Cryopreservation Media Products For Cells, Tissues, and Organs

Optimizing Biopreservation Economics

from Source Material to Finished Product

August 2010 © 2010 BioLife Solutions, Inc.

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FORWARD LOOKING STATEMENT DISCLOSURE!

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This presentation contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995 including, but not limited to, statements about BioLife Solutions, Inc. (the “Company”) and its future operating results, strategies, and product development plans. These forward-looking statements are based on current expectations and assumptions that are subject to risks and uncertainties. Actual results could differ materially from the results expressed or implied in these forward-looking statements. Factors that may cause or contribute to such differences are more fully discussed, as are other factors, in Part I, Item1A. “Risk Factors” of the Company’s Form 10-K for the fiscal year ended December 31, 2009, which is on file with the SEC and available at www.EDGAR.com. In addition, any forward-looking statements represent our estimates only as of today and should not be relied upon as representing our estimates as of any subsequent date. While the Company may elect to update forward-looking statements at some point in the future, the Company specifically disclaims any obligation to do so except as may be legally necessary, even if the Company’s estimates should change.

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We strive to be the leading provider of biopreservation tools for cells, tissues, and organs; !

to facilitate basic and applied research and commercialization of new therapies by

maintaining the health and function of biologic source material!

and nished products during the preservation process.!

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We are committed to manufacturing products in accordance with!applicable current Good Manufacturing Practices and Quality System!Regulations. Every team member in the organization is responsible for!ensuring product quality during the performance of their duties and!identifying opportunities for continuous quality improvement. !

We Will:!

• Provide products and services of the highest possible standards!

to satisfy our customer needs and expectations of quality, safety,! reliability and performance!

• Encourage and promote a corporate culture of continuous!!

quality improvement!

• Maintain effective Quality Assurance Systems!

• Invest to enhance the skills of all team members!

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•! Products:

•! Proprietary, cGMP, serum-free, protein-free biopreservation media products for cells, tissues, and organs:

•! HypoThermosol® hypothermic storage & shipping media

•! CryoStor® freeze media

•! BloodStor™ generic, cGMP cord blood stem cell freeze media

•! Services:

•! Custom biopreservation media formulation, fill, and finish into standard and custom packages

•! Customers include several competitors and the US Army

•! Contracted R & D to optimize biopreservation outcomes

•! Biopreservation media formula development

•! Verification of cell specific freezing/thawing rates and protocols

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PRODUCTS & SERVICES !

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•! Regenerative Medicine is the process of engineering

living, functional cell and tissue-based therapies and administering these to patients to repair or replace tissue

or organ function lost due to age, disease, damage, or congenital defects

•! Target diseases include cancers, diabetes, heart disease,

ALS

•! Target disorders include spinal/movement, hearing loss, vision loss, neurological (i.e., stroke)

•! Nearly all currently available and development stage

regenerative medicine products and therapies utilize

biopreservation processes in the acquisition of source material, isolation and manipulation of specific cells, and

storage and shipment of a final product dose to a patient location

•! Biopreservation economics greatly impact product

commercialization potential

•! (system costs of the shelf life & functional yield environment)

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REGENERATIVE MEDICINE OVERVIEW!

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•! Market activity1:

•! 900 active clinical trials for new therapies

•! 687 companies worldwide

•! Market size and growth estimates2:

•! Market could reach $32B by 2018

•! Demand for biopreservation media3 used in process development, manufacturing, and commercial product storage, transport, and freezing will mirror the end product market growth rate

•! Increasing quality and regulatory pressure to move away from internally formulated ‘home-brew’ media and reagents

•! Limited risk of disruptive, competitive, technologies; BioLife products are the next disruptive technology that will capture share

•! Previous 9 nine quarters: BioLife product

shipments to 200+ accounts

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REGENERATIVE MEDICINE OVERVIEW!

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1Proteus Venture Partners, 2MedMarket Diligence, LLC, 3Management estimates

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BIOPRESERVATION WORKFLOW!

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Enabling end to end biopreservation workflow optimization with newly

integrated solutions; from source material to final product!

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Pre-filled biologic packaging products

from partners

BioLife biopreservation media products

•! Internally formulated biopreservation media products:

•! Based on historical, non-optimized formulas

•! Made daily/weekly and subject to lot-lot variability

•! Often not made with USP grade components

•! Often not made under current GMP

•! Subjected to less stringent (non-lot specific) release testing for sterility, endotoxin, mycoplasma, etc.

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ISSUES WITH HOME-BREW BIOPRESERVATION MEDIA!

