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UNSEEN TRENDS IN

@unseenvalue BIOTECHNOLOGY
MR.SAJAL KAPOOR
SPEAKER: @unseenvalue

ORGANIZED BY: SOIC


S O I C

IN ASSOCIATION WITH: PERFECT FOUNDATION

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TO THE PERFECT FOUNDATION
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A T I this
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participants and not to be construed as investment advice. Please consult


your financial advisor before acting on it. I may have an interest in some of
the stocks discussed.

Registration Status: We are not SEBI Registered Advisors


Reference: Annual Reports, Earnings Calls, Industry veterans and
Management interactions

This video is only meant for education purpose and nothing constitutes as
an investment advice. We are only into providing education services.

@unseenvalue School of Intrinsic Compounding


I NT R ODUC T I ON
“Sajal Kapoor is an operational risk and regulatory
compliance consultancy professional with over two
decades of industry experience working for banks,
healthcare and investment firms.

He’s also a passionate investor always hunting for that


‘unseen undervaluation’. Over the years, both his
profession and investing journey have taught him
some precious lessons including the benefits of staying
inside your core competence, the power of discipline,
patience and time.

Sajal did his MBA from Manchester Business School in


2010 and currently stays in London with his family. He
MR.SAJAL KAPOOR is active on twitter with the handle @unseenvalue.”

@unseenvalue

UNS E E N T R E NDS I N B I OT E C HNOL OGY


ACCELERATING
NON-LINEAR CHANGE
(E.G: CLIMATE CHANGE)

@unseenvalue School of Intrinsic Compounding


BIOECONOMY: INDUSTRY 5.0 (VISION 2)
INDUSTRY 4.0 INDUSTRY 5.0 (VISION 1) INDUSTRY 5.0 (VISION 2)
MOTTO Smart manufacturing Human-Robot Co-working Bioeconomy
MOTIVATION Mass Production Smart Society Sustainability

POWER Electrical Power Electrical Power Electrical Power


SOURCE Fossil-Based Fuels Renewable Power Sources Renewable Power Sources
Renewable Power Sources

INVOLVED Internet of Things (IOT) Human-Robot Collaboration Sustainable Agricultural Production


TECHNOLOGIES Cloud Computing Renewable Resources Bionics
Big Data Renewable Resources
Robotics & Artificial
Intelligence (AI)
INVOLVED Organizational Research Smart Environments Agriculture
RESEARCH Process Improvement & Organizational Research Biology
AREAS Innovation Process Improvement & Waste Prevention
Business Administration Innovation Process Improvement & Innovation
Business Administration Business Administration
Economy

@unseenvalue School of Intrinsic Compounding


UNSEEN TRENDS IN BIOTECHNOLOGY

CDMO

AGRO

ETHANOL

HUMAN

ANIMAL

OIL & GAS

ENERGY

VACCINES

CRISPR/CAS9

DIAGNOSTICS

TEXTILE

PRECISION
FERMENTATION

@unseenvalue School of Intrinsic Compounding


BIOECONOMY
INDUSTRY 5.0 (VISION 2)

MOTTO OF INDUSTRY IMPACT OF


5.0 (VISION 2) IS BIOTECHNOLOGY WILL
BIOECONOMY BE MULTI-SECTOR AND
MULTI-DECADAL

BIOTECHNOLOGY WILL
HAVE A MUCH WIDER
AND DEEPER IMPACT
BY 2025, INDIAN
BIOECONOMY IS
BIOTECHNOLOGY IS
EXPECTED TO BE
SET TO SUSTAINABLY
WORTH $100-150
IMPROVE THE QUALITY
BILLION
OF LIFE

@unseenvalue School of Intrinsic Compounding


INVESTMENT SCREENING CRITERIA

INDUSTRY BUSINESS MANAGEMENT


STRUCTURE ECONOMICS
Critical or essential Walking the talk
Antifragile or positive-
forward rate of change product/service

Favourable 5 forces High entry barriers Capital allocation track


(ROCE impact) record

Chemicals 2010 vs 2020 High exit barriers No major red flags


(fraud, misconduct etc)
Low cyclicality Skin in the game
APIs 2004-2019

@unseenvalue School of Intrinsic Compounding


BIOTECHNOLOGY AS A MEGATREND ?
ACCELERATING NON-LINEAR CHANGE (E.G: CLIMATE CHANGE)

BIOTECHNOLOGY AS A MEGATREND ?

GENOMICS & GENOMIC DIAGNOSTICS

CRISPR/Cas9 & PRECISION MEDICINE (CELL, GENE THERAPY)

AGRI-BIOTECHNOLOGY

BIOPRINTING

INDUSTRIAL BIOTECHNOLOGY

ENZYMES AND FERMENTATION (FERMENTED AND FUNCTIONAL FOODS, CULTURED MEAT, PROBIOTICS,
NUTRACEUTICALS, DAIRY, SUGAR, PAPER, TEXTILES, DETERGENTS, BIOCATALYSIS ETC.)

