Navigen announced the U.S. Food and Drug Administration (FDA) has cleared its Investigational New Drug application (IND) for the initiation of a Phase I study in healthy volunteers to test the safety, tolerability, and pharmacokinetics of its D-Peptide HIV entry inhibitor, CPT31.

In order to enter human cells and replicate, HIV must fuse its membrane with that of a host cell. CPT31 prevents membrane fusion and thus blocks HIV from infecting cells. Results from non-human primate studies conducted by Dr. Malcolm Martin’s group at the National Institute of Allergy and Infectious Diseases (NIAID), demonstrated that CPT31 may be effective for both HIV prevention and treatment. CPT31 fully prevented infection in animals exposed to a high level of virus. Additionally, when infected animals’ viral loads were first suppressed by combination of currently available antiretroviral drugs, switching to treatment with CPT31 alone maintained viral suppression for the 12 weeks of CPT31 monotherapy.

"In pre-clinical testing, CPT31 demonstrated a strong barrier to resistance resulting from an exceptionally high binding affinity to a highly conserved region of HIV," Dr. Michael Kay, professor of biochemistry at the University of Utah and an inventor of CPT31 said. "Additionally, it is active in vitro against all major clades of HIV, suggesting that CPT31 may be a good option for many HIV patients."

"Strong evidence suggests that CPT31 may be a highly effective treatment and preventative to HIV. We are looking forward to establishing CPT31’s safety and efficacy in humans," Dr. Brett Welch, Navigen’s senior director of technology and strategy, also an inventor of CPT31, said.

Navigen plans to formulate CPT31 as a long-acting injectable. Recent surveys of HIV patients and clinicians reveal there is a strong preference among both groups for long-acting formulations, including injections, over daily oral dosing. For maximum safety in early clinical studies, CPT31 is currently formulated for short-acting dosing (every third day).

"We are gratified by CPT31’s IND clearance and are looking forward to advancing a potential new HIV drug that may be an important addition to the HIV treatment and prevention landscape. We are grateful to our collaborators at the University of Utah, our scientific advisors, and to NIAID and the National Institutes of Health (NIH) for their financial and in-kind support of CPT31. Establishing safety and efficacy of this drug will have the added benefit of validating our discovery platform and the outstanding potential of D-peptide therapeutics to enhance human health," Brandi Simpson, Navigen’s CEO said. "We believe there is an excellent opportunity for D-peptides to become an important new class of therapy. Navigen plans to discover and develop multiple D-peptide therapies and is currently advancing three pre-clinical programs. One of these programs targets SIRPα for potential cancer immunotherapy and two others, an anti-TNFα and an anti-Complement 5a (C5a), will be developed as possible treatments for inflammatory and fibrotic conditions."

CPT31 binds to a highly conserved binding pocket on HIV’s membrane fusion machinery (the gp41 protein). CPT31 is the result of research initiated at MIT in the late 90s by PhD candidate Debra Eckert and post-doctoral fellow Dr. Michael Kay in Dr. Peter Kim’s laboratory. Drs. Kay and Eckert went on from MIT to the University of Utah where they continued to advance the technology. In 2011, Navigen began collaborating with the University of Utah and Drs. Kay and Eckert, and together they optimized CPT31. Navigen has an exclusive license on the technology from the University of Utah.

Navigen has built a world-class D-peptide discovery platform. It is leveraging the unique characteristics of D-peptides to develop what it believes will be novel and potentially best-in-class therapies. In addition to CPT31, Navigen has a pipeline of discovery programs targeting inflammatory conditions and cancer.

D-peptides have characteristics that may make them ideal drugs for many diseases and disorders. In general, natural, or L-, peptides should be very good drugs for many diseases except they have a fatal flaw: the human body recognizes them and quickly breaks them down. The human body does not however, recognize D-peptides and thus they have a much longer circulating half-life compared to L-peptides. D-peptides combine the benefits of the shorter discovery and optimization timelines associated with biologics with the production advantages of small molecules. Navigen has established the potential safety of D-peptides in multiple animal species, including non-human primates.

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