Introduction to Drug Development in

Commercializing Biomedical Technology

Jeffrey Larson, Ph.D., DABT

“Turning Your Research Into A Therapeutic

What You Should Think About and When"

Summary

• FDA Exclusivity – How does exclusivity differ from

your patent?

• Development works BACKWARDS from the label

• Your first step – the Investigational New Drug (IND)

submission

FDA Exclusivity

• Patent protection is not the same as FDA exclusivity

• New Chemical Entity (NCE) exclusivity is 5 years

– Exclusivity is around the moiety itself and not the indication

– Other companies cannot pursue other indications

– Competion cannot file ANDA until 5 yr is up (so essentially 7

yr)

– Risk is that another company can file an NDA if they

generate their own clinical data

• Clinical Investigation (CI) exclusivity is 3 years

– New dosage form, new indication, OTC switch

– Exclusivity is specific to indication

– Competition can file ANDA during exclusivity period

FDA Exclusivity

• Orphan Drug exclusivity is 7 years

– 200,000 or fewer patients

– Exclusivity is around the indication, FDA may approve

another company’s NDA for a different indication

– FDA may accept another NDA for the same drug

substance if drug product is clinically superior

• Pediatric exclusivity can add 6 months

– 6 months to all exclusivity

– FDA must first request Sponsor to conduct pediatric trial

Start 0 yrs 3 yr 4.4 yr 14 yr 16 yr 20 yr

I

d

e

a

Patent

Prose-

cution

Paten

t Issues

Preclinical

FD

A R

eview

Market

Exclusivity

Clinical

Expires

How much time is

remaining on your patent?

Prior Art

• Prior art - information made available to the public in

any form before the date a patent is claimed

• If an invention is described in the prior art, a patent

on that invention is not valid

• “I have done groundbreaking work for this DRUG in a

wildly novel indication. Why isn’t pharma

interested?”

• If the work is prior art on a known NCE, the only scenario available is a 3 yr FDA exclusivity

• Likely cannot make money to cover the cost of clinical

development

Path to Drug Development • My therapeutic kills cancer cells

• Throw my drug on cells and they stop dividing

• IP dose my drug and tumor shrinks

• Do my preclinical tox/PK

• Make my drug GMP

• Run clinical trials

• Get FDA blessing to sell and make some money!

Working Backwards? •I just know it kills cancer cells, not

what the label will be! But:

– What is the treatment schedule?

– Neoadjuvant, adjuvant or metastatic

disease?

– First line, second line, fourth line?

– Instead of or on top of standard of care?

– Can you enroll patients in clinical trials?

– Is cost of goods reasonable?

– Reimbursement – can I get

reimbursement and for what indications?

The Patient Population to Whom You

Market the Drug Drives Clinical

Development

• Patient Population

– Single agent or combination?

– Treatment of disease or

prevention of disease?

– Treatment and duration?

– Third line and then move up

to first line?

– Enroll all comers to targeted

patient population?

– Biomarker for patient

selection?

Can you enroll your trial?

What you intend to do in the Clinic

and Marketing Drives Manufacturing

Development

• CMC (Chemistry, Manufacturing &

Controls)

– Can I scale-up the research process to

amounts anticipated commercially?

– Is the drug substance and drug

product stable to meet clinical

expectations?

– What does a formulation look like?

– How am I going to use the drug – how

do I see it being prescribed and how

does it come from the pharmacy?

Preclinical Toxicology and PK •Goals:

– Identify/characterize target

organ toxicities

– Maximum Tolerated Dose

(MTD), No Observable Effect

Level (NOEL) & Lowest

Observable Effect Level (LOEL)

– Assess time to toxicity and reversibility of effects

– At what blood levels (tissue levels) are toxicities observed

– Do systemic exposures vary with number of doses?

•Characterize toxicity profile in animals and not

humans!

What You Intend to do in the Clinic

Drives Preclinical Development

• Preclinical Toxicology and PK

– Determine appropriate species dependent on drug/biologic

– Treatment duration and regimen

determines what the toxicology

program looks like • How often and how long?

