Science Translational Medicine Publication: Innovative Molecules´ Drug Candidate Affects Recurrent Herpes Simplex Virus Infections

— IM-250 reduces viral load, viral shedding and recurrence rate

— Potential treatment for persistent, neurotrophic herpes simplex

Innovative Molecules GmbH, a drug development company focused on developing next-generation treatments for Herpes simplex-induced diseases, today announced preclinical data demonstrating that the Company’s drug candidate IM-250 affects acute as well as chronic neural Herpes simplex virus (HSV) infections in mice and guinea pigs. IM-250 is a proprietary, novel helicase-primase inhibitor.

The study entitled “A helicase-primase drug candidate with sufficient target tissue exposure affects latent neural herpes simplex virus infections” was conducted by a team of researchers from the U.S. and Germany and was published today in Science Translational Medicine.

In various animal models of HSV, IM-250 demonstrated potent anti-herpes activity, a novel mechanism of action, a low frequency of HSV resistance, and a favorable pharmacokinetic and safety profile. IM-250 is devoid of off-target activity observed with other anti-HSV drugs and of potential metabolites of previous drug candidates targeting helicase-primase. It leads to improved target tissue exposure in particular in neurons and exhibits superior efficacy in preventing and treating HSV infection and disease in animal models as compared to standard of care. Of note, the compound not only reduces the duration of symptoms and time to healing, but also reduces the frequency of recurrences and viral shedding.

“IM-250 has distinct advantages over standard-of-care therapies and represents a promising therapeutic for chronic HSV infection, including nucleoside-resistant Herpes simplex,” said Prof. Dr. Gerald Kleymann, CEO and founder of Innovative Molecules, and senior author of the study. “The most outstanding observation is its ability to attenuate recurrent infections and based on our preliminary results there is hope that it could make infections of neurotrophic herpes simplex viruses treatable – even when they have established life-long latency after primary infection. To our knowledge, this has never been observed with any anti-HSV compound before.“

In the study, intermittent monotherapy with IM-250 or combination therapy with IM-250 and Valacyclovir (VAVC) standard of care resulted in a statistically significant reduction in both cumulative recurrent disease score versus placebo and in HSV-2 shedding in the off-treatment period. The reduction in the frequency of viral shedding was accompanied by a reduction in the cumulative mean viral load. All in all, the study observed a statistically significant increase in disease-free animals compared to placebo both on and off therapy from the first treatment cycle.

“IM-250 bears the potential to overcome significant limitations of current HSV therapies regarding resistance, recurrent viral shedding and disease, and severe CNS or disseminated disease,” said infectious disease specialist David I. Bernstein from the Cincinnati Children’s Hospital Medical Center (Cincinnati, OH), and co-author of the study. “Our results also challenge the traditional belief that herpes simplex disease is not effectively treatable. While we do not yet understand how the drug affects latency or reactivation after cessation of treatment, we hypothesize that the application of the drug during an infection leads to a reduction or inactivation of latent DNA in neurons or to a reduction in the number of latently infected neurons.”


About Herpes simplex infection and disease

Herpes simplex disease is a contagious, lifelong infection with high incidence and prevalence data, a quiet pandemic with a huge health burden and a risk factor for acquiring HIV, HPV and Alzheimer’s disease. At least 50 % of the population is infected with Herpes simplex virus type 1 (HSV-1), mostly herpes labialis, whereas approx. 25% of the population is infected with Herpes simplex virus type 2 (HSV-2), mostly genital herpes, a sexually transmitted infection/disease. Latency is established for life by deposit of episomal HSV DNA in sensory neurons. Upon diverse stimuli, HSV reactivates from the latent reservoir causing recurrent herpes disease. Up to 30% of patients suffer from frequent recurrences which could be painful, socially isolating and even life-threatening in immuno-compromised patients. There is currently no treatment available that is able to reduce or eradicate the virus reservoir as such.

About Innovative Molecules

Innovative Molecules GmbH is a drug development company aiming for setting a new treatment standard for Herpes simplex induced diseases. The company is focusing on the development of IM-250, a potent, second-generation helicase-primase inhibitor of HSV-1 and HSV-2. Due to its potency, excellent neuronal tissue exposure and long half-life, IM-250 has the potential to change the way Herpes simplex induced diseases are treated. Preclinical data indicates that IM-250 does not only block active viral replication but might be able to reduce or even eradicate the viral reservoir, ultimately leading to less recurrences or even to a cure from this latent, life-long infection.

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