Transcript M2M16 Class #1 Slides - Rutgers New Jersey Medical School

Rutgers - GSBS PATH N5209
The Business of Science
From Molecules to Medicines
Fall 2016
Course Organizers:
Nick Ponzio
Steve Ritland
Shanon Hunt
Holly Hilton
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Today’s Agenda
• Welcome and Introduction (Nick)
• A whirlwind tour of drug discovery and development
(Shanon)
• Business meets Science: The Drug Innovation Industry
(Steve)
• Course structure and deliverables (Shanon)
Project team: Introduction to your target
Course Website: http://njms.rutgers.edu/gsbs/olc/fmtm/
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Introduction
This course is about how new drugs get created
This course will provide…
• An introduction to the Big Picture of How Things Are
Actually Done in Biotech/Pharma
• Insight into the day-to-day activities of scientists /
clinicians working in industry
• Practical experience in how molecules move through
the drug development cycle (semester project)
• Examples of areas where industry and academia
collaborate to solve healthcare problems
• Examples of career possibilities related to stages of the
drug development cycle for graduates with advanced
degrees in biomedical sciences
Whether you pursue a career in industry or academics, it’s an
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Course Directors
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Will work for Diet Coke!
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Expectations and Evaluation
Expectations:
• Courtesy to our guest speakers and team members
• Active participation in group work and Project Teams
• Critical Thinking – applying concepts from
lectures to the team project that you will develop
Evaluation:
• No Exams
!
(are you kidding me?)
• Several oral team presentations
• Project Portfolio
• Class assignments and participation (by course directors)
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• Peer feedback on team participation
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If you think what you are doing in school is only to please
your teacher or get a grade, you are missing a chance to not
only learn, but also practice what you will be doing in the
“real world” after you graduate. So:
Be on time
Be prepared
Speak up and contribute without fear
Collaborate on your projects
Make professional presentations
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M2M Biotechnology
M2M Biotechnology specializes
in the full drug discovery and
development lifecycle through
first US Registration.
As M2MBio employees,
you will work on one of 3
teams involved in
developing new drugs
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Field Trips!
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Faculty and Student Introductions
Nick
1. Your name
2. Your major (or your job)
3. Your prior experience (if any) with Pharma/Biotech
4. Your favorite way to celebrate after your (successful)
project presentations!
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Course Structure and Organization
Shanon
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Course Overview
When and where you need to be

Session Dates
– Wednesday evenings
– Sept 7 - Dec 21 (see syllabus)

Session Times
– 6:00 PM - 9:00 PM (with one break, if you’re really, really lucky)

Classroom Location
– GSBS Newark Campus
– Medical Sciences Building (MSB) in the Department of Pathology
– Room C-555 (main lecture); breakout rooms for team activities

Critical Due Dates
–
–
–
–
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Date of your assigned Debate Session
MC Presentation #1: October 19
MC Presentation #2: November 16
Final Project Portfolios: December 21th (last day of class)
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Course Overview
How you’ll spend your class time
Lecture (first ~1hour of each class)

Each session will begin with a high level Introduction of the topic and its context for
your semester project
Activities Section (~2 hours for each class)

Activities will apply concepts from that day’s lecture

The activities conducted in class will be part of your Project Portfolio, due at the end
of the course.
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6 pm ~ 7:00
15 mins
7:15 ~ 9 pm
Lecture
Break
Activities
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Game Rules
Lectures
Our guest speakers are industry professionals who
volunteer their time to teach this class.
1. Please come to class on time.
2. Please do not do emails, texts, Amazon shopping, etc.
during lectures.
Computers or notepads are fine for taking notes, and they will be
very useful during project time (the second half of class), so please
bring them.
3. Please feel free to ask questions/interact with lecturers.
This is a good opportunity for you to get to know experts in their
fields who do drug development every day.
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What you will deliver over the semester
The good...
Textbook: There is no expensive text book needed. We
will provide articles as pre-read.
Exams: There are no exams in this course!
Semester Project:
The Project
Portfolio
Project portfolio: You will build you final project portfolio
one step at a time as we proceed through the
individual class sessions
Debates: are more fun than work, honest.
The bad...
Two Class
Presentations
One Topic Debate
Teams: Your team members, therapeutic area, and
target/compound are assigned (welcome to our world)
Team grading: You will be graded as a team on your
project portfolio including a component of peer
feedback
The ugly...
Presentations: Holly has been known to bring students
to tears...but Steve will make it up to you with a beer
afterward.
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Semester Project
Course Overview
Project Portfolios




