RADIUS HEALTH OSTEOPOROSIS INVESTOR DAY

RADIUS HEALTH OSTEOPOROSIS INVESTOR DAY

June 8, 2018

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Safe Harbor

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strategies and other financial or business matters, including regarding the commercialization of TYMLOS® (abaloparatide) injection

in the U.S., the development and potential commercialization of our product candidates, clinical trial results, regulatory actions and

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cautions that these forward-looking statements are subject to numerous assumptions, risks and uncertainties, which change over

time. Important factors that may cause actual results to differ materially from the results discussed in the forward-looking statements

or historical experience include risks and uncertainties, including the failure by Radius to secure and maintain relationships with

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information on the factors and risks that could affect Radius’ business, financial conditions and results of operations and could

cause actual results to differ materially from those indicated by the forward-looking statements made in this presentation are

contained under the caption “risk factors” in Radius’ Annual Report on Form 10-K for the period ended December 31, 2017, along

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represent Radius’ estimate as of the date of this presentation only, and Radius specifically disclaims any duty or obligation to update

forward-looking statements.

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Agenda

TIME TOPIC PRESENTER

08:30 Welcome Elhan Webb, Head Investor Relations, Radius

08:35 Opening Remarks Jesper Hoeiland, Chief Executive Officer, Radius

08:50 Insights on Osteoporosis Treatment Tamara Vokes, MD, University of Chicago

09:15 Douglas Beall, MD, Spine Fracture Institute, Oklahoma

09:40 Q&A

10:00 Coffee Break

10:15 Abaloparatide Life Cycle Management Bruce Mitlak, MD, VP Clinical Development, Radius

10:30 Abaloparatide-patch, R&D Gary Hattersley, PhD, Head R&D Radius

11:10 Insights on Osteoporosis Treatment -Video Paul Miller, MD, Panorama Orthopedics & Spine Center

11:15 Abaloparatide-patch, Commercial Joe Kelly, SVP Sales and Marketing, Radius

11:25 Closing remarks Jesper Hoeiland, CEO, Radius

11:30 Q&A

3

RADIUS OVERVIEW

JESPER HOEILAND CHIEF EXECUTIVE OFFICER

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Radius Health: Mission

Become a leading, fully integrated and innovation

driven biopharmaceutical company

Provide innovative treatment options for women’s

health with significant unmet needs

Guided by a strong scientific foundation, expand and

advance clinical pipeline in osteoporosis and breast

cancer

| 6

Radius History Deeply Rooted in Science and

Women’s Health

RAD1901

Phase 1 data

at SABCS

Abaloparatide-SC Phase 2 initiated in PMOP

Nuvios becomes Radius Health, Inc.

2009 2011 2012 2013 2015 2016

Nuvios founded

Radius in-licenses abaloparatide

Radius in-licenses RAD1901

Abaloparatide-SC Phase 3

initiated in PMOP

Abaloparatide-TD Phase 2 initiated in PMOP

Abaloparatide-SC Phase 3

initiated in PMOP

RAD1901 Phase 1 initiated in

ER+/HER2- breast cancer

Radius completes

IPO

FDA accepts NDA submission for ABL-SC

2017 2003 2006 2005 2008 2014

Radius presents at

ENDO

Radius presents data at ASBMR

FDA Fast

Track for

Elacestrant

(RAD1901)

Phase3

abaloparatide

clinical trial

initiated in

male OP

Initiation of Ph 1 for RAD 140

Elacestrant Follow-

up data at SABCS

2017

Elacestrant

Follow-up

data at

SABCS 2017

Radius and 3M to

enter into

commercial

manufacturing

agreement for

Abalo-Patch

2018

FDA approves

TYMLOS™

(abaloparatide)

PMOP: Post-Menopausal Osteoporosis

ABL-TD: Abaloparatide Transdermal

RAD-1901, Elacestrant: Selective Estrogen Receptor Degrader

RAD140: Selective Androgen Receptor Modulator

®

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Radius Clinical Pipeline

®

| 8

Annual incidence of osteoporotic fractures women in the US is higher than that of stroke, MI, and breast cancer combined

Annual incidence of common illnesses in women1-3

*New and recurrent MI and fatal CHD.

References: 1. Burge R, Dawson-Hughes B, Solomon DH, et al. Incidence and economic burden of osteoporosis-related fractures in the United

States, 2005-2025. J Bone Miner Res. 2007;22(3):465-475. 2. Mozaffarian DM, Benjamin EJ, Go AS, et al; American Heart Association Statistics

Committee, Stroke Statistics Subcommittee. Heart disease and stroke statistics 2016 update. Circulation. 2016;133(15):e38-e360. 3. National

Cancer Institute. SEER stat fact sheets: female breast cancer. http://seer.cancer.gov/statfacts/html/breast.html. Accessed November 1, 2016.

Osteoporotic

fractures Stroke

Myocardial

infarction*

Breast

cancer

1,455,843 425,000 405,000 246,660

3x greater

3.5x greater

5x greater

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Radius: Expanding Franchise in Osteoporosis

TYMLOS: Launched in May 2017

A new anabolic therapy for osteoporosis

ACTIVExtend: First line sequential treatment data with anabolics

Highly efficacious treatment option

Male Osteoporosis: Seeking expansion of label. Ph 3 started in March 2018

Opportunity to address an under-treated condition

Abaloparatide Patch: Expand the use of anabolic therapy by providing

alternative to injection and extend the life of abaloparatide

®

OSTEOPOROSIS MANAGEMENT

KEY OPINION LEADERS

- TAMARA VOKES, MD

- DOUGLAS BEALL, MD

Not for Promotional Use

Osteoporosis management Individual-centered approach

Role of anabolic therapy

Tamara Vokes, MD

Professor, Section of Endocrinology, Diabetes, and Metabolism

Department of Medicine

University of Chicago

Section of Endocrinology, Diabetes, and Metabolism



Disclosures

• Shire – investigator, consultant, speaker

• Radius Health – investigator, consultant, speaker

12

Learning objectives

• Understand what osteoporosis is

• List the therapeutic agents that decrease fracture risk

• Describe how to apply different therapeutic modalities to individual patients

• Define the role of anabolic therapy


Department of Medicine 13

Osteoporosis Definition

Osteoporosis is a systemic skeletal disease characterized by low bone mass and deterioration of bone tissue leading to increased risk of fractures



Osteoporosis diagnosis



• Clinical – fragility fracture

• Fragility fracture = fall from standing height during usual physical activity

• “Classic” fragility fracture - hip or spine (wrist)

• Low Bone Mineral Density (BMD)

Fracture trumps BMD

15

BMD by DXA – gold standard

• High precision

• Low radiation exposure

• Low cost

• Good predictive value



Fracture Risk Doubles With Every SD (1 T-score unit) Decrease in BMD

0

5

10

15

20

25

30

35

-5.0 -4.0 -3.0 -2.0 -1.0 0.0 1.0

Bone Density (T-score)

Relative Risk

for Fracture Normal BMD >-1

Osteopenia -1to -2.5

Osteoporosis <-2.5

WHO classification Novel concept: Treat to target

17

Age is a strong predictor of fracture: At any BMD, fracture risk is higher in older

Adapted from Kanis JA et al. Osteoporosis Int.12:989, 2001.

