2019 Sc ie ntific Re tre a t F RI DAY, APRI L 26, 2019 DI - - PowerPoint PPT Presentation

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2019 Sc ie ntific Re tre a t F RI DAY, APRI L 26, 2019 DI - - PowerPoint PPT Presentation

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2019 Sc ie ntific Re tre a t F RI DAY, APRI L 26, 2019 DI SCOVE RY WORL D PAVI L I ON T URNI NG CANCE R DI SCOVE RI E S I NT O T RE AT ME NT S Brian F. Volkman, PhD T o g e the r, T a king o n Ca nc e r s T o

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2019 Sc ie ntific Re tre a t

F RI DAY, APRI L 26, 2019 DI SCOVE RY WORL D PAVI L I ON

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

T URNI NG CANCE R DI SCOVE RI E S I NT O T RE AT ME NT S

T

  • g e the r, T

a king o n Ca nc e r’ s T

  • ug he st Cha lle ng e s

Brian F. Volkman, PhD

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SFI in Protein Foundry, LLC, manufacturer of recombinant proteins for research use Inventor on multiple issued and pending patents on engineered proteins as potential therapeutic agents

DI SCL OSURE S – BRI AN VOL K MAN

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  • g e the r,

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  • ug he st

Cha lle ng e s 2019 Sc ie ntific Re tre a t

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

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CANCE R COL L ABORAT I VE

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

BUI L D L I NK PROPE L DI SCOVE RY AND DE VE L OPME NT AL T HE RAPE UT I CS PROGRAM DDT = OPPORT UNI T Y

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DRUG DI SCOVE RY AND DE VE L OPME NT

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  • g e the r,

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  • ug he st

Cha lle ng e s 2019 Sc ie ntific Re tre a t

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

TRANSLATIONAL RESEARCH

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DRUG DI SCOVE RY AND DE VE L OPME NT

T

  • g e the r,

T a king o n Ca nc e r’ s T

  • ug he st

Cha lle ng e s 2019 Sc ie ntific Re tre a t

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

MCW excels at basic science research

TRANSLATIONAL RESEARCH

TARGET IDENTIFICATION TARGET VALIDATION

BUIL D the foundation

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DRUG DI SCOVE RY AND DE VE L OPME NT

T

  • g e the r,

T a king o n Ca nc e r’ s T

  • ug he st

Cha lle ng e s 2019 Sc ie ntific Re tre a t

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

MCW excels at basic science research

TRANSLATIONAL RESEARCH

TARGET IDENTIFICATION TARGET VALIDATION

Blake Hill, Francis Peterson, Davin Jensen, Brian Smith, Brian Volkman, Dan Sprague, Mike Olp, John Egner, Liza Lanum, Sarah Rolli

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T ARGE T I DE NT I F I CAT I ON – F YN SH2

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Cha lle ng e s 2019 Sc ie ntific Re tre a t

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

Subramaniam Malarkannan, PhD MCWCC Cancer Biology Program

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T ARGE T I DE NT I F I CAT I ON – F YN SH2

T

  • g e the r,

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  • ug he st

Cha lle ng e s 2019 Sc ie ntific Re tre a t

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

Subramaniam Malarkannan, PhD MCWCC Cancer Biology Program

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T ARGE T VAL I DAT I ON – F YN SH2

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  • g e the r,

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Cha lle ng e s 2019 Sc ie ntific Re tre a t

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

pY peptide binding site

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T ARGE T VAL I DAT I ON – F YN SH2

T

  • g e the r,

T a king o n Ca nc e r’ s T

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Cha lle ng e s 2019 Sc ie ntific Re tre a t

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

Computational solvent mapping identifies ligand binding hot spots

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T ARGE T VAL I DAT I ON – F YN SH2

T

  • g e the r,

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Cha lle ng e s 2019 Sc ie ntific Re tre a t

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

Fyn SH2 for NMR screening of chemical fragment libraries

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MCW I NVE ST ME NT S I N DRUG DI SCOVE RY CAPABI L I T I E S

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

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Translational Accelerator Program

