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Chimerix's Lead Antiviral CMX001 Administered in Combination with Recombinant Human Interleukin-7 in a Patient with PML

   

— Emergency IND Case Study of Broad-Spectrum Antiviral CMX001 and Cytheris’ CYT107 Published in Journal of Antimicrobial Chemotherapy —

RESEARCH TRIANGLE PARK, NC, DECEMBER 1, 2010 - Chimerix, Inc., a pharmaceutical company developing orally-available antiviral therapeutics, today reported the publication of a case study of its broad-spectrum antiviral drug CMX001, which was administered under EIND in an investigational combination therapy with CYT107, a recombinant human interleukin-7, for the treatment of progressive multifocal leukoencephalopathy (PML), a life-threatening neurological disease caused by the human polyomavirus JC (JCV).

The investigational therapy was conducted under an Emergency IND when a patient diagnosed with PML caused by JCV continued to decline after four weeks of treatment with risperidone, iv cidofovir and mefloquine, a [standardly-used] combination of drugs with activity against JCV. Within one week of oral CMX001 treatment, neurological function had stabilized and viral loads were markedly reduced. Following viral load reduction, the patient received investigational agent CYT107 (interleukin-7) to increase her CD4+ cell counts. Clinical investigators reported that the patient has not experienced further decline since the administration of these investigational drugs.

“CMX001 currently is in Phase 2 clinical trials in immunocompromised transplant and cancer patients for the treatment of cytomegalovirus and adenovirus, but the demand to provide it under an emergency basis continues to grow. This patient case study in PML, along with many others, shows great promise for CMX001 as a much-needed treatment for critical infections caused by double-stranded DNA viruses,” said George Painter, Ph.D., Chairman and Chief Scientific Officer of Chimerix. “To date, CMX001 has been used to treat patients with 12 different dsDNA viral infections including JCV, cytomegalovirus, adenovirus and vaccinia, among others. Positive clinical outcomes from uncontrolled EIND studies underscore the importance of our drug development efforts.”

About the Emergency IND Case Study

“A case of progressive multifocal leukoencephalopathy and idiopathic CD41 lymphocytopenia,” was published in the December 2010 issue of the Journal of Antimicrobial Chemotherapy (Patel A, et. al., 2010, Vol. 65: 297-98). A research team under the direction of Julie Y. Patel, MD, Assistant Professor, Clinical Science and Translational Research Institute, Texas A&M Health Science Center College of Medicine, presented the case of a 69-year-old female patient with progressive multifocal leukoencephalopathy (PML), caused by human polyomavirus JC. She was found to have a CD4+ count of 87 cells/mm3 and was subsequently diagnosed with idiopathic CD4+ lymphocytopenia (ICL).

Because the available options for the treatment of PML are limited, it was decided to provide a combination of agents shown to be active against JC virus. The patient was started on cidofovir, risperidone and mefloquine. After two weeks of cidofovir treatment, the patient’s neurological function continued to decline as noted by increasing weakness in her left hand and difficulty swallowing and speaking. Repeat MRI testing showed a new area of dysfunction in the right portion of the brain that correlated with weakness in the left hand and persistent presence of demyelination in multiple areas of the brain.

CMX001 was then initiated and one week later, the serum viral load had significantly decreased.

The patient also received an investigational interleukin-7 (CYT107) to increase her CD4+ cell counts. Initiation of this therapy was delayed until viral loads decreased, in order to avoid immune reconstitution syndrome. By day seven of CMX001 treatment, neurological function had stabilized and the patient has not experienced further decline.

Recombinant human interleukin-7 (CYT107) is being developed by Cytheris for its potential as an immune-modulator for immune T-cell recovery and enhancement. Endogenously produced IL-7 has a critical and, at some steps, a non-redundant stimulating effect on T lymphocyte development, notably on thymopoiesis and, downstream from the thymus, on homeostatic expansion of peripheral T-cells.

This is the first case report to demonstrate the use of multiple agents, including investigational medications, as a possible therapeutic strategy in the treatment of PML with ICL. Dr. Patel notes that the patient’s clinical symptoms are slowly improving and the marked reduction in viral load over the course of the investigational therapy is promising, but long-term evaluation will be necessary. In addition, further controlled studies are important to determine whether these approaches are effective against the two rare and debilitating diseases.

A copy of the publication is available on the Chimerix website, www.chimerix.com.

About JC Virus and Progressive Multifocal Leukoencephalopathy (PML)

A double-stranded DNA virus, JCV infects about two-thirds of the world’s population without producing clinically obvious signs or symptoms, but can be life-threatening in patients who are immunosuppressed, either associated with transplantation and immunosuppressive drugs or due to infections such as HIV.

Progressive multifocal leukoencephalopathy (PML) is a rare and usually fatal neurological disease caused by the polyomavirus JC. First identified in 1971, the virus multiplies in and destroys oligodendrocytes, which are cells of the brain that produce the myelin sheath surrounding neurons. Symptoms include loss of vision, impaired speech, paralysis, cognitive decline and weakness. The disease occurs in immunocompromised patients such as organ transplant patients; people undergoing chronic corticosteroid or immunosuppressive therapy; and individuals with cancer, such as Hodgkin’s disease, lymphoma, and sarcoidosis. PML is most common among individuals with acquired immune deficiency syndrome (AIDS). There is no known cure for PML.

About Chimerix and CMX001

Chimerix is developing novel antiviral therapeutics with the potential to transform patient care in multiple settings, including transplant, oncology, acute care and global health.

The company’s lead candidate, CMX001, is in Phase 2 clinical studies in immunocompromised transplant and cancer patients for the treatment of life-threatening viruses, including cytomegalovirus and adenovirus. Over 300 people have received CMX001 to date. CMX001 has been well tolerated in all studies, with a growing body of evidence of the compound’s antiviral activity in humans. In Chimerix’s ongoing placebo-controlled studies, CMX001 has been administered to more than 200 patients and healthy volunteers. In addition, at the request of leading physicians at over 45 medical centers throughout the United States, Canada, Europe and Israel, CMX001 has been administered to more than 120 patients under investigator-held Emergency Investigational New Drug applications (EINDs) for the treatment of a wide range of infections caused by dsDNA viruses for which there are either no approved treatments or where patients have failed the available treatment. To date, CMX001 has been used to treat patients with 12 different dsDNA viral infections across all five families of dsDNA viruses that affect humans. CMX001 is also being developed as a medical countermeasure in the event of a smallpox release. Chimerix has received significant funding from the National Institutes of Allergy and Infectious Disease to develop CMX001 for smallpox.

Chimerix’s second clinical-stage antiviral compound, CMX157, has completed Phase 1 clinical studies. CMX157 is in development as a potent nucleoside analogue against multi-drug resistant HIV infections.

Led by a world-class antiviral drug development team, Chimerix is also leveraging the company’s extensive chemical library to pursue new treatments for hepatitis C virus, malaria and other global public health needs.