curaxin program updatecontent.stockpr.com/cbiolabs/media/6c108699838320bef72f0... · 2012-03-05 ·...
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Curaxin Program UpdateInvestor DayJune 9, 2010
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This presentation includes forward-looking statements and predictions, including statements about potential revenue-bearing transactions, the market potential of CBLI’s technologies and product candidates, and the potential value of pipeline
products. These statements represent the Company’s judgment as of the date of this presentation and are subject to risks and uncertainties that could cause actual
results of events to differ materially from those expressed in such forward-looking statements. In particular, CBLI faces risks and uncertainties that it may not be able to sustain its business model, that revenues may be lower or expenses higher than
projected, that product sales may not increase, that development of product candidates in the Company’s pipeline may not succeed or that commercial
transactions may not go forward as planned.
Safe-Harbor
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CBLI’s Products – Modulators of Apoptosis
ApoptosisNecrosis,etc.Apoptosis
ProtectansInhibit apoptosis.
Do not protect tumor cells
CuraxinsKill cancer cells by restoring apoptosis inhibited in tumors
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Curaxins Overview
• First-in-class broad-spectrum anticancer drugs
• Small molecules suitable for oral administration
• Novel mechanism of action – simultaneous targeting three major pathways deregulated in cancer
• Composition of matter patent applications
• Efficacy in multiple animal models of major cancer types including breast and prostate cancer
• Proof of concept: Phase II trial in prostate cancer of Curaxin precursor drug quinacrine
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Full-scale hit-to-lead optimization program has been completed.Resulting drug candidates are >100 times more potent than CBLC102
From Quinacrine to Curaxins
Resulting compounds have unique proprietary structure
(US and international patents pending)
quinacrine
CBLC000
Curaxins
CBLC137CBLC100
Structure-activity relationshipHit-to-lead optimization
MTD
IC50Activ
e co
nc. v
is-à
-vis
QC
000 137 100
Therapeutic window
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Efficacy: Curaxin CBLC137 against solid tumors
0
5
10
15
20
25
30
35
40
0 4 7 11 13 15 18 21 25
Mea
n fo
ld tu
mor
siz
e
control
CBL137
* * * **
Vehicle control
30mg/kg CBLC137
0
5
10
15
20
25
30
35
40
0 4 7 11 13 15 18 21 25
Mea
n fo
ld tu
mor
siz
e
control
CBL137
* * * **
Vehicle control
30mg/kg CBLC137
0
2
4
6
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14
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0 10 20Days from start of treatment
Mea
n Fo
ld T
umor
Gro
wth
0
2
4
0 10 30* *
* * * *
Vehicle Control30mg/kg CBL13742mg/kg 5FU50mg/kg Irinothecan7.5mg/kg Oxaliplatin
0
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6
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12
14
0 5 10 15 20 25 30 35
Vehicle control30 mg/kg CBL013740 mg/kg
0
2
4
6
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0 5 10 15 20 25 30 35
Mea
n fo
ld tu
mor
siz
e 40 mg/kg Sunitinib
** * * * * *0
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4
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12
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0 5 10 15 20 25 30 35
Vehicle control30 mg/kg CBL013740 mg/kg
0
2
4
6
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0 5 10 15 20 25 30 35
Mea
n fo
ld tu
mor
siz
e 40 mg/kg Sunitinib
** * * * * *
02468
101214161820
1 5 7 10 12 14 16 19 21 23 25 28
Vehicle control30mg/kg CBL137
* * * * * * * * * *02468
101214161820
1 5 7 10 12 14 16 19 21 23 25 28
Vehicle control30mg/kg CBL137
* * * * * * * * * *
Days from start of treatmentDays following treatment initiation
kidney colon
melanoma pancreas
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Curaxins demonstrated anti‐tumor effects in all tumor models tested, including spontaneous and transplantable mouse tumors and human
xenografts of solid tumors and leukemias
Efficacy: Curaxin CBLC137 against leukemia
ALL-3 ALL-8
Days following treatment initiation
Xenografts of pediatric human leukemias grown in immunodeficient mice
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Deep structural analysis revealed unique mechanism of Curaxin binding to cellular DNA and facilitated the deciphering of
mechanism of action and identification of molecular targets of Curaxins
From Structure to Mechanism of Action
Active compounds
Inactive compounds DNA binding
Curaxin
Doxorubicin
No DNA damage by Curaxins
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Mechanism of Action and Curaxins Target
NFκB
p53
RNA-polNFκB
RNA-pol
p53
RNA-polNFκB
RNA-pol+ Curaxin
Trap of FACT on chromatin Trap of FACT on chromatin results in blocking FACTresults in blocking FACT‐‐
dependent transcription and dependent transcription and CK2CK2‐‐mediated p53 activationmediated p53 activation
NFNF‐‐κκBB‐‐dependent dependent transcription transcription requires FACTrequires FACT
Curaxins are “first in class” prospective anticancer drugs
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Antitumor Effects of Curaxins
Multi‐targeted molecules. Triple effect on cancer cells.
