Redefining Regenerative Medicine · Human-derived collagen and extracellular matrix dermal filler...

Redefining Regenerative Medicine

2019 BIO Investor Forum

Richard W. PascoeCHAIRMAN AND CEO

October 22-23, 2019

Forward Looking Statement

This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, including statements regarding our future results of operations and financial position, business strategy, prospective products, product approvals, research and development costs, timing and likelihood of success, plans and objectives of management for future operations, and future results of current and anticipated products, are forward-looking statements. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplates,” “believes,” “estimates,” “predicts,” “potential” or “continue” or the negative of these terms or other similar expressions. These statements involve known and unknown risks, uncertainties and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Except as required by applicable law, we do not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. All forward-looking statements are qualified in their entirety by this cautionary statement and we undertake no obligation to revise or update this presentation to reflect events or circumstances after the date hereof. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size and growth and other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions, and estimates of our future performance and the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk.

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Corporate Overview

A private company with an innovative biological technology to replace and regenerate tissues in the body, addressing underserved, multibillion dollar global markets

Corporate Overview

Histogen

A regenerative

therapeutics company

with a unique biological

platform that replaces and

regenerates tissues in the

body

Technology

Our proprietary

manufacturing process

yields multiple biologic

products from a single

bioreactor. This

innovative technology

platform delivers several

attractive product

opportunities

Marketed Product

Cell Conditioned Media

(CCM) cosmetic skincare

products

Product Candidates

• HST 001 – Hair

Stimulating Complex

(HSC) – hair growth in

men

• HST 002 – Human

Extracellular Matrix

(hECM) – dermal filler



(hECM) – joint cartilage

regeneration



(hECM) – spinal disc

regeneration

1. 2. 3. 4.

Intellectual

Property

Strong intellectual

property portfolio with

50 global patents

issued and pending

Markets

• Large, global and

accessible

• Facial dermal fillers

for facial wrinkles,

cheek and lip

augmentation

• Joint cartilage repair

• Hair regrowth

2019 2020

Submit IDE for

HSC002 – Q4

Submit IND

Amendment for

HSC001 – Q1

Initiate HST 002

Pilot Trial – Q1

Submit IND

for HST 003 – Q2

Initiate HST 001

Phase 1b Trial – Q2

Initiate HST 003

Phase 1 Trial – Q2

Complete HST 002

Pilot Trial – Q3

Complete HST 001

Phase 1b Trial – Q4

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Executive Leadership Team

5

Closed multiple business

development transactions

valued at over $2.2

billion.

Led companies

through development

and approval of multiple

prescription drugs

in the U.S. and Europe.

Commercially launched

prescription drugs in

the U.S. generating

net sales of over $1 billion in multiple

therapeutic categories.

Gail Naughton, Ph.D.

Founder/Chief Scientific Officer

Martin Latterich, Ph.D.

Sr. VP of Technical Operations

Richard Pascoe

Chairman and CEO

Technology Platform

Histogen’s unique technology utilizes human proteins and growth factors produced by hypoxia-induced multipotent cells to replace and regenerate tissues, addressing underserved, multibillion dollar global markets

Technology Platform

Histogen has successfully developed a production process which is highly

scalable and economically viable. All of the derivatives from this single

proprietary manufacturing process can be used, creating a spectrum

of products for a variety of markets from one core technology:

1. An insoluble human extracellular matrix (hECM) for applications such

as orthopedics and soft tissue augmentation which can be fabricated into a

variety of forms for tissue engineering and clinical applications

2. A biologic for hair growth – Hair Stimulating Complex (HSC)

3. A soluble multipotent cell conditioned media (CCM) that is the starting

material for products for skin care and other applications

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More than 50 patents

have been issued and

filed worldwide on

Histogen’s technology

and the compositions

produced through its

manufacturing process.

Histogen Manufacturing Process


(hECM)

Hair Stimulating Complex

(HSC)

Cell Conditioned Media

(CCM)

Histogen Product Pipeline

Preclinical Phase 1 Phase 2 Phase 3 Marketed

CCM Cosmetics

HST 001 Hair Growth

(HSC)

HST 002 Dermal Filler

(hECM)

HST 003 Joint Cartilage

(hECM)

HST 004 Spinal Disc

(hECM)

Marketed – Allergan and HydraFacial

Phase 1b

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HSC Hair Growth

A minimally-invasive treatment to promote new hair growth where existing treatments only reduce hair loss

HST 001 - Hair Growth US Market Opportunity

Addressable Market:

$3.6 billion spent on hair loss, targeting men aged 30 – 491

Nature of Treatment:

HSC injections of 0.1mL throughout thinning area of the scalp,

administered by dermatologists and cosmetic surgeons

Market Growth:

2% per year, driven by aging population1

Market Need:

Patients seek a safe, minimally-invasive treatment to achieve cosmetically

relevant new hair growth

Peak Sales Potential:

$684 million2

1 Histogen market research2 Histogen estimate

The hair growth market

is an underserved,

multi-billion dollar global

opportunity.

