Creative Bio-Peptides, Inc has been funded as part of the NIH’s HEAL Initiative on building technologies to stop the opioid crisis for our program to develop our novel chemokine receptor antagonist R103 to block opioid reinforcement, relapse, and physical dependence (BioSpace, Oct 22, 2020). Creative Bio-Peptides, Inc. is committed to providing effective and safe non-opioid treatments for the 50 million Americans suffering daily pain and the 2 million who live with opioid dependency or addiction. Current decades-old addiction treatments like methadone or naloxone are not up to the magnitude of this problem, and themselves have abuse liability concerns. Chemokines (hormones of the immune system that mediate innate immune inflammation) enhance pain, reduce opioid analgesia, and promote drug-seeking behavior and addiction – giving them a central role at the crossroads of chronic pain and the opioid crisis. Blocking chemokines (rather than opioid receptors) provides an exciting and untested treatment opportunity for opioid-sparing treatment of chronic pain and opioid use disorders (OUD). Our lead chemokine CCR2/CCR5 antagonist (blocker) peptide R103 (aka RAP-103) stops neuropathic pain and enhances the potency of morphine to relieve acute pain. Recent studies conducted by scientists at Temple University suggests that R103 could also become an effective treatment for OUD as blocking CCR5 lowers the rewarding, locomotor and reinforcing effects of drugs of abuse, with a better safety profile compared to current approved chemokine antagonists that cause liver toxicity or must be injected. We have been funded to assess, in animal self-administration models that mimic human drug-taking, whether R103 reduces morphine intake. Physical dependence develops during chronic opioid exposure and upon discontinuation of opioid intake, presents as a withdrawal syndrome that triggers opioid relapse. We will further assess if R103 will prevent or blunt naloxone-precipitated withdrawal signs in morphine-dependent rats. We will also evaluate the safety of R103 by determining a maximum tolerated dose. Successful execution of this program will help establish a regulatory approval plan for subsequent human efficacy studies in OUD’s.
RAP-103 is the new oral analog of Peptide T ( Dala1-peptide T-amide, aka”DAPTA”) which was discovered as an anti-viral for HIV and developed by the NIH as a treatment for cognitive impairments in Neuro-AIDS. Peptide T also was featured in the 2013 movie Dallas Buyers Club. These peptides were the first CCR2/CCR5 receptor antagonsists, identified a decade before chemokine receptors had been identified and CCR5 or CCR2 were discovered as HIV entry receptors. Now CCR2/CCR5 antagonists are of broad therapeutic interest in stroke, brain injury, dementia, chronic pain and preventing cancer metastases. Our peptides target specific chemokine receptors that cause the neuro-degeneration after ischemic stroke, in loss of neurons in aging, traumatic brain injuries, and chronic pain, such as occurs in diabetes. Oral R103 overcomes the formulation limitations (nasal spray, lost potency with storage) that stopped development of Peptide T/DAPTA as its successor analog R103 may be administered as a pill. After a long search for this solution, we are excited to bring R103 into an IND-enabling program that builds on the clinical successes of Peptide T/DAPTA.
CREATIVE BIO-PEPTIDES COLLABORATES WITH LEIDOS ON CHEMICAL NERVE AGENT THERAPEUTIC
Creative Bio-Peptides, Inc. (CBP) today announced a collaboration with Leidos to develop CBP’s third-generation oral peptide CCR2/CCR5 chemokine receptor antagonist, R103, as a chemical nerve agent therapeutic. This development is being completed under a study contract awarded to Leidos, by the Defense Threat Reduction Agency (DTRA), an agency within the US Department of Defense. CBP will work with Leidos and other organizations to secure the required analytical methods, GMP peptide manufacture, IND-enabling studies (non-GLP and GLP) and Phase I clinical trials to support the use of R103 as a medical countermeasure for chemical weapons exposure.
CCR5, an important receptor of the rapid response innate immune system, promotes seizure activity which may occur after nerve agent exposure damages the brain. Reducing CCR5 responses could mitigate the epileptic, neurodegenerative, and cognitive effects of exposure.
“We are pleased to collaborate with Leidos and have access to their chemical and nerve agent proficiency to develop our oral chemokine antagonist peptide R103,” said Dr. Michael Ruff, CBP president. “Together, we look forward to delivering an effective neuro-protective treatment.”
CCR5 has recently been identified as a therapeutic target in traumatic brain injury and stroke recovery. Persistent CCR5 activation plays a central role in neurodegeneration and loss of synapses in Alzheimer’s and Parkinson’s Diseases, as well as memory loss in Neuro-AIDS. R103 is a potential treatment for the persistent neuroinflammation that results in neurodegeneration and cognitive deficits.
“Leidos looks forward to working with Creative Bio Peptides on this novel approach for mitigating the long-term neurological sequelae in survivors of acute nerve agent intoxication,” said Kenneth Tucker, principal life scientist with Leidos. “We believe this development may have benefits for other types of brain injury as well.”
CBP was started in late 2017 with the mission of bringing to market innovative, first-in-class oral neuro-protective peptides for therapeutic use in multiple conditions characterized by neuroinflammation and neurodegeneration. CBP’s current developmental focus is in chronic pain conditions, such as diabetic neuropathy.