Therapeutic Areas

Problem to be solved:

Inability to regenerate tissue (bone, skin, collagen, hair) after SEVERE injury, disease, aging – Inhibitors to regrowing tissue – severity of injury, age, obesity, diabetes, smoker

Solution:

Provide the body the natural tissue regrowth enhancer of growth factors locally at the site with the ability to reside in the tissue for days and weeks constantly bathing the area with regenerative factors to promote enhanced and accelerated tissue growth.

Published evidence suggests that PBMs in different forms (paste, putty, liquid, etc.) can be a viable treatment for various medical challenges. Carmell’s revolutionary technology can be applied to address tremendous unmet need across orthopedics, soft tissue healing, burn, dermatology and other aspects of medicine. Below is just the sampling of applications where Carmell’s PBMs are likely to have a lasting impact.

Orthopedics

pbm putty

Bone fracture requiring open reduction surgery

It is estimated that 12.9 million extremity bone fractures occur annually in the U.S., of which 1.3M are open reductions (open reduction refers to the method wherein the fracture fragments are exposed surgically by dissecting the tissues). The most complex and most difficult to treat are open compound fractures (skin is penetrated) due to bacterial contamination and exposure with a prevalence of over 300,000 / year in U.S. In addition, 125,000 of open tibia fractures are treated each year of which 20% (~24,600) will become infected with bacteria, further compromising healing. The data for injuries in the military are much worse, with the majority of blast injuries being grossly contaminated and infected. Bacterial infection has been identified as one of the major contributors to the complications of bone healing. Antibiotics are typically administered systemically to patients with contaminated bone fractures at high doses and for long terms, ideally for at least 4-6 weeks. Growing resistance to antibiotics is an urgent healthcare concern providing significant motivation for the healthcare providers to find treatment solutions that don’t include the use of antibiotics.

From www.Bloodcure.com June 11, 2015 - “The economic costs of musculoskeletal care in the United States is approaching $800 billion or about 5.7% of annual GDP. (Ref: http://www.boneandjointburden.org/) These costs are expected to increase significantly as our population ages. This is clearly not a sustainable path. A recent article published by the American Academy of Orthopedic Surgeons (AAOS) suggests the "early evidence is promising" for biologics to revolutionize musculoskeletal care. (AAOS Article in full) More than three of every five unintentional injuries that occur annually in the United States are to the musculoskeletal system - of the estimated 70 million musculoskeletal injuries in the U.S., bone fractures account for 26%, or 16 million patients annually. Biologic therapies represent a rapidly evolving frontier similar to arthroscopy in the 1970s and 1980s.

“First in the population that we look after now – the aging and sick – we see fractures in people with bad diabetes, renal heart disease and people who frankly would have died before who are now being kept alive. The risk of infection with some of these patients is extremely high with fracture fixation. Yet, they have fractures that require fixation to keep them moving and alive. We are seeing more patients who have infections and who are sicker.” Dr. Michael D. McKee, Chairman of the Department of Orthopeadic Surgery at the University of Arizona College of Medicine

Spine

A product that not only promotes bone fusion but also the repair of soft tissues while reducing infections would have enormous potential in the spine and related markets. Pre-clinical data suggests that Carmell’s first PBM product, Bone Healing Accelerant, can be used with DBM to allow for less DBM usage and produce a stronger bone. Carmell is also testing BHA’s upper limit (defect size) when used alone as a bone void filler.

Dental Bone Repairs

The Global Dental Bone Grafts & Substitutes Market size was estimated at USD 492.68 Million in 2020 and expected to reach USD 532.90 Million in 2021, at a Compound Annual Growth Rate (CAGR) 8.50% to reach USD 803.84 Million by 2026. Research and Markets, Guinness Centre, Taylors Lane, Dublin 8, Ireland. The biggest challenge with dental implants, socket preservation and ridge augmentation, is that it takes too long to regrow bone and the quality of bone is poor, making it difficult to establish a secure post for the implant. This is made more difficult with co-morbidities such as: diabetes, obesity, smoking and age. The time to implant the post can be extended months waiting for the bone to regrow to sufficient density and quality and then there is another multi-month wait for the implant to be properly secured in the bone before the implant can be mounted on the post.