The Project Portfolio (PP) is a collection of deliverables that you will
prepare over the course of the semester
Each group will be required to submit a project portfolio at the end of the
semester
PPs will count for 30% of your semester grade
Due Date: December 21
Project Portfolios include the following:
1.
2.
3.
4.
5.
6.
7.
8.
9.
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Executive Summary
Overview of Disease Pathogenesis, Epidemiology, and Current Treatment
Target Rationale
Investigator’s Brochure (Non-clinical Section)
Phase 1 Protocol Synopsis Summary
Investigator’s Brochure (Clinical Section)
Target Product Profile (Start of Phase 3)
Gantt Chart
Lifecycle Strategic Plan
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Course Overview
Group Presentations
Management Committee Requests for Decision



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Each group will develop and deliver two Management Committee Presentations (20
min. each)
This is a “decision point” presentation, with a request to management
Teams must select 2-3 presenters for each of the presentations (all team members
must present at least once)

Week 7: MC Presentation #1 – Entry into Development Portfolio
– Therapeutic Area
– Target, MoA, Scientific Rationale
– Pharmacology
– 20% of your final grade

Week 11: MC Presentation #2 – Proof of Concept, Entry into Phase 3
– Opportunity assessment, market potential
– CMC strategy to FMI
– Clinical Proof of Concept (Ph1 & 2 data, efficacy & safety)
– 20% of your final grade
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Course Overview
Class Debates; Assignments and Participation
Debates:
• 4 – 6 people will be assigned to each debate, assignments to follow
• Students will need to prepare for their role ahead of class
• More details on the debates will be provided as we get closer
• Debates will count for 10% of your final grade
Week 8 (Oct 26)
Ethics of Ph1 studies: How much risk?
Week 12 (Nov 30)
Expedited Approvals: Success or Failure?
Week 14 (Dec 14)
Drug Pricing and Access: What is fair?
Class Assignments and Participation:
•
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These count for 10% of your final grade
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Course Overview
Peer Evaluation - Teams
Feedback from your teammates will determine 10% of your final grade
Team Peer Feedback Form
Evaluator: ___________
Team member being evaluated: _______________________
1. This team member contributed substantially to developing the project strategy
Yes ___
No ___
Comments:
2. This team member contributed substantially to management committee presentations
Yes ___
No ___
Comments:
3. This team member contributed substantially to the final project portfolio
Yes ___
No ___
Comments:
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Overall peer review rating: ____ (score 5% for each “Yes” answer to a maximum of 15%)
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Course Overview
Session Evaluation
Your feedback helps lecturers and course design
Student Feedback Form
Session Date: ___________
Session Topic: _______________________
My satisfaction level with the overall course thus far is: (circle one)
1
Low
2
3
4
5
6
Medium
7
8
9
10
High
9
10
High
My satisfaction with this particular session is: (circle one)
1
Low
2
3
4
5
6
Medium
7
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Specific comments and suggestions (What worked well? Do you have any constructive
feedback?):
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Course Website
Resources for Students
Course Overview
http://njms.rutgers.edu/gsbs/olc/fmtm/
Course Syllabus
Schedule of Classes and Topics
Course logistics
Project information
Background Reading
Course Files
Organized by session date
Reference articles/pre-read material
Lecture presentations
Examples and templates for exercises
Relevant websites
Faculty contact info
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M2M Biotechnology
M2M Biotechnology specializes
in the full drug discovery and
development lifecycle through
first US Registration.
M2M’s expertise covers
oncology, inflammation and
autoimmune diseases.
The current M2M pipeline
includes:
 CDK4/6 in solid tumors
 FGFR in solid tumors
 PDE4 in chronic
inflammation
 JNK in fibrosis
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Project Team and Debate Assignments
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Assignment for Tonight
Team Introductions
 Collect your group into a breakout room
 Introduce yourselves and your background
Research and discuss your target for the semester project
 Start with the articles we provided
 Understand the target, the pathway, and potential therapeutic
applications
 What other companies are developing agents with this target, and
what diseases are they in?
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Q&A
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A Whirlwind Overview of DD
(Shanon)
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Overview of Drug Discovery and Development
The fairy-tale version
2-6 years
Target identification, lead identification, lead optimization, clinical
candidate selection
Discovery
Starts after a lead molecule (clinical candidate) is found
Lab testing, animal studies for safety (tox studies) and efficacy
Phase 0
IND
Phase 1
20-80 Healthy Volunteers
Purpose: determine safety and dosage
Health Authority
End of Ph 1 Meeting
Phase 2
100-300 Patients
Purpose: demonstrate efficacy
Health Authority
End of Ph 2 Meeting
1000-5000 Patients
Purpose: monitor adverse
reactions to long term use
Phase 3
NDA
Launch!
0
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2
4
6
8
10
Years
12
14
16
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Q: Is it really this simple?
A: No way.