0

10

20

30

40

50

1.0 0.5 0.0 -0.5 -1.0 -1.5 -2.0 -2.5 -3.0 -3.5 -4.0

Femoral Neck T-score

Ten Year Fracture Probability (%)

Age

80

70

60

50

Probability of first fracture of hip, distal forearm, proximal humerus, and symptomatic vertebral fracture in women of Malmö, Sweden.

18



Pre-existing vertebral fractures predict future fractures independent of BMD

• 2x risk for hip fx (Kotowicz, 1994; Black, 1999)

• 5x risk for spine fx (Davis, 1999; Black 1999)

• 25x risk if 1 vertebral fracture and low BMD

• 75x risk if multiple vertebral fractures and low BMD

75

25.1

14.910.2

7.4 4.41

Low BMD Med BMD Hi BMD

No Fx

1 Fx

> 1 Fx

Vertebral Fx + BMD = Improved Fracture Risk Assessment

Ve

rte

bra

l fra

ctu

re r

isk

19

Calcium

Vitamin D

Weight-bearing and muscle strengthening exercises

Avoidance of tobacco and limit alcohol

Counseling on fall prevention

Osteoporosis management

Nutrition &

Lifestyle

Drug Therapy

Exercise

(Activity)

All patients: Lifestyle Interventions

20

Bone remodeling and pharmacologic therapy

Anabolic agents- stimulate osteoblastic bone formation

Antiresorptive agents- interfere with osteoclastic bone resorption

21

Pharmacologic Therapy



Antiresorptives (widely used)

• Bisphosphonates • Alendronate

• Risedronate

• Ibandronate

• Zolledronate

• Estrogen

• SERM: Raloxifene

• Calcitonin (??)

• Denosumab

Anabolic agents (reserved for patients at highest fracture risk or those failing antiresorptive therapy)

• Teriparatide

• Abaloparatide

Bone resorption and formation are coupled

Individualize therapy

22

Bisphosphonates



Alendronate (Fosamax): 70 mg weekly

Risedronate (Actonel): 35 mg weekly; 150 mg monthly

Ibandronate (Boniva): 150 mg monthly (P.O.); 3 mg IV injection every 3 months

Zoledronic acid (Reclast): 5 mg IV infusion (15-20 min) yearly

Disadvantages:

- GI side-effects

- Osteonecrosis of the Jaw (ONJ)

- Atypical femur fractures

- ?Long term suppression of bone turnover?

- Diminished response to anabolic agents

Advantages:

- Bone specific

- Increase BMD

- Fracture reduction

- Easy to take

- Drug holiday

23

Declining use of bisphosphonates – fear of rare side effects

Fearing Drugs’ Rare Side Effects, Millions Take Their Chances With Osteoporosis By Gina Kolata June 1, 2016 Jha et al. JBMR 30:2179, 2015

24

http://www.nytimes.com/by/gina-kolata

http://www.nytimes.com/by/gina-kolata

17.9%

14.8%

13.2%

11.3%

693

884

738

500

550

600

650

700

750

800

850

900

10%

12%

14%

16%

18%

20%

22%

24%

26%

Fra

ctu

res

pe

r 10

0,0

00

Wo

me

n A

ge

65

+

Ag

e-a

dju

ste

d to

the

20

14

Ag

e D

istrib

utio

n

Pe

rce

nt

of

Wo

me

n A

ge

65

+

Lewiecki EM et al. ASBMR Oral Presentation #1077. 2016.

14,391 additional hip fractures

$576 million additional expenses

2,878 additional deaths

DXA Medicare Payments

DXA Testing

$82

Osteoporosis Diagnosis

$139

Hip Fracture Rates

$42

US Hip Fracture Trends 2002-2015

25

Anabolic therapy: Teriparatide (Forteo): 20 mcg s.c. daily (1-34 rhPTH) Abaloparatide (Tymlos): 80mcg sc daily (1-34 rhPTHrP analogue)

Advantages:

- Builds new bone

- Large increase in BMD

- Fracture reduction



Disadvantages:

- Daily injection

- Cost

- Osteosarcoma (rats)

- Bone loss after discontinuation, without sequential therapy

Candidates for anabolic Tx?

High fracture risk (fracturing on therapy)

Treatment naïve patients with very low BMD or prevalent

vertebral fractures

If contemplating anabolic Tx use it first (before antiresorptives)

Good choice after drug holiday

26

ITT Population N=2463; Secondary Efficacy Endpoint

Placebo Abaloparatide-SC Teriparatide

P values in statistical analysis plan are versus placebo at 18 months and versus teriparatide at 6 months for femoral neck and total hip. All other p values were not adjusted for multiple comparisons. Values shown are mean percent

change from baseline using a mixed-effect repeated-measures model.

Total Hip Lumbar Spine Femoral Neck

Me

an C

han

ge

fro

m B

ase

line

, %

Months from Randomization

-1

0

1

2

3

4

5

0 6 12 18

*†

*†

*

*

*

*†

-1

0

1

2

3

4

5

0 6 12 18

*†

*†

*

*

*

*†

0

2

4

6

8

10

12

0 6 12 18

*†

*†

*

*

*

*

*P < 0.001 vs. placebo; †P < 0.001 abaloparatide vs. teriparatide. Error bars indicate 95% confidence interval.

BMD response to abaloparatide, teriparatide and placebo

Miller et al. JAMA. 2016;316:722

27

Risk Reduction of New Vertebral Fractures Modified ITT Population* N=2118

Primary Efficacy Endpoint

*Includes all ITT patients who had pretreatment and postbaseline evaluable radiologic assessments. †P < 0.001 vs placebo.

0

1

2

3

4

5

Placebo n=711

Abaloparatide-SC n=690

Pro

po

rtio

n o

f P

ati

en

ts w

ith

N

ew

Ve

rte

bra

l Fra

ctu

res,

%

-86%† -80%†

4.2% (n=30)

Teriparatide n=717

0.6%

(n=4)

0.8% (n=6)

Relative Risk Reduction

P values were not adjusted for multiple comparisons

Miller et al. JAMA. 2016;316:722 28

0

1

2

3

4

5

Risk Reduction of Nonvertebral Fractures ITT Population N=2463

Secondary Efficacy Endpoint

*P = 0.049 vs placebo; †NS vs placebo (exploratory endpoint) Based on cumulative Kaplan-Meier estimates ITT at 19 months.

-43%*

NS†

Placebo n=821

Abaloparatide n=824

Teriparatide n=818

4.7% (n=33)

2.7% (n=18)

3.3% (n=24)

Pro

po

rtio

n o

f P

ati

en

ts w

ith

N

on

ve

rte

bra

l Fra

ctu

res,

%

Relative Risk Reduction

Adapted from Miller et al. JAMA. 2016;316:722 29

Time to Event of Nonvertebral Fractures

Time to Event, Months

Hazard Ratios (95% CI) Abaloparatide vs Placebo: 0.57 (0.32 to 1.00) Teriparatide vs Placebo: 0.72 (0.42 to 1.22) Log-rank P value 0.049 Abaloparatide vs Placebo 0.22 Teriparatide vs Placebo 0.44 Abaloparatide vs Teriparatide

0

0 .0

1 .0

2 .0

3 .0

4 .0

5 .0

6 1 2 1 8

Pl a c e bo A b a l o p a r a t i de T e r ipa r a t i d e

Pa

tie

nts

wit

h

No

nve

rte

bra

l Fra

ctu

re,

%

ITT Population N=2463

Secondary Efficacy Endpoint

P values were not adjusted for multiple comparisons. The median durations in days of follow-up for all 3 fracture categories were 568 (interquartile range [IQR], 557-572) for placebo, 568 (IQR, 477-572) for abaloparatide, and 567 (IQR, 558-571) for teriparatide.