Aesthetics

pbm liquid

The aesthetics market is growing at a rapid rate as the world continues to seek treatments that enhance beauty and reduce the impact of aging on appearance. Three of the fastest growing segments are hair regrowth, facial rejuvenation and skin tightening with wrinkle reduction. The market is being driven by several less invasive procedures and increase in global disposable income. The average age at which patients begin getting aesthetic treatments has gotten lower because people do not wait for the wrinkles to form and are taking pre-emptive measures to maintain their natural youthful appearance for as long as they can. Another market shift that has been observed recently is that the percentage of male clients consulting with dermatologists and aesthetic clinics is increasing. According to International Association for Physicians in Aesthetic Medicine (IAPAM) in 2019, PRP procedures had the largest share in aesthetic procedures compared to the previous year accounting for 58.1% of the total number of treatments. In the same report, PRP was 2nd only to “Defined ABS” procedures.
(Aesthetics Trends IAPAM Article)

Hair Regrowth

Androgenetic Alopecia – Androgenetic alopecia is a common form of hair loss in both men and women. In men, this condition is also known as male-pattern baldness. Hair is lost in a well-defined pattern, beginning above both temples. Over time, the hairline recedes to form a characteristic "M" shape. Hair also thins at the crown (near the top of the head), often progressing to partial or complete baldness. The pattern of hair loss in women differs from male-pattern baldness. In women, the hair becomes thinner all over the head, and the hairline does not recede. Androgenetic alopecia in women rarely leads to total baldness. Androgenetic alopecia is a frequent cause of hair loss in both men and women. This form of hair loss affects an estimated 50 million men and 30 million women in the United States. Androgenetic alopecia can start as early as a person's teens and risk increases with age; more than 50 percent of men over age 50 have some degree of hair loss. In women, hair loss is most likely after menopause.” NIH – U.S. National Library of Medicine – Medline Plus

The global alopecia market was valued at USD 2,536.07 million in 2018 and is expected to reach a value of USD 4,797.29 million in 2026. The market is expected to be collectively driven by technological advancements, rise in disease prevalence, treatment of alopecia, improvement in reimbursement scenario, and increase in per capita driving the market growth healthcare expenditure across the globe. (Grand View Research Report ID: 978-1-68038-733-9 Page 12) Introduction of new products dedicated to patient compliance will increase the market in the forecast. (Grand View Research Report ID: 978-1-68038-733-9 Page 25)

Increasing global prevalence of alopecia
The growing prevalence of alopecia is one of the crucial factors driving the market growth. According to data published by the American Hair Loss Association, it was stated that over 95% of hair loss in men is caused due to androgenetic alopecia. The occurrence of hair loss in men increases proportionately with age. Based on the report published by the International Society of Hair Restoration Surgery, it was estimated that nearly 40% men encounter some degree of hair loss by 35 years of age, 65% at 60 years, 70% at 80 years, and 80% at the age of 85. (Grand View Research Report ID: 978-1-68038-733-9 Page 23)

Market Size, & Forecasts, Revenue and Trend Analysis, 2018 to 2026 | North America

Fig. 23 North America
North America

North America held the largest share of the alopecia market in 2018. According to data published by the American Hair Loss Council, alopecia areata affects approximately 7 million people in the U.S. The data also state that androgenetic alopecia is responsible for more than 95% of hair loss in men. Moreover, rise in prevalence of chronic diseases, such as rheumatoid arthritis, cancer, and Polycystic Ovary Syndrome (PCOS), is resulting in an increase in incidence of alopecia in North America.

