On October 14, 2014 MOLOGEN reported that it has presented preclinical data on its EnanDIM technology at the 10th Annual Meeting of the Oligonucleotide Therapeutics Society (OTS) in San Diego, United States (Press release Mologen, OCT 14, 2014, View Source [SID:1234501174]). EnanDIM represents a new generation of the company’s immunoactivating TLR-9 agonists that is expected to trigger a broad immune activation while being well tolerated. Potential applications include the fields of anti-tumor and anti-infective therapies.
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DNA-based TLR-9 agonists are potent activators of the innate immune system and of a variety of immune cell populations. So far, two different types of TLR-9 agonists have been established. The first consists of linear, single-stranded DNA molecules. Most of these linear TLR-9 agonists are chemically modified to protect them against degradation, which is known to produce off-target effects and toxicity. MOLOGEN’s lead product, the cancer immunotherapy MGN1703, represents the second type of TLR-9 agonist, a covalently-closed, dumbbell-shaped DNA molecule. As it consists entirely of natural DNA components, it is safe and well tolerated.
EnanDIM (Enantiomeric, DNA-based, ImmunoModulator), the new class of linear TLR-9 agonists, combines the immunoactivatory properties of molecules containing only natural DNA components with the advantages of linear molecules. Despite its linear structure, no chemical modifications are needed as the specific linear structure of EnanDIM protects the molecules against degradation. This protection is achieved by incorporation of mirror-imaged components, which are chemically identical to the naturally occurring DNA components but that are not recognized by DNA-degrading enzymes. Consequently, a favorable safety and tolerability profile is expected to be shown in the planned subsequent preclinical and clinical development.
The broad immune activation induced by EnanDIM in preclinical models has been presented at OTS in an oral presentation. Therefore, the mode of action should enable the use in various cancer indications either as monotherapy, in combination with other targeted therapies or immune modulators, such as so called checkpoint inhibitors or with other immunotherapeutic approaches. Furthermore, it could potentially be used in the field of infectious diseases.
Dr. Matthias Schroff, CEO of MOLOGEN AG, commented: "We are very pleased about the positive feedback at the OTS meeting. EnanDIM is expected to have a safety and tolerability profile in clinical tests comparable to the profile of our lead product MGN1703. Based on its broad immune activation potential EnanDIM may be used in a variety of indications including cancer immunotherapy. This again shows our innovative capacity and expertise in the field of immune therapies and in immuno oncology in particular."
Detailed information on EnanDIM, as discussed at the oral presentation, is summarized in the poster with the title "EnanDIM: A new class of enantiomeric oligodeoxynucleotides for TLR‐9 activation" (poster no. 056).
For more information please visit the OTS website www.oligotherapeutics.org.