DGAP-News: MOLOGEN AG: Lefitolimod - First clinical data in combination with a checkpoint inhibitor and further preclinical results presented at SITC 2018

PRESS RELEASE N 26/2018 of 12 November 2018

MOLOGEN AG: Lefitolimod - First clinical data in combination with a checkpoint inhibitor and further preclinical results presented at SITC 2018

Berlin, 12 November 2018 - The biopharmaceutical company MOLOGEN AG presented two posters on its lead compound, the TLR9 agonist lefitolimod at the SITC 2018 Congress (The Society for Immunotherapy of Cancer) in Washington D.C., U.S. (07 - 11 November 2018). The first poster from the MD Anderson Cancer Center in collaboration with MOLOGEN is featuring results from the ongoing clinical combination study of lefitolimod with the checkpoint inhibitor ipilimumab (Yervoy^(R)). The data confirm the favorable safety profile of lefitolimod, also in combination with ipilimumab. Importantly, the detected increase of cytotoxic T cells in tumor biopsies supports the mode-of-action of lefitolimod regarding the beneficial modulation of the tumor microenvironment (TME) already established in pre-clinical models now also in humans. The second poster presents data on lefitolimod-mediated changes of the TME and the induction of a sustained anti-tumor immune memory. Monotherapy with lefitolimod resulted in a clear beneficial modulation of the TME together with a reduced tumor growth in a murine colorectal cancer model. Pronounced effects were also observed in a breast cancer model with a complete tumor regression in the majority of mice. In a subsequent re-challenge study all surviving mice rejected not only the initially used but also a different tumor cell line, indicating the induction of a broad systemic immune response against various tumor types. In summary the presented data impressively support the assumption that lefitolimod beneficially modulates the TME and may hence be an ideal partner for immuno-oncology combination approaches, i.e. with checkpoint inhibitors.

"We are excited about the first clinical data on lefitolimod in combination with a checkpoint inhibitor. Importantly, besides confirming the favorable safety profile, we see clear hints for beneficial TME-modulating effects in patients. These clinical results are nicely complemented with further pre-clinical data impressively supporting the potential of lefitolimod in immuno-oncology. We all know that checkpoint inhibitors need help to fully unfold their enormous potential and we have now even more reasons to believe that our TLR9 agonist lefitolimod will play a major role also in this context", said Dr Matthias Baumann, CMO of MOLOGEN AG.

First data of combination study (lefitolimod and ipilimumab) confirm safety and mode-of-action of the TLR9 agonist
The aim of the study titled "A Phase I Trial of Ipilimumab (Immunotherapy) and lefitolimod (TLR Agonist) in Patients with Advanced Solid Malignancies" is to initially find the highest tolerable dose of lefitolimod that can be given in combination with the commercially available immunotherapeutic agent Yervoy^(R) (ipilimumab) to patients with solid tumors. The safety as well as pharmacodynamic effects of this drug combination are also being studied. The data presented at the SITC Conference by the team of the MD Anderson Cancer Center, Houston, Texas, who is conducting the clinical study, confirm lefitolimod's mode-of-action with respect to an increased proportion and activation of cytotoxic T cells in tumor biopsies. Furthermore, PD-1 expression increased after treatment suggesting potential benefit from additional PD-1 blockade. The combination of MOLOGEN's TLR9 agonist with the checkpoint inhibitor presented with a favourable safety profile and no dose-limiting toxicities (DLTs) have been encountered up to the highest dose level.
The clinical combination study is conducted by MD Anderson Cancer Center. MOLOGEN provides the TLR9 agonist lefitolimod and funds the study. This is the first time that lefitolimod is being clinically evaluated in combination with a checkpoint inhibitor. If lefitolimod enhances the efficacy of immune checkpoint blockade, this could expand the potential range of applications of the compound.

Impressive immuno-oncological effects of lefitolimod in preclinical models
After intratumoral injection of lefitolimod an increased infiltration of T cells (CD3+ T cells, especially CD8+ T cells) as well as of anti-tumoral M1 macrophages into the tumor was observed. Importantly, this beneficial TME modulation from an immunosuppressed ("cold") towards a more immunoreactive ("hot") stage translated into a reduction of tumor growth in the mice. Beyond that the tumors of the majority of mice in another model completely disappeared. Notably, all surviving mice presented with a sustained anti-tumor immune memory not only against the same cancer cells, but also against various types of other tumors. This indicates the lefitolimod-induced generation of a systemic immune memory against shared tumor antigens expressed across different tumor cell lines.

For more information on SITC 2018 please visit the website: https://www.sitcancer.org/2018/home

MOLOGEN AG
MOLOGEN AG is a biopharmaceutical Company and a pioneer in the field of immunotherapy on account of its unique active agents and technologies. Alongside a focus on immuno-oncology, MOLOGEN develops immunotherapies for the treatment of infectious diseases.
The focus of the development work is on the product family of DNA-based TLR9 agonists. This includes the lead compound lefitolimod and the next-generation molecule family EnanDIM^(R).

The immunotherapeutic agent lefitolimod is the Company's lead compound and is currently being investigated in a pivotal trial. It is regarded as the best-in-class TLR9 agonist. Treatment with lefitolimod triggers a broad and strong activation of the immune system. On account of this mode of action, lefitolimod could potentially be used in various indications. Lefitolimod is currently being developed within the framework of a pivotal study for first line maintenance therapy for colorectal cancer. Key data of the phase II IMPULSE study in extensive-stage small cell lung cancer (ES-SCLC) and the data from the extension phase of the TEACH study in HIV have been published. In addition, lefitolimod is currently being investigated in a phase I combination study with the checkpoint inhibitor ipilimumab (Yervoy^(R)) in various cancer indications. Along with various checkpoint inhibitors, lefitolimod, which is being investigated as part of a phase III clinical trial currently, is one of the few near-to-market product candidates in the field of immuno-oncology.
MOLOGEN's pipeline focus is on new innovative immunotherapies to treat diseases for which there is a great medical demand in particular.

MOLOGEN AG is a publicly listed Company, headquartered in Berlin. The shares (ISIN, DE000A2LQ900/SIN: A2L Q90) are listed in the Prime Standard of the German Stock Exchange.

www.mologen.com

Contact

Claudia Nickolaus
Head of Investor Relations & Corporate Communications
Tel: +49 - 30 - 84 17 88 - 38
Fax: +49 - 30 - 84 17 88 - 50
investor@MOLOGEN.com

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