Can an antibody therapy prevent fentanyl overdoses?

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DDW Editor Reece Armstrong speaks to Tracy M Woody, President and Chief Executive Officer of Cessation Therapeutics, about the company’s goal to develop an antibody therapy to prevent fentanyl overdoses.

Cessation Therapeutics is a pharmaceutical company that is developing antibody therapies to prevent and reverse overdosing caused by fentanyl. Recently, the company was awarded an additional grant from the National Institute on Drug Abuse (NIDA) to support the development of its anti- fentanyl mAb, CSX-1004 SQ, for the prevention of fentanyl overdose.

As it stands, there are no FDA-approved products designed to prevent a fentanyl overdose. One available drug, Naloxone (Narcan) is able to reverse an opioid overdose but has limitations in that it must be given reactively, in the form of a nasal spray or as an injection. And despite the drug’s availability, opioid deaths and particularly fentanyl overdoses, remain staggeringly high in the United States, representing a major healthcare crisis in the country.

RA: Naloxone is currently widely available on the market and can reverse an opioid overdose. Yet opioid deaths are high in the US. How important is it that you can ensure CSX-1004 helps as many people as possible?

TW: Narcan (or naloxone) is a very important treatment for fentanyl overdose. However, due to the high potency of fentanyl, Narcan can sometimes be ineffective. Another challenge is that a fentanyl overdose can occur in two to three minutes and a bystander – if one is present – may not have the ability to administer Narcan in time to saves someone’s life. Fentanyl also produces certain life-threatening effects, such as extreme chest wall rigidity and airway closure, that are resistant to naloxone reversal. CSX-1004 is designed to be taken prophylactically in individuals who are at elevated risk for an overdose. CSX-1004 will block all the effects of fentanyl, including the respiratory depressant effects that lead to life-threatening overdose, and the euphoric feeling (or ‘high’) people receive from fentanyl.

RA: Following that, does that happen through better communication with healthcare providers and patients?

TW: Once approved by the FDA, CSX-1004 would be introduced to healthcare providers similar to other drugs. The primary focus would be healthcare providers who treat patients with Opioid Use Disorder (OUD) since this population is at the highest risk for overdose.

RA: Could you discuss the mechanism of action behind CSX-1004?

TW: CSX1004 is a recombinant human IgG monoclonal antibody specific for fentanyl and related synthetic opioids. CSX-1004 works by sequestering fentanyl molecules as they enter the bloodstream effectively neutralising them in the blood before they reach the brain and preventing them from exerting their harmful effects.

RA: Do more steps need to be taken by industry and government to tackle the root causes of opioid addiction?

TW: Cessation believes that addiction is a disease, like diabetes, like Alzheimer’s, like cancer, but often stigmatised by medical professionals. The American Medical Association (AMA) acknowledged that alcohol and drug dependence are diseases, a quarter of a century ago. Yes, we believe that industry, government, and healthcare providers can all help in this area. There are very few treatments available to treat opioid use disorder (OUD) and we do believe the ones that are FDA approved should be made widely available to patients. We also believe that the stigma that surrounds addiction contributes to patients not being screened and not wanting to acknowledge to themselves or a loved one they have a problem. Finally, there are very few investments made by venture capital (VC) firms in addiction treatments. According to BIO (Biotechnology Industry Trade Group) VC firms invested $130 million in novel addiction treatments in the past 10 years compared to nearly $35 billion in oncology. Yet, there are as many Americans living with addiction as living with cancer.

RA: Can CSX-1004 be adapted to help with opioid abuse disorders?

TW: Initially, we are studying CSX-1004 for the prevention of a fentanyl overdose. However, the recent grant received from NIDA will go towards studying the CSX- 1004 subcutaneous in the area of OUD.

RA: Speaking of that grant from NIDA – which will total $14.8 million – how will this help the development of CSX-1004?

TW: The new grant is part of a multi-year award to specifically support the development of a subcutaneous injectable formulation of CSX-1004 (‘’CSX-1004 SQ’). The grant will fund a variety of activities, including the formulation, development, and manufacturing of CSX-1004 SQ and the evaluation of its ability to attenuate the effects of fentanyl in preclinical models of fentanyl self-administration and relapse.

RA: Why does an antibody-based approach work well to counter opioid effects?

TW: Monoclonal antibodies can be designed to have high (picomolar) affinity and specificity for fentanyl and fentanyl analogues, thereby neutralising the effects of these drugs. Because the antibodies bind to a foreign target (in this case fentanyl) and have no endogenous binding site in the body, they tend to be quite safe and well-tolerated with few adverse events. The antibodies stay in the bloodstream and never enter the brain. As such, they have no intrinsic abuse potential. Additionally, the half-life of many monoclonal antibodies is several weeks, thus enabling the potential for once-monthly dosing.

DDW Volume 25 – Issue 1, Winter 2023/2024

Tracy M WoodyBiography

Tracy M Woody, President & Chief Executive Officer, Cessation Therapeutics, has over 25 years of commercial experience in pharmaceuticals, biologics, and medical devices, across a range of therapeutic areas in diverse markets. She has previously served as a board member of Esperion Therapeutics since May 2019, and currently serves as a board member of Shorla Oncology.

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