It is not a stepwise linear process.
–
–

There is considerable overlap of activities between Phases.
–
–
–

Toxicology animal studies continue to the NDA
Phase 1 or Phase 2 clinical trials can be running concurrently with Phase 3 trials
Phase 1/2 studies...Phase 2/3 studies....
There are other aspects of drug development beyond the Clinical Plan
–
–
–
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The compound could be sent backward to further explore a safety issue or even skip
phases
Some phases might be duplicated (e.g, combinations)
Health Authorities beyond the FDA, like MHRA (UK), Health Canada, Ministry of Health
(China), PMDA (Japan)
Parallel development processes: drug manufacturing (CMC), companion diagnostics
New competitor activities or changes in market demand could change the development
strategy (Business teams)
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LEE011
Clinical Development Overview
2013
2012
Q1
Q2
2015
2014
2014
2013
Q3
Q4
Q1
Q2
Q3
Q4
Q1
Q2
Q3
2016
2015
Q4
Q1
Q2
Q3
Q4
LEE011X2101 FIH single agent
FPFV
May
LEE011X2102 Ph1 s.a.
FPFV
June
Pediatric MRT/NB
LEE011X1101 Japan s.a.
solid tumors
LEE011 s/a in teratoma
FPFV
June
PHASE 1/2
MEK162X2114
Ph1b/2 combo
MELANOMAFPFV
STUDIES
June LEE011X2105 Ph1b/2 combo
FPFV
Sept
FPFV
Sept
PHASE 1/2 BC
STUDIES
LEE + MEK162 N-RAS melanoma
LEE + LGX818 BRAF melanoma
LGX818X2102 Phase 2 rational combo study
BRAF melanoma
MEK162X2110 Phase 2 triple combo LGX+MEK+LEE
BRAF melanoma
LEE011X2106 Ph1b/2 combo LEE + RAD011 and exemestane in BC
LEE011X2107 Ph1b/2 combo
LEE + Let ± BYL in ER+ BC
LEE011X2108 Ph1b/2 combo LEE + Fulv + BYL/BKM in ER+ BC
MONALEESA-1
Ph2 pre-surgical PD dose opt
MONALEESA-3
MONALEESA-5
PHASE 3
STUDIES
MONALEESA-2
Ph2 Neoadjuvant ER+ HER2- Premenopausal Women
Phase 1/2, HER2+ mBC, Trastuzumab-Resistant Patients
Phase 3: ER+ HER2- untreated mBC
MONALEESA-4
Ph3: ER+ HER2- mBC after NSAI
MONALEESA-6
NSCLC
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Phase 3 HR+ HER2+ Untreated mBC
LEE011 + LDK378 in pts with NSCLC
| LEE011 | LEE F2F 2013 | S Hunt |
LEE at 40K | Confidential
TRD Development Plan
CD&MA
4Q2013
1Q2014
DDP/FDP
2Q2014
3Q2014
4Q2014
1Q2015
2Q2015
4Q2015
1Q2016
2Q2016
3Q2016
4Q2016
SDP
ML-2, ER+ HER2- untreated mBC
ML-4, ER+ HER2- mBC after NSAI
BE study DiC vs FCT
CPIC DS (March)
PC1-500kg
CHAD
3Q2015
Decision Point: if BE +, decide between tablet and DiC
if BE -, continue both development streams
LC1-750kg
PAC3-300kg
Resupply 2 - 750kg
PAC4-350kg
LC2-500kg
Resupply 1 - 750kg
DS reg stabs program
CPIC DP (March)
PHAD / PharmOps
DiC
New equipment
qualification
PDC WS2
order,
PDC WS3
DiC resupply
installation,
PDC WS2
PDC WS3
Scale-up
(405)
PED oral liquid
PDC WS2
Transfer to
PharmOps/
WST
QbD3.1–
verificati
on 1
QbD3.2–
verificati
on 2
PDC WS4
QbD1&2 -FMI lab/pilot
PDC WS3
Scale-up
(Siegfried)
Transfer to
PharmOps
PDC WS4
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QbD3.2–
verificati
on 2
DiC DP reg stab program
QbD2 -FMI lab/pilot
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QbD3.1–
verificati
on 1
PDC WS4
QbD2 -FMI pilot
FCT-RC
delivery,
