Transforming Critical Care Medicine
ADS Biotechnology, Ltd. (ADS) is a pre-IND biomedical company founded to pursue the commercial development of a novel, blood volume expander created by scientists at the University of Toledo’s College of Medicine. These scientists developed an original technology to create ADS4203, a patent-protected Pegylated Albumin biologic that promises to become the optimal blood volume expander for the treatment of any condition that triggers capillary leak syndrome (CLS) with an initial targeted indication of acute respiratory distress syndrome (ARDS).
Problem Definition & Market Opportunity
CLS, a serious medical condition that has been defined and discussed in the medical literature for decades, is a counter-adaptive response of the body that can occur as a result of any severe injury or insult. When triggered, CLS compromises the integrity of capillary vessel walls. As a result, there is a markedly increased permeability (i.e. propensity to leak) within the damaged vessel walls, followed by recurrent episodes of hypotension (i.e. low blood pressure). These episodes are characterized by the sudden transient shifting of 10% – 70% of the body’s blood proteins and plasma water from the damaged, leaking capillary vessels into surrounding tissues. The body’s subsequent response is persistent, dangerously low blood pressure, interstitial edema (i.e. swelling of the surrounding tissues), hypo-perfusion and edema of vital body organs, and a significant decrease in oxygen delivery to vital organs of the body. When left untreated, CLS develops into a deleterious iterative cascade of recurrent episodes of hypotension that can lead to multi-organ dysfunction and failure and, in many cases, death.
Medical and traumatic conditions that trigger CLS include, but are not limited to the following: Acute respiratory distress syndrome (ARDS), poly-trauma (with our without hemorrhagic shock), traumatic brain injury (TBI), pancreatitis, burns, complex surgical procedures (e.g. open-heart surgery and large organ transplants), and severe sepsis. In the U.S., the combined incidence of these medical and trauma conditions is estimated at greater than 2.6 million cases per year. In the U.S. military, CLS is a leading cause of morbidity and mortality among soldiers injured in battle and/or infected with microbiological pathogens[1], [2].
Current conventional treatment for CLS is the intravenous administration of a blood volume expander. This treatment is largely empirical and generally ineffective. There is presently no commercial blood volume expander available that can safely and effectively treat CLS[3], creating a clear unmet clinical need.
ADS Biotechnology Ltd. has a drug development plan that targets ARDS as the first indication for ADS4203. ARDS is a life threatening manifestation of acute lung injury with mortality rates 40-60%5. It is characterized by the acute onset of diffuse, bilateral pulmonary infiltrates secondary to non-cardiogenic pulmonary edema, refractory hypoxia, and decreased lung compliance. Acute respiratory distress syndrome occurs most frequently in the setting of sepsis, aspiration of gastric contents, trauma, or multiple transfusions. No specific therapy for ARDS exists. Treatment is primarily supportive using a mechanical respirator and supplemental oxygen. Intravenous fluids are given to maintain blood pressure. While these supportive measures may provide short-term benefit, they can also lead to serious problems including fluid overload especially in the lungs (i.e. pulmonary edema) and oxygen toxicity. According to the NHLBI, 150,000 Americans will be diagnosed each year with ARDS.
Value Proposition
ARDS is one of a number of diseases with high mortality rates and limited therapy options due to CLS. ADS4203 has the potential to become the definitive, first-in-class treatment for hypovolemic conditions. The estimated accessible market is $2.7 billion domestically. It is the goal of ADS to position ADS4203 as the primary treatment choice of physicians by providing the only safe and effective treatment for patients with CLS including ARDS. In addition, ADS4203 has the potential to lower non-reimbursable acute care and hospital aftercare costs by reducing hospital stays and edema related complications commonly associated with hypovolemic conditions and associated CLS and ARDS by optimizing a patient’s clinical and functional outcomes.
Product & Technology
ADS4203 is created through the chemical bonding of human serum albumin (the most abundant protein in human blood plasma) and polyethylene glycol (PEG)—an inert, polyether compound with many applications from industrial manufacturing to medicine. In the presence of CLS, ADS4203 will not leak through compromised capillary walls to the extent of currently available products. Upon intravenous administration, ADS4203 works immediately to re-establish total blood volume, systemic blood flow and arterial blood pressure. It (1) reduces further edema, leakage of blood proteins and plasma water into surrounding tissue, and (2) reverses CLS, thereby giving the body the critical time it needs to heal its damaged capillary vessel walls and to recover from the underlying insult or injury.
ADS4203 is protected by three issued U.S. patents centered on the treatment of hypovolemic conditions and the necessary composition to maintain critical protein function, three pending U.S. utility patent applications, one Patent Cooperation Treaty (PCT) application for international patent processing and three international patents. The development of commercial clinical applications for the ADS4203 product and derivative products will be recipient of ongoing development by the Company.
[1] Petty, T.L. “Initial observations that led to the definition of ARDS”. Proc Am Thorac Soc. 2008;5(3):290.
[2] Bone, R.C. et al. “Sepsis Syndrome: a valid clinical entity. Methylprednisolone severe sepsis study group”. Crit Care Med. 1989;17(5):389-393.
[3] Mortelli, M,P et al. “Acute Respiratory Distress Syndrome”, Am Fam Physician. 2002:65(9):1823-1831