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•! Preservation induced cell damage and death

•! Metabolic activity decreases

•! Ionic and osmotic balances are disrupted

•! Free radicals accumulate

•! Molecular stress responses are initiated

•! Two injury mechanisms

•! Necrosis – mechanical destruction of cell membrane

•! Apoptosis – enzyme based, programmed cell death

•! Two injury exposure periods

•! During hypothermic storage and freezing

•! During re-warming/thawing

•! Delayed preservation induced cell injury – not apparent or appreciated

•! Immediate post-thaw assays do not accurately indicate cell viability

•! Perceived Viability ! True Viability

•! Traditional preservation media formulations do not adequately protect cells from preservation induced stress

•! Innovation opportunities to re-formulate preservation media to mitigate underlying causes of preservation related cell damage and death

BIOLIFE RESEARCH DISCOVERIES!

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•! Overall system performance is

constrained by limited stability, yield loss, and processing costs

•! Incremental and cumulative

optimization of biopreservation processes can maximize the yield-

cost relationship

•! System optimization should strive to move up and to the left

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BIOPRESERVATION ECONOMICS!

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IMPACT OF LIMITED SHELF LIFE!

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•! Intracellular-like media: •! Ionic concentrations are tuned to balance the intracellular state at low temperature to

reduce gradient formation and water flux

•! pH buffering capacity: •! Organic and inorganic buffers include bicarbonate and HEPES

•! Effective from 15°C to 2°C

•! Free radical scavengers

•! Osmotic stabilizing components •! To reduce and control shrinking and swelling of cells during preservation process

temperature changes

•! Serum-free energy substrates

•! Pre-formulated with cryoprotective agents (2%, 5%, or 10% DMSO)

•! No user mixing required

•! Fully-defined components

•! USP/multi-compendial or highest available grade

FORMULATION INNOVATION!

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PROPRIETARY PRODUCTS!

HypoThermosol® !

Storage & Shipping Media !

CryoStor®!

Freeze Media!

!! Formulary improvements to organ preservation media

!! Serum-free and protein-free

!! For 2 - 8°C short term storage and shipment of biologics

!! Enables functional restart upon return to normothermic temperature

!! Extends stability of specimens, pancreata, liver sections, tumor biopsies, tissue samples, bone marrow

!! Based on HypoThermosol formula

!! For cryopreservation of biologics at - 80°C to -196°C

!! Pre-formulated with 2%, 5%, or 10% DMSO

!! Serum-free and protein-free

!! Outperforms other commercial products and home-brew freeze cocktails

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PRODUCT VALUE PROPOSITION!

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•! Preservation solutions are not devices or drugs; considered excipient or ancillary material in clinical applications

•! Ancillary material: used in manufacturing cell, gene, or tissue-engineered products, but not intended to be in final product (washed or removed) •! Excipient: component intended to be part of the final product at clinical application

•! We help customers comply with Good Tissue Practices (GTP – 1271.210) •! Highest quality reagents must be utilized in the process of developing Human Cellular, Tissue, and Tissue-Based Products (HCT/Ps)

•! “all reagents must be verified to meet specifications designed to prevent circumstances that increase the risk of the introduction, transmission, or

spread of the introduction, transmission, or spread of communicable diseases”

•! Type II FDA Master Files regularly updated for both HypoThermosol® and CryoStor® product platforms

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REGULATORY STATUS!

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•! Certified to: •! ISO 13485:2003 medical device quality systems management

•! Adherence to: •! 21 CFR part 820 Quality Systems Regulation of Good Manufacturing Practices for medical

devices (GMP)

•! 21 CFR parts 210 and 211 covering GMP for Aseptic Production

•! ISO 13408 manufacturing processes for aseptically-processed health care products

•! Volume 4, EU GMP Guidelines, Annex 1: Manufacture of Sterile Medicinal Products

•! ISO 14644 Clean Rooms and Associated Controlled Environments

•! Product Release Criteria: •! Sterility Tested USP <71>

•! Endotoxin Tested USP <85>

•! Cell based preservation efficacy assay

•! pH

•! Appearance

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QUALITY SYSTEMS!

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•! Our biopreservation media products are incorporated into numerous development stage and commercial biologic products

•! cell therapies

•! umbilical cord blood units

•! cells and cell lines used in drug screening

•! Critical supplier status with leading regenerative medicine and life science tools companies

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PRODUCT ADOPTION!

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CRYOPRESERVATION MEDIA PRODUCTS – 5% DMSO!

alamarBlue® stain for metabolic activity

0

25

50

75

100

125

37C CryoStor CS5

95% Serum *

FBM Medium

FGM Medium *

Normosol Normosol * Plasma-lyte Plasma-lyte *

5% DMSO

% R

eco

very

of

Via

ble

Cells

Recovery of Human Mesenchymal Stem Cells Following Cryopreservation With Serum-Free CryoStor®

Comparison to Serum Containing Home-Brew Media

* Contains serum

20!20!

