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Emiliano S. Lopez , Oscar J. Croxatto, Juan E. Gallo
Facultad de Ciencias Biomédicas, Universidad Austral; Oftalmologia, Hospital Universitario
Austral , Pilar- Buenos Aires ; Patologia Ocular, Fundación Oftalmológica Argentina "Jorge
                            Malbran", Buenos Aires, Argentina.
SURAMAB

- EP 2186529; granted 28 March 2012.

- US Patent pending.
Suramin




Bevacizumab
   We have previously shown that Suramab,
    a novel pharmaceutical compound, has
    antiangiogenic properties.

   ES Lopez , MM Rizzo, JO Croxatto , G Mazzolini , JE Gallo.
    Suramab, a novel antiangiogenic agent, reduces tumor
    growth and corneal neovascularization. Cancer Chemother
    Pharmacol 2011; 67:723–728
   To analyse the role of VEGF, bFGF, LYVE-1
    and P2X2 in the antiangiogenic mechanism of
    suramab in a rabbit model of corneal
    neovascularization.
9 Rabbits         9 Rabbits         9 Rabbits




Photographs   d9       d15     d21
d35
Anesthesia                          filter disc (7mm)                Na(OH) 1M (1min)                    Wash SB




-L. David Ormerod. Standard Models of Corneal Injury Using Alcali-Inmersed filter discs. Investigative Ophthalmology & Visual
  Science, Vol. 30, Nº. 10, October 1989.
CLINICAL FOLLOW-UP
         Suramab    Bevacizumab    Control



DAY 9




DAY15




DAY 35
   Rabbits treated with Suramab
    showed a lower neovessel index
    than that seen in controls at 35
    days (T student, p<0.0001).



   Suramab had a greater
    antiangiogenic effect than
    that seen in animals treated
    with Bevacizumab (T
    student, p<0.02).
CONTROL   TREATED GROUPS




Suramab         Control
Control           Suramab           Bevacizumab




                       S       C   B

VEGF         42kDa




ACTIN        43kDa
SURAMAB              BEVACIZUMAB   CONTROL




                      S   C   B

             40 kD
    LYVE-1


    ACTIN    43 kD
Control          Bevacizumab       Suramab




                        C     S       B
                 50kD
P2X2


                 43kD
ACTIN
Western Blot
                   B   C   S

           19 kD
  bFGF


                   B   C   S

           43 kD
 ACTIN
CONCLUSIONS

-   Suramab has a strong antiangiogenic
    effect.

-   VEGF, P2X2, LYVE-1 and bFGF are
    involved in the antiangiogenic
    mechanism.
CONTROL
        Control                    Suramab+P                                         Suramab




                                                                             Clinical evolution
                                                                50

                                                                40




                                               Area of NV (%)
Control   38.22   35.3   30   29    31   22                     30

Suramab   19.4     3     6    5      8    9                     20

                                                                10
S+P        5       0     1    2      1    1
                                                                 0


                                                                            S

                                                                                 P
                                                                     ol



                                                                                S+
                                                                     tr
                                                                 on
                                                                C




                                                                          Groups ( 14 days postinjury)
CONCLUSIONS

-   Drug delivery systems are being
    currently developed to improve
    suramab ´s performance in the
    treatment of corneal and retinal
    neovascularization.
THANK YOU!
3 Conejos   3 Conejos   3 Conejos
Evolución clínica
         Control          Suramina EV   Bevacizumab



DIA 9




DIA 35
INV promedios




                Días post-lesión
P407/P188/NaCl/Chitosan (24/20/0.9/0.5 % w/w)

    1,00E+04




    1,00E+03




    1,00E+02




    1,00E+01
P
V
o
a
y
c
s
)
(
t
.
i




                                                                                               Poloxamers
                                                                                               Poloxamers-Hialuronato
                                                                                               Poloxamers-Chitosan

    1,00E+00
               0   5      10            15         20           25        30            35          40               45




    1,00E-01
                                                    Temperatura °C




                                                        Polímero               T gel         T gel II       Viscosidad a
     P407/P188     Vehículo                             % (w/w)                I (°C)        (°C)           35°C (Pas)
                   NaCl 0.9%                                                   26,4          27,9           14100
     (24/20)
                   NaCl 0.9%                                                   24,8          26,4           17800
      %w/w
                                                    0,5 (Chitosan)
                   NaCl 0.9%                      0,25 (Hialuronato            25,3          27,9           14100
                                                      de Sodio)
         Dr. Santiago Palma, Daniela Quinteros. Universidad Nacional de Cordoba

