Translational Medicine: Transforming Science into Medicines

1
Translational Medicine Transforming Science
into Medicine(s)

• Mason W. Freeman, M.D.
• Director, Translational Medicine
• Center for Computational Integrative Biology
• Clinical Research Program
• Massachusetts General Hospital

2
Is there a new partnership opportunity ?

• The Problems
• Drug development costs have skyrocketed
• Productivity from big pharma is declining
• Failures in late clinical development hugely
  expensive
• Pharma downsizing to accommodate
  revenue/productivity gap
• The Opportunities
• Tools for drug discovery are becoming more widely
  accessible
• Outsourced activities in lower cost environments
  emerging
• Scientific discoveries produced at accelerating
  pace
• Pharma and biotech seeking new approaches to
  development
• New clinical investigation tools emerging rapidly
• New generation of investigators excited by
  translation

3
Lost in Translation

• Translation medicine has become a buzzword
• For industry- doing things differently than
  before
• For academia-doing things it didnt do before
• What is Translational Medicine ?
• Is it an academic discipline ?
• Is it a set of skills ?
• Is it a mind set ?
• Is it an illusion ?
• Is it a delusion ?

4
Translational Medicine-the first stage

• The first translation block- bench to bedside
• Exploration of new pathways for treatment and dx
• Development of biomarkers of disease
• Identification and validation of new therapeutics
• From bedside to bench- human genetics- and back
  again
• The second translational block
• From clinical trial/academic medicine to clinical
  practice
• How do we implement the knowledge advances we
  have made

5
Translational Medicine Getting past the first
block

• What are human ingredients needed for success
• Physician-scientists translate lab science into
  practice
• Must have solid grounding in modern science
• Must be collaborative and team oriented
• Basic scientists who want to study clinical
  problems
• Must know some human physiology and
  pathophysiology
• Must be collaborative and team oriented
• Supportive infrastructure
• Financial backing

6
MGH-CCIB approach

• CCIB- basic science laboratories-Brian Seed, PhD
• Chemistry
• Biologics screening capacity
• Animal models
• Development team- Mason Freeman, MD
• Basic pharmacology/bioassays
• Clinical expertise-tapping academic faculty
  talent
• Project management experience
• Regulatory expertise- toxicology, CMC, FDA
  interactions
• Contacts for outsourcing tox and manufacturing
  activities

7
What projects are we doing at the MGH ?

• Diabetes- small molecule development
• Chemical synthesis with a Chinese pharmaceutical
• MGH TM team responsible for all CMC, toxicology,
  regulatory, and clinical trial design- utilize
  in-house expertise and external consultants
• Goal Successful proof of concept clinical trial
• Inhibitor successfully blocks target
• Obtain blood sugar response in diabetic
  population in phase I
• Pharma support required for phase 2b/phase 3
  studies

8
MGH Projects Polycystic Kidney Disease

• Partnership with Stowers Research Institute
• Novel pathway inhibition inhibits cyst formation
  in rodents
• Drugs that block pathway already approved for
  other diseases
• MGH will oversee pre-clinical development program
• MGH convened Academic Advisory Board
• Using advisors from inside MGH as well as
  external academics
• Yale, Mayo, Pitt, Kansas academics have agreed to
  participate
• MGH will design and coordinate clinical trial if
  preclinical outcomes prove favorable

9
MGH projects Muscle atrophy

• Muscle atrophy and wasting
• Steroid myopathy
• Disuse atrophy
• ? Metabolic derangements
• MGH scaffold protein-not blocked by Ab or other
  IP
• Designed to stimulate muscle growth
• Have compound with nanomolar affinity
• Now testing in animal models of muscle atrophy
• Goal is to take through to proof of concept in
  humans
• If successful, partner with large biotech or
  pharma

10
Producing the next generation of clinical
investigators Proposed MGH Translational
Fellowship program

• Combined fellowship MD/MD-PhD and PhDs eligible
• Will tap into existing training programs
• Harvard graduate program in TM
• Clinical and basic science training programs at
  MGH
• Exploit science infrastructure in the new Simches
  Center
• Genetics Stem cell and tissue regeneration
  CCIB Imaging Mol Biol
• Will have didactic and mentored research project
• Dual mentors- clinical and basic science
• Fund late-stage fellows as early faculty -
  provide career path
• Create cadre of translational investigators who
  can form teams
• Partner with industry groups for training and
  projects

11
Business model TM/biotech partnerships

• Academia assembles pre-clinical and early
  clinical development team and supports its cost
• Academia taps faculty expertise to design trials
• Biotech reduces burn rate with lower personnel
  costs while accessing high level expertise
• Biotech brings NME pays development costs
• Academia provided small royalty payment if
  successful, enabling ongoing program support

12
SummaryTranslational Medicine

• Requires new academic structures and training
• Partnership of PhDs and MD/MD-PhD
• Evaluations focused on contribution to team
  success
• Include role for individuals with industry
  experience
• Infrastructures that support time-sensitive work
• Dedicated financial support with program income
  return
• Requires new relationship with industry
• More collaborative rather than simply
  consultative
• Solutions to confidentiality conundrums
• Risk-sharing with some royalty reward for success