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A multi-pronged approach to treat cancer. Jonathan Rios-Doria, Ph.D. Bite of Science Towson University, Baltimore, MD September 10 th , 2014. Outline of my talk. 1. My career path. 2. Fundamentals of cancer biology and why cancer is hard to treat. 3.

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A multi pronged approach to treat cancer

A multi-pronged approach to treat cancer

Jonathan Rios-Doria, Ph.D.

Bite of Science

Towson University, Baltimore, MD

September 10th, 2014


Outline of my talk
Outline of my talk

1

My career path

2

Fundamentals of cancer biology and why cancer is hard to treat

3

MedImmune’s approach to cancer therapy

4

A day in the life at MedImmune and critical skills needed


Education and experience
Education and Experience

  • Eisenhower H.S, Shelby Twp., MI

  • University of Michigan, B.S., Cellular and Molecular Biology

  • University of Michigan, Ph.D. Cellular and Molecular Biology

    • Cancer Biology focus

  • Postdoctoral fellowship at Moffitt Cancer Center in Tampa, FL

  • Employed at startup biotech company in Tampa, FL

    • Nanomedicines to treat cancer

  • Joined MedImmune in 2011


Hallmarks of cancer
Hallmarks of Cancer

Hanahan and Weinberg, Cell. Volume 144, Issue 5, 2011, 646 - 674


Cancer statistics 2014
Cancer Statistics, 2014

Siegel R., et all. CA Cancer J Clin. 2014 Jan-Feb;64(1):9-29


Why is cancer hard to treat
Why is cancer hard to treat?

  • Cancer is not one disease, it is a collection of diseases

  • Cancer is heterogeneous

    • Identifying which patients will respond to a therapy is challenging

  • Cancer cells are good at avoiding death

  • Most cancers recur and are develop drug resistance



Fast facts medimmune and astrazeneca
Fast Facts: MedImmune and AstraZeneca

  • MedImmune: a world-leading biologics company

    • Founded 25 years ago

    • Combines several former biotechs; merged with CAT in 2008

    • Biologics subsidiary of AstraZeneca

  • MedImmune “Firsts”

    • First approved fully human MAb drug: Humira (world’s top selling drug)

    • First FDA-approved MAb for infectious disease: Synagis

    • First VLP technology for HPV vaccines

    • First advance in flu technology in 60+ yrs: FluMist

  • AstraZeneca: world leading oncology company

    • tamoxifen (Nolvadex), bicalutimide (Casodex), gefitinib (Iressa), fulvestrant (Faslodex), anastrozole (Arimidex)


Two major areas of focus

Tumor Targeted Therapies

Immune Mediated Therapies

Directly and specifically attacking tumor cells with powerful biologics

  • Activating and shaping a potent and durable anti-tumor immune response


We Match the Target to the Best Therapeutic Technologies

  • MedImmune is a world leader in the development of antibody drugs

  • Multiple sophisticated biologics platforms within our tool kit

ADCC enhanced

YTE

(half life extension)

Antibody Drug Conjugate

Bi-Specific

NK

TM

(effector null)

The biologics IMEDs

Ligand

Mimetic

Target Cell

10


Adc mechanism of action
ADC Mechanism of Action

Schrama et al 2006. Nat Rev. Drug Disc


Anatomy of adcs
Anatomy of ADCs

  • http://www.biooncology.com/research-education/adc/about-adcs/index.html

Target

  • High expression in tumors

  • Very limited normal expression

    Antibody

  • Target specific

  • Internalized to lysosome

  • Site-specific conjugation technology

Linker

  • Non-cleavable, cleavable

  • Stable to prevent release of the warhead

    Cytotoxic warhead

  • Highly potent small molecule

  • Chemically-modifiable to attach linker

  • Payload = Linker + Warhead

12


Cancer stem cells a paradigm shift
Cancer Stem Cells: A paradigm shift

Targeting cancer stem cells may provide a durable clinical response


Cancer immunotherapy 2013 breakthrough of the year
Cancer Immunotherapy – 2013 Breakthrough of the year*

Pardoll., et al. Nat Rev Cancer. 2012 Mar 22;12(4):252-64

*as chosen by the editors of Science


My primary role at medimmune
My primary role at MedImmune

  • In vivo pharmacology

    • New model development

  • Evaluating in vivo efficacy of various anti-cancer drugs in the pipeline

  • Determining pharmacokinetics and mechanisms of action of drugs

  • Identifying which tumor models and types in which the drugs work

  • Identifying molecular markers of drug response


Drug development timeline
Drug Development Timeline

Clinical Trials (~10 years)

Preclinical

Research (~3-5 years)

Target

Discovery

Approval

IND

Where most of my work is



Patient derived xenograft pdx models
Patient-Derived Xenograft (PDX) models drug

-Tumor is directly from patient

-Never cultured in vitro



Exploring mechanism of action of antibodies
Exploring mechanism of action of antibodies drug

Nonspecific

IgG

Antibody X

mg/kg

30

10

3

30

pAkt

Akt

pSrc

Src


Fluorescent imaging of ovarian cancer

Untreated drug

Untreated

B07

B07

Antibody 1

Antibody 1

Fluorescent imaging of ovarian cancer


Why i chose this career
Why I chose this career drug

  • Patient is the primary focus

  • Discovery is exciting

  • Opportunities for innovation and novel therapies

    • New technologies

  • Variety and dynamic nature of work


Example of typical day
Example of typical day drug

  • 7:30-9:00am – catch up on emails, prepare for meetings

  • 9:00-10:00am – meeting with project team

  • 10-11am – seminar from invited speaker or candidate interview

  • 11-11:30am – chat in hallway around cool idea or recent piece of data

  • 11:30-12:30pm – lunch

  • 12:30-1:00pm – respond to emails received in the morning

  • 1:00-2:00pm – meeting with another project team

  • 2-3:30pm – individual or team meetings with members of staff

  • 3:30-4:00pm – teleconference or video chats with colleagues or external partners

  • 4-5:00pm – catch up on emails and start to prepare for next day’s activities

  • 5:00pm- Leave


What i look for in a job candidate
What I look for in a job candidate drug

  • Creative thinker and intellectually sharp

  • Evidence of problem solving ability

  • Good educational background and record of accomplishment

  • The ability to work in a team environment

  • Good communication skills



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