Rheological of a Novel Agarose Gel Filler

Safety and Clinical ImplicationsBrian M. Kinney, M.D.

VCS SymposiumJune 10th 2021

Las Vegas, Nevada

Dermal Fillers in the United States:History, Present and Future

Dr. Brian Kinney

Associate Clinical Professor

University of Southern California

Lead Clinical Researcher – BTL

Served as paid consultant for leading trial

Former Founding Shareholder - Thermi

Board of Directors/Medical Director – Advanced Aesthetic Technologies - Algeness

Former Clinical Trial Advisor – Klox Technologies

Former R & D Consultant – Crisalix

Scientific Advisory Board/Director – Motiva

Former Medical Director – Sientra

FDA Trials – Teoxane

Teosyal vs Perlane – NL Folds

Brian M. Kinney, MD, FACS Disclosures

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Former Ad hoc Educational consultant – Kythera

Chairman, Advisory Council – ThermiAesthetics

Selected society and journal activities

Past Chairman, Board of Trustees, Board of Directors – ASPS

Archives of Plastic Surgery (Korea) – Associate Editor

Aesthetic Plastic Surgery Journal – Associate Editor

Past President, PSEF

Past Deputy Sec’y General – IPRAS

Parliamentarium, ISPRES

Committees – ASAPS, ISAPS, ASPS, IPRAS 4

Brian M. Kinney, MD, FACS Disclosures

Brian M. Kinney, MD, FACS Disclosures

Former Educational Advisory Council / Ad hoc Consultant – Mentor, LPG Systems, Merz

FDA Clinical Trial Advisor – Klox Technologies

R & D Consultant – Crisalix, Sientra

FDA Trials - Mentor

HA Puragen vs. Restylane in NL folds

Puragen continuing access study in NL folds

Puragen in lips

Prevelle Lift/DGE clinical monitor

Purtox trial (randomized versus saline)

Purtox long term follow-up

Clinical Consultant/Researcher - MTF

AAM – acellular adipose matrix

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*Status of Product

*Company*AAT, Brookline, MA

*Product Trade Name *What is it? – Algeness

*Other names: none

*Specific FDA status*FDA clinical trial to start within weeks

*Specific CE status*CE Mark – original 2004

*Soft tissue filler in plastic surgery

*Serving on Board of Company and leading oversight of trial

*** ***

What Do I Use?What Do I Want To Use Tomorrow?

What Do I Want To Use Day After

Tomorrow?

Still Needs Work for Stem Cells

Not Ideal for Intradermal

Not Ideal for Fine Lines

Good For Volume

Innovation in Filler Technology?

Excellence in Plastic Surgery8 Brian M. Kinney, MD, MSME, FACS

Patients are Looking for Natural and Safe Alternatives

The Quest for the Ideal Filler

Safety First

Biocompatability

Clinical tolerability

Reversibility

Natural

Cross Linking Agents?

Clinical Performance

Clinical outcome – in the office and over time

Control of shape & contour

Control of volume

Longevity of result

Is an enzyme the only answer?Does Hyaluronidase solve all problems?

Primary Goal?

Second Goal?

Excellence in Plastic Surgery

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Brian M. Kinney, MD, MSME, FACS

Algeness®

CE Marked

Expanded clinical and safety evaluation ongoing in 25+ markets

No reported emboli, blindness, necrotic events, or granulomas

Injectable implant allowing sculpting and molding

Retains shape post injection: “What You See is What You Get”

Integrated Into Tissue – Natural Feel and Movement

Complete, 100% Resorption / Degradation – Macrophages, no Residual Cross-Linking Chemicals

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What is agarose gel?

Algeness is a biomaterial consisting of a purified agarose gel

What is Agarose Gel?

Agarose is a neutral polysaccharide

100% natural with no chemical cross-linking

A hydrocolloid with unique physical properties –dispersion in the presence of water

Non-hygroscopic (not water absorbing – no physical swelling of injected implant)

Highly purified and does not contain any protein

Safe and totally biocompatible to the human body12

What is Agarose gel?

