This is a first-in-human, phase I, open-label, monocenter, single dose-escalation study with 4 cohorts. The total trial duration for each participant will be not more than 98 d from screening to the end of the follow-up.
Twenty-four participants are planned to be enrolled in the trial. Each cohort may be expanded by up to 6 additional volunteers, resulting in a maximum of 48 participants possibly enrolled in the trial.
Ninety-six volunteers may need to be screened to include 48 volunteers.

开始日期2023-04-25

申办/合作机构

Innovative Molecules GmbH

100 项与 IM-250 相关的临床结果

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100 项与 IM-250 相关的转化医学

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100 项与 IM-250 相关的专利（医药）

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项与 IM-250 相关的文献（医药）

2023-11-01·Antiviral Research

Intermittent therapy with helicase-primase inhibitor IM-250 efficiently controls recurrent herpes disease and reduces reactivation of latent HSV

Article

作者: Kleymann, Gerald ; Sawtell, Nancy M ; Bravo, Fernando J ; Gege, Christian ; Bernstein, David I ; Dixon, David A

Herpes is a contagious life-long infection with persistently high incidence and prevalence, causing significant disease worldwide. Current therapies have efficacy against active HSV infections but no impact on the latent viral reservoir in neurons. Thus, despite treatment, disease recurs from latency and the infectious potential remains unaffected within patients. Here, efficacy of the helicase-primase inhibitor (HPI) IM-250 against chronic neuronal HSV infections utilizing two classic herpes in vivo latency/reactivation animal models (intravaginal guinea pig HSV-2 infection model and ocular mouse HSV-1 infection model) is presented. Intermittent therapy of infected animals with 4-7 cycles of IM-250 during latency silences subsequent recurrences analyzed up to 6 months. In contrast to common experience, our studies show that the latent reservoir is indeed accessible to antiviral therapy altering the latent viral reservoir such that reactivation frequency can be reduced significantly by prior IM-250 treatment. We provide evidence that antiviral treatment during HSV latency can reduce future reactivation from the latent reservoir, supporting a conceptual shift in the antiviral field, and reframing what is achievable with respect to therapy of latent neuronal HSV infections.

2022-05-01·Liver International2区 · 医学

Comprehensive clinical and virological characterization of three cases of fulminant liver failure owing to HSV1 primary infection

2区 · 医学

Article

作者: Kleymann, Gerald ; Spahn, Stephan ; Lohrengel, Kristina ; Riessen, Reimer ; Ganzenmueller, Tina ; Hamprecht, Klaus ; Malek, Nisar P. ; Emrich, Marzena H. ; Iftner, Thomas ; Berg, Christoph P.

AbstractHerpes simplex virus 1 (HSV‐1) is a frequently unrecognized, yet deadly cause of acute liver failure (ALF). We, therefore, analysed three cases of fatal HSV‐1‐induced ALF. All patients shared clinical (extremely elevated transaminases, LDH and AST/LDH ratio < 1) and virological characteristics (ratio of viral load in plasma versus throat swabs: 60–700‐fold, lack of anti‐HSV‐1‐IgG antibodies or low IgG‐avidity during primary infection), which may help to identify patients at risk. Additionally, in vitro chemosusceptibility assays revealed high efficacy of the helicase‐primase inhibitors (HPI), pritelivir and drug‐candidate IM‐250 compared to acyclovir (ACV) using HSV‐1‐isolates from two patients; hence, ACV/HPI‐combinations might offer new therapeutic options for HSV‐induced ALF.

2021-11-01·Antiviral Research2区 · 医学

Helicase primase inhibitors (HPIs) are efficacious for therapy of human herpes simplex virus (HSV) disease in an infection mouse model

2区 · 医学

Article

作者: Donner, Anne-Kathrin ; Lange, Franziska ; Grunwald, Thomas ; Kleymann, Gerald ; Gege, Christian ; Uhlig, Nadja

Although the seroprevalence of Herpes simplex virus type 1 (HSV-1) currently amounts to ∼ 67% worldwide, the annual incidence of a severe disease progression, particularly herpes encephalitis, is approximately 2-4 cases per 1,000,000 infections. Nucleoside analogues, such as acyclovir (ACV), valacyclovir (VACV) or famciclovir, are still the therapeutic treatment of choice for HSV infections. However, nucleoside drugs have limited efficacy against severe HSV disease and for treatment of nucleoside-resistant viral strains, alternative therapies such as helicase-primase inhibitors (HPIs) which are highly potent by inhibiting viral replication are under development. In preclinical studies we analyzed the antiviral efficacy of drug candidates of a novel compound class of HPIs for the treatment of HSV to identify the most active eutomer structure in an intranasal infection mouse lethal challenge model. HSV-1 infected BALB/c mice treated with vehicle control developed fatal disease according to humane endpoints after 5-7 days. In contrast, the animals dosed orally once daily with the HPI compounds at 10 or 4 mg/kg/day showed a significantly increased survival (70% and 100% for 10 mg/kg/day; 90% and 100% for 4 mg/kg/day, respectively) compared to the vehicle treatment (0-10%), when therapy was initiated 6 h post HSV-1 inoculation. We observed a significantly improved outcome in clinical parameters and survival over 21 days in the group receiving novel HPI candidates using even the lowest dose of 4 mg/kg/day. With VACV treatment of 75 mg/kg daily survival was also significantly increased (80%-90% for 75 mg/kg/day) but to lesser extent. Initial IM-250 therapy at 10 mg/kg/day could be delayed up to 72 h resulting in significantly increased survival compared to the vehicle control. Furthermore, we detected significantly fewer viral genome copies in the lungs and brains of HPI treated animals compared to vehicle (440-fold reduction for 4 mg/kg/day IM-250 in the brain) or VACV controls by quantitative PCR. In conclusion the preclinical studies of the novel HPI compounds showed superior efficacy in comparison to the current standard HSV treatment represented by VACV with respect to the survival according humane endpoints, the clinical score and virus load in lungs and brains. Thus, candidates of this new drug class are promising antivirals of HSV infections and further translation into clinical trials is warranted.

项与 IM-250 相关的新闻（医药）

2021-06-16

·GlobeNewswire

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 Munich, Germany, June 16, 2021 - 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 diseaseHerpes 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 MoleculesInnovative 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.For more information: Media InquiriesakampionDr. Ludger Wess / Ines-Regina ButhManaging Partnersinfo@akampion.comTel. +49 40 88 16 59 64 /Tel. +49 30 23 63 27 68

100 项与 IM-250 相关的药物交易

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