HUMAN AND ANIMAL BIOTECHNOLOGY (VACCINES, THERAPEUTIC PROTEINS LIKE INSULINS MABS, BIOINFORMATICS
AND XAAS (X = DRUG DISCOVER, DRUG DEVELOPMENT, DRUG MANUFACTURING, FOOD MANUFACTURING AND SO ON)

@unseenvalue School of Intrinsic Compounding


GENOMICS &
GENOMIC DIAGNOSTICS

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GENOME: THE BIG PICTURE

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@unseenvalue
GENOMICS & DIAGNOSTICS
GENOME: OPERATING MANUAL
CELL AND COMMAND CENTRE (NUCLEUS)
CHROMOSOMES
DNA: BLUEPRINT OF LIFE
MESSENGER RNA (mRNA)
GENE: ROLE?
GENETIC MUTATIONS
GENOMIC SEQUENCING
RARE DISEASES
GENOMIC DIAGNOSTICS
School of Intrinsic Compounding
@unseenvalue GENOMICS & DIAGNOSTICS

DNA GENE
CELL CONTAINING NUCLEUS CHROMOSOME

School of Intrinsic Compounding


@unseenvalue
GENOMICS & DIAGNOSTICS
GENETIC SIMILARITY BETWEEN VARIOUS SPECIES

BANANA: 60% FRUIT FLY: 61% DOG: 84%

CHIMPANZEE: 96% MOUSE: 85% HUMAN: 99.90%


School of Intrinsic Compounding
GENOMICS & GENOMATICS DIAGNOSTICS
Artificial intelligence, genomics and new age therapies are converging

Genomic sequencing is the process of analysing and understanding the exact order of a
individual’s DNA
The entire genetic code of a human was first sequenced in 2003

Genomic diagnostics helps in early detection of life-threatening diseases like cancer

Genomics helps identify parts of an individual’s genomes that make them more likely to
have certain medical conditions (from birth or later in life)
Human genes are 99.9% identical. That 0.1% difference accounts for all variations and
diseases
Whole-genome sequencing allows doctors to address medical problems much more
effectively
Cost of DNA sequencing will continue to drop, making it affordable for masses

Missing sequences / global misrepresentation problem [only 2% African and 10% Asian
ancestry]
@unseenvalue School of Intrinsic Compounding
@unseenvalue
GENOMICS & DIAGNOSTICS

School of Intrinsic Compounding


GENOMIC DIAGNOSTIC:
SAMPLE BUSINESS
Pioneering genomic diagnostics company
Changing today's clinical practice standards (invasive procedures in all suspicious
cases)
Diagnostics that give physicians and patients a clearer path forward

Genomic technology and machine learning to enable more confident diagnostic,


prognostic and treatment decisions in challenging diseases such as thyroid cancer,
lung cancer, breast cancer and idiopathic pulmonary fibrosis
Speeding time to diagnosis and treatment while removing costs from the healthcare
system
“To improve the lives of patients by resolving diagnostic uncertainty
and reducing risky, costly and often unnecessary surgeries.”
– Mission @ Veracyte

@unseenvalue School of Intrinsic Compounding


GENOMIC DIAGNOSTIC:
SAMPLE BUSINESS
GENOMIC TESTS TARGETING MULTIPLE DISEASES ACROSS CARE CONTINUUM
@unseenvalue

School of Intrinsic Compounding


VERACYTE + DECIPHER BIOSCIENCES

@unseenvalue School of Intrinsic Compounding


VERACYTE + DECIPHER BIOSCIENCES

@unseenvalue School of Intrinsic Compounding


VERACYTE + DECIPHER BIOSCIENCES

@unseenvalue School of Intrinsic Compounding


VERACYTE + DECIPHER BIOSCIENCES

@unseenvalue School of Intrinsic Compounding


CRISPR/Cas9 &
PRECISION MEDICINE
(CELL, GENE THERAPY)

@unseenvalue School of Intrinsic Compounding


@unseenvalue School of Intrinsic Compounding
CRISPR-Cas9 = HOPE & HAPPINESS
Sickle cell disease is caused by the mutation in a single
letter out of > 3 billion base pairs in a person’s genome

Haemoglobin protein defect restricting oxygen flow into


the tissues and organs causing severe pain and death
by the age of 50 in most cases

Victoria Gray is the first person in the US to be


successfully treated for a genetic disorder with the help
of CRISPR

Where the cells can be easily extracted for ex vivo


CRISPR gene editing and then returned back to the
patient (in vivo). Sickle cell disease is one such example Victoria Gray (second from the left) with children Jamarius
as blood cells are easy to extract Wash, Jadasia Wash and Jaden Wash. Now that the gene-
editing treatment has eased Gray's pain, she has been able
90k US; 40m worldwide (mostly in sub-Saharan Africa) to be more active in her kids' lives and looks forward to the
future. "This is really a life-changer for me" she says
Victoria Gray

@unseenvalue School of Intrinsic Compounding


CRISPR: Cas9 & PRECISION MEDICINES
WHAT IS GENE-EDITING SCIENCE IN SIMPLE TERMS?
Gene editing inserts, deletes or replaces DNA in part of a
genome

Treat fatal and incurable genetic diseases. Modify


immune cells to target cancer cells. Stop the spread of
diseases like Malaria.

CRISPR, a biochemical tool is at the forefront of gene


editing revolution

Clustered Regularly Interspaced Short Palindromic


Repeats [CRISPR-Cas9]

Cas9 (CRISPR Associated Protein)

gRNA

@unseenvalue School of Intrinsic Compounding


WHAT
IS CRISPR ?

@unseenvalue School of Intrinsic Compounding


CRISPR: CAS9 & Viral vectors are currently the most common
method for getting CRISPR-Cas9 genes into
cells
PRECISION MEDICINES
CDMOs partner with various gene-editing
innovators to develop these vectors and
treatments
Hacking the CRISPR system

Engineer the gRNA in a CRO/CDMO or


in-house lab

Attached gRNA to Cas9

Search for a match using gRNA

Find-and-Cut

Find-and-Replace
Gene expression and mutations

@unseenvalue
Social & ethical angle
School of Intrinsic Compounding
@unseenvalue CRISPR: Cas9 & PRECISION MEDICINES
Customised DNA based precision medicines (PMs)
Lung cancer cells are present in ALK or EGFR
genes. PMs can target those cells w/o damaging
normal cells
PMs offer potential to cure many rare and
orphan diseases
400m children worldwide suffer from many rare
inherited diseases
PMs reduce trial-and-error medication

