Anti-Overdose Antibodies
Medical Need
Our current efforts in the area of anti-overdose immunotherapeutics focus on fentanyl. One of the main reasons for the rapid escalation in opioid-involved deaths is the widespread availability of illicit fentanyl. A synthetic opioid with a potency 100 times that of morphine, fentanyl is prescribed medically to manage the extreme pain of cancer patients, patients in hospice, and surgical procedures. Today, fentanyl is often found spiked into other drugs to mask their impurity. 2-3 mg of fentanyl, equivalent to several grains of salt, delivers a lethal dose to an average-sized adult. In 2007, fentanyl involvement accounted for approximately 11% of overdose fatalities. In 2017, fentanyl involvement accounted for approximately 67% of all fatalities.
Fentanyl acts by binding the μ-opioid receptors (MOR) with higher affinity than prescription opioids or heroin, causing sedation, vomiting, and severe respiratory depression at high doses. Because of this high affinity, treatment of fentanyl overdose with competitive opioid receptor antagonists, such as naloxone (i.e. NARCAN®) is often ineffective. Multiple doses of naloxone are needed (due to the long half-life of fentanyl), and often not delivered in time. Patients overdosing on fentanyl often present with Wooden Chest Syndrome (WCS), where the drug causes the muscles of the chest walls and abdomen to become rigid, rendering chest compressions from CPR useless. Current prophylactic approaches to combat overdose have poor compliance.
“Fentanyl deaths are up. We have a heroin and synthetic opioid epidemic that is out of control and needs to be addressed.” -Dr. Dan Ciccarone, UCSF
“The idea that a developed wealthy nation like ours has declining life expectancy just doesn’t seem right." -Robert Anderson, CDC
Fent-VAST for anti-Overdose Immunotherapy
Our goal is to produce monoclonal antibodies protecting from fentanyl overdose.
Hepione uses a novel, proprietary technology (VAST) to create immune responses against opioids and other drugs of abuse. Fent-VAST elicits potent antibodies that target fentanyl.
Initial preclinical data with Fent-VAST has achieved: (1) high titres and memory, (2) consistency in immune responses across individuals, (3) trapping of drugs in the blood and blocking transit to the brain, and (4) complete protection of individuals to near lethal challenge with fentanyl with monoclonal antibody therapy.
Hepione was awarded a SBIR Phase I grant from the NIH to continue development of immuno-therapy to prevent fentanyl overdose toward clinical trials.
Commercial Potential
We plan to make treatments available to all Americans struggling with addiction, the primary aim not to curb addiction but rather to block overdose. According to the National Survey on Drug Use and Health, about 7.5 million people battled addiction to illicit substances in 2017. Antibodies from Fent-VAST would be delivered to patients at rehabilitation programs, methadone clinics, needle exchanges, ambulatory clinics, and pharmacies; as well as to first responders who might be accidentally exposed.
We intend to carry our product through clinical trials and FDA approval, and seek its coverage by Medicare, Medicaid, and all other major insurance carriers. By comparison, the pneumococcus vaccine Prevnar® costs $230 and must be delivered every 5 years to maintain immunity. Using these numbers, we estimate $345 million annual market for this vaccine in the U.S. alone. The overall commercial market for therapeutic antibodies and vaccines is predicted to reach $200 billion by 2024.
Beyond Fentanyl
The VAST platform can be used to quickly generate antibodies that are responsive to changes in the epidemiology of drug overdose. Hepione Therapeutics, Inc. holds the exclusive intellectual property rights to the application of the patented VAST technology to develop immunotherapies against opioids and other drugs of addiction. Currently, fentanyl is the main adulterant but as this evolves, VAST can be quickly adapted to front other public health priorities (such as responsive to the rise of deaths from opioids adulterated with carfentanil or “gray death,” or to tramadol, the abuse of which is reaching epidemic proportions in parts of Africa and Asia).
Finally, the ability to generate monoclonal antibodies to drugs of addiction opens the doors to creating products for the research, diagnostic, as well as therapeutic sectors.