No. at risk Abaloparatide 824 692 638 602 Placebo 821 726 669 614 Teriparatide 818 730 677 637 Cumulative No. with Events Abaloparatide 5 12 15 Placebo 10 17 33 Teriparatide 12 18 23

Adapted from Miller et al. JAMA. 2016;316:722

30

Safety and Adverse Events Safety Population N=2460

Placebo n=820

Abaloparatide n=822

Teriparatide n=818

All treatment-emergent adverse events 87.6% 89.4% 88.9%

Serious treatment-emergent adverse events 11.0% 9.7% 10.0%

Deaths 0.6% 0.4% 0.4%

Adverse events leading to discontinuation 6.1% 9.9% 6.8%

Discontinuation due to >7.0% BMD decrease 6.5% 0.5% 0.6%

Hypercalcemia (prespecified)* 0.4% 3.4%†‡ 6.4%‡

Adverse events of special interest

Orthostatic hypotension 16.4% 17.1% 15.5%

Neoplasms 3.5% 2.4% 3.8%

Fall 0.2% 0.5% 0.5%

Drug hypersensitivity 0.2% 0.2% 0.0%

Renal impairment 0.5% 0.2% 0.4%

Myocardial infarction 0.2% 0.1% 0.2%

*Serum albumin-corrected calcium value ≥10.7 mg/dL at any time point, prespecified safety endpoint. †P = 0.006 abaloparatide-SC vs teriparatide; ‡P < 0.001 vs placebo. P values were not adjusted for multiple comparisons


Most Frequently Observed Adverse Events (≥5%) Safety Population N=2460

Most common AEs reported by ≥5% in any treatment group

Placebo n=820

Abaloparatide n=822

Teriparatide n=818

Hypercalciuria 9.0% 11.3% 12.5%

Dizziness 6.1% 10.0% 7.3%

Arthralgia 9.8% 8.6% 8.6%

Back Pain 10.0% 8.5% 7.2%

Nausea 3.0% 8.3% 5.1%

Upper respiratory tract infection 7.7% 8.3% 8.9%

Headache 6.0% 7.5% 6.2%

Hypertension 6.6% 7.2% 5.0%

Influenza 4.8% 6.3% 4.2%

Nasopharyngitis 8.0% 5.8% 6.5%

Urinary tract infection 4.6% 5.2% 5.0%

Palpitations 0.4% 5.1% 1.6%

Pain in extremity 6.0% 4.9% 5.1%

Constipation 5.1% 4.5% 4.2%


ACTIVE and ACTIVExtend Trial Design

*A 1-month gap in treatment was allowed for rollover from ACTIVE to ACTIVExtend.

Teriparatide 20 μg daily SC (n=818)

Abaloparatide 80 μg daily SC (n=824)

Ran

do

miz

atio

n

Placebo (n=821)

Months 6 12 18

ACTIVE ACTIVExtend

Preplanned 6-month interim analysis

25 19* 43

Alendronate 70 mg weekly (n=558)

Alendronate 70 mg weekly (n=581)

Cosman F et al. Mayo Clin Proc. 2017;92(2):200-210; Bone H et al., JCEM May 24, 2018 online publication

33

84% Relative Risk Reduction

P<0.001

Sustained Vertebral Fracture Risk Reduction

Modified intent to treat population was used for new vertebral fracture rate. *Miller PD et al. JAMA. 2016;316:722-733. ABL, abaloparatide; ALN, alendronate; PBO, placebo.

0

1

2

3

4

5

6

ACTIVExtend Cohort, 43 Months

PBO/ALN n=568

ABL/ALN n=544

5.63% (n=32)

0

1

2

3

4

5

6

PBO n=711

ABL n=690

Pro

po

rtio

n (

%)

of

pat

ien

ts w

ith

n

ew v

erte

bra

l fra

ctu

res

ACTIVE* Cohort, 18 Months

4.22% (n=30)


P<0.001

0.58% (n=4)

0.92% (n=5)

Bone H et al., JCEM May 24, 2018 online publication 34

Sustained Nonvertebral Fracture Risk Reduction

ABL, abaloparatide; ALN, alendronate; PBO, placebo.

Pati

ents

wit

h f

ract

ure

, %

0

2

4

6

8

10

0 6 12 18 24 30 36 42

Study Month

ALN monotherapy began at 19 months

PBO/ALN

ABL/ALN 39% risk

reduction P=0.038

ACTIVExtend

N=1,139

Bone H et al., JCEM May 24, 2018 online publication 35

Pretreatment with bisphosphonate impedes the response to anabolic therapy

Finkelstein et al. JCEM 92:1838, 2010

Alendronate Alendronate and Teriparatide Teriparatide

36

Sequence of therapies: anabolic therapy first!



Leder et al. Lancet 386:1147, 2015 37

Role of anabolic therapy in treating osteoporosis

• We can achieve (almost) normal BMD even in patients starting at very low levels – treat to target

• Rapid decrease in fragility – advantage for patients who are fracturing and have high risk of new fractures

• Long-term efficacy (and likely even cost-effectiveness) is better using anabolic therapy first

• Not associated with risk of osteonecrosis of the jaw or atypical femur fracture

• Ideal therapy for treatment naïve patients with low BMD and/or high fracture risk

• Strong consideration for patients with at risk for fractures who are coming off a bisphosphonate drug holiday

38

Radius Health, Osteoporosis Day June 8, 2018 Palace Lotte Hotel, New York

Douglas P. Beall, M.D.

Spine Fracture Institute

Oklahoma Spine Hospital

Oklahoma City, OK


Disclosures: Douglas P. Beall, M.D., DAAPM, FIPP

• Medtronic – Advisory Board, Consultant, Research

Funding • Amendia – Consultant • Spineology – Consultant, Stock Owner • Dfine – Consultant • Osseon – Consultant • Lilly - Advisory Board, Consultant • Xten – Consultant • Smith & Nephew – Consultant • Ascendx Spine - Consultant, Research Funding • Vertiflex – Consultant • Synthes – Consultant • Depuy – Consultant • Johnson & Johnson – Consultant • Orthovita - Consultant, Research Funding • Vitacare - Consultant, Research Funding • Ortho Kinematics - Consultant, Research Funding

• Alphatech Spine - Consultant, Research Funding • Dfine - Consultant, Research Funding • Advanced Technologies and Regenerative Medicine -

Research Funding • Algea-Globus – Consultant • Benvenue - Consultant, Research Funding

• Bone Support - Consultant, Research Funding

• Convatec - Advisory Board, Consultant

• Integral Spine Solutions – Advisory Board, Consultant

• Spinal Ventures – Consultant

• Peterson Enterprises – Consultant

• Medical Metrics

• Radius Health – investigator, consultant, speaker

40

Objectives

• Prevalence of Osteoporosis & VCFs & Magnitude of Treatment Gap

• Number of Pts Being Treated w/ Anabolic Bone Agents

• The Difference Betw Anti-resorptives & Anabolics & Repercussions of Disease Process

• Future of Treatment &Treatment Sequence

41

High Prevalence, Low Treatment

• \

Approximately 1 in 2

women & 1 in 4 men

over the age of 50 will

have an osteoporosis-

related fracture in their

remaining lifetime1

42

• VCFs are prevalent (40% of pts by age 80) and costly (> $5B annually in U.S.), & increasing annually

Proportion of Elderly Population in the

United States (65 Years Old)

Per

cen

tage

of

Peo

ple

Age

65 Y

ears

Old

0

10

30

20

1950

25

15

5

60 70 80 90 00 10 20 2030

Year

• Census Bureau, > 65yo • 1960 was 16.6 million

• 2030 will be an estimated 70.2 million

43

Slide Courtesy of Douglas P. Beall, M.D.