Avoid known side-effects and adverse reaction


Improve quality of life
Affordability and Accessibility a major issue
Risk of unknown unknowns
School of Intrinsic Compounding
@unseenvalue IMMUNOTHERAPY
DNA mutations (UV, radiations,
smoke etc)
Malignant tumour

CRISPR-Cas9 can edit cancer cells to


make conventional therapy more
effective
Proxy war with cancer

T-cells + B-cells = Super T-cells

Role of CRISPR in Immunotherapy


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@unseenvalue School of Intrinsic Compounding
IMMUNOTHERAPY

Infuse super T-cells


back into the
Grow millions of patient to fight, kill
Genetically super T-cells cancer cells
engineered T-
Insert gene for T- cell/B-cell
cell/ B- cell receptor
Draw blood
receptor
from patient to
collect T-cells

@unseenvalue School of Intrinsic Compounding


School of Intrinsic Compounding @unseenvalue
@unseenvalue
CELL & GENE THERAPY
Cell therapy introduces new, healthy
cells into a patient’s body, to treat the
diseased cells

Allogeneic / Autologous - cells for


therapy may originate from the patient
(autologous) or a donor (allogeneic)

Cells are cultivated or modified


outside the body before being injected
into the patient

School of Intrinsic Compounding


@unseenvalue CELL & GENE THERAPY
Gene therapy aims to treat diseases by
introducing, inactivating or replacing genes
into cells - either inside the body (in vivo) or
outside of the body (ex vivo)
Certain therapies are a mix of both cell &
gene (e.g. CAR-T). These therapies work by
changing genes in specific types of cells and
injecting them into the body
Scientists expect that gene therapy will
eventually treat or cure majority of genetic
and rare diseases

USFDA receives over 200 applications for


gene therapy annually
School of Intrinsic Compounding
@unseenvalue CAR-T THERAPY
In CAR-T, immune system cells
are removed from the blood and
a gene is added

Modified cells are added back


into the body to bind to proteins
in the patient’s cancerous tumour

The cost of cell and gene therapy


is exorbitantly high today

Like any new therapy, there will


be unknown unknows (risks)
despite various clinical and
regulatory checks
School of Intrinsic Compounding
@unseenvalue AFFORDABILITY & ACCESSIBILITY
CRISPR offers great hope in lasting happiness
for the patients and their close family and
associates]
CRISPR can cure a rare form of blindness and
may restore patient’s eyesight
Many patients suffering from rare diseases
may never benefit from super expensive
CRISPR
USD 1 million or more as the per patient
treatment costs can make healthcare system
go bust
CAR-T therapy costs about USD1 million to
USD 1.5 million
Immuneel Therapeutics aims to offer CAR-T at
USD 50,000 per treatment School of Intrinsic Compounding
RISKS IN CRISPR TECHNOLOGY & GENE EDITING

Precisely targeting CRISPR/Cas9 to


CRISPR-Cas9 could cause harmful changes
parts of the body is still challenging
elsewhere in a person’s genome

Issue is to get CRISPR only to the cells of


Need a proven ability to precision-target
interest.
CRISPR-Cas9 to the target area and have a
Ensuring enough editing takes place at the ‘off switch’
target location to realise the desired benefits
Immune response risk? Both CRISPR-
What if gene-editing goes wrong? What if Cas9 and AcrIIA4 are non-human origin
there are undesired effects? (expression
of Cas9 in the wrong place, or for too
Other risks? – Unethical, terrorism,
long)
clinical & regulatory pathway is still
emerging and uncertain
AcrIIA4 (Anti CRISPR protein) – could
be that ‘off switch’. Further research
is WIP

IF <Organ specific unique RNA


molecule> THEN …..

@unseenvalue School of Intrinsic Compounding


BIOPRINTING

@unseenvalue School of Intrinsic Compounding


@unseenvalue BIOPRINTING
Bioprinting is an extension of 3D
printing in healthcare industry

Promise to repair/replace tissues,


organs using a patient’s own stem
cells
Promise to mitigate a shortage of
donor organs (over 110k waiting in
US)
Challenge lies in printing larger and
complex body parts (like liver, kidneys)
School of Intrinsic Compounding
@unseenvalue BIOPRINTING
Bioink - cells and biomaterials used in
bioprinting

Bioprint cells and materials that makeup


human tissues

Bioprinting organs can reduce the need for


animal testing in medicines (making pieces
of tissue that can be used to test drugs)

Fully functional organs available for


transplants may well be a distant dream
School of Intrinsic Compounding
@unseenvalue BIOPRINTING
Challenges in fabricating and mirroring complex
biology – cell density and blood flow
For some patients, even a patch could be a life-
saving treatment

Researchers at WFIRM been using bioprinters to


create bio-printed body parts (ears, skin, muscle,
bone) for animal testing*
The Wake Forest Institute for Regenerative Medicine
(WFIRM) is recognized as an international leader in
translating scientific discovery into clinical therapies

School of Intrinsic Compounding


“There are a number of companies who are
attempting to do things like 3-D print ears....The
difficulty is kind of coming together and producing
complex patterning of cells and biomaterials
together to produce different functions of the
different tissues and organs”
- Robby Bowles, Bioengineer

“For any cells to stay alive, [the organ] needs that


blood supply, so it can’t just be this huge chunk of
tissue.......“an individual cell will have to be within
200 microns of your nearest blood supply. . . .
Everything has to be very, very close."
- Courtney Gegg, Prellis Biologics

@unseenvalue School of Intrinsic Compounding


RISKS IN BIOPRINTING
Tissue Heterogeneity:
Tissues and organs are made up of a Quality Compliance Risk:
variety of different cell type Bioprinted tissues are bespoke,
dedicated and printing locally
Blood Supply: Cells and tissues die
without continuous blood supply Accessibility and Affordability :
Bioprinting is for a specific purpose
Immune rejection: Being the other
challenge
Supply Chain is Complex:
Regulatory Risk: New technology with Various components of a bioprinted
emerging guidelines and approval organ
pathway