Increasing investments in R&D of alopecia treatment, along with developed healthcare facilities, are significantly contributing to the growth of the market in this region. The North American Hair Research Society and the American Hair Loss Association conduct research on the treatment of alopecia by involving scientists from different disciplines. They also periodically conduct meetings and programs to discuss and spread awareness about hair loss and associated treatments.
Source: WHO, U.S. CDC, FDA, Investor Presentations, Primary Interviews, Grand View Research

8.7.1.1 North America market estimates and forecast, 2014-2026 (USD Million)
The North America alopecia market was valued at USD 881.4 million in 2018 and is expected to grow at a CAGR of 7.7% during the forecast period. (Grand View Research Report ID: 978-1-68038-733-9 Page 37 & 38)

Billions of dollars are spent on treatments every year with significant shortcomings, i.e., side-effects from topical and oral applications, and cost for hair transplants. There is growing use of autologous Platelet Rich Plasma injected into the scalp after drawing the patient’s blood and separating the red blood cells on a desktop centrifuge. Dr. Amelia Hausauer conducted a randomized clinical study showing PRP was successful at increasing hair volume and density at six months by 29% each. Carmell’s technology is a combination therapy utilizing microneedling (radio frequency) to create the micro channels in the scalp and then massaging Carmell’s proprietary stickly liquid paste into the scalp where the material will reside for days and weeks, constantly bathing the area with growth factors and other regenerative factors. Utilizing the work by Dr. Hausauer and others that have shown autologous PRP to have some benefit in regrowing hair as a proof of concept, Carmell will conduct randomized clinical trials with its Plasma-based Bioactive Material (PBM) that is off the shelf, ready-to-use with no mix or prep as a substitute for the Autologous PRP. The study is designed to show improvement versus baseline for hair volume and hair density at six months. The company’s hypothesis it seeks to prove in a clinical study is that the PBM technology is safe and effective at regrowing hair at six months greater than 30% increase in volume and density based on the PBM’s guaranteed biologics and ability to reside in the scalp for days and weeks.

Facial Rejuvenation

Like the use of autologous PRP in hair regrowth, PRP is being used in combination with micro needling for facial rejuvenation. After performing micro needling (RF) on the face, the auto PRP is then massaged into the newly created pores. Carmell Therapeutics believes the PBM technology can improve on the auto PRP outcomes by guaranteeing the bioactivity, which is a requirement from FDA on a BLA approved product, and the ability to have the bioactive material reside below the surface of the skin for days, constantly bathing the area in regenerative factors. The proposed mechanism of action is the PBM has known clinically relevant quantity of multiple growth factors that are activated over days to provide the cells that are preprogrammed to grow collagen to enhance proliferation to provide a natural face filler. Face fillers are known to enhance beauty be reducing lines and wrinkles.

Wound Care Overview

Healing difficulties may arise from a variety of causes, such as severity of injury, age and co-morbidities such as obesity, diabetes, smoking, cardiovascular and peripheral vascular disease and other chronic conditions. The underlying etiology for different tissue healing challenges my vary. At a cellular level many of the problems with tissue healing are the same. Some of these problems are uncontrolled inflammatory processes, shortages of growth factors that are critical to healing and are part of the cell signaling pathways.

Carmell Therapeutics’ technology has been designed to deliver growth factors directly to the injured site over days and weeks to enhance and amplify the healing environment with important growth factors and other regenerative factors found in whole platelet-enriched plasma.

Advanced Wound Care Market

Multiple Advanced Wound Care Research reports value the Global Advanced Wound Care market at $9B in 2021, with a CAGR of 3.5% to 4.6% over the next ten years and expected to reach over $14B by 2030.

The Advanced Wound Care market is sub segmented into advanced wound dressings, biologics, negative pressure wound therapy and other treatments. The biologics segment represents about $1.5B of the Advanced Wound Care total market, and is made up of skin substitutes and growth factors. Growth factors may be used in combination with Standard of Care (SOC) or skin substitutes as a healing enhancer and accelerator. Acceleration and enhancing the healing of both acute and chronic wounds is associated with significant health care savings.

