Scalp Injection of Active Embryonic-like Cell-secreted Proteins and Growth Factors

Gail K. Naughton, Ph.D.

1

2

DISCLOSURES: Speaker has disclosed conflict of interest. Dr. Gail K. Naughton serves as CEO and Chairman of the Board for Histogen, Inc.

Conflict of Interest

Technology Focus: Regeneration

Bioactive human growth factors VEGF KGF Follistatin Stem Cell Factor

Human matrix components

Collagens Laminin GAG Decorin Fibronectin C-propeptide

Histogen’s technology focuses on stimulating a patient’s own stem cells by delivering a proprietary complex of human proteins that have been shown to support stem cell growth and differentiation. This multipotent cell conditioned media has a broad range of applications in both aesthetics and therapeutics:

Current and near-term: Skincare and Cosmetics

First therapeutic, no reimbursement: Hair growth

Second therapeutic: Oncology

Other Opportunities for soluble and insoluble extracellular matrix: Wound care, Device Coating, Bone and Muscle regeneration, Dermal filler 3

Hair Stimulating Complex (HSC)

Cells grow in suspension under low oxygen, simulating embryonic

environment

Stem Cell signaling proteins are secreted into the growth medium

ReGenica skincare

Oncology

4

Intradermal injection of HSC stimulates hair follicle stem cells to

create new hair

Phase I/II Clinical Trial

HSC Baseline + 6 wks

Control Baseline + 6 wks

Double-blind, placebo controlled, randomized, each subject acts as their own control

Single Treatment Site

Subjects – 56 men (50 to complete) MPHL. 21-65 years old

Treatments (at Baseline, 6 weeks) – Control (DMEM, Dulbecco’s Modified Eagles Medium) – Hair Stimulating Complex (HSC) concentrated/conditioned

Assessment Times – Baseline, Week 12, Wk 24, Wk 48 – Wk 36 supplemental informational visit (EC approved)

Endpoints – Primary: Safety

Clinical Evaluation for SAEs or AEs Blood and urine for liver and kidney tox ADA analysis

– Secondary: Safety Investigator and Subject self assessments

– Primary: Efficacy (12 weeks) Trichoscan (Macrophotography, FotoFinder) quantify change in total and non-vellus hair counts and hair thickness

– Secondary: Efficacy Clinical macrophotography (hair counts, etc.) 21 CFR Part 11 compliant (closed system)

Investigators – Dr. Julieta P. Arambulo and Dr. Theresa Reyes Cacas

5

Hair count + 61.41% Terminal hair + 55.63% Thickness + 63.03%

Hair count + 35.88% Terminal hair + 45.83% Thickness + 42.76%

3 month

Subjects sites treated with HSC - representative samples

Hair Stimulating Complex (HSC) – Phase I/II Clinical Trial

6

S1016

3 month Baseline

S2018

7

• Phase I/II trial design produced 46.5% better results in total hair count than the pilot trial at 12 weeks

• A 10.45% Increase in Mean Total Hair Count over baseline was seen

• The increase in hair count is statistically significant, unlike the pilot trial, at 12 weeks

Total Hair Count – 12 Weeks

0

2

4

6

8

10

12

14

16

Honduras Philippines

46.5%

% C

hang

e

Pilot Phase I/II p=0.0013

*

8

• Statistically significant increase in terminal hair count, a primary efficacy measure

• An increase in vellus hair count was also seen, supporting the hypothesis that HSC rescues dying follicles, in addition to converting vellus to terminal hairs and increasing the number of hairs per follicle.

p=0.0135

Terminal & Vellus Hair Counts – 12 Weeks

-2

3

8

13

18

23

28

Vellus Hair Count Terminal Hair Count

% C

hang

e

**

*

p=0.033

Hair Thickness – 12 Weeks An increase in hair thickness density is a result of: 1) An increase in hair count, 2) An increase in the number of terminal hairs and 3) An increase in hair shaft diameter, all of which are important to cosmetic impact.

7.20

7.40

7.60

7.80

8.00

8.20

8.40

8.60

8.80

Baseline 12 Weeks

Cm

Thi

ckne

ss D

ensi

ty (m

m/c

m2 )

*

p=0.026

9

No indication of toxicity or blood/urine abnormalities in the patient population following both sets of HSC injection. Clinical evaluation of blood serum chemistry, hematology and urinalysis showed no changes from baseline over the course of the treatment. No evidence of toxicity is observed in any of the clinical indicators.

