meeting the world s demand for universal red blood cells · no undesired blood components –100%...

Proprietary & Confidential

COMPANY PRESENTATION

Meeting the world’s demand for universal Red Blood Cells

Key People

Ari Gargir, PhDFounder, CEO

• 20 years in biotech, leading innovative products

from design to production and commercialization.

• Head of R&D in several startup and global

companies bringing dozens of consumable and

device products to the biomedical industry

• 4 years Scouting and Business Development

assessing over 150 technologies and companies

for Life Technologies

Michal Amit, PhDCEO and CTO of Accellta

RedC Project Scientific Lead

• 19 years research pluripotent stem cells culturing

• World expert in derivation of primary cell lines,

culture medium development, cells mass

production using dynamic systems, stem cells

directed differentiation, and GMP

• PhD - isolation of human embryonic stem cells

and their directed differentiation into blood cells

• >45 papers, >10,000 citations

• >7 Patent families, >40 patents in the field

Proprietary & Confidential 3

Motti VakninFounder & Business Management

• Successful serial entrepreneur & CEO led

startups from initiation to successful exits

in variety of domains

• VC partner and investor at Cedar Fund

• Generated exceptional returns

Introducing RedC Biotech

▪ Our missionto meet the world’s demand for universal, safe and high-quality blood

▪ Technology

Innovative red blood cell production technology allows production in massive scale at low cost

▪ End product Universal Red Blood Cell Transfusion Kit

▪ StatusIn development

✓ Universal

✓ High Quality

✓ Diseases free

✓ Clean

✓ Simple to produce

✓ Cost effective

✓ Available everywhere

RedC Transfusion Kit


The Blood Transfusion Market

Blood transfusion is essential in medical practice

▪ Worldwide

▪ Over 100 million blood units donated every year

▪ Shortage of about 40 million units

▪ A $20 billion market

▪ United States

▪ Approximately 11 million units transfused every year

▪ One blood unit costs a hospital approximately $200

▪ Hospitals charge HMOs about $400-450 per unit


An Antiquated Process

A century old practice for blood donation/transfusion:

▪ Risky ▪ One person’s blood is transfused to another▪ New disease threats continue to be introduced (i.e. HIV, Zika in the recent years)▪ Donors, volunteers, patients and medical teams are at risk

▪ Complex ▪ Complex and spread supply chain to collect, process, test, store and deliver blood

▪ Limited Availability▪ Blood supply agencies operate at 3-7 days blood inventory levels▪ Matching the demand and supply of blood types – ABO blood types are not aligned▪ Low income countries, with inadequate infrastructure and cultural barriers, suffer from

an annual global shortage of 40M blood units

▪ Costly ▪ One blood unit costs a hospital approximately $200▪ Hospitals charge HMOs about $400-450 per unit


“Although the blood

system appears, from

the outside, to be

functioning today, we

assess it as very fragile.”

The federal Advisory Committee

on Blood and Tissue Safety and

Availability (ACBTSA)

A Global Need for New Blood

The Industry is seeking an alternative that will meet these criteria:

▪ Universal – one blood type that fits all patients, removing the need of matching blood types

▪ High Quality – prime quality Red Blood Cells, elastic and with strong oxygen capacity

▪ Disease free – current pathogen list or any other blood-borne contamination

▪ No undesired blood components – 100% clean of foreign white blood cells, plasma components, anti-bodies, DNA etc.

▪ Simple to produce – remove the need of donors and volunteers from the equation

▪ Cost effective – price to be competitive or equal to the current method

▪ Access and availability – meet demand where and when needed, worldwide


The RedC Biotech Plan

▪ Development of Red Blood Cells Production Technology and Processes Innovative 3D method for red blood cell production based on a multi-patent protected, exclusively licensed core technology

▪ Mass Scalability Red blood cell production from lab scale (wave reactors) to very large scale (stir reactors)

▪ Cost ReductionDuring the scale-up stage cost of production per unit will be reduced through process automation, advanced / smart raw material selection, and sourcing

▪ Practical go to market strategyAddress regulatory requirements and establish production sites globally in a phased manner


Innovation in Production Technology

Growing cells in suspension (3D) carrier free

and free of human or animal source materials

Patented. Exclusively licensed.

• Simple to produce

• Safe for all humans

• Highest yield

• Best cost (orders of magnitude)

RedC : Pure 3D

Feeding & Adherent Surface

Growing cells on flat surfaces that

provide nutrition and growth factors

• Very low quantities

• Used mainly in labs or medically

oriented application

• Expensive approach

2D cultivation

cells

From 2D and micro-carriers to massive scale capabilities

Growing cells on microcarriers in

suspension is an improved 2D cultivation

• Requires micro-carriers and a

process to remove them

• Scales better then 2D

• Better cost, but still expensive

3D Micro-Carriers


Breakthrough Technology

▪ Uniform, undifferentiated, self-renewable, efficiently cultured human stem cells as single-cells in suspension at high concentration, Xeno-free medium, Scalable