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HST 001 Clinical Proof of Concept

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Early trials have shown

stimulation of new hair

growth in both men and

women1

Male

Baseline 18 Weeks

Female

1 Investigator-initiated Phase I

clinical study of HSC in male and

female volunteers (US IND 114184)

HST 001 Clinical Proof of Concept

Three Completed Company-Sponsored Clinical Trials

Pilot in male pattern hair loss

Phase 1a in male pattern hair loss

Phase 1a in female diffuse hair loss

Statistically and Cosmetically Significant New Hair Growth

Over 85% of men treated showed new terminal hair growth across all studies

Strong Safety Profile

No kidney, liver or bone marrow toxicity

No severe adverse events

Treatment well tolerated across all subjects

Active IND

US IND 108935

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Pilot Trial

Phase 1a

12 Weeks

*

**

*p=0.033 **p=0.0135

*

**

*p<0.050 **p=0.029

HST 001 Phase 1b Protocol Summary

Objective:

• To determine optimal dosing of HSC in male pattern hair loss

Enrollment Criteria:

• 21 men, aged 20-55

• Male Pattern Hair Loss identified as Norwood-Hamilton 2A, 3, 3V, 4,& 4A

Treatment Regimen:

• 20 injections of HSC week 0, week 6, & week 12

• 20 injections of HSC week 0 & week 6, placebo (PBS) week 12

• 20 injections of placebo (PBS) week 0, week 6, & week 12

Endpoints:

• Adverse events, and other safety parameters

• Non-vellus hair count vs. baseline week 18, measured by Canfield

macrophotography

• Total count, hair thickness density, terminal and vellus hair counts at week 26,

as measured by Canfield macrophotography

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Male Pattern Hair Loss

Phase 1 clinical study

target enrollment Q1/2020

HST 001 - Hair Growth Competitive Differentiation

HSC’s human proteins and growth factors have been shown in early studies to

stimulate resting hair follicles to produce new cosmetically-relevant hair.

A treatment showing efficacy in new patients groups could not only capture

existing market share but expand the size of the market overall.

Target Profile:

• Stimulating new long-lasting hair growth

• Effective over the entire head

• Effective in treating temporal recession

• Effective on both men and women

• Minimally invasive

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Results from additional

clinical trials may support

a high value

pharmaceutical

partnership or exit

hECM Fillers

Human-derived collagen and extracellular matrix dermal fillers for delivering longer-lasting effects for the treatment of facial folds and wrinkles addressing a fast growing global market

HST 002 - Dermal Filler US Market Opportunity

Addressable Market:

1.2 million receiving dermal fillers,10 million considering dermal fillers1


Lower face, cheek, and lip account for ~60% of treatments. Patients receive

approximately 1.7 treatments per sitting

Market Growth:

7% per year, driven by growing acceptance and higher volumes1

Market Need:

Physicians seek extended longevity beyond 6-9 months


$520 US million2


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HST 002 Phase 1 Protocol Summary

Objective:

• Evaluate an all human extracellular matrix (hECM) as a dermal filler, in direct

comparison to Restylane-L in moderate to severe nasolabial folds


• 22 subjects, men and women, with moderate to severe nasolabial folds

• 2 clinical sites

Treatment Regimen:

• hECM filler (up to 3 mL per nasolabial fold)

• Restylane-L (up to 3 mL per nasolabial fold)

Endpoints:


• Responder rate based on Evaluating Investigator assessment of nasolabial

folds at month 3

• FACE-Q Appraisal at month 3

• Participant assessments of global aesthetic improvement at months 3 and 6

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Dermal Filler

IDE filing expected 2019

Phase 1 clinical study

target enrollment Q1/2020

HST 002 - Dermal Filler Competitive Differentiation

Human-derived collagen and extracellular matrix dermal filler injected into

dermis.

Long-lasting effects for the treatment of facial folds and wrinkles.

hECM filler that provides the natural proteins found in young healthy skin

Target Profile:

• Only filler providing all-human and naturally produced collagen with dermal

matrix proteins

• Provides ECM proteins as a volumetric filler to produce long-lasting effects

~12 months

• Potentially reduces risk of inflammation seen with other fillers

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hECM Joint Cartilage

Histogen’s human extracellular matrix for regenerating hyaline cartilage for the treatment of articular cartilage defects with a unique malleable scaffold that stimulates the body’s own stem cells.