Data protection legislation:


Distribution of CAD files for
biofabrication requires
sensitive patient data in order
to design the construct

@unseenvalue School of Intrinsic Compounding


CASE STUDY: CELLINK
Thinly traded (relatively speaking) with just 3,000 shareholders (AR screenshot below)
Concentrated holdings in the hands of very few shareholders
Worth tracking the business for updates

@unseenvalue
School of Intrinsic Compounding
CRISPR CAN RESOLVE
@unseenvalue
SHORTAGE OF DONOR ORGANS
CRISPR can edit the pig’s genome
Removing specific genes to disable essential proteins that make
pigs organs (step 3)
Extract hiPSCs from patient (highlighted extract from research
journal)
Gene-edited pigs act as factories for custom made organs
Developed organ transplanted from pig to patient (step 7)
Donor’s (pig’s) gene-edited organs are less likely to trigger an
immune response risk
Bioprinting stock’s inflated valuations justified?
MEAT PRODUCTION USING
@unseenvalue
BIOPRINTING

School of Intrinsic Compounding


AGRI-
BIOTECHNOLOGY

@unseenvalue School of Intrinsic Compounding


AGRI-BIOTECHNOLGY
Many Japanese, EU, US and very few Indian companies are active in
CRISPR gene-editing and biopesticides

CRISPR-Cas9 offers great promise for agriculture


Suppress unfavourable characteristics (e.g. disease vulnerability)

Empower beneficial characteristics (e.g. drought tolerance)

Break genetic linkages b/w genes conferring positive traits (e.g. disease
resistance) with less desirable traits (e.g. drought sensitivity)

Help cultivate plant varieties with most desirable combination of traits (e.g.
disease-resistant crops implies reduced chemical sprays)

Help reduce the consumption of natural resources (e.g. water)


Help improve crop yield and farm productivity
GMOs (genetically modified organisms) contain DNA from other species.
CRISPR gene-editing does not introduce DNA from a different plant species

@unseenvalue School of Intrinsic Compounding


@unseenvalue AGRI-BIOTECHNOLGY
Today global food-chain is heavily genetically modified
(GMOs). ~90% of major global crops like corn, corn and
soyabeans are genetically engineered
Lot of CRISPR based research is focused on Potato (being a
top global crop)
Potato crops are under attack from fungi, viruses and
bacteria
CRISPR can make potatoes blight-resistant by knocking a
few genes out of potato’s genome

Successful gene-editing can limit or even eliminate some


harmful chemical pesticides

School of Intrinsic Compounding


@unseenvalue AGRI-BIOTECHNOLGY
CRISPR can also address the ‘cold-induced
sweetening’ (during storage starches in potato
naturally convert to sugar)
During high-temperature cooking, sugar gets
converted into acrylamide
Acrylamide is detrimental for CNS and can even
cause cancer
CRISPR-Cas9 can knockout the single gene that
converts starch into sugar
CRISPR can fix many other negatives (like the
natural toxin solanine) by knocking out specific
genes
CRISPR can also make vegetables more nutritious
(e.g. more vitamin C, B6) and more delicious School of Intrinsic Compounding
CRISPR GENE EDITING VS GMOs
JAPAN Approved gene-edited food to be sold to consumers without any additional
safety evaluations as long as the techniques involved meet prescribed criteria

NORTH Gene-edited crops that don’t contain foreign DNA don’t require the same
AMERICA strict regulation and testing as in case of GMOs

EUROPEAN Genomic-edited crops are heavily regulated like GMO. Challenged by France
UNION [https://www.chemistryworld.com/news/fresh-calls-for-eu-to-review-gene-edited-crops-regulations/4012738.article#/ |
https://www.reuters.com/article/us-france-agriculture-gmo/france-backs-non-gmo-regulation-for-crop-gene-editing-in-eu-
idUKKBN29N1T9]

CRISPR GENE GENETICALLY MODIFIED


EDITING ORGANISMS
DNA ORIGIN No genes outside the species family are introduced No genes outside the Genes from another species
or are synthetically made
DNA LOCATION DNA change is made to precise location in the DNA variations are implanted at random locations
genome within the genome
PLANT
EUROPEAN UNION

Modified plants are identical to their traditional Modified plants are different from traditional
IDENTIFICATION equivalents
plants
REGULATION US currently not regulating gene-editing (when GMOs on the other hand face stringent
own family genes are edited which is natural regulations from authorities
process)
@unseenvalue
CASE STUDY: TROPIC BIOSCIENCES
By 2030, tropical nations will have - 500m
additional people; inhabit 8 of the world’s 10
largest cities; account for over 50% of global
population
Tropic Biosciences develops high-performing
commercial varieties of tropical crops using
cutting edge genetic editing technologies

Tropic Biosciences has a proprietary technology


platform GEiGS™ (Gene Editing induced Gene
Silencing) used in the development of disease
resistant plant varieties (e.g. banana, rice, coffee)

Banana is most commonly eaten fruit worldwide


and rice is a staple food for 50% population

@unseenvalue School of Intrinsic Compounding


CASE STUDY: TROPIC BIOSCIENCES
DNA, RNA and RNAi – a quick refresh

GEiGS leverages the existing gene editing tools like CRISPR to


edit existing RNAi genes and direct their silencing functions
towards new targets (insects, fungi, viruses or even plant’s
own genes)
TR4 or Panama Disease is caused by a soil-based fungus
resistant to fungicides [http://www.fao.org/world-banana-
forum/fusariumtr4/en/]