▪ High cell concentration

▪ Lower cell culture volume and surface area

▪ Reduced amounts of reagents

▪ Continuous, computerized cell monitoring, feeding & harvesting

▪ Virtually unlimited volumes

▪ Differentiation in suspension

▪ Specialized media

▪ Less labor

▪ RedC Biotech secured an exclusive license to use a Revolutionary Stem Cell Cultivation Technology


• Scalable

• Homogenous

• High Quality

• Three times faster

• Xeno-Free

• Order(s) of Magnitude Cheaper

IP and Patents

▪ RedC is licensing globally patented technology covering 7 patent families and over 40 individual patents for:

▪ 3D suspension stem cell cultivation

▪ Xeno-free growth media for suspension cultivation of stem cells

▪ Licensing is exclusive for the red blood cell production process


Proprietary & Confidential

Development

RedC’s Red Blood Cell Production Process

Main Materials DescriptionStage

NIH approved CD34+ Universal donor iPSCs from RedC’s proprietary master cell bank

Seeding the primary cultureBatch initiation

• IL6RIL6 chimera, ROCK inhibitor• Chemically defined xeno-free culture media

Suspension culture of iPSCs grown in stir reactors propagate cells into extremely high densities >1011 cells/liter

Massive expansion

• Erythropoietin, SCF, IL-3, IL-6• Terminal maturation involves additional factors• Chemically defined xeno-free culture media

Differentiation of the iPSCs into Erythroblasts, enucleation and maturation to Erythrocytes

Erythropoiesis

• Microbiology testing• RBC quality testing

• RBC harvest by gravity and/or filtration• Rinsing and packaging

Down-stream processing


Hematopoietic Markers Expression Targets


0

10

20

30

40

50

60

70

80

90

100

0 10 20 30 40 50 60

Ce

lls e

xpre

ssin

g m

ark

er

(%)

Days to culture

CD31 CD34 CD36

CD45 CD71 CD235a

Differentiation

target for

scale-up phase

CD31, CD34, CD36 and CD45 are markers characteristic to non erythroid hematopoietic cells;

CD71 is present in erythroblasts and premature erythrocytes; CD235a is typical of mature erythrocytes

Expression of the CD71 Marker


Representative FACS analyses of CD71 in hiPSCs (line Kyou) after 33 days of differentiation into erythrocytes. Red histogram represents indicated Ab, blue histogram represents matched isotype control. Cells debris and dead cells were excluded from the analysis based on scatter signals and propidium iodide (PI ) fluorescence

C – Day 0 to differentiation

D – Day 33 to differentiation

C D

Expression of CD235a - Day 60

Representative FACS analyses of CD235a expression during erythroid differentiation of hiPSCs (line Kyou). Expression of CD235a significantly increased during erythroid differentiation up to >70% CD235a positive cells. Red histogram represents indicated Ab, blue histogram represents matched Unstained cells. Cells debris and dead cells were excluded from the analysis based on scatter signals. Day 0 – A, Day 55 – B, Day 60 – C.


CD235a-FITC

Co

un

tA B C

5.61%Day 0

62.8%Day 55 Day 60

73.9%

Erythropoiesis in RedC’s Process


StatusMarkersCell type

CD235aErythrocyte (mature)

CD235aReticulocyte (peripheral blood)

CD235aReticulocyte (bone marrow)

✓CD71,

CD235aNormoblast/Orthochromatic erythroblast

✓CD71,

CD235aPolychromatic erythroblast

✓CD71,

CD235aBasophilic erythroblast

✓CD71,

CD235aProerythroblast

✓CD34, CD71Colony forming unit erythroid (BFU-E)

✓CD34Burst forming unit erythroid (BFU-E)

✓CD34Myeloid colony forming unit (CFU-GEMM)

✓CD34Hematopoietic multipotential stem cell

(HSC)

Visuals


Uncharacterized mix of nucleated and enucleated erythroblasts

Morphology of cells after dissociation. From 3 wells of Kyou cells produced 0.57x106 cells

Changes in cell color during the final steps of erythroid differentiation. Red-brownish cell pellet strengthened as

erythroid maturation progressed. (A) - Erythroid expansion, (B) - Erythroid maturation, (C) - Terminal maturation

Year 1 Year 2 Year 3-4 Year >5 Year >10

Cell Production Scale & Cost Targets


107 1013 1015 1018 1020

$5,000/unit $50/unit

Creation of RedC’s Master Cell Bank (MCB)


Recruit universal donors

• Identify genetically & serologically proven universal donors

•Legal engagement with donors

Collect stem cell donation from peripheral blood

• Isolate CD34+ cells (apheresis and isolation kits)

• Induce pluripotency

•Select clones

•Test clones in small scale production process

•Select super clones for production

Establish Master Cell Bank

•NIH cell line characterization, authentication and registration

•Proliferate and maintain cell bank

RedC Production Site Plans

▪ RedC plans to design and deploy highly automated Red Blood Cell Production Sites