Carmell Solution

Carmell’s second product candidate, Tissue Healing Accelerant (THA), is formulated from the same active ingredient (API) as Bone Healing Accelerant (BHA), which is Carmell’s Plasma-based Bioactive Material (PBM). BHA has shown in clinical studies to accelerate soft tissue healing after traumatic injury with less infections (see clinical resources page). THA has been studied in pre-clinical studies and has shown to significantly promote angiogenesis and reduce infections (see publications page, Schwartzmann). Also, in a radiation burn model in rodents, THA substantially provided accelerated and enhanced healing (see publications page, Miller).

The wound healing market is divided into acute and chronic, with the later accounting for most of the expenses due to the complexity and length of treatment.

Chronic Wounds

Chronic wounds are wounds that have not appropriately closed after four weeks of treatment with traditional treatment such as dressings. Chronic wounds include:

  • VLUs: wounds that occur in the leg veins when blood does not circulate properly to the heart.
  • DFUs: open sores or wounds that occur in patients with diabetes and are commonly located on the bottom of the foot.
  • Pressure Ulcers: localized injuries to the skin and/or underlying tissues as a result of pressure or pressure in combination with shear.
  • Surgical Wounds: acute wounds caused by surgical incisions that become chronic wounds if they do not heal properly.

Acute Wounds

An acute wound is an injury that causes a rapid break in the skin and sometimes the underlying tissue. Acute wounds can be traumatic wounds, such as abrasions, lacerations, penetrating injuries and burns, or surgical wounds from surgical incisions.

“Acute wounds can become chronic wounds due to poor underlying health status or poor treatment. Acute wounds are a common health problem, with 11 million people affected1 and approximately 300,000 people hospitalized yearly in the United States.2 Typically, acute wound healing is a well-organized process leading to predictable tissue repair where platelets, keratinocytes, immune surveillance cells, microvascular cells, and fibroblasts play key roles in the restoration of tissue integrity.3,4 The wound repair process can be divided into 4 temporarily and spatially overlapping phases: coagulation, inflammation, formation of granulation tissue (proliferative phase), and remodeling or scar formation phase.”

MECHANISMS OF NORMAL WOUND HEALING

“Normal wound healing processes can be divided into 4 overlapping phases: coagulation (not shown), inflammatory phase (A), proliferative phase/granulation tissue formation (B), and remodeling phase (C). During coagulation and inflammatory phases (A) of the healing, blood-borne cells—neutrophils, macrophages, as well as platelets—play critical roles. These cells provide growth factors and provisional matrices that are necessary for recruitment of epidermal and dermal cells into the wound bed. The proliferative phase (B) starts at approximately 3 days after injury and is characterized by increased levels of keratinocyte and fibroblast proliferation, migration, and ECM synthesis in response to autocrine, paracrine, and juxtacrine growth factors. Angiogenesis/neovascularization also occurs during this phase. Because of the presence of blood vessels, the tissue has a granular appearance (granulation tissue). Finally, at approximately 1 to 2 weeks after injury, differentiated fibroblastic cells (myofibroblasts) that present within the granulation tissue begin to remodel extracellular matrix (C). Extracellular matrix remodeling followed by apoptosis of resident cells leads to the formation of an acellular scar.”

Acute and Impaired Wound Healing: Pathophysiology and Current Methods for Drug Delivery, Part 1: Normal and Chronic Wounds: Biology, Causes, and Approaches to Care
Tatiana N. Demidova-Rice, PhD, Michael R. Hamblin, PhD, and Ira M. Herman, PhD

Adv Skin Wound Care. Author manuscript; available in PMC 2013 Jul 1.
Published in final edited form as: Adv Skin Wound Care. 2012 Jul; 25(7): 304–314.
doi: 10.1097/01.ASW.0000416006.55218.d0