HST 003 - Joint Cartilage US Market Opportunity

Addressable Market:

0.2 million receiving joint cartilage repair, 17.5 million considering joint cartilage

repair1


Patients receiving arthroscopic microfracture or cartilage transplant treatments

due to acute injury and/or osteoarthritis

Market Growth:

2% per year, driven by aging population and growing obesity1

Market Need:

Physicians desire treatments that reverse cartilage degeneration


$1.18 US billion2


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HST 003 -Preclinical Proof of Concept

In vivo efficacy in rat model

• Untreated defects (10): extensive fibrotic tissue and no articular cartilage at

6 weeks

• Treated defects (10): congruent and smooth cartilage regeneration and

integration with surrounding cartilage at 6 weeks

• Statistically significant integration of repaired tissue (O’Driscoll score

p<0.001)

In vivo efficacy in rabbit model

• Untreated defects (12): fibrous tissue that did not restore the articular surface

at 24 weeks

• Treated defects (12): articular cartilage formation with structural integrity and

homogeneity at 24 weeks

• Statistically significant integration of repaired tissue (O’Driscoll score

p<0.001)

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POC firmly established in multiple animal models

HST 003 -Preclinical Proof of Concept

In vivo efficacy in goat osteochondral defect

• Untreated defects (16) were characterized by large voids filled with fibrotic

tissue at 12 months

• At 12 months, all hECM-treated defects (16) showed:

• Mature hyaline cartilage

• Mature, vascularized bone

• Integration of regenerated tissue with adjacent tissue

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hECM Treated

Hyaline cartilage regeneration seen in large animal model

Untreated

HST 003 -Phase 1 Protocol

Objective:

• Evaluate the safety of hECM paste delivered arthroscopically during

microfracture procedure


• 12 subjects, men and women, who are candidates for microfracture surgery

• Recent focal cartilage defects of 2 - 4 cm2 in size in the knee

• 3 clinical sites: Walter Reed Medical Center, The Steadman Clinic,

Balboa Naval Medical Center

Treatment Regimen:

• Microfracture + ECM HST 003

• Microfracture alone

Endpoints:


• Evaluate presence of cytokines and inflammatory cells in knee fluid

• MRI to quantify cartilage regeneration

• KOOS and IKDC scores to evaluate pain and joint function23

Joint Cartilage

Evaluation of naturally

secreted human

extracellular matrix for

articular cartilage defects

IND submission expected

Q1/2020

HST 003 - Joint Cartilage Competitive Differentiation

Malleable scaffold applied to full-thickness chondral lesions as part of an

arthroscopic microfracture procedure for the treatment of knee disorders

Target Profile:

• Regenerate hyaline cartilage, potentially improving function/mobility

• Provide reduction in inflammation, potentially reducing pain

• Produce no immune response, potentially improving safety/tolerability

• Increase angiogenesis allowing for improved cell proliferation and

differentiation, potentially improving the healing process and time

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Results from planned

Phase 1 clinical trials may

support a high value

pharmaceutical

partnership or exit.

Anticipated Regulatory Path for all Assets

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HST 001 Hair Growth

HST 002 Dermal Filler

HST 003 Joint Cartilage*

2019

Preclinical

Preclinical

Preclinical CMC

2020 2021 2022 2023 2024

Phase 1

Phase 1

Phase 1

Phase 2

Pivotal

Phase 2

Phase 3 BLA

Phase 3 BLA

PMA

*Potential for Regenerative Medicine Advanced Therapy designation

for accelerated approval

Financial

A track record of successful funding combined with prudent financial management provides the necessary foundation for growth

Financial Snapshot

Company has raised $38.4 million to date in equity offerings and

$20 million to date through licensing transactions, with an additional

$10.5 million in future milestones under these licenses.

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Cash, cash equivalents

and marketable

securities: $6.3MM

as of 6/30/19

Strengthened Finance

Team in Q1 2019

Shares Outstanding: 56,950,168

Fully Diluted Shares: 67,798,463

Fully Audited

Financials through

2018 expected in

November 2019

Cash on hand expected

to fund current

operating plan into Q1

2020

Looking Forward

Creating value by advancing innovative therapeutics to address unmet medical needs in the aesthetics and orthopedic markets

Creating Value

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Multiple near-term value

inflection upon anticipated

initiation of multiple clinical

trials in first half of 2020

and data read-outs

starting in the second half

of 2020

Histogen is advancing

innovative

therapeutics to address

unmet medical needs in

the aesthetics and

orthopedic markets

Validated platform

technology – partnered

and marketed cosmetic

products

Developing a broad portfolio of

therapeutic clinical-stage

regenerative medicine

product candidates with

demonstrated mechanisms

of action1

Advancing three

clinical programs in

therapeutic indications

with large commercial

market opportunities

Strong research, product

development, clinical and commercial leadership

experience

Positioning the Company for potential

licensing or

strategic

transactions in 2020

1 Demonstrated in vitro, in preclinical models and/or in human clinical studies

Redefining Regenerative Medicine

2019 BIO Investor Forum

Richard W. PascoeCHAIRMAN AND CEO

October 22-23, 2019

Redefining Regenerative Medicine · Human-derived collagen and extracellular matrix dermal filler...

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