▪ A typical RedC factory

▪ Production Capacity: 1,000,000 units/year

▪ Target Cost per unit: $50

▪ Target Price per unit: $200

▪ Annual Revenue: $200,000,000

▪ Gross Margin: 75%


Production Stage Financial Projections

Sites in Production 0 1 2 3 5

Units sold 1,000,000 2,000,000 3,000,000 5,000,000

Total revenue $200,000,000 $400,000,000 $600,000,000 $1,000,000,000

Cost of new sites setup ($50M) $50,000,000 $50,000,000 $50,000,000 $100,000,000 $150,000,000

COGS (30%) $60,000,000 $120,000,000 $180,000,000 $300,000,000

Gross Profit ($50,000,000) $150,000,000 $350,000,000 $500,000,000 $850,000,000

• While site setup costs are immediate, revenue booked only after site enters production in the following year

• Rollout of production sites, costs, revenue at this early stage of the project are naïve, yet provide some reference

• Note: 11,000,000 blood units are transfused in the US alone every year

Naïve projection for reference only


Go to Market

Launch – Initial Market Penetration

▪ Address the high paying, ‘must have’ and ‘extreme’ user markets

▪ Anemia patients with immune incompatibility (Cancer, Sickle Cell, Beta Thalassemia, Fanconi etc…)

Expansion to Address the Main Blood Transfusion Markets

▪ Superior transfusions at a price tag competitive to donated blood units

▪ Emergency services, hospitals, blood donation agencies worldwide

▪ At price of $200 per unit, an estimated market of over $20B

Meet the Global Demand

▪ Competitively priced

▪ UN, governments at low income regions

▪ Meet the annual shortage of 40 million units


Regulatory Aspects

▪ Rubius Ltd. started (October 2019) recruiting 12 Phenylketonuria (PKU) patients for their RTX-134 clinical trial in which they will administer doses of allogeneic human red blood cells expressing the AvPAL(Anabaena variabilis phenylalanine ammonia lyase) gene inside the cell▪ These stem-cells are cultivated from iPSCs▪ The iPSCs are genetically manipulated

▪ RedC is applying to the FDA’s INTERACT meeting (Initial Targeted Engagement for Regulatory Advice on CBER products).▪ The outcome of this meeting will enable RedC to obtain preliminary informal consultation with the Agency at this

early stage of development prior to a pre-IND meeting

▪ General aspects:▪ Red blood cell transfusions are a lifesaving therapy▪ RedC's product is safer than donated blood▪ Currently there are minimal regulations on blood testing and quality▪ Production will obtain highly purified red blood cells:

▪ Cells are washed and contain residual raw materials▪ Nucleated cells eliminated from red blood cells using double separation techniques, gravity/density and sieving

▪ Postulating whether RBCs will be considered as Regenerative medicine▪ Orphan Drug Regulatory Pathway for special transfusion, Thalassemia patients for example▪ Non-inferiority or non-different


Market Players

▪ Now, there is no similar product in the market

▪ Synthetic blood alternatives failed (NorthField Labs and others)

▪ Several attempts producing very small amounts of red blood cells from stem cells, but neither advanced to a commercial product or company

▪ EryPharm (Paris, France)

▪ Led by Professor Luc Douay

▪ Megakaryon (Kyoto, Japan), and Platelet BioGenesis (Boston, USA)▪ Developing platelet production methods from stem cells

▪ Rubius Therapeutics (Boston, USA)

▪ Recently raised about $500M (including $270M IPO July 2018)

▪ Developing red blood cells modified to carry therapeutic agents

▪ Several other companies use donated RBCs to deliver drugs

▪ Potential path for RedC technology as well


Other Applications for RedC’s Technology

▪ Drug Delivery – charge RBCs with therapeutic agents

▪ Express therapeutics in genetically modified erythropoietic cell lines


Company Therapeutic area Technology

Rubius Cancer, metabolic, autoimmuneExpression by genetically modified stem

cells

EryDel Neuro-medicine Osmo-encapsulation

EryTech Cancer; Asparginase related Osmo-encapsulation

Anokion CancerAttachment of genetically modified

molecules to RBCs

Development Plan


Year 5+ Commercialization

Year 3-4Mfg Scale

Year 1-2Scale-up

Year 0R&D

• Clinical trials

• Regulatory approvals

• Production Plants

• Marketing

• Sales

• Partnerships

• Scale business & production

• Scaling to stirred-tank reactors

• 10 cubic meter reactors

• Yield optimization

• Cost Optimization

• Regulatory process

• Business development

• Initial scale

• 15-liter Red Blood Cells

• Yield and quality optimization

• Initiate Business Development

• Initiation of Regulatory process

• Stem Cells Lines

• Proof-Of-Concept

• <1-liter Red Blood Cells

• Design of scale processes

• Partnerships & Collaborations

$20 + for Go to Market$50M per production site

$10M$3-5MFinanced ($0.5M)

RedC Biotech - Summary

▪ Moonshot project to address worldwide need for red blood cells

▪ Promising technology to meet scale, quality and cost

▪ Exceptional return opportunity

▪ Massive impact


Ari Gargir

Founder & CEO

[email protected]

+972 -547444992

Thank you.

meeting the world s demand for universal red blood cells · no undesired blood components –100%...

Documents