MCW I NVE ST ME NT S I N DRUG DI SCOVE RY CAPABI L I T I E S

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

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DRUG DI SCOVE RY AND DE VE L OPME NT

T

  • g e the r,

T a king o n Ca nc e r’ s T

  • ug he st

Cha lle ng e s 2019 Sc ie ntific Re tre a t

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

TRANSLATIONAL RESEARCH

TARGET IDENTIFICATION TARGET VALIDATION

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DRUG DI SCOVE RY AND DE VE L OPME NT

T

  • g e the r,

T a king o n Ca nc e r’ s T

  • ug he st

Cha lle ng e s 2019 Sc ie ntific Re tre a t

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

The Translational Research Unit helps MCW deliver the latest treatments to more patients

checkpoint inhibitors CAR-T cell therapy

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DRUG DI SCOVE RY AND DE VE L OPME NT

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  • g e the r,

T a king o n Ca nc e r’ s T

  • ug he st

Cha lle ng e s 2019 Sc ie ntific Re tre a t

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

CHALLENGE: Promising

new drug candidates are stranded

TRANSLATIONAL RESEARCH

LI N K

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Goal: first-in-human clinical trials at MCW with MCW- derived discoveries Inception: Formed in 2017, led by Bill Clarke, MCW’s first Director of Research Commercialization Portfolio approach:

  • Identify MCW-derived discoveries with therapeutic

potential

  • Meet with PIs to assess commercial promise,

identify gaps in preclinical development

  • Facilitate next steps toward IND

DRUG DI SCOVE RY AND DE VE L OPME NT : MCWD3

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Cha lle ng e s 2019 Sc ie ntific Re tre a t

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ST RAT E GI CAL L Y MANAGE D PORT F OL I O

2019 Sc ie ntific Re tre a t______T

  • g e the r, T

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  • ug he st Cha lle ng e s
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ST RAT E GI CAL L Y MANAGE D PORT F OL I O

2019 Sc ie ntific Re tre a t______T

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MCWD3: ST RAT E GI CAL L Y MANAGE D PORT F OL I O

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  • ug he st

Cha lle ng e s 2019 Sc ie ntific Re tre a t

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

MCWD3 Members Bill Clarke (OTD) Blake Hill John Imig Mike Dwinell Nita Salzman Ravit Boger Jim Thomas Ben George Paul Ornstein Matt Lasokowski Brian Volkman

Target Honokiol Hippo Mortalin CRR9 p38G Glucosidase II MitoMetformin PBRM1 Fyn Drp1 NAMPT Lif K-Ras Fis1 Cancer Indication Head and Neck Breast Thyroid Pancreatic Pancreatic and Colon Breast Pancreatic and Colon Gall bladder and Breast Leukemias Breast and Testicular Breast and Esophageal Ovarian, Lung, Melanoma Lung, Pancreas, Colon Breast, Pancreas, Esophageal

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MCWD3: ST RAT E GI CAL L Y MANAGE D PORT F OL I O

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  • g e the r,

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Cha lle ng e s 2019 Sc ie ntific Re tre a t

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

MCWD3 Members Bill Clarke (OTD) Blake Hill John Imig Mike Dwinell Nita Salzman Ravit Boger Jim Thomas Ben George Paul Ornstein Brian Volkman Matt Lasokowski

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CXCR4: VAL I DAT E D T ARGE T F OR ME T AST AT I C CANCE R

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Cha lle ng e s 2019 Sc ie ntific Re tre a t

Murphy, PM (2001) NEJM 345, 833-835.

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CXCR4: VAL I DAT E D T ARGE T F OR ME T AST AT I C CANCE R

T

  • g e the r,

T a king o n Ca nc e r’ s T

  • ug he st

Cha lle ng e s 2019 Sc ie ntific Re tre a t

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

Murphy, PM (2001) NEJM 345, 833-835.