Elderly Population Percentage by State

High Percentage and Growing

44

Pts w/ Osteoporosis After Fragility Fracture Not

Routinely Receiving Care to Prevent Future

Fractures • In a retrospective study, many pts w/

osteoporosis did not receive treatment

after a fragility fracture*1

– Approximately 4 of 5 pts (78%) w/ hx

of hip or wrist fracture did not fill a

prescription for tx of osteoporosis in

the 6 mos after the fracture1

1. Solomon DH, et al. Am J Med. 2003:398-400.

2. Dell RM, et al. J Bone Joint Surg Am. 2009;91(Suppl 6):79-86.

A significant treatment gap exists for patients with

osteoporosis who have sustained a fragility fracture.1,2

Patients who received treatment Patients who did not receive treatment

22%

78%

45

Treatment Rates Are Declining Annual Probability of Osteoporosis Med Use w/in 12 mos After Hip Fx

Solomon DH, et al. J Bone Miner Res 2014;29:1929-37

46

Anabolic Bone Agent Market

Market %

Antiresorptive Osteoprosis Meds Anabolic Osteoporosis Meds 47

Difference Between Anabolics and Antiresorptives

• Anabolics:

– Stimulate new bone formation

– Can repair disordered bone architecture

– Increase bone mass to a greater extent than

antiresorptive therapies

– Work faster (fracture risk decreases in 1 – 1.5 yrs

compared to 3 yrs for anti-resorptives)

– Greater fracture reduction

48

Tymlos Significantly Reduced the Risk of New Vertebral Fractures at 18 months

49

Denosumab Data ( FREEDOM)

50

Osteoporosis Treatment Can Decrease Mortality

• Meta-analysis

• Study Selection: PC RCT’s w/ optimal doses of meds w/ proven efficacy; study duration ≥ 1yr

• Data Synthesis: 8 studies of 4 meds (risedronate, strontium ranelate, zoledronic acid, & denosumab); Tx was assoc w/ 11% ↓ in mortality; Mortality ↓ unrelated to age or hip/nonvertebral fx

• Conclusions: Tx for osteoporosis w/ meds shown to ↓ fx’s reduce mortality in older, individuals at high risk of fracture.

51

“ …Medicare pts w/ a VCF

had an overall mortality rate

twice that of the matched

controls.”- Lau et al. JBJS 2008

Mortality Rate per 1000 person

years of observation

85.6

231.6

NO VCF WITH VCF

52

Mortality Risk VCF PATIENTS HAVE HIGHER MORTALITY RISK THAN NON VCF

PATIENTS

Lau E, Ong K, Kurtz S, et al. Mortality following the diagnosis of a vertebral compression fracture in the Medicare

population. J Bone Joint Surg Am. 2008 Jul;90(7):1479-86. doi: 10.2106/JBJS.G.00675

Why Treat?

• Primary cause of death is pulmonary

• Degree of kyphosis (curvature of spine) sig related to risk of pulm death (p=0.005)9

• M & M of VCF’s ≥ hip fx6

Age-

Matched

Control

Hip FractureSpine

Fracture

1

6.7

8.6

0

3

6

9

Relative Risk of Death

53

• Est 59,389 to 75,452 pts at higher mortality risk due to change in treatment patterns

• Est 5,287 to 6,814 extra lives lost 54

55

Why Aren’t Anabolic Agents Used More Often or

as a First line Medication in High Risk Pts?

• Medication:

– Is Expensive

– Is Administered by Injection

– Was Traditionally

Recommended After Anti-

Resorptive Meds 56

Economic Benefits of Emerging Bone-Forming Agents

• O’Hanlon et al:

– During a 1.5 yr period bone formers

can reduce fxs & provide

improvements in QALY’s & cost

savings & monetary benefit of

$17,000,000 per 10,000 pts tx’ed

Is Expensive:

57

Cost Effectiveness of Sequential Therapy w/

Abaloparatide & Alendronate

US postmeno women at high risk for fractures, ABL followed by ALN leads to

improved health outcomes and lower healthcare costs than treatment starting w/ ALN

Table 1. Lifetime Costs, QALYs, Number of Fractures and Incremental Cost-Effectiveness Ratio (ICER) of ABL/ALN

Compared with ALN/ABL/ALN for Women 70 Years of Age With BMD T-score ≤-3.5

ABL/ALN ALN/ABL/ALN

Costs (US$) 83,304 86,417

QALYs 8.638 8.566

Fractures (N) 2.021 2.175

ICER Dominant Dominated

Source: AMCP Nexus 2018; 1 Maastricht University, the Netherlands, 2 Radius Health, Inc., MA, 3 Cedar-Sinai Medical Center and UCLA School of

Medicine, Los-Angeles, CA, 4 University of Liège, Belgium

Is Expensive:

58

A transdermal patch delivering the PTHrP1-34

analog, abaloparatide (BA058), dose-dependently

increases spine and hip bmd compared to

placebo

• Study provides – “strong proof of concept that an investigational transdermal patch delivering abaloparatide

produces meaningful increases in spine and hip BMD. ABLTD was generally well tolerated.

Is Administered by Injection:

John Yates1, Peter Alexandersen2, Annesofie Krogsaa2, Bettina Nedergaard2, Marcie Clarkin1, Gary

Hattersley1, Kris Hansen3, Morten Karsdal2 & Claus Christiansen2

59

Treatment Sequence Matters

• Cosman et. al.,

– Common practice of using anabolics

only after pts have inadequate

response to antiresorptives is not

the optimal utilization of anabolic

treatment

& may result in transient loss of

hip BMD and strength

Was Traditionally Recommended After Anti-Resorptive Meds:

60

Data-Switch Study

• Leder et. al.,

• Switching from TPD to Denosumab = BMD cont to ↑, but from Denosumab to TPD = progressive or transient bone loss

• Results should be considered when choosing the initial & subsequent mgt of postmeno osteoporotic pts


61

Prolia Drug Safety Labeling

• 6.1 Clinical Trials Experience

• Multiple Vertebral Fractures (MVF) Following Discontinuation of Prolia Treatment

• In the clinical trial program, multiple vertebral fractures were reported in patients after discontinuation of Prolia. In the phase 3 trial in women with postmenopausal osteoporosis, 6% of women who discontinued Prolia and remained in the study developed new vertebral fractures, and 3% of women who discontinued Prolia and remained in the study developed

multiple new vertebral fractures. The mean time to onset of multiple vertebral fractures was 17 months (range 7- 43 months) after the last injection of Prolia..


62

Sustained Vertebral Fracture Risk Reduction w/

Abaloparatide followed by ALN

• Modified intent to treat population was used for new vertebral fracture rate. *Miller PD et al. JAMA. 2016;316:722-733.

