IMMUTEP ENTERS INTO CLINICAL TRIAL COLLABORATION AND SUPPLY AGREEMENT WITH MERCK KGAA, DARMSTADT, GERMANY, AND PFIZER
SYDNEY, AUSTRALIA ? Immutep Limited (ASX: IMM; NASDAQ: IMMP) (?Immutep? or ?the Company?) is
pleased to announce that it has entered into a clinical trial collaboration and supply agreement with
Merck KGaA, Darmstadt, Germany and Pfizer Inc., to evaluate the combination of Immutep?s lead
immunotherapy product candidate eftilagimod alpha (?efti? or ?IMP321?) with avelumab*, a human
anti-PD-L1 antibody, in patients with advanced solid malignancies.
?We are delighted to have the opportunity to collaborate with Merck KGaA, Darmstadt, Germany, and
Pfizer on this Phase I clinical trial that will evaluate the clinical benefits of combining our immune
stimulator, eftilagimod alpha, with avelumab, a PD-L1 blocking mechanism of action. We feel that this
new collaboration, with these industry leaders, further supports our hypothesis that there is a
potentially meaningful therapeutic benefit in combining eftilagimod alpha with a checkpoint inhibitor in
the treatment of cancer. We look forward to the initiation of this clinical trial, planned for later this year,
and the prospects of further clinical investigations,? said Marc Voigt, CEO of Immutep.
?This novel combination regimen adds to our clinical development program to further evaluate the
potential in different challenging cancers,? said Alise Reicin, Head of Global Clinical Development at the
biopharma business of Merck KGaA, Darmstadt, Germany, which in the US and Canada operates as EMD
Serono. ?We are eager to assess the opportunity of combining eftilagimod alpha with avelumab to
improve patient outcomes.?
?We continue to focus on opportunities to advance combination trials with avelumab, as we believe the
pathway to progress in immuno-oncology lies in combination approaches,? said Chris Boshoff, M.D.,
Ph.D., Senior Vice President and Head of Immuno-Oncology, Early Development, and Translational
Oncology, Pfizer Global Product Development. ?We look forward to collaborating with Immutep on this
clinical trial collaboration, which will help us accelerate and advance treatment options that will
potentially benefit more patients.?
The planned clinical evaluation will be an amendment to the existing INSIGHT Phase I clinical trial and
will evaluate the safety, tolerability and recommended Phase II dose of efti when combined with
avelumab in patients with advanced solid malignancies. The Institute of Clinical Cancer Research,
Krankenhaus Nordwest GmbH in Frankfurt, Germany (?IKF?) will be the sponsor of the clinical trial and it
will be conducted under the existing protocol of the ongoing INSIGHT clinical study. Prof. Dr. Salah-Eddin
Al-Batran, the lead investigator of INSIGHT and member of Immutep?s clinical advisory board, will be the
lead investigator of the trial.
Prof. Dr. Al-Batran commented: ?We are excited to have the opportunity to sponsor this clinical trial of
two complementary mechanisms of action and build upon the existing relationship between IFK and
Immutep. This clinical trial will be conducted through an amendment to our existing protocol which will
hopefully allow us to commence the clinical trial before the end of the year.?
The clinical trial will evaluate the clinical benefits of releasing the brakes and pushing the accelerator of
the body?s immune system at two different positions in the cancer immunity cycle. Immutep?s efti is a
first-in-class antigen presenting cell (?APC?) activator which stimulates cancer-fighting T cells, while
avelumab is an anti-PD-L1 therapy that works by increasing the ability of the body?s immune system to
help detect and fight tumor cells.
Avelumab has received accelerated approval** by the US Food and Drug Administration (FDA) for the
treatment of patients with metastatic Merkel cell carcinoma (MCC) and previously treated patients with
locally advanced or metastatic urothelial carcinoma (mUC), and is under further clinical evaluation
across a range of tumor types under a global strategic alliance between Merck KGaA, Darmstadt,
Germany, and Pfizer.
*Avelumab is under clinical investigation for treatment of solid malignancies and has not been
demonstrated to be safe and effective for these uses. There is no guarantee that avelumab will be
approved for solid malignancies by any health authority worldwide.
About Eftilagimod Alpha
Eftilagimod alpha (?efti? or ?IMP321?), a LAG-3Ig fusion protein, is a MHC class II agonist that activates
antigen-presenting cells (?APCs?) such as dendritic cells and monocytes (primary target cells) and then
CD8 T-cells (secondary target cells). The activation of the dendritic cell network and the subsequent T
cell recruitment at the tumour site with efti may lead to stronger anti-tumor CD8 T cell responses than
observed with checkpoint inhibitor monotherapy, as in the case of the TACTI-mel (Two ACTive
Immunotherapies in melanoma) Phase I clinical trial (clinicaltrials.gov identifier NCT02676869). In
combination with chemotherapy, the activation of the APC network with efti the day after injection of a
single agent chemotherapy may lead to stronger cytotoxic cellular responses associated with an
improved long-term Th1 (IFN-?) immune status, both parameters being essential for a potent immune
response against the tumour, as in the case of the AIPAC (Active Immunotherapy PAClitaxel) Phase IIb
clinical trial (clinicaltrials.gov identifier NCT02614833).