– Treatment indication determines what

toxicology program looks like • Genotoxicity, reproductive toxicology

– Route and excipients

To sum, studies are not conducted in a vacuum

What You Intend to do in the Clinic

Drives Pharmacology Development

• What is the appropriate species?

• How can I build value?

– What is the dose? What is the route? How often and for

how long? Would the regimen translate into the clinic?

– Can I focus on a particular indication?

– Is there a biomarker I can use to tell the drug has reached

the site of action at the required concentration and is

doing what I intend for it to do?

• How high should I set the bar for positive results?

Again, studies are conducted to inform the clinical team about how to use the drug and in which patient

Other Issues in Pharmacology

Development

• There is no guidance on the number of studies that

you have to conduct – you have to generate data

that convinces FDA to allow you to put people at

risk

• Studies do not have to be GLP, but I always

recommend in the “spirit of GLP” with regards to

record keeping and reporting

– You are going to have to report data to FDA at some point

– Characterize the drug to the best of your current

knowledge, including formulation

Investigational New Drug

Application (IND)

• The document is a request from the

company/investigator to the FDA to administer an

investigational drug to people for a particular

indication

• Essential Components

– Results of preclinical efficacy, PK and toxicology

– CMC: Information on composition, manufacturing and

quality control

– Clinical study protocol for your human trial

• INDs are either commercial or research

Investigational New Drug

Application (IND)

• You need to provide sufficient efficacy data to

convince FDA that the drug will work

– Data can be your data and/or data from the literature

– Include mechanistic data showing that the target is in the

disease pathway; POC data does not have to be only with your compound

• You need to convince FDA that drug is reasonably

safe at the intended clinical use

– Risk: benefit profile will depend on disease being treated

– Data on analogous compounds also important for class

effects

Investigational New Drug

Application (IND)

• The FDA has 30 days in which to act on an IND

submission

• No news is good news, OK to proceed

• If FDA doesn’t like something, they can slap a

partial or complete clinical hold

•A clinical hold could be avoided by having first

had a pre-IND meeting to discuss potential issues

with FDA

An Informative Pre-IND Meeting is

critical for a Successful IND Submission

• FDA wants you to succeed

• FDA is willing to provide

guidance on the data that

you need to submit to

support your IND

•Meeting may be in person

or via teleconference (if at

all) – and you only get ONE

•Asking the right questions is

key

Pre-IND Meeting – On what issues do

you want FDA concurrence?

• Pharmacology

– Do the pharmacology studies support the intended clinical regimen?

• Toxicology

– Do the proposed GLP toxicology studies support the proposed clinical trial

– Species, dose levels, dose regimen, dose duration?

• CMC

– We are changing xxx for the clinical GMP production, will

the drug substance produced by yyy and tested in GLP

toxicology studies support the proposed clinical trial?

Pre-IND Meeting – On what issues do

you want FDA concurrence?

• Clinical

– Does FDA concur with the first clinical trial in the intended disease population?

– Does FDA concur with the proposal to enroll patients on

investigational drug alone?

– Does the Agency agree with the time (duration) between

enrolling and dosing individuals within a cohort?

– Does the Agency agree in the proposal to enroll patients

in the first two cohorts on investigational drug alone and the subsequent cohorts on drug plus standard of care?

– Does FDA agree with the primary endpoint in the Phase 2

trial?

Pre-IND Meeting – What to Expect

• You may obtain concurrence on all issues and have no pre-

IND meeting, or they will be a teleconference or you may be

invited to in person meeting

• The Sponsor (you) will have a team of all relevant players and

FDA will have a team of relevant players

•Generally an hour is the time allotted for the entire meeting

• No visual presentation– you will have provided a detailed pre-IND meeting package – you get straight to the questions

• Don’t ask open ended questions and have back-up strategies

•You keep minutes and FDA issues draft minutes on which you

can comment. Final minutes are issued by FDA.

Recommendations are not absolutely binding, but very

unusual for FDA not to be bound by their recommendations

Summary

Protect your IP !!! Loose lips sink ships

Development of target product

profile is essential for early

development.

Discussions with FDA early and as

often as necessary are crucial

Empowering Innovation In Life Sciences

Contact:

Jeffrey.larson@texasbioalliance.org

6500 Main Street, #1040

Houston, TX 77030

713-979-9107