Tropic Biosciences is using CRISPR gene-editing tool as the


basis to address Panama Disease and lengthening the shelf
life of bananas (by reducing ethylene in banana - the
compound that causes it to rot)

School of Intrinsic Compounding PANAMA DISEASE


CRISPR GENE EDITING VS GMOs
Tropical crops, their producers and consumers stand to
benefit from Tropic’s IP
Coffee is another area of focus for Tropic Biosciences

Globally, coffee is a USD 80bn industry with almost half


of production at risk due to diseases
Tropic is working on creating coffee with reduced
caffeine and improved solubility – features that could
significantly reduce the need for chemical processing
of the product
Proprietary technology platform GEiGS™ has strong out-
licensing, collaboration potential (e.g. BASF)
“Gene editing process can take as many as 10 years,
incurring significant costs, with no guarantee of
achieving the desired outcome”
– Tropic Biosciences

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@unseenvalue AGRI-BIOTECHNOLGY
SHARE OF LAND USED FOR ARABLE AGRICULTURE,2015
The share of land used for arable agriculture, measured as a percentage of total land area. Arable land
includes land defined by the FAQ as land under temporary crops (double-cropped areas are counted
once), temporary meadows for mowing or for pasture, land under market or kitchen gardens & land
temporarily fallow.

AGRICULTURAL BIOLOGICALS

BIOFERTILIZERS BIOSTIMULANTS BIOPESTICIDES

BIOHERBICIDES BIOFUNGICIDES BIOINSECTICIDES

School of Intrinsic Compounding


@unseenvalue AGRI-BIOTECHNOLGY
ADVANTAGES OF BIOPESTICIDES BIO-CONTROL VS CHEMICAL CONTROL
Growing market preference worldwide
Biopesticides do not cause pollution
Pests never develop resistance
Harmless to non target species
Relatively difficult to identify, develop, clear regulatory
challenges and manufacture with consistency
DISADVANTAGES OF BIOPESTICIDES
Slow acting relative to chemical sprays
Target specific action implies multiple approaches
Shorter shelf life compared to chemical pesticides
Lower volumes due to highly selective target

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CASE STUDY: RALLIS INDIA
Rallis India has been researching and
developing ideas in the field of biotechnology

Cutting-edge technology development in the


Agri-biotech arena (e.g. produce more with
less fertilizer)
Genetically modified (‘GM’) traits developed
for maize and cotton having insecticides and
herbicides tolerance
Developing designer microbes that produce
nitrogen in the soil, leading to lower
supplemental fertilizer

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AGRI-BIOTECH: GLOBAL PLAYERS

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AGRI-BIOTECH: GLOBAL PLAYERS

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AGRI-BIOTECH: GLOBAL PLAYERS

AMPLUS
It is a novel technology micro-
organisms based bio-fertilizer
product. It helps to improve
the crop yield through fixing
up of more atmospheric
nitrogen, improving soil
structure and water holding
capacity and improving
fertilizer use efficiency

@unseenvalue School of Intrinsic Compounding


BIOPESTICIDES: JUST STARTING

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HUMAN AND ANIMAL
BIOTECHNOLOGY (VACCINES,
THERAPEUTIC PROTEINS LIKE
INSULINS MABS, BIOINFORMATICS
AND XAAS (X = DRUG DISCOVER,
DRUG DEVELOPMENT, DRUG
MANUFACTURING, FOOD
MANUFACTURING AND SO ON)

@unseenvalue School of Intrinsic Compounding


HUMAN & ANIMAL BIOTECHNOLOGY

@unseenvalue
THE SHAPE OF DRUGS TO COME:
Antibody Drug Conjugate
Bispecific Antibody
BiTE® Molecule
Car T Cell
Fusion Protein
Monoclonal Antibody
Oncolytic Immunotherapy Virus
Peptides
RNA Interference
Small Molecule
@unseenvalue
Therapeutic Protein
School of Intrinsic Compounding
MONOCLONAL ANTIBODIES (mAb)
Monoclonal antibodies are bioengineered molecules that
are designed to target specific proteins involved in disease
The targeted antigen might be a protein found on a
pathogen or a protein marker found on malignant or
infected cells
Like natural antibodies, they are potent and highly
selective in terms of the targets they engage
mAbs tend to stay in the body longer than most other
medicines, so in general, they need to be dosed less
frequently
Antibody drugs can be used against targets that are
outside cells or on the cell surface, but because of their size,
they generally can’t reach targets inside cells

Most major CDMOs, Biopharma players research,


develop and manufacture mAbs (e.g Thermo Fisher,
@unseenvalue Lonza, Syngene, Amgen, Biocon, Lupin, Intas)
ANTIBODY DRUG CONJUGATES (ADCs)
Many drugs used to treat cancer have toxicities that
lead to serious side effects, which limit the dose
and effectiveness
The goal is to deliver the cytotoxic payload more
directly to tumour cells and reduce the collateral
damage to healthy tissue

The antibody portion of the ADC can be designed to


target specific proteins found primarily on tumour
cells

Antibody Drug Conjugate (targeting region and the


payload)

Bio-CDMOs offer this (Piramal, Lonza, DCAL, Syngene)

@unseenvalue School of Intrinsic Compounding


PEPTIDES
Peptide is a term applied to small proteins
comprised of short chains of amino acids
(roughly 40 or fewer)

Peptide medicines can be used to replace or


mimic the functions of naturally occurring
peptides or to emulate the ability of peptides to
engage targets in a highly potent and selective
manner

Some peptide therapies can be made using


chemical processes (e.g. Neuland Labs), while
others are produced inside genetically modified
cells (e.g. Amgen, Biocon)

