Biotech Management Quiz 2

Lock and Key metaphor

The “lock” is the mechanism within the body (ex: receptor) that a virus bind to vs the “key” is the drug developed that can bind to the receptor

Founding scientific principle of Vertex and their management principle. How did it change?

Founded on developing drugs mechanistically rather through screening. Later had to implement some screening. Originally had a non-hierarchical structure. Later increased corporate structure.

Therapeutic index meaning? Do you want it to be low or high?

TI = LD50/ED50. Measures dosage that killed 50% of animals tested compared to the non-lethal dosage. Want TI to be high.

What is required for an invention to be patentable

Novel, Useful, Non-obvious

accredited investor?

someone allowed to invest in private companies due to their high net worth, income, or professional expertise

What was Grunenthal? What did they do wrong?

Grunenthal was the company that first put out thalidomide. They conducted poor animal trials, didn’t do small clinical trials, and didn’t properly document things

ADME and relation to thalidomide?

Absorption, Distribution, Metabolism, and Excretion. Grunenthal did not properly test how how drug moves through body in their animal trials

Biotechnology company vs. Pharmaceutical

Biotechnology = large molecule company (protein-based therapies). Pharmaceutical = small molecule company (chemicals)

Problem with proteins as drugs?

Protein structure depends on the environment, leading it to easily denature.

Lock and Key in terms of FK506

FK506 would be a “Key”, what it binds to is the “lock”, once lock identified they designed better key = FKBP

What is “freedom to operate”?

No one else has a patent that covers what you’re doing

Simple preferred stock

You get what you invested back

Convertible preferred stock

what you invested OR the percent of the company you own (ex: If you own 30% of the company you get post-money valuation * 0.3)

Participating preferred stock

what you invested AND your percent of the company

If a company’s pre money valuation is 20 million, you invest 10 million, how much of the company do you own?

invested/total = 10/30. You own a 1/3 of the company.

What does going public allow a company to do?

sell to non-accredited investors

What do you need to practice (sell) your invention

freedom to operate

Manuel Navia’s job at Vertex?

VP and Senior scientist

“most admired corporation in America” in 1980s-1990s

Merck

Why doesn’t FDA regulate supplements like drugs

Lobbying

Pill bottle vs. Syringe slide

Pill bottle = for solid medications, long term storage, portable; Syringe slide = liquid medications, accuracy in dosage

What birth defects did thalidomide cause

Seal limbs

How does Thalidomide cause limb deformities

Its anti-angiogenic (blocks blood vessel growth), it binds to the same receptor that growth hormone binds to, and it can cross placenta

Why wasn’t vertex negotiating with American Drug Makers?

They were rejected because American companies thought they lacked research and standing

Heinrich Muckter job before Grünenthal

Head of spotted fever research in Auschwitz

Why does NJ have concentration of pharma companies? Why aren’t biotech companies in the same place

NJ already had the established manufacturing from chemical companies with evolved into pharma companies. Biotech founded closer to concentration of famous and innovative universities.

What is Read Length?

length of the molecule fragments that can be read which distinguishes the ability to do an assembly

Long vs. short read sequencing

long read = better and reveals more about the structure of the genome, but you need to get signal one molecule at a time; short read = more popular bc its cheaper

Name two long read companies

Oxford Nanopore and Pacific Biosciences

Main short read company and how does it work?

Illumina; sequencing by synthesis

Jonathan Rothberg

CEO of Cura Gen, founded Ion Torrent, and founded 454 Life Sciences

454 Life Sciences vs Ion Torrent

Ion torrent is the next generation of sequencing from 454 Life sciences. Used Electrical detection rather than optical 

George Church

Geneticist and Co-founded Veritas Genetics

Eugene Chan

Dropped out of Harvard Medical school to found a genome mapping company called U.S. Genomics

Genome mapping

Not looking at the whole sequence, but the distance between some of the sequences motifs

somatic mutation vs. germline mutation

somatic mutation = acquired, present in small fraction of cells (ex: tumor); germline mutation = inherited, present in all cells.

Heritability

for a given phenotype, statistical measure of variance (variance due to genetics/total variance in trait you’re observing)

GWAS (Genome-Wide Association Study)

taking two large groups of people, looking at their genome, and comparing (to characterize a disease); more complex and polygenic diseases is , more people you need

How does GWAS work (measurment)

Used microarrays to measure single nucleotide variant (single letter changes in places that are more variable)

Relative Risk vs. Odds Ratio

how much more likely are you to have a phenotype based on a genotype 

Kári Stefánsson

founder of deCODE

SNP

Single Nucleotide Polymorphism; variation at a single base in DNA sequence