3. Russian Pharmaceutical Technologies is a research and development company focused
on transforming innovative scientific discoveries into novel therapeutic agents.
Brief company description
City and country: Saint-Petersburg, Russian Federation
Date of foundation: 12 April 2012
Residence status: Skolkovo Foundation Resident, Moscow
Team: Russian and World experts in oncology and drug development
Brief product description
Product: RPT835, allosteric inhibitor of fibroblast growth factor receptor 2
Indication: FGFR2-expressing tumors
Stage of development: Late-preclinical studies
Expected date of Phase I/II clinical study: February 2015
Overview
4. Fibroblast Growth Factor Receptor 2 as a target for RPT835
The recent identification of fibroblast growth factor receptor 2 (FGFR2) overexpression or
mutations in different cancer types has generated an opportunity for a novel target-based
therapy
Advanced cancer Efficacy of standard therapy FGFR2
Gastric
cancer
Poor efficacy and poor overall survival
No approved targeted therapy except
trastuzumab in HER2-positive patients
5-7%, amplification
poor prognostic factor
Triple-negative
breast cancer
Poor efficacy and poor overall survival
No approved targeted therapy
4%, amplification
poor prognostic factor
Endometrial
cancer
Poor efficacy and poor overall survival
No approved targeted therapy
10%, amplification
poor prognostic factor
Colorectal cancer Poor efficacy of second-line treatment
Poor overall survival
3-25%, amplification
poor prognostic factor
Papillary renal cell
carcinoma
Poor efficacy and poor overall survival
No approved targeted therapy
5%, overexpression
Other tumors Resistance to targeted therapy
Poor overall survival
1-50%
5. RPT835 is one of the first allosteric inhibitors in oncology
Allosteric inhibitors decrease activity of receptor by binding an allosteric site at
the receptor (that is, a site other than the receptor's active site). There are no
approved allosteric targeted agents in oncology.
RPT835 is a low-molecular weight allosteric inhibitor of FGFR2.
Principle benefits of allosteric inhibitors
High specificity | Low toxicity
Cells with mutations sensitive to treatment
Different isoforms of receptor could be targeted
RPT835 inhibitor binds to allosteric
site of extracellular part of FGFR2 and
changes the conformation of receptor
6. Characterisation and comparison of RPT835
RPT835 Brivanib Bevacizumab
Molecular weight 413.4 g/mol 441.5 g/mol 149 kDa
IC50, FGFR2 kinase 10 nmol/L 125 nmol/L -
IC50, Phospho-FGFR2 11 nmol/L 289 nmol/L -
Specificity FGFR2 only VEGFR1-3, FGFR1-3 VEGF
Effective dose1 for inhibition:
FGF-stimulated angiogenesis
VEGF-stimulated angiogenesis
15 mg/kg
NA
50 mg/kg
4 mg/kg
NA
10 mg/kg
Route of administration Orally Orally Intravenous
Brivanib , a tyrosine kinase inhibitor in clinical studies
Bevacizumab, approved anti-VEGF monoclonal antibody
1Dose for significant inhibition of angiogenic effects in comparison with control
The preclinical data obtained with RPT835 are consistent with potent inhibition of FGF signaling,
angiogenesis, and cancer growth.
7. Development plan
2014 2015 2016 2017
Phase I/II study
2018
Patients with FGFR2-
expressing tumors
Late-stage
preclinical
studies
Phase III randomized study
Patients with
FGFR2-expressing tumors
Application for accelerated
approval, Russia & C.I.S.
Conclusions and Final approval
Market