About Avelumab
Avelumab is a human anti-programmed death ligand-1 (PD-L1) antibody. Avelumab has been shown in
preclinical models to engage both the adaptive and innate immune functions. By blocking the
interaction of PD-L1 with PD-1 receptors, avelumab has been shown to release the suppression of the T
cell-mediated antitumor immune response in preclinical models.1-3 Avelumab has also been shown to
induce NK cell-mediated direct tumor cell lysis via antibody-dependent cell-mediated cytotoxicity
(ADCC) in vitro.3-5
In November 2014, Merck KGaA, Darmstadt, Germany, and Pfizer announced a
strategic alliance to co-develop and co-commercialize avelumab.
Avelumab is currently being evaluated in the JAVELIN clinical development program, which involves at
least 30 clinical programs, including seven Phase III trials, and more than 8,600 patients across more
than 15 different tumor types. For a comprehensive list of all avelumab trials, please visit
clinicaltrials.gov.
**Indications in the US
The US Food and Drug Administration (FDA) granted accelerated approval for avelumab (BAVENCIO?
) for
the treatment of (i) adults and pediatric patients 12 years and older with metastatic Merkel cell
carcinoma (mMCC) and (ii) patients with locally advanced or metastatic urothelial carcinoma (mUC) who
have disease progression during or following platinum-containing chemotherapy, or have disease
progression within 12 months of neoadjuvant or adjuvant treatment with platinum-containing
chemotherapy. These indications are approved under accelerated approval based on tumor response
rate and duration of response. Continued approval for these indications may be contingent upon
verification and description of clinical benefit in confirmatory trials.
Important Safety Information from the US FDA Approved Label
The warnings and precautions for avelumab (BAVENCIO?
) include immune-mediated adverse reactions
(such as pneumonitis, hepatitis, colitis, endocrinopathies, nephritis and renal dysfunction and other
adverse reactions), infusion-related reactions and embryo-fetal toxicity.
Common adverse reactions (reported in at least 20% of patients) in patients treated with BAVENCIO for
mMCC and patients with locally advanced or metastatic UC include fatigue, musculoskeletal pain,
diarrhea, nausea, infusion-related reaction, peripheral edema, decreased appetite/hypophagia, urinary
tract infection and rash.
For full prescribing information and medication guide for BAVENCIO, please see www.BAVENCIO.com.
Alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, U.S.
Immuno-oncology is a top priority for Merck KGaA, Darmstadt, Germany, and Pfizer Inc. The global
strategic alliance between Merck KGaA, Darmstadt, Germany, and Pfizer Inc., New York, US, enables the
companies to benefit from each other's strengths and capabilities and further explore the therapeutic
potential of avelumab, an anti-PD-L1 antibody initially discovered and developed by Merck KGaA,
Darmstadt, Germany. The immuno-oncology alliance will jointly develop and commercialize avelumab
and advance Pfizer's PD-1 antibody. The alliance is focused on developing high-priority international
clinical programs to investigate avelumab as a monotherapy, as well as in combination regimens, and is
striving to find new ways to treat cancer.
About Immutep
Immutep is a globally active biotechnology company that is a leader in the development of
immunotherapeutic products for the treatment of cancer and autoimmune disease. Immutep is
dedicated to leveraging its technology and expertise to bring innovative treatment options to market for
patients and to maximise value to shareholders.
Immutep?s current lead product candidate is eftilagimod alpha (?efti? or ?IMP321?), a soluble LAG-3Ig
fusion protein based on the LAG-3 immune control mechanism. This mechanism plays a vital role in the
regulation of the T cell immune response. Efti is currently in a Phase IIb clinical trial as a
chemoimmunotherapy for metastatic breast cancer termed AIPAC (clinicaltrials.gov identifier NCT
02614833) and a Phase I combination therapy trial in metastatic melanoma termed TACTI-mel
(clinicaltrials.gov identifier NCT 02676869). Additional LAG-3 products, including antibodies, for immune
response modulation in autoimmunity and cancer are being developed by Immutep?s large
pharmaceutical partners. Immutep is also developing an agonist of LAG-3 (IMP761) for autoimmune
disease. Immutep is listed on the Australian Securities Exchange (IMM), and on the NASDAQ (IMMP) in
the U.S.
Further information can be found on the Company?s website at www.immutep.com or by contacting:
U.S. Investors:
Jay Campbell, Vice President of Business Development and Investor Relations, Immutep Limited
+1 (917) 860-9404; jay.campbell@immutep.com
Garth Russell, LifeSci Advisors
+1 (646) 876-3613; garth@lifesciadvisors.com
Australian Investors/Media:
Matthew Gregorowski, Citadel-MAGNUS
+61 2 8234 0105; mgregorowski@citadelmagnus.com
References
1. Dolan DE, Gupta S. PD-1 pathway inhibitors: changing the landscape of cancer immunotherapy.
Cancer Control 2014;21(3):231-7.
2. Dahan R, Sega E, Engelhardt J et al. Fc?Rs modulate the anti-tumor activity of antibodies targeting
the PD-1/PD-L1 axis. Cancer Cell 2015;28(3):285-95.
3. Boyerinas B, Jochems C, Fantini M et al. Antibody-dependent cellular cytotoxicity activity of a novel
anti-PD-L1 antibody avelumab (MSB0010718C) on human tumor cells. Cancer Immunol Res
2015;3(10):1148-57.
4. Kohrt HE, Houot R, Marabelle A et al. Combination strategies to enhance antitumor ADCC.
Immunotherapy 2012;4(5):511-27.
5. Hamilton G, Rath B. Avelumab: combining immune checkpoint inhibition and antibody-dependent
cytotoxicity. Expert Opin Biol Ther 2017;17(4):515-23.