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• 100% Natural product▪ Sustainable Source (Seaweed)▪ No added chemicals (pure)▪ Biocompatible

• Predictable - Fully hydrated hydrocolloid▪ Does not absorb water and swell after injection▪ Treatment outcome is apparent the day of the

injection

• Looks, feels, and moves naturally• Integrates into existing tissue on histology• Stimulates fibroblasts

• Naturally safe• Hydrostatic interactions, rather than crosslinking,

forms an easily dispersed gel

• Unique and Versatile – Physical Properties• Deep, structural filler with differentiated

characteristics• Manufacturable in multiple concentrations for specific

uses

Rhodiphyta

Agar to Agarose

ECM-like gel

AGAROSE IS BIOCOMPATIBLE AND WELL TOLERATED

Three dimensional

reticulum of

agarose gel

• 3D lattice• Sufficiently low viscosity• Gel extruded through thin needle• 27 or 30g

What is Agarose?

Agaraose Compared to HA

AgaroseHA

Purified Agarose – 100% Natural

Non Hygroscopic – non-swelling implant

100% Breakdown – Macrophages With No Residual, no crosslinking agents needed or used

Synthetic Material

Hygroscopic – Absorbs Fluid From Surrounding Tissues, potentially a swelling implant

Degradation of HA by Hyaluronadase, no breakdown of crosslinking agents

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New Findings – Rheology (DF 3.5%)

HA

(VOLUMA®)AGAROSE (ALGENESS)

Frequency

(rads)Frequency

(rads)

Better Contour Stability - Viscous modulus (G”): Agarose >> HA

G”G”

G’G’

Better Tissue Lift / Projection: Elasticity (G’): Agarose >> HA

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New Findings – Rheology (DF 3.5%)

Agarose >> HA

Rheological Static Compression Testing (rate = 0.1 mm/s):

HA and Agarose both resistant to constant deformation

Response of subcutaneous fillers to weight of overlying tissues

HA (VOLUMA) AGAROSE (ALGENESS)

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• Almost instantaneous decrease in Viscosity

• Resulting Viscosity is at least Equivalent

• Low Viscosity maintained over 30-minute observation period

New Findings - Rheology and Dispersion

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HA mixed 1:1 with Hyaluronidase

Algeness DF 3.5% mixed 1:1 with 0.9% saline

HA

Algeness DF 3.5%

+ Saline

+ HYL

Biocompatability

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T3 (6 months). In the hypodermis a good amount of filler is still present. Newly formed collagenous bundles are clearly visible around the filler and in the context of the surrounding tissue. There is no capsule or granuloma formation (hematoxylin and eosin; original magnification X40)

New Findings, Efficacy – Tissue Integration

Histologic Study of Biocompatibility and Tissue Interactions between an Agarose Gel Filler and the Human Skin (Pirino, Maullu, Kinney, Rocca manuscript under review)

New Findings, Efficacy – Fibroblast Response

Human fibroblasts cultured in agarose vs control media(Pirino, Maullu, Kinney, Rocca manuscript in preparation)

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New Findings – Fibroblast Response

Human fibroblasts cultured in Algeness vs control media

(Pirino, Maullu, Kinney, Rocca manuscript in preparation)

human hyaluronan synthase 2

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New Findings – Clinical Efficacy

Baseline Day 14 Day 30 Month 3 Month 4 Month 6 Month 7 Month 8 Month 9 Month 10 Month 11 End Of

Study

0

1

2

3

4

5

WS

RS

Sco

re

WSRS Scores Over Time (ITT)

2.5% Agarose

NASHA-L

Prof. Nicolo Scuderi et al, Univ of Roma

In a blinded, split face study (n=68) over 1 year of (manuscript submitted):• Algeness VL 2.5% demonstrated clinical

equivalence to Restylane Perlane(NASHA-L) in NLF

• Similar Clinical Efficacy• WSRS Physician GAIS• Subject Satisfaction

• Similar persistence in the mid face (complete resorption was most often between 8 and 9 months - ultrasound)

• Similar adverse event profile (generally mild anticipated injection site reactions)

Day 14 Day 30 Month 3 Month 4 Month 6 Month 7 Month 8 Month 9 Month 10 Month 11 12 Months

0

2

4

6

8

10

Sati

sfa

cti

n s

co

re (

0 t

o 1

0)

Mean Subject Satisfaction Over Time

2.5% Agarose NASHA-L

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New Findings – Clinical Efficacy

Day 14 Day 30 Month 3 Month 4 Month 6 Month 7 Month 8 Month 9 Month 10 Month 11 Month 12

0

1

2

3

4

5

Avera

ge G

AIS

Sco

re

Investigator GAIS Scores Over Time (ITT)

