DGAP-News: MOLOGEN AG announces top line data of pivotal IMPALA study in metastatic colorectal cancer

PRESS RELEASE N 13 / 2019 of 8/5/2019

MOLOGEN AG announces top line data of pivotal IMPALA study in metastatic colorectal cancer

- Primary endpoint not met: median overall survival of 22 months in lefitolimod group compared to 21.9 months in control group; p=0.2765; hazard ratio HR: 1.12 (95% CI: 0.91 - 1.38)

- No new safety signals detected

- Future focus on combination approaches for both lefitolimod and the first clinical candidate from the EnanDIM^(R) family

Berlin, 5 August 2019 - The biopharmaceutical company MOLOGEN AG (ISIN DE000A2LQ900, SIN A2L Q90) announced today the top line data of its pivotal phase III IMPALA study. The study compares the TLR9 agonist lefitolimod (MGN1703) with local standard of care as a maintenance therapy in patients with metastatic colorectal cancer presenting with an objective tumor response following first-line induction therapy. The primary endpoint - overall survival (OS) - was not met showing a median OS of 22.0 and 21.9 months in the lefitolimod and control group respectively (p=0.2765; HR=1.12; 95% CI 0.91 - 1.38). Timepoint related OS and predefined sub-group analyses did also not indicate a benefit, while regarding Progression Free Survival (PFS) standard of care was superior to lefitolimod treatment. No new safety signals were detected; hence the favorable safety and tolerability profile was confirmed.

MOLOGEN is a pioneer in the field of immunotherapy, especially in the TLR9 field with the product family of DNA-based TLR9 agonists including its lead compound lefitolimod, as well as its follow-up molecules EnanDIM^(R). Given its mode of action and confirmed favorable safety profile, lefitolimod is being used as combination partner in anti-cancer and anti-HIV immunotherapies.

Dr med Stefan M. Manth, CEO of MOLOGEN, noted: "We are disappointed with these top-line results and will now analyze the bountiful data coming out of IMPALA in depth. We will then build on these analyses from IMPALA to further inform the development of lefitolimod and its successor molecules from the EnanDIM^(R) platform for cancer and HIV patients. We are grateful to the patients and investigators for their participation in this important study."

Dr med Matthias Baumann, CMO of MOLOGEN, stated: "Unfortunately the positive results in our single agent lefitolimod phase II IMPACT study did not translate into a successful outcome of our phase III IMPALA trial despite the fact that all learnings have been incorporated into the trial design. In contrast to the time when the IMPALA design was conceived, it now appears that for successful anti-cancer immunotherapies a combination approach is of paramount importance. Due to the large body of evidence indicating the potential of TLR9 agonism in this context we remain committed to the further development of our candidates."

The detailed data from this first top line analysis of the IMPALA trial will be submitted for presentation at an upcoming international scientific congress.

Strategic focus on combination therapies in indications with high medical need and significant market potential
In light of these results the strategy of MOLOGEN going forward will focus on combination approaches for both lefitolimod and the first clinical candidate from the EnanDIM(R) family in ongoing and planned clinical trials. This strategy serves as cornerstone for ongoing licensing and funding efforts.

Further to the IMPALA single-agent approach, lefitolimod is currently being evaluated in a phase I/II clinical study in combination with the checkpoint inhibitor Yervoy^(R) (ipilimumab) in a broader variety of solid tumors. The study is being conducted at the renowned MD Anderson Cancer Center, Texas, USA. In addition to studies in the field of oncology, lefitolimod has also been tested in HIV patients in a phase Ib/IIa study, the TEACH trial. Based on the encouraging study results, lefitolimod will be investigated in a phase IIa combination study, the TITAN trial, in HIV-infected patients in combination with innovative virus-neutralizing antibodies developed by the Rockefeller University in New York, USA. The trial will be conducted in cooperation with the Aarhus University Hospital in Denmark, which was also the academic partner of MOLOGEN in the TEACH trial. TITAN is funded by the US biotech company Gilead Inc. Furthermore, plans for another clinical combination study in HIV with a prominent US center are at an advanced stage.

The next generation TLR9 agonistic molecules of the EnanDIM^(R)-family coming out of the research labs of MOLOGEN offer additional potential for development in various cancer indications and HIV. A first clinical candidate from the EnanDIM^(R) platform is presently in late pre-clinical testing and expected to launch into clinical development in oncology at the end of 2019.

Checkpoint inhibitors alone are expected to generate sales of approximately US$ 25 billion by 2022 (acc. to Research and Markets) in a growing variety of indications. However, the greatest potential of checkpoint inhibitors is still to be realized, i.e. with adequate combination partners to target indications non-amenable to checkpoint inhibitor monotherapy. Estimates from the market research organization Research and Markets project that the market for cancer immunotherapies could rise to more than US$100 billion by 2024.

Background to the IMPALA study
IMPALA (Immunomodulatory MGN1703 in Patients with Advanced Colorectal Carcinoma with tumor reduction during induction treatment) is a pivotal, randomized, international, multicenter, open-label phase III trial. The study involves more than 540 patients from eight European countries, including the five major European pharmaceutical markets. Recruitment was completed in May 2017. The study includes patients with metastatic colorectal cancer who have responded to standard first-line treatment. Lefitolimod is subsequently administered subcutaneously 60 mg twice weekly as maintenance therapy. The primary endpoint is overall survival and secondary study endpoints include progression-free survival, safety and tolerability, as well as Quality of Life (QoL).

The study is conducted in collaboration with three highly profiled national collaborative study groups: Arbeitsgemeinschaft Internistische Onkologie (AIO) in Germany, Grupo Español de Tratamiento de Tumores Digestivos (TTD) in Spain and Groupe Coopérateur Multidisciplinaire en Oncologie (GERCOR) in France.

For more information on IMPALA please visit www.clinicaltrials.gov.

MOLOGEN AG
MOLOGEN AG is a German 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 HIV and infectious diseases.

The focus of MOLOGEN's development is on DNA-based TLR9 agonists, where it has consistently been ahead of the course. This includes the lead compound, the immunotherapy lefitolimod, and its next generation molecules EnanDIM^(R), building the foundation for a next generation immunotherapy platform in areas of unmet need.

Forthcoming milestones include: the start of the TITAN study in HIV, the start of the clinical development of EnanDIM^(R) and additional combination studies in cancer, including one with our strategic partner Oncologie Inc., which are in an advanced planning stage.

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 - 37
Fax: +49 - 30 - 84 17 88 - 50
investor@mologen.com

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