5 years, which are above cancers such as prostate, breast,and colon.The current treatment options for complex wounds are scarce. Bioengineered skin sheets are unable to buildnew tissue over these exposed bone surfaces, and basic wound care has little effect as well. Negative PressureWound Therapy (NPWT) has shown improved healing, but this management tool requires intensive outpatientcare and is cumbersome. There is a clear need for a regenerative therapy that can have effect in the "˜vertical'phase of wound healing, where building new tissue volume is paramount to success. This significant clinicalneed creates a considerable market opportunity.To answer this market need, Tempo Therapeutics has developed the MAP Wound Matrix - a flowable synthetictissue scaffold based on our proprietary Microporous Annealed Particle (MAP) technology. MAP Wound Matrixis flowable (ease of application) and fills wounds of any shapes and sizes, and then converts to a hyper-poroussponge-like network in the wound site after exposure to white light. The hyper-porosity geometry promotes fastgranulation tissue, and early vascularization, when compared to leading decellularized tissue-based matrices,with minimal inflammatory response in multiple animal models including diabetic pigs. Unlike most of thesematrices, MAP does not require multiple applications. Tempo has already completed the necessary studies tosupport clinical trial application to FDA with safety and performance data and has completed initial scale-up ofproduct manufacturing.In the proposed Direct-to-Phase II work, we will pursue the development of MAP Wound Matrix and conduct amulticenter, randomized pilot clinical study to evaluate its efficacy and safety to treat complex wounds in diabeticpatients. Successful completion of this study will bring clinical evidence of the performance of MAP Wound Matrixas well as crucial information to set the next larger clinical study in order to drive adoption in wound care industry.

Public Health Relevance Statement:
NARRATIVE In this proposed direct-to-phase II work, Tempo Therapeutics, Inc. will continue the development of our MAP biomaterial technology and conduct a pilot clinical study to evaluate the efficacy and safety of the MAP Wound Matrix in treating complex non-healing wounds with exposed bone in diabetic patients after limb preservation surgery - a high risk patient population with no regenerative therapy available. MAP Wound Matrix has unique characteristics that enable it to completely fill a wound site, integrate rapidly with surrounding tissue, and promote fast tissue regrowth - as demonstrated in multiple clinically relevant animal models and 27 case studies of complex wounds in veterinary medicine.

Project Terms:
Adoption ; Ambulatory Care ; Outpatient Care ; outpatient treatment ; Amputation ; Bandage ; Biocompatible Materials ; Biomaterials ; biological material ; Biodegradation ; Biological Factors ; Biologic Factor ; Biology ; Biomechanics ; biomechanical ; Biomedical Engineering ; bio-engineered ; bio-engineers ; bioengineering ; Blood Vessels ; vascular ; bone ; Breast ; Malignant Neoplasms ; Cancers ; Malignant Tumor ; malignancy ; neoplasm/cancer ; capsule ; Capsules ; Cartilage ; Cartilaginous Tissue ; Cells ; Cell Body ; Centers for Disease Control and Prevention (U.S.) ; CDC ; Centers for Disease Control ; Centers for Disease Control and Prevention ; United States Centers for Disease Control ; United States Centers for Disease Control and Prevention ; Clinical Research ; Clinical Study ; Clinical Trials ; Colon ; Cessation of life ; Death ; Dermis ; Corium ; Cutis ; Diabetes Mellitus ; diabetes ; Canis familiaris ; Canine Species ; Dogs ; Dogs Mammals ; canine ; domestic dog ; Edema ; Dropsy ; Hydrops ; Engineering ; Extracellular Matrix ; Cell-Extracellular Matrix ; ECM ; Limb structure ; Extremities ; Limbs ; Non-Trunk ; Fascia ; Foundations ; Gold ; Granulation Tissue ; Cyclic GMP ; Guanosine Cyclic Monophosphate ; cGMP ; Hemorrhage ; Bleeding ; blood loss ; Immunity ; Incidence ; Industry ; Infection ; Kinetics ; Lower Extremity ; Lower Limb ; Membrum inferius ; Light ; Photoradiation ; mortality ; Persons ; Osteomyelitis ; Bone Infection ; Pain ; Painful ; Patients ; Physicians ; Podiatry ; Chiropody ; Porifera ; Sponges ; pressure ; Prostate ; Prostate Gland ; Prostatic Gland ; Publishing ; Safety ; stem cells ; Progenitor Cells ; Swelling ; Family suidae ; Pigs ; Suidae ; Swine ; porcine ; suid ; Technology ; Tendon structure ; Tendons ; Time ; Tissue Preservation ; Tissues ; Body Tissues ; Vascularization ; Veterinary Medicine ; Work ; wound healing ; Wound Repair ; wound resolution ; Measures ; Porosity ; Foot Ulcer ; Case Study ; case report ; Mediating ; Journals ; Magazine ; base ; crosslink ; cross-link ; improved ; Procedures ; Site ; Area ; Surface ; Chronic ; Clinical ; Phase ; Biological ; Chemicals ; Epithelial ; diabetic ; Therapeutic ; Exposure to ; Shapes ; Contracting Opportunities ; Contracts ; tool ; scaffolding ; scaffold ; Diabetes Complications ; Diabetes-Related Complications ; Diabetic Complications ; Complications of Diabetes Mellitus ; programs ; mechanical ; Mechanics ; Investigation ; Immunes ; Immune ; Complex ; In Situ ; Operative Procedures ; Surgical ; Surgical Interventions ; Surgical Procedure ; surgery ; Operative Surgical Procedures ; Surgeon ; American ; computer imaging ; digital imaging ; particle ; Performance ; success ; Animal Models and Related Studies ; model of animal ; model organism ; Animal Model ; Immunomodulation ; immune modulation ; immune regulation ; immunologic reactivity control ; immunomodulatory ; immunoregulatory ; immunoregulation ; Devices ; Reporting ; Bone Surface ; Property ; response ; Adverse Experience ; Adverse event ; Skin Substitutes ; Skin ; Inflammatory Response ; Patient Compliance ; patient adherence ; patient cooperation ; therapy compliance ; therapy cooperation ; treatment compliance ; compliance behavior ; CSPG4 ; MCSPG ; MEL-CSPG ; MSK16 ; NG2 ; CSPG4 gene ; diabetic foot wound ; Diabetic Foot Ulcer ; Data ; Direct Costs ; Preclinical Models ; Pre-Clinical Model ; randomisation ; randomization ; randomly assigned ; Randomized ; Clinical Data ; Characteristics ; Development ; developmental ; Pathway interactions ; pathway ; synthetic tissue scaffolding ; cost ; healing ; design ; designing ; efficacy evaluation ; efficacy analysis ; efficacy assessment ; efficacy examination ; evaluate efficacy ; examine efficacy ; manufacturing process ; scale up ; wound ; tissue wound ; wounding ; wounds ; Population ; clinically relevant ; clinical relevance ; regenerative therapy ; regeneration based therapy ; regeneration therapy ; regenerative therapeutics ; high risk ; patient population ; diabetic patient ; regenerative ; preclinical safety ; pre-clinical safety ; safety testing ; efficacy testing ; Geometry ; treatment group ; Growth Factor ; Growth Agents ; Growth Substances ; Proteins Growth Factors ; wound closure ; non-healing wounds ; nonhealing wounds ; persistent wounds ; recruit ; readmission rates ; hospital re-admission rates ; hospital readmission rate ; re-admission rates ; re-hospitalization rate ; rehospitalization rate ; preservation ; first-in-human ; first in man ; secondary endpoint ; secondary end point ; automated image analysis ; wound care ; wound assessment ; wound monitoring ; clinical center ; wound treatment ; treat wound ; wound management ; wound therapeutics ; wound therapy ; necrotic tissue ; tissue necrosis ;