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Gallo et al (iser 2012)

  • 1. Emiliano S. Lopez , Oscar J. Croxatto, Juan E. Gallo Facultad de Ciencias Biomédicas, Universidad Austral; Oftalmologia, Hospital Universitario Austral , Pilar- Buenos Aires ; Patologia Ocular, Fundación Oftalmológica Argentina "Jorge Malbran", Buenos Aires, Argentina.
  • 2. SURAMAB - EP 2186529; granted 28 March 2012. - US Patent pending.
  • 4. We have previously shown that Suramab, a novel pharmaceutical compound, has antiangiogenic properties.  ES Lopez , MM Rizzo, JO Croxatto , G Mazzolini , JE Gallo. Suramab, a novel antiangiogenic agent, reduces tumor growth and corneal neovascularization. Cancer Chemother Pharmacol 2011; 67:723–728
  • 5. To analyse the role of VEGF, bFGF, LYVE-1 and P2X2 in the antiangiogenic mechanism of suramab in a rabbit model of corneal neovascularization.
  • 6. 9 Rabbits 9 Rabbits 9 Rabbits Photographs d9 d15 d21 d35
  • 7. Anesthesia filter disc (7mm) Na(OH) 1M (1min) Wash SB -L. David Ormerod. Standard Models of Corneal Injury Using Alcali-Inmersed filter discs. Investigative Ophthalmology & Visual Science, Vol. 30, Nº. 10, October 1989.
  • 8. CLINICAL FOLLOW-UP Suramab Bevacizumab Control DAY 9 DAY15 DAY 35
  • 9. Rabbits treated with Suramab showed a lower neovessel index than that seen in controls at 35 days (T student, p<0.0001).  Suramab had a greater antiangiogenic effect than that seen in animals treated with Bevacizumab (T student, p<0.02).
  • 10. CONTROL TREATED GROUPS Suramab Control
  • 11. Control Suramab Bevacizumab S C B VEGF 42kDa ACTIN 43kDa
  • 12. SURAMAB BEVACIZUMAB CONTROL S C B 40 kD LYVE-1 ACTIN 43 kD
  • 13. Control Bevacizumab Suramab C S B 50kD P2X2 43kD ACTIN
  • 14. Western Blot B C S 19 kD bFGF B C S 43 kD ACTIN
  • 15. CONCLUSIONS - Suramab has a strong antiangiogenic effect. - VEGF, P2X2, LYVE-1 and bFGF are involved in the antiangiogenic mechanism.
  • 16. CONTROL Control Suramab+P Suramab Clinical evolution 50 40 Area of NV (%) Control 38.22 35.3 30 29 31 22 30 Suramab 19.4 3 6 5 8 9 20 10 S+P 5 0 1 2 1 1 0 S P ol S+ tr on C Groups ( 14 days postinjury)
  • 17. CONCLUSIONS - Drug delivery systems are being currently developed to improve suramab ´s performance in the treatment of corneal and retinal neovascularization.
  • 19.
  • 20. 3 Conejos 3 Conejos 3 Conejos
  • 21. Evolución clínica Control Suramina EV Bevacizumab DIA 9 DIA 35
  • 22. INV promedios Días post-lesión
  • 23. P407/P188/NaCl/Chitosan (24/20/0.9/0.5 % w/w) 1,00E+04 1,00E+03 1,00E+02 1,00E+01 P V o a y c s ) ( t . i Poloxamers Poloxamers-Hialuronato Poloxamers-Chitosan 1,00E+00 0 5 10 15 20 25 30 35 40 45 1,00E-01 Temperatura °C Polímero T gel T gel II Viscosidad a P407/P188 Vehículo % (w/w) I (°C) (°C) 35°C (Pas) NaCl 0.9% 26,4 27,9 14100 (24/20) NaCl 0.9% 24,8 26,4 17800 %w/w 0,5 (Chitosan) NaCl 0.9% 0,25 (Hialuronato 25,3 27,9 14100 de Sodio) Dr. Santiago Palma, Daniela Quinteros. Universidad Nacional de Cordoba