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Curaxinactivator
inhibitor
inhibitor
live tumor cell dead tumor cell
Non‐genotoxic anticancer drug candidates with triple mechanism of action suitable for use in combinations with
conventional drugs
Antitumor Effects of Curaxins
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Complete cure of mouse fibrosarcomas treated by combination of Curaxin and HSP90 inhibitor (DMAG)
Similar effect is shown in B16 melanoma model
Mechanism of action suggests rational drug combinations
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Curaxins in Cancer Prophylaxis
50% reduction in breast tumor incidence in transgenic MMTV-neumice that were maintained on drinking water with non-toxic doses of curaxinCBLC137 during 10 months
Lack of genotoxicity combined with triple-targeting opens the opportunity of using Curaxins as cancer preventing agents
Breast tumor onset
months1 2 3 4 5 6 7 8 9 10 11 12 13
tum
or-fr
ee m
ice,
%
0
20
40
60
80
100
** *
*
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Advantages of Curaxins
p53 activation
NF-kB inhibition
Heat shock inhibition
Genotoxicity
CuraxinsConventional drugsProperty
p53 activation
NF-kB inhibition
Heat shock inhibition
Genotoxicity
CuraxinsConventional drugsProperty
yes
no
no
yes
yes YES
no yes
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Projected Clinical Opportunities
• Treatment of broad variety of cancers• Low probability of development of drug resistance• Rational combinations with approved anticancer
drugs• Combined use with radiation (radiosensitizers)• Lack of genotoxicity opens an opportunity to use
Curaxins for cancer prophylaxis
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Recent Milestones - Curaxins• Cell Cycle peer review publication (Dec. 2009) –
highlighted ability of prototype curaxin (CBLC102) to inhibit heat shock response in tumors, making them selectively susceptible to heat shock inhibitors
• Oncogene peer review publication (Jan. 2009) – indicated that treatment of cancer cells with CBLC102 resulted in inhibition of additional molecular pathway considered to be highly relevant anticancer treatment target
• Feature presentation at American Association for Cancer Research (AACR) Annual Meeting, April 2010
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INCURON – Curaxins Development Company
• Completed 50/50 joint venture with Bioprocess Ventures, Moscow, Russia- ~$18M to reach Phase II for new generation of Curaxins- Incuron operations launched April 2010
• Curaxin CBLB102: phase I/II trial in patients with liver tumors (planned for 2010 in Russia)
• Completion of preclinical tox and GMP manufacturing of Curaxin CBLB137, IND submission (planned by mid 2011)
• Multicenter (US and Russia) phase I trial in cancer patients with refractory solid tumors (planned for 2011-2012)
• Phase II multicenter trial in patients with specified refractory tumors (planned for 2012-2013)