Involvem emen ent o t of chem emokine r ne recep eptors in breast c cancer metastasi sis ( s (2001) 2001) Müller er A A et et al. Nature 410, 410, 50 50-56 56

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CXCR4: VAL I DAT E D T ARGE T F OR ME T AST AT I C CANCE R

T

  • g e the r,

T a king o n Ca nc e r’ s T

  • ug he st

Cha lle ng e s 2019 Sc ie ntific Re tre a t

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

Murphy, PM (2001) NEJM 345, 833-835.

Involvem emen ent o t of chem emokine r ne recep eptors in breast c cancer metastasi sis ( s (2001) 2001) Müller er A A et et al. Nature 410, 410, 50 50-56 56

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CB program

E PI GE NE T I C RE GUL AT I ON OF CHE MOK I NE E XPRE SSI ON

2019 Sc ie ntific Re tre a t______T

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E PI GE NE T I C RE GUL AT I ON OF CHE MOK I NE E XPRE SSI ON

2019 Sc ie ntific Re tre a t______T

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a king o n Ca nc e r’ s T

  • ug he st Cha lle ng e s
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CXCR4 I NDUCE S DI ME RI ZAT I ON OF I T S L I GAND CXCL 12

T

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T a king o n Ca nc e r’ s T

  • ug he st

Cha lle ng e s 2019 Sc ie ntific Re tre a t

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

Veldkamp, CT et al (2006) J Mol Biol Veldkamp, CT et al (2008) Science Signaling 1:RA4

[CXCL12] (mM) Fluorescence Polarization

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PROT E I N E NGI NE E RI NG: CXCL 12 L OCK E D DI ME R

2019 Sc ie ntific Re tre a t______T

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a king o n Ca nc e r’ s T

  • ug he st Cha lle ng e s

CXCL122 dimer 10 nM wt CXCL12

IC50 ~ 5 nM THP-1 cells

Veldkamp, CT et al (2008) Science Signaling 1:RA4

[CXCL12] (mM) CXCL12 L36C/A65C

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T RANSL AT IONAL OPPORT UNIT Y: AN

E NGI NE E RE D PROT E I N T HAT BL OCK S CANCE R ME T AST ASI S

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

Drury LJ et al (2011) PNAS 108 17655-60.

untreated L12 dimer treated

Takekoshi T et al (2012) Mol Cancer Ther 11 2516-25.

Colon cancer Pancreatic cancer

Roy et al (2015) Cancer Res 75 3529-42.

Melanoma: lung metastases Liver metastases

MCW technology #1548

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TRANSLATIONAL RESEARCH

MCW technology #1548

T RANSL AT IONAL OPPORT UNIT Y: AN E

NGI NE E RE D PROT E I N T HAT BL OCK S CANCE R ME T AST ASI S

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

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TRANSLATIONAL RESEARCH

PRECLINICAL DEVELOPMENT Licensed to biopharma company

T RANSL AT IONAL OPPORT UNIT Y: AN E

NGI NE E RE D PROT E I N T HAT BL OCK S CANCE R ME T AST ASI S

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

PROPE L pr

  • mising

the r ape utic le ads

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CANCE R COL L ABORAT I VE

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

BUIL D o n e sta b lishe d

e xpe rtise a nd re c e nt institutio na l inve stme nts

L INK disc o ve ry re se a rc h

a nd pre c linic a l de ve lo pme nt

PROPE LMCW-inve nte d

the ra pie s to the c linic

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CANCE R COL L ABORAT I VE

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

BUIL D o n e sta b lishe d

e xpe rtise a nd re c e nt institutio na l inve stme nts

L INK disc o ve ry re se a rc h

a nd pre c linic a l de ve lo pme nt

PROPE LMCW-inve nte d

the ra pie s to the c linic

DDT = OPPORT UNI T Y

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CANCE R COL L ABORAT I VE

mc w.e du/ de pa rtme nts/ c a nc e r-c e nte r @ MCWCa nc e rCe nte r

BUIL D o n e sta b lishe d

e xpe rtise a nd re c e nt institutio na l inve stme nts

L INK disc o ve ry re se a rc h

a nd pre c linic a l de ve lo pme nt

PROPE LMCW-inve nte d

the ra pie s to the c linic

T HANK YOU!

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