@unseenvalue School of Intrinsic Compounding


PROTEINS & PEPTIDES ARE BUILDING BLOCKS
KEY THERPEUTIC AREAS:
Research around possibilities of age reversal
GLOBAL R&D PIPELINE IS
SHIFTING TOWARDS BIOLOGICS Personalised/Precision Therapy (Cell and gene,
CAR-T)
Rare and orphan diseases across therapeutic
areas from CNS and Respiratory to Diabetes
Live biotherapeutic products (Lonza-Hansen JV)

Peptides

Affordability and Accessibility (Biosimilars)

Fermentation-based immunosuppressants and


APIs (import substitution India)
School of Intrinsic Compounding
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AGE REVERSAL BY DESTROYING
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SENESCENT CELLS ?
Advances in public health, sanitation, nutrition,
new drug discoveries add few years to life every
decade
90 could be the new 60 few decades out
Clinical trials are underway to find out if ageing
can be reversed by targeting senescent cells
Zombie cells – refuse to die and release
cytokines causing inflammation and age related
diseases
The major research focus of James L. Kirkland,
M.D., Ph.D., is the impact of cellular aging
(senescence) where research on lab mice
extended their lifespan by 36%.
(https://www.mayoclinic.org/medical-professionals/endocrinology/news/senescent-
cells-promising-anti-aging-targets-for-health-span-extension-and-the-treatment-of-
osteoporosis/mac-20431073)
School of Intrinsic Compounding
INVESTING OPTIONS: HUMAN & ANIMAL BIOTECH
Technology is the biggest moat as For an average investor
well as the risk for a biotechnology Biotechnology, ETFs or Mutual
company Funds are a better risk/reward
option (medium to high risk)
Regulatory risk is also
significantly higher for a XaaS vs direct exposure to
biotechnology company businesses working with
disruptive science?
Legal/litigation risk fighting the
patents war Discovery as a Service (CRO)

Compounding cash flows visible Development as a Service (CDO)


today vs promise of mammoth
Manufacturing as a Service (CMO
cash flows in future?

Direct exposure to smaller Integrated DDM (CRO-CDMO)


biotechnology plays are high to as a Service
very high risk (rewards could well
be high to very high as well)
@unseenvalue
CDMOs HAVE SIGNIFICANTLY
@unseenvalue
OUTPERFORMED
CDMOs MAKE MONEY
@unseenvalue
REGARDLESS OF R&D OUTCOME
Global small, mid and large companies rely on
outsourced Science-as-a-Service model
Intellectual property is owned by the innovator
outsourcing their requirements to a XaaS provider

Any player following XaaS model shall make money


from Day 1
If a (discovery, development) project fails to clear
regulatory hurdle – XaaS are paid for their services

If a project clears regulatory hurdles and goes


commercial – XaaS may continue making money
(manufacturing the novel compound)
REFERENCE: A Masterclass on Global Custom
Development & Manufacturing Opportunity
(https://indianinvestingconclave.com/recordings/97)
@unseenvalue BIO CDMO NON-LINEAR GROWTH
@unseenvalue CASE IN POINT: SYNGENE

School of Intrinsic Compounding


LAURUS BIO
(ERSTWHILE RICHCORE)
Laurus Bio identifies, develops and manufactures Animal
Origin Free recombinant proteins and enzymes for
Biopharma and Industrial Biotechnology

Laurus Bio’s solutions are used in - Stem Cells &


Regenerative Medicine, Vaccines & Biological Drugs,
Cultured Meat and Bio-Manufacturing industries
Laurus Bio’s solutions are used in the global food, water,
energy, textiles, paper, sugar and biopharma

Enzymes for multiple Industrial Biotechnology usages like


Plant-based protein, Textiles, Paper, Sugar

IP in Rc Proteins (Rc Carboxypeptidase B, Rc Trypsin


standard, Rc USP Trypsin, Rc Transferrin, Rc Human
Albumin 20%, Rc Human Albumin 10%, RC Thermolysin)

@unseenvalue School of Intrinsic Compounding


LAURUS BIO
(ERSTWHILE RICHCORE)

@unseenvalue School of Intrinsic Compounding


INDUSTRIAL
BIOTECHNOLOGY

@unseenvalue School of Intrinsic Compounding


INDUSTRIAL BIOTECHNOLOGY
Fermentation comes from the Latin word Fervere, which means to boil (though fermentation is possible w/o heat)

Industrial Fermentation also called White Biotechnology relies on the cultivation of living cells both for the
production of whole-cell biomass (yeast or probiotics as an example), or a valuable fraction thereof biomolecules
of interest (enzymes, antibiotics, insulin, amino acids, etc.)

“Fermentation is a scientific process that breaks down the sugar found in organic materials. Through a series of
chemical reactions during fermentation, glucose is converted to ethanol, an alcohol-based biofuel that can be used
to power cars, trucks, and airplanes.

While most ethanol fuel is produced from corn, sugar cane, and sweet potatoes, it can also be made from wheat,
barley, oats and rice.” - Novozyme

@unseenvalue
INDUSTRIAL BIOTECHNOLOGY
IB leverages the science and processes of living organisms to develop useful everyday products

Microbial fermentation technology platforms are the backbone of a multitude of sectors


Climate Change and Clean Energy (electricity, multimodal transportation, heating etc)

Increased production efficiencies and yields across the industries (e.g. bio-nutrients enhancing
fermentation yields)
Industrial enzymes (Sugar, Textiles, Detergents, Paper, Biocatalysis)
Fermented Foods (kefir, cultured milk, yoghurt, wine, beer, cheese, bread, other non-meat foods)
Cultured meat – genuine meat manufactured in a bioreactor
Functional Foods - Probiotics, Nutraceuticals, HMOs
Cost-effective enzymes can partially replace surfactants
Renewable chemicals and materials (potential to replace almost all fossil-fuel based plastics & materials)
Sustainable and circular economy (waste as input, value as output)
@unseenvalue School of Intrinsic Compounding
CELLULAR & ACELLULAR AGRICULTURE