Clinical Chemistry

10

11

Trend Analysis

0%

5%

10%

15%

20%

25%

30%

35%

Philippines Honduras

Following the trend, a 25% increase is forecasted for the 48 week timepoint.

12wk 24wk 48wk • HSC injections result in the stimulation of bulge stem cells and the conversion of vellus to terminal hairs

follicles from late telogen to anagen.to result in increased terminal and vellus hairs at the 12 week time point.

• HSC injections are compressing the anagen phase and accelerating the catagen and telogen cycles which explains the decline in terminal and increase in vellus at 24 weeks and subsequent increase in total, terminal, and vellus hairs at week 48.

0

5

10

15

20

25

30

12 Weeks 24 Weeks 36 Weeks % C

hang

e fr

om B

asel

ine

Mid-Scalp Treatment Locations

0

5

10

15

20

25

30

12 Weeks 24 Weeks 36 Weeks % C

hang

e fr

om B

asel

ine

Vertex Treatment Zones Total Hair Count

Terminal Density

Vellus Density

• Graphs show the % Change in Total, Terminal and Vellus Densities at each time point.

• Mid-Scalp and Vertex treatment regions show similar growth trends and are consistent with the trends shown to date

Philippines Phase I/II Regional Data

12

• % Change each time point for treatment zones in the Temporal Recession shown below

• Unlike currently available treatments, HSC produced visible growth in subjects treated in TR region.

-10

-5

0

5

10

15

20

25

30

12 Weeks 24 Weeks 36 Weeks

Temporal Recession

Total Hair Count

Terminal Density

Vellus Density

13

S2005

Baseline

36 Weeks

Philippines Phase I/II Regional Data

Subjects Age 40+ % Change from Baseline

Total Terminal Vellus

12wk 19.35 39.11 15.67

24wk 13.39 16.96 17.26

Pilot Trial -Subjects Age 40+ % Change from Baseline

Total Terminal Vellus 12wk 8.52 21.94 5.09 24wk 5.42 12.88 -0.05 48wk 18.30 37.17 18.34

Age Analysis Unlike current non-surgical treatments, with efficacy limited to younger patients or earlier stages of hair loss, HSC has the potential to expand the hair restoration market by offering a successful option to older patients.

Cosmetically significant results seen in subjects 40-59 years of age in both trials.

14

Dr. Ziering - Phase I U.S. IRB approved Original Design: • Open Label, safety study • 10 Subjects (5 Female and 5 Male) • Baseline, 6 Week repeat dose

Enrollment: 100% Enrollment 100% of Subjects have completed 6 week Repeat dose 100% of Subjects have re-consented and have had increased volume

40 x 0.1cc injections in the same areas and surrounding areas ~97% of the injectate is retained in the tissue

Amended Design: • Patient consent obtained • Up to 40 intradermal injections (0.1mL each) of HSC in broader treatment area (at the 12 week time point and

again at 18 week time point) • Subjects who have completed amended design will have a total of 120 injections throughout study

15

Safety Update: • No SAEs • All injections well-

tolerated

Treatment: • Up to 20 0.1mL injections of HSC in two treatment

areas at baseline with an additional 20 0.1mL intradermal injections at Week 6.

Re-consented female subject received an additional 20 injections of 0.1 cc HSC with a repeat dose at 6 weeks.

.

Baseline 19 Weeks

*Photo reflects total of 30 injections

16

U.S. Physician-sponsored Trial- Dr. Craig Ziering

Baseline 19 Weeks

Female Subject received 20 injections of 0.1cc HSC in area of thinning, with a repeat of this dose at 6

weeks.

U.S. Physician-sponsored Trial- Dr. Craig Ziering

17

Baseline 12 Weeks

Re-consented female subject received an additional 20 injections of 0.1 cc HSC in new treatment location- frontal thinning, with a repeat dose at 6 weeks

U.S. Physician-sponsored Trial- Dr. Craig Ziering

18

Baseline 24 Weeks

Reconsented male subject received an additional 40 injections of 0.1 cc HSC in the same regions- broadening the treatment area, with a repeat dose at 6 weeks .

