CC7: How can biotech solve grand challenges?

Question 1

What are red, green and white biotech? Give examples.

Answer 1

Red: health/medicine e.g., drugs and vaccines
Green: agritech e.g., new plants and pesticides
White: manufacture w/v microorganisms e.g., enzymes and biofuels

Question 2

What are technology readiness levels (TRLs)?

Answer 2

The TRL scale is designed to provide a common framework for communicating the state of technology across different organizations, and to help decision-makers understand the level of risk and uncertainty associated with a particular technology.

TRLs are measured on a scale from 1 to 9, with each level representing a different stage of technology development.

Question 3

Describe the different phases of clinical trials.

Answer 3

Pre-clinical: animal model/organoid testing
Phase I: finding of suitable dose (10-100 people)
Phase II: initial indications of efficacy (100-1000 people)
Phase III: randomized, double-blind test of efficacy compared to standard-of-care (~1000 people)
Phase IV: post-approval monitoring to pick up toxicities (>1000 people)

Question 4

What is the Gartner hype cycle?

Answer 4

The hype cycle describes a pattern of over-enthusiasm, disillusionment, and eventual acceptance or adoption of new technologies over time.

1. Technology trigger
2. Peak of inflated expectations
3. Trough of disillusionment
4. Slope of enlightenment
5. Plateau of productivity

Question 5

Why aren’t monoclonal antibodies from mice successful in human therapies?

Answer 5

They aren’t suitable for repeated dosing due to the likelihood of it triggering an immune response in humans.

Question 6

What 3 methods can be used to select antibodies?

Answer 6

Phage display libraries
Transgenic mice
Human experience (take those with good clinical responses to diseases and recover their antibodies)

Question 7

How can an antibody act on a cell?

Answer 7

1. Alone
   - Block receptor signaling (antagonist)
   - Induce receptor degradation
   - Activate signaling (agonist)
2. Complement-dependent cytotoxicity
3. Cell-mediated
   - Ab-Dep cellular cytotoxicity
   - Ab-Dep cellular phagocytosis

Question 8

How can PTMs impact antibody effects?

Answer 8

Glycosylation of the Fc region can impact its ability to interact with Fc receptors. Can also impact half-life and stability.

Phosphorylation of antigen-binding site can impact affinity for the target antigen.

Question 9

Describe complement-dependent cytotoxicity.

Answer 9

Process by which antibodies trigger the complement system, leading to the formation of a membrane attack complex (MAC) on the cell membrane, causing cell lysis and death.

• Can be used in therapy to kill cancer and infected cells.

Question 10

Describe antibody-dependent cellular cytotoxicity and phagocytosis.

Answer 10

ADCC: binding of antibody causes release of cytotoxic molecules e.g., perforin and granzyme.

ADCP: antibodies opsonize the target cell, facilitating recognition for phagocytosis.

Question 11

What are bispecific antibodies? Why are they useful in therapies?

Answer 11

Engineered antibody that binds to different antigens.

Can be used to target a cancer cell and T cell, facilitating the killing of the cancer cell by the immune system.

Question 12

What are warheads in antibody therapies? Give an example of one.

Answer 12

Cytotoxic molecules that are conjugated to antibodies to enhance their therapeutic activity.

e.g., Kadcyla for breast cancer

Question 13

What are some key criticisms against biotech currently?

Give two examples of drugs that have been pulled from the market, and why.

Answer 13

High drug prices
Overly optimistic view of drug efficacy

e.g., Vioxx and Theranos

Vioxx is a COX-2 selective inhibitor that went to market. However, data showing an increase in serious heart problems and death wasn’t disclosed so it had to be withdrawn, despite over 20 million Americans having taken this drug by that point.

Theranos was an at-home blood test machine that was later shown to not be reliable. The company collapsed and the founder was convicted of fraud.

Question 14

What is a clinical outcome assessment?

Answer 14

Measurement used in clinical trials to evaluate the effectiveness of an intervention by measuring the change in a patient’s condition before and after treatment.

Question 15

What are the 6 types of intellectual property? How much does each roughly cost a company?

Answer 15

1. Patents: exclusive rights granted to inventors for a limited time period (>£10 000)
2. Copyright: exclusive rights for creators of original works of authorship e.g., music (free)
3. Design rights: protect aesthetic and visual aspects of products e.g., shape and pattern (£100+)
4. Trademarks: distinctive signs, logos, or symbols that identify goods/services. (£200+)
5. Know-how: any form of technical information relating to the practical knowledge of products. (free)
6. Trade secrets: confidential information, including formulas and processes that provide a competitive advantage to a company. (free)

Question 16

What is assigning and licensing of IP?

Answer 16

Assigning: selling of IP
Licensing: renting of IP

Question 17

What’s the difference between know-how and trade secrets?

Answer 17

Know How is owned by an individual and travels with them. It often may be licensed to others to gain revenue.

Trade secrets are held within a company and employees/individuals are contractually bound to secrecy. The knowledge is bound within the organization until it’s within the public domain.

Neither of these have protection from reverse engineering.

Question 18

What is bootstrapping of a company?

Answer 18

Starting and growing a business without external funding or investment.

Question 19

Define proof of concept.

Answer 19

Proving that an idea works. This helps to ‘de-risk’ the concept for investors.

Question 20

Define seed funding.

Answer 20

Smaller amounts of money (up to £1m) required to get the company started, once you have initially shown proof of concept.

Question 21

Define venture capital.

Answer 21

Form of private equity financing that’s provided by VC firms to start-ups that have been deemed to have high growth potential.

Question 22

What are the various sources of funding before and after company formation, and at exit for a start-up?

Answer 22

Before: translational funding for ‘proof of concept’ work
After: seed funding from VCs, angels and grants
Exit: trade sale or IPO

Question 23

What are the key patenting criteria?

Answer 23

Novelty, inventiveness, and industrial applicability

Question 24

What is a business model? What is meant by standard, loss-leading, or apparently free?

Answer 24

Describes how a company will make money and includes who the customers are, products/services, and costs.

Standard business model: companies charge customers for their products/services to generate profit.
Loss-leading: deliberately price below cost to attract customers and generate sales.
Apparently-free: offers a product/service for free with the intention of generating revenue through other means e.g., advertising or selling of customer data.

Question 25

What are the challenges in red biotech?

Answer 25

Diagnostics/vaccines are low cost per sample so need large sales.
Making something applicable to multiple diseases.
Software is easy to get to market, but there’s a risk of privacy and how much people are willing to pay.
Clinical trials are hard to get approval when concerning children or pregnant women.

Question 26

What are the challenges in green biotech?

Answer 26

Few commercially viable seed-stocks
Substantial and time-consuming regulatory steps
GM regulations differ by territory and the EU is very anti-GM

Question 27

What are the challenges in white biotech?

Answer 27

Hard to compete on price against others
Harder to have monopoly

Question 28

Define value inflection point.

Answer 28

A landmark where there’s a major increase in company value.

In red biotech these could be kitting out a lab, proof of principle or entering clinical trials.

Question 29

Define minimal viable product.

Answer 29

Version of a product with just enough features to be usable by early customers who can then provide feedback for future product development.