Product Development

Immunostimulatory Factors and Therapeutic Antibodies

Setting # 1

Product	ImmuFact IMP321
Therapeutic indications	Metastatic Renal Cell Carcinoma (MRCC)
Approach	IMP321 alone (high dose for systemic exposure)
Mechanism of action	T cell immune response stimulation as a monotherapy
Development Phase	Phase Ib
Status of development phase	MRCC: completed
Preclinical results	Proof of concept in animal models No toxicity
Clinical results	MRCC: 21 pt phase I/IIa studies to show safety and immune response. POC in patients.
	IMP321 induced both sustained CD8 T cell activation and an increase in the percentage of long-lived effector-memory CD8 T cells in all patients at doses above 6 mg.  Tumor growth was reduced and progression-free survival was better in those patients receiving higher doses (>6 mg) of IMP321: 7 out of 8 evaluable patients treated at the higher doses experienced stable disease at three months compared to only 3 out of 11 in the lower dose group (p=0.015). Brignone, C., B. Escudier, C. Grygar, M. Marcu, and F. Triebel. 2009. A phase I pharmacokinetic and biological correlative study of IMP321, a novel MHC class II agonist, in patients with advanced renal cell carcinoma. Clin. Cancer Res. 15:6225.

 

 

Setting # 2

Product	ImmuFact IMP321 Chemo-Immunotherapy
Therapeutic indications	Metastatic breast cancer (MBC) in the EU Advanced pancreatic cancer in the US
Approach	Chemotherapy followed by IMP321 alone (high dose for systemic exposure)
Mechanism of action	T cell immune response stimulation in patients receiving first-line chemotherapy
Development Phase	Phase I/IIa
Status of development phase	MBC (paclitaxel + 12 IMP321 s.c. injections) : completed Advanced pancreatic cancer: in progress (gemcitabine + 12 IMP321 s.c. injections): terminated
Preclinical results	Proof of concept in animal models No toxicity
Clinical results	MBC: 30 evaluable  patients. IMP321 induced both a sustained increase in the number and activation of APC (monocytes and dendritic cells) and an increase in the percentage of NK and long-lived cytotoxic effector-memory CD8 T cells.  Clinical benefit was observed for 90 % of patients with only 3 progressors at 6 months.  Also, the objective tumor response rate of 50 % compared favourably to the 25 % rate reported in the historical control group (p=0.005).   Brignone, C., M. Gutierrez, F. Mefti, E. Brain, R. Jarcau, F. Cvitkovic, N. Bousetta, J. Medioni, J. Gligorov, C. Grygar, M. Marcu, and F. Triebel. 2010. First-line chemoimmunotherapy in metastatic breast carcinoma: combination of paclitaxel and IMP321 (LAG-3Ig) enhances immune responses and antitumor activity. J Transl Med 8:71.
	Pancreatic cancer: 17 pt phase I/IIa (analysis in progress)

 

 

Setting # 3

Product	ImmuFact IMP321 Adjuvant
Therapeutic indications	Post-surgery disease-free melanoma Metastatic melanoma Prostate cancer with biochemical failure
Approach	Low dose IMP321 mixed with antigen
Mechanism of action	T cell immune response stimulation as an adjuvant for therapeutic vaccines
Development Phase	Phase I/IIa
Status of development phase	Post-surgery melanoma: completed Metastatic melanoma: in progress (2 trials) Prostate cancer: in progress
Preclinical results	Proof of concept in animals models No toxicity
Clinical results	37 pt phase I/IIa studies to show safety and immune response.

 

 

Setting # 4

Product	ImmuTune IMP701 Antagonist Antibody
Therapeutic indications	Cancer Chronic infectious diseases
Approach	Monoclonal antibody
Mechanism of action	Blockade of LAG-3-mediated immune down-regulation
Development Phase	Preclinical
Status of development phase	Optimisation

 

 

Setting # 5

Product	ImmuTune IMP731 Depleting Antibody
Therapeutic indications	Autoimmune diseases and transplantation
Approach	Monoclonal antibody (chimeric)
Mechanism of action	Killing activated Effector-Memory LAG-3+ T cells
Development Phase	Clinical
Status of development phase	Moving into clinical production and then phase I