CRYOPRESERVATION MEDIA PRODUCTS – 5% DMSO!

alamarBlue® stain for metabolic activity

0

25

50

75

100

125

Control (37°C)

CryoStor CS5

ProFreeze Aedesta Cellvation Cell Guardian

Synth-a-Freeze

Recovery * Sigma Freeze *

FGM + 5% DMSO *

% R

eco

very

of

Via

ble

Cells

Recovery of Normal Human Dermal Fibroblasts Following Cryopreservation With Serum-Free CryoStor®

Commercial Solution Comparison: Serum and Serum-Free

* Contains serum

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CryoStor® CS5 ProFreeze® Cellvation® Aedesta®

Cell Guardian® Synth-a-Freeze® Sigma Recovery

Representative Fluorescent Micrographs Illustrating Post Cryopreservation Morphology of NHDF Stored in Serum-Free CryoStor®

CRYOPRESERVATION MEDIA PRODUCTS – 5% DMSO!

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CRYOPRESERVATION MEDIA PRODUCTS – NO NEED FOR SERUM!

alamarBlue® stain for metabolic activity

0

25

50

75

100

125

Control CS2 CS5 CS10 FGM + 2% DMSO *

FGM + 5% DMSO *

FGM + 10% DMSO *

CryoStor Culture Media

% R

ec

overy

of

Via

ble

Cells

Recovery of Human Mesenchymal Stem Cells Following Cryopreservation With Serum-Free CryoStor®

Comparison to Serum Containing Home-Brew Media

* Contains serum

23!23!

FGM + 2% DMSO FGM + 5% DMSO FGM + 10% DMSO

CryoStor® CS2 CryoStor® CS5 CryoStor® CS10

CRYOPRESERVATION MEDIA PRODUCTS – NO NEED FOR SERUM!

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Representative Fluorescent Micrographs Illustrating Post Cryopreservation Morphology of hMSC Stored in Serum-Free CryoStor®

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CRYOPRESERVATION MEDIA PRODUCTS – NO NEED FOR SERUM!

alamarBlue® stain for metabolic activity

0

25

50

75

100

125

37C CryoStor CS10

(no serum)

90% Serum * MSCGM (Medium)

MSCGM (Medium) *

Normosol Normosol * Plasma-lyte Plasma-lyte *

10% DMSO

% R

eco

very

of

Via

ble

Cells

Recovery of Human Mesenchymal Stem Cells Following Cryopreservation With Serum-Free CryoStor®

Comparison to Serum Containing Home-Brew Media

* Contains serum

25!25!

hMSC (Undifferentiated) hMSC Osteoblasts

POST PRESERVATION DIFFERENTIATION CAPACITY!

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Representative Fluorescent Micrographs Illustrating Post Cryopreservation Differentiation Capacity and Morphology of hMSC Stored in CryoStor®

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CRYOPRESERVATION MEDIA PRODUCTS – NO NEED FOR SERUM!

0

25

50

75

100

125

Control CS2 CS5 CS10 MSCGM + 2% DMSO *

MSCGM + 5% DMSO *

MSCGM + 10% DMSO *

% R

ec

overy

of

Via

ble

Cells

Recovery of hMSC Differentiated Osteoblast Cells Following Cryopreservation With Serum-Free CryoStor®

Comparison With Serum Containing Home-Brew Media

alamarBlue® stain for metabolic activity * Contains serum

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CRYOPRESERVATION MEDIA PRODUCTS – NO NEED FOR SERUM!

alamarBlue® stain for metabolic activity

0

25

50

75

100

125

37C CryoStor CS10

(no serum)

90% Serum * RPMI (Medium)

RPMI (Medium) *

Normosol Normosol * Plasma-lyte Plasma-lyte *

10% DMSO

% R

eco

very

of

Via

ble

Cells

Recovery of Human Dental Pulp Stem Cells Following Cryopreservation with Serum-Free CryoStor

Comparison to Serum Containing Home-Brew Media

* Contains serum

•! Scientific validation across a broad set of biologics, offering significant performance and quality advantages

•! Proven ability to extend stability and improve post-preservation viability, recovery, and function of specimens, source material, and isolated cells

•! Viewed as a critical manufacturing reagent supplier by numerous cell therapy companies and cell suppliers

•! Demand for our proprietary products will closely follow pace of increased regulatory and quality oversight of reagents used in clinical product development, processing, storage, transportation, and infusion

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TECHNOLOGY SUMMARY!

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