CELLULAR ACELLULAR
Generating living cells (like fat, fibre and Persuading a living microscopic organisms (e.g.
connecting tissue) that can proliferate and yeast, algae, bacteria or fungi) to synthesise specific
become food or non-food consumable material organic molecules such as protein and fats that
(e.g. clothing) aren’t actually alive themselves
Starting point is yeast or some other
Starting point is biopsy and cell line creation
microorganism to make the same exact proteins
Final product is made of cells found in the animal products they are seeking to
displace
Foods or products that are made by cells

Genetically engineered organisms are removed


from the final product, these foods are GMO-free.
Supporters call it “precision fermentation”;
Opponents call it synthetic biology or even GMO 2.0

School of Intrinsic Compounding

@unseenvalue
WHY DO WE NEED BIOTECHNOLOGY IN
FOOD PRODUCTION ?
Dairy allergies (second biggest childhood allergy in the US) School of Intrinsic Compounding

Water usage (1L milk requires approximately 1KL water)


Food shortage (A cow consumes 75-300x of dry matter to produce just 1x of protein)
Climate change (world's livestock account for 18% of GHGs)
Unkindness (Over 56b farmed animals are killed every year by humans)
Land shortage (One-third of the planet's arable land is occupied by livestock feed crop cultivation)
No Foodborne Illness. No Contaminants. No Antibiotics traces

@unseenvalue
ENZYMES AND FERMENTATION
(FERMENTED AND FUNCTIONAL
FOODS, CULTURED MEAT,
PROBIOTICS, NUTRACEUTICALS,
DAIRY, SUGAR, PAPER, TEXTILES,
DETERGENTS, BIOCATALYSIS ETC.)

@unseenvalue School of Intrinsic Compounding


CASE FOR ALTERNATE PROTEINS ?
Global population pegged at 10 billion by 2050

Demand for protein rising faster than population


growth
Record $3.1 billion invested in alternate proteins
in 2020
Signals growing market momentum for sustainable
proteins

Cultivated meat has seen fastest growth in capital


investments

Plant-based and fermented foods have attracted


significant capital in 2020

@unseenvalue School of Intrinsic Compounding


ALTERNATE PROTEIN LANDSCAPE
PLANT BASED BEYOND MEAT; QUORN;IMPOSSIBLE FOODS; GARDIEN
CULTURED MEAT Bluenalu; Memphis Meats; Mosa Meats; Aleph Farms; Shiok Meats; Clear Meat

CULTURED PET FOOD Wild Earth; Because Animals; Hownd

EGGS Clara Foods; Eat Just

FERMENTATION - DAIRY Biomilk; TurtleTree; Perfect Dairy; New Cultures

AIR FERMENTATION PROTEIN Air Protein; Deep Branch; Novonutrients; Solar Foods

GROWTH MEDIA Merck KGaA; Scinora; Cultured Blood; Richcore; Multus Media; Biftek; Heuros

BIOREACTOR Thermo Fisher; Merck Millipore; Applikon Biotechnology; Celltainer Biotech


BIOPRINTING Vivax Bio; Better Diary; SunP Biotech

SCAFFOLDING Matrix Meats

@unseenvalue School of Intrinsic Compounding


PRECISION FERMENTED
'AIR MEAT'
Air Meat = microbes making proteins using carbon dioxide
pulled from the air (late 60s technology prototype)
Technology essentially borrowed from NASA’s research to
feed scientists on ultra-long space missions
Step 1: CO2 + Energy + Microbes (Hydrogenotrophs)
Step 2: Fermentation (growth media + time in a fermenter)

Step 3: Air Protein flour (~80% protein content compared to


40% in typical soy protein flour)

You think fermentation an old science? Biotechnology in


future can enable what was previously
unviable/unthinkable!

@unseenvalue School of Intrinsic Compounding


PRECISION FERMENTED
'AIR MEAT'
Solar Foods competes with Air Protein as underlying patented-technology
is similar but not the same (different microorganisms, equipment design
and process IP)
Solein has higher amount of essential amino acids than other comparable
sources (e.g. beef, soy)
Solein can be used to enrich traditional foods like breakfast cereals,
yoghurt, bread, pasta and other ready meals
Solein can also go with other plant-based protein formulations (e.g.
Impossible Foods, Beyond Meat)

Price parity b/w Solein and Soy is likely in next 5 years


Much lower GHG emissions due to energy-efficient manufacturing process
Reference: https://www.forbes.com/sites/brianfrank/2019/07/17/making-protein-from-thin-air-yes-startups-are-doing-it/?sh=7ddb763f61ee

"Conventional food production wastes water at unsustainable and unreasonable levels. We


wanted to fix that. Our bioprocess produces natural protein from CO2 and electricity. It's 100
times more climate-friendly than meat and 10 times better than plants. Unlike conventional
protein production, it takes just a fraction of water to produce 1kg of Solein® – the purest
protein in the world.“- Solar Foods

@unseenvalue School of Intrinsic Compounding


PRECISION FERMENTED
'AIR MEAT'
22% of 2018 greenhouse gas emissions were from
Industries

How about recycle CO2 from polluting industries into


sustainable protein feed?
Bacteria proteins fed on CO2 and incubated in bioreactors
to create animal feed

Natural, non-GMO, complete proteins, with all the amino


acids found in meat

Substantially reduced impacts on environment, wildlife


and natural resources

“The annual CO2 emissions from a large cement plant would create 3 billion
dollars of our protein flour, worth the same as the entire annual soy
production of the state of Nebraska — 330 million bushels a year.”
- Novonutrients

@unseenvalue School of Intrinsic Compounding


PRECISION FERMENTED
'AIR MEAT'
Recycling CO2 using microorganisms into
nutritious animal feeds

Better gross margins. Better economics

Bespoke nutritional profile to animal feed


producers demand for precision nutrition

Technology differentiation (CO2 vs sugar or


methane)

Unlike fishmeal or soy, there is no fluctuation in


price or yield caused by seasonality
Import traditional protein or make locally with
90% less carbon burn?