• ABL, abaloparatide; ALN, alendronate; PBO, placebo.

0

1

2

3

4

5

6

ACTIVExtend Cohort, 43 Months

PBO/ALN n=568

ABL/ALN n=544

5.63% (n=32)

0

1

2

3

4

5

6

PBO n=711

ABL n=690

Pro

po

rtio

n (

%)

of

pat

ien

ts w

ith

n

ew v

erte

bra

l fra

ctu

res

ACTIVE* Cohort, 18 Months

4.22% (n=30)


P<0.001

0.58% (n=4)

0.92% (n=5)


P<0.001

63

Summary

• Osteoporosis is one of the largest & most rapidly growing pt demographic that exists

• Patients currently being undertreated & this is especially true anabolic bone agents

• Repercussions of undertreatment are prominent & include increased mortality

• Anabolic bone agents are more effective at treating osteoporosis than anti-resorptive agents

• Recent evidence indicates earlier use of anabolics may be more clinically effective & cost effective

64

Q&A

| 66

Agenda

TIME TOPIC PRESENTER

08:30 Welcome Elhan Webb, Head Investor Relations, Radius

08:35 Opening Remarks Jesper Hoeiland, Chief Executive Officer, Radius

08:50 Insights on Osteoporosis Treatment Tamara Vokes, MD, University of Chicago

09:15 Douglas Beall, MD, Spine Fracture Institute, Oklahoma

09:40 Q&A

10:00 Coffee Break

10:15 Abaloparatide Life Cycle Management Bruce Mitlak, MD, VP Clinical Development, Radius

10:30 Abaloparatide-patch, R&D Gary Hattersley, PhD, Head R&D Radius

11:10 Insights on Osteoporosis Treatment -Video Paul Miller, MD, Panorama Orthopedics & Spine Center

11:15 Abaloparatide-patch, Commercial Joe Kelly, SVP Sales and Marketing, Radius

11:25 Closing remarks Jesper Hoeiland, CEO, Radius

11:30 Q&A

66

ABALOPARATIDE LIFE CYCLE MANAGEMENT

BRUCE MITLAK, MD VP CLINICAL DEVELOPMENT

| 68

68

Future Areas of Research

Adjacent populations /

Non-injectable

Deepen Understanding

PMO Indication

Life Cycle Management

Life Cycle Strategies

Future Areas of Research

ACTIVE Extend, ACTIVE subsets

Histomorphometry Study

ACTIVE registrational trial

Launch Indication

Male OP (ATOM study)

Abaloparatide Patch

Adjacent populations / Non-injectable

Research in Bone Health supporting IIS

Launched in

2017

Deepen Understanding

®

| 69

ACTIVExtend study demonstrates that abaloparatide followed by

alendronate can provide a rapid and sustained favorable effect

• The study demonstrates effectiveness of a treatment sequence

of abaloparatide (ABL), an anabolic followed by alendronate

(ALN) for two years

• Favorable effects on fracture risk across anatomic sites and

consistent, progressive gains in BMD at the Total hip, Femoral

Neck, and Lumbar Spine

• Nominally significant effect on hip fracture incidence (0 in

ABL/ALN group vs 5 in PBO/ALN group)

• First time treatment sequence employing a PTH1R-mediated

anabolic agent has been tested in a fracture-endpoint trial

• ABL/ALN sequence can provide a rapid and substantial initial

benefit as well as a sustained favorable effect, employing a

relatively inexpensive medication in the continuation phase

Manuscript now published and available online at https://doi.org/10.1210/jc.2018-00163

| 70

TYMLOS Mechanism of Action is Differentiated from PTH and

PTHrP ligands

Abaloparatide has unique PTH1 receptor RG/RO selectivity, compared with PTH or PTHrP, that promotes a marked net anabolic activity

• High affinity and > 1000-fold greater selectivity for the G protein-coupled (RG) vs the non-G protein-coupled (R0)

• Results in potent and transient intracellular cyclic AMP (cAMP) signaling

Hattersley et al. Endocrinol 2016.

| 71

Numbers of osteoclasts formed

Differential Downstream Effects of abaloparatide leads to

Limited Bone Resorption

PTH

osteoblasts

bone formation osteoblasts

bone formation

RANKL

osteoclasts

bone resorption osteoclasts

bone resorption

Difference in RANKL ligand

Persistence RANKL with PTH

Transient RANKL with Abaloparatide in Bone cells RANKL

Abaloparatide

ADD SOURCE

| 72

Upcoming Histomorphometry Study designed to help understand and

differentiate early effects of TYMLOS on Bone Formation and Structure

• Quadruple label technique will be employed to allow measurement of dynamic bone formation variables before and after

initiation of three months of treatment in a single biopsy; eliminates side-to-side variability in the traditional paired biopsy

study design

• Demonstrate the early effects of abaloparatide on tissue-based indices of bone formation and resorption

• Assess the degree to which increased bone formation is achieved by modeling, remodeling, and overflow bone formation

• Changes in bone microarchitecture will be evaluated by high resolution pQCT in a subset of patients

• Study initiated expected in 2018

Cortical bone, 6 months, Teriparatide

Dempster, D. et al. JBMR 2016

Mean percent change in BMD at the Ultradistal Radius

| 73

Male Osteoporosis: Serious Health Concern, currently Under-treated

Osteoporosis Prevalence

Women Aged 50+ Women 0-49 Men

12.4 M

2.6 M

Prevalence of Osteoporosis in the US1

• Males represent approx. 20% of the prevalent Osteoporosis population in

the US, but only 10% of the treated population

• Pre-clinical studies demonstrate that abaloparatide fully reversed the

orchiectomized-related deficit by increasing bone mass and density at

cortical and trabecular sites

• ATOM study, Abaloparatide for the Treatment of Osteoporosis in Men:

• Initiated in March 2018

• Randomized, double-blind, placebo-controlled bridging trial

• Enroll approximately 225 men with osteoporosis

• Primary endpoint is change in spine bone mineral density (“BMD”) at 12

months compared with placebo

• Include specialized high-resolution imaging of bone structure in a subset

of the study participants

• Basis of a supplemental NDA

1. Decision Resources 2017

| 74

Adjacent Populations

/ Non-injectable

Fracture Healing

Other bone health

indications

Spine Fusions

Future Opportunities

Adjacent populations –

Glucocorticoid Induced Osteoporosis Abaloparatide robustly increased BMD in rabbits

rendered severely osteopenic by the combined

effects of OVX plus GCC therapy

Fracture Healing Abaloparatide increased callus bridging, callus area,

callus bone volume, and callus strength and stiffness

in rats with closed femoral fractures

Spine fusions Pre-clinical PoC collaboration ongoing

Total callus area/Length of the healing area

6 weeks

Abaloparatide Patch In development; Phase 3 initiation expected mid-2019

Investigator Initiated Studies

®

ABALOPARATIDE PATCH

ABALOPARATIDE-PATCH R&D

GARY HATTERSLEY, PHD HEAD R&D

| 77

Novel Patch Technology Provides a Patient Friendly Alternative for

Anabolic Treatment

Short wear time patch provides alternative to self-injection enhancing

patient convenience

• Alternate route of administration may make anabolic treatment more accessible

and accepted by patients

• Majority of patients are not offered a daily injectable by their healthcare providers