NASHA-L

2.5% Agarose

New Findings – Time to Resorption (ultrasound)

Month 7 Month 8 Month 9 Month 11

0

20

40

60

80

100

Perc

en

tag

e o

f S

ub

jects

(N

=27)

Time of Complete Product Absorption

2.5% Agarose

NASHA-L

Study Photographs – Split Face Design

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Source: Prof. Nicolo Scuderi

Pre

3 months post

6 months post

Study Photographs – Split Face Design

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Source: Prof. Nicolo Scuderi

Pre

3 months post

6 months post

Real World Clinical Performance

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Mid-Face/Cheek/Zygomatic Volumizing

Source: Dr. Joan Vandeputte

6 months

Real World Clinical Performance

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Mid-Face/Cheek/Zygomatic Volumizing

Source: Dr. Omer Bushem

6 months PostPre-treatment

The “Aha Moment” – Agarose Dispersed in Saline

Almost instantaneous decrease in

Viscosity maintained over 30-minute

observation period

New Findings - Rheology and Dispersion

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HA mixed 1:1 with Hyaluronidase

Algeness DF 3.5% mixed 1:1 with 0.9% saline

HA

Algeness DF 3.5%

Algeness Dispersion - Plasma

HA Agarose

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Previously published work: Chiang, Zhou, Liu Plast. Reconstr. Surg. 137: 114, 2016

Algeness Pilot Work,

Dr Ohmer Bhusem, Dr. El Khousa et al.

Pending Findings - Safety

Previously published work: Chiang, Zhou, Chen, Ho, Zhang, Liu Plast.

Reconstr. Surg. DOI: 10.1097/PRS.0000000000002803

Algeness Pilot Work,

Rabbit Retinal Model

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Rapidly Growing Scientific & Clinical Publications - 2020

Vandeputte

Where are We Going with Volumising Injections?

Prime-Journal.com, May/June 2020

Karapantzou, Jakob, Kinney, Vandeputte, Vale and Canis

The use of algeness in the face and neck: a safe, alternative filler for cosmetics and reconstruction

Ann Transl Med 2020;8(6):362 | http://dx.doi.org/10.21037/atm.2020.02.52

Perino, Maullu, Rocca and Kinney

Histology and Biocompatibility of Agarose Gel Filler in Human skin

J Cosm Derm – under review

Scuderi, Fanelli, Fino and Kinney

Comparison of 2.5% Agarose gel versus Hyaluronic Acid Filler, for the correction of moderate to severe nasolabial folds

JCD – DOI: 10.1111/jocd.13962, 2021:00:1-8

Perino, Maullu, Rocca and Kinney

Fibroblast Expansion and Upregulation of Natural HA Precursors in Agarose Media

Manuscript submitted

Sundaram and Kinney

Rheology and Reversibility of Agarose versus Hyaluronic Acid – Novel Characteristics and Clinical Implications

Manuscript in development

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Does Algeness Represent Innovation?

Safety First

Biocompatability

Clinical tolerability

Reversibility

Natural

Cross Linking Agents?

Clinical Performance

Clinical outcome – in the office and over time

Control of shape & contour

Control of volume

Longevity of result

Dispersion is a unique attribute which may yield a unique and important safety profile

High G’ & G” plus non-Hygroscopic

High G’ & G” plus non-Hygroscopic

Algeness 2.5% equivalent to Restylane Lyft® in head-to-head trial. 3.5% TBD – Longer?

Unique, 100% natural product

Unique, none used or needed to achieve durability

Unique, What You See is What You Get, WYSIWYG

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Advanced Aesthetic Technologies - Status

Algeness CE Marked & Registered in Multiple Countries

In process of FDA Registration, Agreed & Defined Path

Preclinical completed

Pivotal trial delayed by Covid

First injections, June 2021

Product shipped to sites37

Conclusion

Market Poised For New Fillers Offering Advances Over HA Technology

Demonstrated Potential for a New Safety Paradigm

Demonstrated, Real-World Safety Experience

Demonstrated Efficacy & Unique Product Profile

Head-to-Head Clinical Performance, Longevity, and Safety

Unique Histology

Unique Rheology

100% Natural & Fully Resorbable

Rapidly Expanding Scientific Support & Publications

Defined US & China Studies

US – 3.5% Mid-Face, China – 2.5% NLF

Pre-clinical for China Complete, US last study ongoing

Both studies start mid-2021

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