@unseenvalue School of Intrinsic Compounding


PRECISION FERMENTED
'AIR MEAT'
School of Intrinsic Compounding

@unseenvalue
PRECISION FERMENTED DAIRY
Discovery of secret milk proteins (whey and casein)
Identify the genes that produce milk proteins

Insert those genes into the genome of a efficient and fast multiplying
microflora (micro-organism likes bacteria, yeast or fungi)
Fermentation in a bioreactor fed with essential growth nutrients

Separate proteins from cells and purify


Start-ups such as ‘Perfect Day’ and ‘New Culture’ are using precision
fermentation to make animal-free proteins
@unseenvalue School of Intrinsic Compounding
TurtleTree:
CELLULAR TECHNOLOGY
Singapore based TurtleTree Labs claims to have replicated the human breast milk by growing mammary gland
cells
Extract viable (healthy) and productive human mammary cells from milk

Proliferate and grow by feeding and nourishing the essential micronutrients

Proprietary cellular technology to culture mammary cells (in vitro) including the HMOs (Human Milk Oligosaccharides)

Harvest by separating the cell biomass using filtration

@unseenvalue School of Intrinsic Compounding


BIOMILQ:
HUMAN MILK FOR BABIES

@unseenvalue School of Intrinsic Compounding


CULTIVATED MEAT
Cultivated meat production process is inspired by the proven biotechnology in therapeutics
Cultivated meat = lab-grown meat = cell-based meat = cultured meat = in vitro meat

@unseenvalue School of Intrinsic Compounding


@unseenvalue CULTIVATED MEAT: E2E PROCESS
Cell lines – Type (pluripotent, multipotent,
specialised); Proliferation and Stability (consistency
across batches)

Growth Media – Basal Medium (amino acids, salts,


sugars etc) and Growth Factors (signalling proteins
that can control animal cell behaviour)

Scaffold – 3D support structure that may or may not


be biodegradable. High porosity is a must

School of Intrinsic Compounding


@unseenvalue
CULTURED MEAT VS PLANT MEAT
KEY DIFFERENTIATORS

Savvy marketing and trade secrets are the main differentiating factors in plant based meats

Intellectual Property and process innovation are the main differentiating factors in cultured meat
Entry barriers in cultured meat are higher than plant based meats

Risk of technology-failure or inability to scale-up production is higher in cultured meat

Many start-ups in cultured meat may fall by the wayside

Cultured meat market may be less crowded than plant based, with PaaS/licensing opportunity

School of Intrinsic Compounding


@unseenvalue
CULTURED MEAT VS PLANT MEAT
KEY DIFFERENTIATORS

Economics of cultured meat will improve over time

Cultured meat can grow faster due to a very low base

Food disruption does not necessarily mean 0 or 1 (e.g. sugar vs


several natural and artificial sweeteners)
Food production and distribution are regulated differently in each
jurisdiction worldwide (e.g. Singapore vs US states)
Precision and ethical farming will add transparency and
economics of livestock farming
USDA promotes US farm exports as well as protects the interests
of conventional farm industry

Powerful farm lobbies often oppose novel foods that pose threat
to their livelihood

Today we know almost everything about conventional or


livestock meat
Today we know very little about risks associated with lab-meat
School of Intrinsic Compounding
@unseenvalue
CULTURED MEAT VS PLANT MEAT
KEY DIFFERENTIATORS
“By 2035, after alternative proteins reach full parity in taste, texture, and price with conventional animal proteins,
11% of all the meat, seafood, eggs, and dairy eaten around the globe is very likely to be alternative. With a push from
regulators and step changes in technology, that number could reach 22% in 2035.” – BCG, March 2021

“The extrusion capacity needed for plant-based proteins, for example, will require up to $11 billion to reach the
baseline case of 11% adoption by 2035 and as much as $28 billion if the greatest upside scenario happens. Almost
30 million tons of bioreactor capacity for microorganisms and animal cells will also be needed in the base case,
requiring up to $30 billion in investment capital.” – BCG, March 2021
LAB MEAT: BARRIERS / RISK FACTORS
Is lab-grown meat halal? “This is new to us, something I’ve never thought about. This isn’t something you would find in the Quran”
- Chernor Saad-Jalloh.
Source: https://gulfnews.com/business/is-lab-grown-meat-halal-what-experts-say-1.62531421

Science behind the process deserves detailed scrutiny (genetically modified rapidly growing animal muscle cells vs non-
genetic which only proliferate to a certain degree and proliferate slowly)

Foetal Bovine Serum (FBS) is 80-90% of the cost of cultured meat (FBS is derived by extracting blood from the foetus of a pregnant
cow)

Equal or lower cost than conventional meat (growth media being the main culprit). Economies of scale / mass production

Taste, texture, aroma, fragrance and overall feel has to match the conventional meet

Ultimately there has to be a consumer/market-pull factor for lab meat Animals have an immune system that naturally protects
them against bacterial and other infections. This is not the
case for cell culture, and in a nutrient-rich environment ,
Local regulatory approval (FDA’s cell culture guidelines not designed for food) bacteria multiply much faster than animal cells. To avoid
producing a steak made up of more bacteria than meat, it is
essential to avoid contamination, and that requires a high
https://www.onegreenplanet.org/natural-health/is-lab-grown-meat-healthy-and- level of sterility.
safe-to-consume/

@unseenvalue School of Intrinsic Compounding

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