Provides

Patients with

Options

Robust

development

plan

Experienced

Manufacturing

Partner

Plan to bridge patch to approved abaloparatide-SC based on

pharmacodynamic endpoint (BMD)

• Optimized drug device combination

• FDA alignment on development plan that provides pharmacodynamics, clinical

benefit, long-term safety and patient experience data

• Clinical data supports a high probability to success

Experience manufacturing partner

Commercial supply agreement with 3M executed

| 78

316 individual microprojections

each 500mm tall

Abaloparatide coated on the

tip of each microprojection

Overview of the Abaloparatide Patch (Solid Microstructured Transdermal

System; sMTS)

The abaloparatide patch is a drug device combination product consisting of the

drug/excipient coated onto the microprojection tips

In partnership with

PATCH DEVELOPMENT

| 80

Abaloparatide Patch is on Track to be the First Transdermal Anabolic

Approved Molecule

Optimized drug device combination

Wealth of clinical data

Development path with a high probability of success

| 81

Technical Hurdles

Rapid, pulsatile

delivery

Failure to Achieve BMD

Gains Variability

Manufacturing

Scaleability

While other companies have attempted to develop alternatives to injection for

anabolics, to date, known programs have been discontinued or are on hold

Significant Technical Hurdles for Transdermal Delivery of Anabolics

| 82

Abalo

Patch

2nd

Prototype

1st

Prototype

Patch Development History

• Achieved target abaloparatide profile through further optimization:

• Finalized formulation and dose selected

• Improved process

• New clinical applicator

• Consistently delivered in over 100 patient applications

• Increases the exposure and half-life relative to earlier generation patches

• Demonstrated suitability, safety and tolerability of the patch technology platform

• Patch technology used in over 36,000 patient applications with consistent

delivery and favorable safety and tolerability profile

• Demonstrated that formulation technology can modify the PK profile

• Abaloparatide exposure increased, Tmax delayed and T1/2 extended vs 1st

prototype

Optimizing the Drug Device Combination to Achieve Target Profile

| 83

• Evaluated in three Phase 1 studies and one Phase 2 (6 month safety/efficacy study)

• Patch technology used in over 36,000 patient applications with consistent delivery

• Demonstrated suitability and encouraging safety and tolerability

• More pulsatile delivery than SC (earlier Tmax, shorter half-life, lower AUC) but comparable Cmax

• BMD gains not comparable to SC

• Suboptimal efficacy did not support selection of this patch prototype for further development

1st Prototype Drug-Device Combination Demonstrates Suitability of the

Patch Technology

1st

Prototype

Plasma Concentrations for Patch 150µg and Abaloparatide SC 80µg

0

100

200

300

400

500

600

0 0.5 1 1.5 2

abalo

para

tid

e c

oncentr

atio

n (

pg/m

l)

time (hr)

1st

Prototype

SC

Source: ASMBR 2016

| 84

First Prototype Patch Phase 2 Clinical Study

Placebo-Patch (N=50)

Abaloparatide-SC 80 mcg (N=51)

Abaloparatide-Patch 50 mcg (N=50)



Randomized, double-blind, placebo-controlled, multicenter 6 month dose range finding study

Randomized

250 patients

Study Endpoints (versus placebo and SC):

• Change in lumbar spine, total hip and forearm BMD at 6 months

• Safety and dermal tolerability

• PK

Month 0 3 6

| 85

0.985

1.333

1.506

2.753

0.00

0.50

1.00

1.50

2.00

2.50

3.00

TD 50 mcg TD 100 mcg TD 150 mcg SC 80 mcg

Mean D

iff B

etw

een A

ctive a

nd P

lacebo

First Prototype Patch Phase 2:

Significant BMD Gains at Lumbar Spine and Total Hip

Lumbar Spine BMD Total Hip BMD

Phase 2 (mITT Population, n=231)

• Dose dependent increase in BMD gain

• Highly pulsatile delivery with similar Cmax, did not demonstrate BMD gains equivalent to SC

1.834

2.294

2.908

5.764

0.00

1.00

2.00

3.00

4.00

5.00

6.00

7.00


Mea

n D

iff

Be

twee

n A

ctiv

e an

d P

lace

bo

(%

)

* *

*

* *

* *

* p<0.05 vs placebo patch

Source CSR BA058-05-007, ENDO 2014

| 86

• Similar incidence of treatment emergent adverse events (TEAE) across dose groups

• Nasopharyngitis (21%), influenza (8%), and headache (8%) most frequent AEs


Clinical Safety Profile Comparable to SC

Summary of Adverse Events in Phase 2

Safety Population, N=249

Placebo

(N=50)

ABL-TD

50 µg

(N=50)

ABL-TD

100 µg

(N=51)

ABL-TD

150 µg

(N=47)

ABL-SC

80 µg

(N=51)

At Least 1 TEAE N (%) 39 (78.0) 41 (82.0) 42 (82.4) 38 (80.9) 45 (88.2)

At least 1 Related TEAE N (%) 11 (22.0) 12 (24.0) 18 (35.3) 15 (31.9) 22 (43.1)

At Least 1 Severe TEAE N (%) 0 0 2 (3.9) 0 1 (2.0)

At Least 1 Severe Related TEAE N (%) 0 0 1 (2.0) 0 1 (2.0)

At Least 1 Serious TEAE N (%) 1 (2.0) 0 2 (3.9) 2 (4.3) 4 (7.8)

At Least 1 TEAE leading to discontinuation N (%) 0 3 (6.0) 2 (3.9) 4 (8.5) 7 (13.7)

At Least 1 TEAE leading to drug interruption N (%) 3 (6.0) 1 (2.0) 1 (2.0) 1 (2.1) 7 (2.0)

| 87


Encouraging Dermal Tolerability

Patient Reported Assessment of Local Tolerance daily for 2 months

(dermal response, swelling, pain and tenderness)

Se

ve

rity

Sco

re

Percent of Patients

0 10 20 30 40 50 60 70 80 90 100

0

1

2

3

4

5

6 TD150 (N=47)

TD100 (N=51)

TD50 (N=50)

Placebo (N=50)

Dermal Response

Source: CSR BA058-05-007

| 88


PD and PK Endpoints Demonstrate Consistent Abaloparatide Delivery

Change in Bone Mineral Density at 6 Months

0.00

1.00

2.00

3.00

4.00

5.00

6.00

7.00


0.00

0.50

1.00

1.50

2.00

2.50

3.00

3.50


Dose Study N %CV

(AUC)

%CV

(Cmax)

20 mcg SC Phase 2 35 55.5 36.8

40 mcg SC Phase 2 35 86.0 88.2

80 mcg SC Phase 3 822 82.5 42.6

50 mcg TD Phase 2 47 44.3 46.5

100 mcg TD Phase 2 46 39.1 38.8

150 mcg TD Phase 2 43 39.4 40.9

Lumbar Spine BMD

Total Hip BMD

Analysis of Abaloparatide Pharmacokinetics

Variability of PD and PK endpoints comparable between SC and patch

Mean B

MD

Change (

% +

/- S

E)

Mean B

MD

Change (

% +

/- S

E)

CV: Coefficient of variation

Source: CSR BA058-05-007, Certara analysis 2018

| 89

Phase 2 Exploratory Pharmacokinetic-Pharmacodynamic Analysis:

Exposure (AUC) is a Key Driver of Bone Mineral Density Increase

Analysis provides critical insight into

PK-PD (BMD) relationship

Demonstrates that despite similar

Cmax, the lower AUC of the first patch

prototype lead to failure to match SC

BMD

*Peak values from 10 min point in P2 data

** AUC derived from P2 Cmax and estimated P2 T1/2 and P1 calculated T1/2

[CELLRANGE]

[CELLRANGE]

[CELLRANGE]

[CELLRANGE]

R² = 0.3529

0

2

4

6

8

0 200 400 600 800

BM

D (

% c

han

ge f

rom

bas

elin

e)

Cmax (pg/ml)

AUC (pg/ml*min)

BM

D (

% c

han

ge f

rom

bas

elin

e)

AUC vs BMD

Cmax vs BMD

[CELLRANGE]

[CELLRANGE]

[CELLRANGE]

[CELLRANGE]

R² = 0.9948

0

2

4

6

8

0 10000 20000 30000 40000 50000 60000

Source: CSR BA058-05-007

| 90

Changes in Lumbar Spine BMD at 12 Months with Abaloparatide-SC in ACTIVE

Phase 3 Study

Analysis of Phase 3 ACTIVE Confirms PK-BMD Relationship

AUC

(pg/ml*hr)

N BMD

(% change from baseline)

200 -< 300 43 7.28

300 -< 400 51 8.17

400 -< 500 69 8.31

500 -< 600 68 9.49

600 -< 700 61 9.56

700 -< 800 70 8.58

800 -< 900 61 8.02

900 -< 1000 43 10.83

1000 -< 1100 46 12.27

1100+ 130 12.66

Cmax

(pg/ml)

N BMD

(% change from baseline)

200 -< 300 46 10.73

300 -< 400 91 9.36

400 -< 500 78 9.74

500 -< 600 94 9.28

600 -< 700 97 10.22

700 -< 800 80 9.64

800+ 75 11.66

• The combined Phase 2 and Phase 3 PK-BMD analysis confirms that exposure (AUC) is a key driver of PD

• Optimized patch should to match exposure to SC, but while retaining pulsatile delivery

SOURCE: CSR BA058-05-003

| 91

Abalo

Patch

2nd

Prototype

1st

Prototype









• Patch technology used in over 36,000 patient applications with consistent delivery

and favorable safety and tolerability profile



prototype

Optimizing the Drug Device Combination Through Formulation Technology

| 92

Abalo

Patch

2nd

Prototype

1st

Prototype









• Patch technology used in over 36,000 patient applications with consistent

delivery and favorable safety and tolerability profile



prototype

Completion of Abaloparatide Patch Optimization

| 93

Optimized Drug-Device Combination Achieves PK Target Profile

Compared to SC

Abaloparatide Tmax (hour)

T1/2 (hour)

Cmax (pg/ml)

AUC (pg*h /ml)

Subcutaneous

Injection (n=77) 0.47 1.7 598 936

Optimized Patch

(n=20) 0.50

1.6 447 915

• Optimized patch achieves retains

the pulsatile delivery profile of SC

• Tmax and T1/2 comparable to SC

• Achieves target drug exposure

(AUC)

• Individual patient PK supports

good consistency of delivery

Measurements taken at 0 to 4 hours, and at 24 hours

| 94

Population PK Model for SC-Abaloparatide

Time-Profiles of BMD

Population PK/PD Model

* Certara® provides regulatory strategy, model-informed drug

development services and technology, for optimizing drug development

and improving health outcomes.

%𝐶𝐹𝐵 𝐵𝑀𝐷 =𝑡𝑖𝑚𝑒𝛾 × (𝑃𝑙𝑎𝑐𝑒𝑏𝑜 + 𝐷𝑟𝑢𝑔_𝑒𝑓𝑓𝑒𝑐𝑡 ×

𝐴𝑈𝐶

𝐴𝑈𝐶50+ 𝐴𝑈𝐶)

Development of a Robust Population PK/PD Model Using Extensive

Abaloparatide Clinical Data

• Population PK of abaloparatide derived from extensive data:

• 822 postmenopausal women with osteoporosis

• 155 healthy volunteers

• Six Phase I studies

• Two Phase II studies

• One Phase III studies

• 8,903 PK samples (SC & IV dosing)

• 4,718 PK samples (TD dosing)

• Individual patient PK profile at steady state correlated to

lumbar spine BMD measurements at months 6, 12, and 18

Parameter Estimate BSV% IOV% Shrinkage

CL/F (L/h) 454 50.4% 27.2%

Vc/F (L) 167 49.1% 19.1%

CLp/F (L/h) 388 92.1% 12.6%

Vp/F (L) 3340 20.7% 15.4%

Frel (Dose/150)-0.644 34.3% 24.0%

Error-Model

Log Error

0.373

Model enables predictions of BMD gains for any PK dataset

| 95 1 Phase 2 studies BA058-05-002 and BA058-05-007 2 Certara, exposure for TD150mcg was based on phase 1 study -008, and SC based on PopPK from phase 3 -003

PK/PD model predictions consistent with Phase 2 BMD data from SC and patch

supporting the validity of the model

Validation of the Population PK-BMD Model

Treatment Model Predicted2

Lumbar Spine BMD (% change at 6 months)

Observed1

Lumbar Spine BMD (% change at 6 months)

SC 80 mcg 5.35 5.80

SC 40 mcg 4.75 5.24

SC 20 mcg 3.98 2.88

1st Prototype Patch 3.39 2.95

| 96 Source: Certara

Time-Course of Gains of BMD L1-L4 (%) up to 12

Months (mean, 95% CI)

Patch Lumbar Spine BMD SC Lumbar Spine BMD

Abaloparatide Patch is Predicted to Achieve BMD Comparability to SC

| 97

• FDA meeting in January 2018 provided alignment on development path

• Pathway enables bridge to the established efficacy and safety of TYMLOS

• Agreement on a single, pivotal BMD non-inferiority study to support NDA

FDA Alignment on a Pivotal Study to Bridge to SC

| 98

Pivotal Phase 3 Bridging Study Design

• Primary endpoint is the change in lumbar spine

BMD at 12-month

• Two-arm, 1:1 randomization SC vs patch

• Alignment on study power, sample size and non-

inferiority margins

• Enroll up to 500 patients with postmenopausal OP

at high risk of fracture

• Agreement on supportive studies required for NDA

Study to be initiated by mid 2019

Screening

Phase

Pre-treatment

Period Treatment Period

Follow-up

Period

Up to 2 Months 1 Week 1 Month

1:1

R

A

N

D

O

M

I

Z

A

T

I

O

N

Abaloparatide Patch

Abaloparatide SC

0 3 6 9 12

Months

| 99

M1 = 8.557%. Effect of abalo-SC on LS BMD at

12 months [in ACTIVE Ph 3: 9.096% (95% CI:

8.557%, 9.534%)]

M2 = 2.1%

95% CI TD BMD > 6.4%

Abaloparatide NI margin Patch treatment effect versus SC

ACTIVE Ph 3

Patch BMD

Window Non-inferiority

margin= +/-2.1%

BMD Non-inferiority Margin for Pivotal Study

*Miller et al. JAMA 2016. MMRM

Non-inferiority (NI) guidance Treatment effect versus active control

M1 = Lower bound of 95% confidence interval

of entire known effect of the active control

relative to placebo

M2 = 25% of M1 = non-inferiority margin to

preserve 75% of the reference treatment

effect

Test drug effect > M1 - M2

| 100

Source: Certara

Time-Course of Gains of BMD L1-L4 (%) up to 12

Months (mean, 95% CI)