19

U.S. Physician-sponsored Trial- Dr. Craig Ziering

Local Tolerance

20

• Subject self assessments (SSA) from IND trial reflect an excellent tolerance for the procedure, with the majority of subjects reporting no discomfort. These results are consistent with those reported in other trials.

• Visual examination for redness, inflammation, swelling or edema continues to show overall excellent safety profile for HSC in all subjects

0 1 2 3 4 5 6 7

No Discomfort

Mild Discomfort

Slightly Painful

Moderately Painful

Extremely Painful

Num

ber o

f Res

pons

es

Subject Self Assessment on Local Tolerance

Proof of Concept Clinical Trial

SAFETY (primary objective) 2 year follow-up • No adverse reactions, hamartomas, toxicity; normal histology

EFFECTIVENESS (secondary objective) • 12 Weeks: HSC injection resulted in significant increase in terminal hairs and thickness density

Cumulative thickness density (mm/cm2) p=0.0249 Terminal hair density p=0.029

• 1 Year: HSC injection resulted in continued significant hair growth Total hair count p=0.032

Phase I/II Clinical Trial – 56 Subjects PRIMARY SAFETY 12 weeks

• Clinical chemistry showed no indication of toxicity or blood/urine abnormalities PRIMARY EFFICACY 12 weeks

• 10.45% increase in mean total hair count over baseline p=0.0013 • 19.5% increase in mean terminal hair count over baseline p=0.0135 • Statistical significance in all efficacy measurements • No indication of toxicity or blood/urine abnormalities following both treatment timepoints

Clinical Experience Summary

21

U.S. Physician sponsored IND- 10 Subjects 5 men, 5 women

• All patients have shown new hair growth by 6 weeks • 9/10 subjects have had 20 injections at baseline and 6 weeks, and achieved safe

passage to 40 injections at 12 and 18 weeks. • 4/10 subjects have completed the study • 4/4 of the subjects that have completed the study all answered that they would

participate in future clinical studies

Responder rate: • 84.6% in Proof of Concept Trial at 24 weeks • 86% in Phase I/II at 24 weeks • 100% in Physician IND trial

22

Clinical Experience Summary (cont)

23

Clinical Update Summary

Further analysis of the data suggests a tremendous marketing advantage over other approved treatments, offering a treatment option to those patients that currently have none:

• Regional analysis shows that HSC grows new hair in all regions of the scalp – temporal recession, mid scalp and vertex. (Minoxidil and Propecia do not have positive results in hard-to-treat temporal regions)

• Data shows that men over 40 respond extremely well to HSC, as shown in both Honduras and Philippine trials (current products are most effective in men in their 20s and 30s, in the early stages of hair loss)

• Furthermore, investigator-initiated trial shows great efficacy results in women • HSC continues to have a very strong safety profile, even at 36 weeks

24

Questions?

Gail K. Naughton, Ph.D. CEO & Chairman of the Board

Histogen, Inc. www.histogen.com

Histogen’s focus is on the development and manufacturing of products from its novel core technology process.

As such, Histogen will achieve profitability through research partnerships, upfront licensing payments and post-commercialization royalty streams attached to each of its product applications.

Research Partnerships Example: use of Histogen’s extracellular matrix (hECM) as a coating to improve biocompatibility of existing medical devices.

Licensing Deals Example: license for specific product applications, such as the ReGenica skincare products, hECM for wound healing or soft tissue augmentation, or the HSC injectable for hair growth.

Biomaterial Supplier Example: supplying of Histogen’s soluble extracellular matrix as a raw material for product formulations such as a private label skin or hair care line.

Business Model

Attachment to material presented on October 19, 2012

The Company is currently looking to sell 23 million shares of Series B Preferred Stock at $1 per share to accredited investors (i.e., investors whose net worth, including the fmv of their home, exceeds $1 million and whose annual income exceeds $200,000). To date, $3.3 million is committed. The proceeds from the financing will be used to:

Complete large animal and clinical serum (ADA) testing required before starting the next HSC clinical trial

Complete Scale-up of GMP Manufacturing Complete two preclinical studies with oncology product Prepare and submit IND for Phase I pancreatic cancer trial Support worldwide development of patent portfolio

Current Private Placement Financing

Attachment to material presented on October 19, 2012