| LEE011 EPT Feb 14, 2014 | TRD Update | Business Use Only
QbD3.1–
verificati
on 1
QbD3.2–
verificati
on 2
Targeting 50-200-300 mg tablet strengths.
Details tbd at PDC WS2
Overview of Drug Discovery and Development
The fairy-tale version
2-6 years
Target identification, lead identification, lead optimization, clinical
candidate selection
Discovery
Starts after a lead molecule (clinical candidate) is found
Lab testing, animal studies for safety (tox studies) and efficacy
Phase 0
IND
Phase 1
20-80 Healthy Volunteers
Purpose: determine safety and dosage
Health Authority
End of Ph 1 Meeting
Phase 2
100-300 Patients
Purpose: demonstrate efficacy
Health Authority
End of Ph 2 Meeting
1000-5000 Patients
Purpose: monitor adverse
reactions to long term use
Phase 3
NDA
Launch!
0
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4
6
8
10
Years
12
14
16
18
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All said and done, Drug Development can rival
the US Immigration Process
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Drug Development
...is typically organized into three groups
Discovery
• Research
• Pre-clinical Dev’t
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Early
Development
Full
Development
• PoC Dev’t
• Exploratory Dev’t
• Phase 1 Dev’t
• Late Stage Dev’t
• Global Dev’t
• Confirmatory Dev’t
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Overview of Drug Discovery and Development
Discovery
Target
Assessment
(TA)
Lead
Series
Identified
(LSI)
Clinical
Lead(s)
Selected
(CLS)
Target Identification and
Validation
Lead
Identification
Lead
Optimization
Identify a biological
pathway and molecular
structure of interest
Identify one or more leads (biological
or chemical compounds) that interact
with the target to get the desired
therapeutic effect.
Optimize the physicochemical
characteristics of the compound to
make it more druggable.
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Clinical
Candidate(s)
Selected
(CCS)
Entry Into
Human
(EIH)
Preclinical or
Nonclinical Testing
Demonstrate
safety in animals
prior to human
trials, show
therapeutic
advantages
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Overview of Drug Discovery and Development
Exploratory Development
Entry Into
Human (EIH)
or FIH FIM
Phase 1
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Start of
Phase 3
Start of
Phase 2
Phase 2
Evaluate safety in healthy
human volunteers
Evaluate efficacy and
side effects in patients
Establish PK and PD
profile for better
characterized drugs.
Establish PK and PD
profile for better
characterized drugs.
PoC
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Overview of Drug Discovery and Development
Confirmatory Development
Filing
Decision
Phase 3
NDA
Post Marketing
Approval
and
Launch
Demonstrate/confirm the
compound is as effective
as existing drugs, if not
more so
Refine safety profile
(long-term toxicity,
undesirable side effects)
across a large number of
patients
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Evaluate use of the drug in
different patient groups
Identify new therapeutic
opportunities
Develop new formulations
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