Patch Lumbar Spine BMD

SC Lumbar Spine BMD

Abaloparatide Patch is Predicted to Achieve BMD Comparability to SC

Non-inferiority

margin

| 101

Pop PK Model

Distribution of AUCSC based

on popPK of SC at 80 µg

NCA parameters

Distribution of AUCTD at 300

µg from study -015

Population PK/PD model

% change from baseline of BMD driven by AUC of abaloparatide and relevant covariates

Patient

Characteristics Distributions of

Baseline T-

Score and Age

Based on Phase

3 Study

Monte-Carlo Simulation

A total of 14,800 BMD

profiles were simulated for

each treatment arm in

postmenopausal women

with osteoporosis

(200 virtual populations of

224 subjects)

Monte-Carlo Simulations to Evaluate the Probability of Patch BMD

Non-Inferiority

| 102 Probability assessed by a third party drug development consultancy, Certara.

Treatment Dose Probability of Achieving

Lumbar Spine BMD Non-

inferiority to SC

Subcutaneous Injection 80 µg -

1st Prototype Patch 150 µg 0%

Optimized Patch 300 µg >98%

Simulations Predict High Probability of Achieving BMD Non-Inferiority

| 103

Next Steps

• Continued focus on commercial manufacturing scale-up activities for patch and applicator

• Completion of supportive activities in preparation for pivotal study and NDA

• CMC preparation and manufacturing of clinical supplies to support study initiation in mid-2019

Supportive Studies

NDA Submission + Review

Pivotal Ph 3 study

Mfg Installation + Scale-up, 1 year Stability

Supportive Clinical + Non-clinical Studies

Commercial supply

agreement entered

NDA Preparation and

1 year Review

2020 mid 2019

CMC preparation for

clinical supplies

1

2

3

| 104

• Proven molecule and mechanism of action

• Established safety and efficacy

• Enables path to bridging to TYMLOS SC

Abaloparatide Patch is on Track to be the First Transdermal Anabolic

Approved Molecule

• Partnership with an experienced manufacturing partner

• Novel technology and various formulations tested and optimized to

achieve desired abaloparatide profile

Optimized drug device

combination

• Five clinical studies conducted to date to achieve optimal drug device

combination and PK profile

• Favorable safety and efficacy demonstrated in over 36,000 applications

• Large ACTIVE Phase 3 study supports exposure-response relationship

Wealth of Clinical data

• PK–PD analysis predicts BMD gains comparable to SC

• FDA aligned development path; study initiation in mid-2019

• PK data and MS-simulations support high probability of success

Aligned development

path with a high

probability of success

KOL VIDEO

PAUL MILLER, MD PANORAMA ORTHOPEDICS & SPINE CENTER


ABALOPARATIDE PATCH COMMERCIAL

JOE KELLY SVP SALES AND MARKETING

| 107

Osteoporosis: A Market of Substantial Opportunity

Small proportion of post menopausal women with osteoporosis are diagnosed and receive treatment;

Patients treated with bone building anabolic agents are only in the range of 50k

US Osteoporosis Prevalent Population: ~ 10 M (Post Menopausal Women)

Diagnosed: ~ 5.2 M Undiagnosed: ~5 M

Treated: ~ 3 M

With Fracture:

~ 1.5 M

Without Fracture:

~ 3.7 M

Treated with

Anabolics ~ 0.05 M

Sources and references:

National Osteoporosis Foundation; Decision Resources; Definitive Healthcare; HCUPNet; Truven Treatment Pathways

Wright NC, et al. J Bone Minder Res. 2014

Treated: ~ 0.9 M

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Reasons for patients to decline to take injectable anabolics*

*Source: market research fielded 2017 on 300 prescribers; conducted for Radius by third party consultant. Respondents evaluation of reasons for a patient to decline a self-injectable medication like Forteo®

61%

54%

24%

15%

11%

13%

8%

7%

29%

30%

41%

40%

37%

31%

27%

18%

10%

16%

35%

44%

52%

56%

65%

75% Patient OOP Cost

Product not covered by

insurance

Patient opposed to daily

self-injectable

Patient preference for

oral

Patient not confident in

administrating injection

Patient concerned about

pain

Patient concern about

forgetting to take it

Patient concerned about

traveling with injection

Low Impact Medium Impact High Impact

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Abaloparatide- patch has the potential to address challenges for

initiation and choice of treatment with anabolics

Overcome resistance

to starting treatment

Address concerns with

choosing an anabolic Impact choice of anabolic

“It’s hard to get people to

take medicine for something

that hasn’t happened yet,

they haven’t had a fracture

and they feel fine”, “There’s

no compelling reason like

diabetes, it’s very difficult to

get them to inject”1

A lot of patients do not

want shots, primarily

teriparatide since it’s

daily, so I put them on

bisphosphonates even

though they should be on

something more potent”2

“I have to spend a lot of

time with patients to

train them on injectibles.

This seems like a much

easier way to

administer”3

“All the years that I’ve

been doing the other

medications, I feel like a

pincushion. A patch

would be a welcome

change” 4

*Source: Market research fielded December 2017 with prescribers and PMOW patients; conducted for Radius by third party consultant.

1. PCP: Primarily prescribes bisphosphonates, denosumab; rarely teriparatide 2. PCP: Prescribes bisphosphonates, denosumab, teriparatide 3. PCP: Prescribes teriparatide 4. Patient (prior treatment included BPs, teriparatide)

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Abaloparatide-patch profile meets key attributes for selection of

osteoporosis therapy for high risk patients

TOP 3 ATTRIBUTES FOR SELECTION OF OSTEOPOROSIS THERAPY

HCP and Patient: Product Attribute Ranking

HCP Patient

Top 3

Reduces risk of fracture Easy to take

Sustained fracture risk reduction Is safe for long term use

Consistent fracture risk reduction

across patient types

Covered on healthcare

insurance

Patch provides

convenience versus

injectable

Highest reduction

of fractures in high

risk patients with

anabolic therapy

18-24 months use

only

Abaloparatide s.c.

with 263 million

covered lives

Source: Market research fielded 2017 on 300 prescribers and 302 patients/caregivers; conducted for Radius

by third party consultant

CLOSING REMARKS

JESPER HOEILAND CHIEF EXECUTIVE OFFICER

| 112

Expected Upcoming Milestones

Elacestrant clinical regulatory pathway for global registrational study

Abaloparatide patch FDA alignment in Jan 2018 and commercial agreement with 3M in Feb 2018

Initiation of Phase 3 Abaloparatide Male Osteoporosis Bridging Study in Q1 2018

Radius Osteoporosis Investor Day (June 8th, NYC)

CHMP opinion on MAA for abaloparatide-SC*

Publication of ACTIVExtend Phase 3 data

Initiate elacestrant Phase 3, potential global registrational study, in breast cancer in 2H 2018

Update on RAD140 Phase 1 development program by the end of 2018

Collaboration agreement for elacestrant combination studies Ex-US partnership for abaloparatide

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* Under appeal process with CHMP

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Q&A

Documents

RADIUS HEALTH OSTEOPOROSIS INVESTOR DAY