RESTORATIVE MEDICINE PLATFORM FOR - ir …ir-scienceday.unither.com/...SAMUMED_IPF_Osman_Kibar_Final_0924.pdf · > degenerative diseases > oncology and other proliferative indications

> DEGENERATIVE DISEASES> ONCOLOGY AND OTHER PROLIFERATIVE INDICATIONS> INFLAMMATORY CONDITIONS

RESTORATIVE MEDICINE PLATFORM FOR:

Osman Kibar, PhD Founder, Chief Executive Officer, Samumed, LLC

UTHR Science Day 2018 / IPF / Osman Kibar

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SAFE HARBOR STATEMENT

SAMUMED® is a registered trademark of Samumed, LLC

Remarks today concerning United Therapeutics may include forward-looking statements which represent United Therapeutics’ expectations or beliefs regarding future events. We caution that such statements involve risks and uncertainties that may cause actual results to differ materially from those in the forward-looking statements. Consequently, all such forward-looking statements are qualified by the cautionary language and risk factors set forth in United Therapeutics’ periodic and other reports filed with the SEC.

There can be no assurance that the actual results, events or developments referenced in such forward-looking statements will occur or be realized. United Therapeutics assumes no obligation to update these forward-looking statements to reflect actual results, changes in assumptions or changes in factors affecting such forward-looking statements.

This presentation and any related discussions or statements are intended to educate investors about our company. Sometimes that process includes reporting on the progress and results of clinical trials or other developments with respect to our products. This presentation and any related discussions or statements are not intended to promote our products, to suggest that our products are safe and effective for any use other than what is consistent with their FDA-approved labeling, or to provide all available information regarding the products, their risks, or related clinical trial results. Anyone seeking information regarding the use of one of our products should consult the full prescribing information for the product available on our website at www.unither.com.


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RESTORATIVE MEDICINE PLATFORM

SCIENTIFIC OVERVIEW


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SAMUMED AND RESTORATIVE MEDICINE

DISEASE > DECLINING HEALTH > PREMATURE DEATHAging


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CELL DIFFERENTIATION: BEFORE WE’RE BORN

EMBRYONIC STEM CELLS

PROGENITOR STEM CELLS

Mesenchymal Stem Cells

Dermal Stem Cells

Bone Cartilage

Epithelial Stem Cells

EpendymalStem Cells Etc.

Etc.ADULT CELLS

> > > >

Hair ColonSkin Neurons


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CELL DIFFERENTIATION: AFTER WE’RE BORN



Dermal Stem Cells

Bone Cartilage



Etc.ADULT CELLS Hair ColonSkin Neurons

Wnt +

Wnt -

NO EMBRYONIC STEM CELLS REMAIN


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WNT PATHWAY REGULATES TISSUE HEALTH IN ALL ANIMALS

Brian Gratwicke / CC-BY-SA-3.0


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CELL DIFFERENTIATION: AS WE GET OLDER

TISSUE DAMAGE AND DEGENERATION




Dermal Stem Cells



Wnt x

Wnt x

Bone Cartilage


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SAMUMED PLATFORM:WE’RE HEALTHY AGAIN

TISSUE REPAIR & REGENERATION > HEALTH RESTORED




Dermal Stem Cells



Wnt +

Wnt -

Bone Cartilage


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RESTORATIVE MEDICINE PLATFORM:SCIENTIFIC OVERVIEW

Aging De-Aging

HEALTH RESTORED > LIVE YOUNGER (HEALTHSPAN) > LIVE LONGER (LIFESPAN)


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SELECTPROGRAMS


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REGENERATE CARTILAGE

Normal KneeSUBJECT: Rat instability

TREATMENT: Single intra-articular (IA) injection

RESULTS AT:3 months

Damaged Knee Treated Knee

Cartilage loss

New & thicker cartilage

This slide relates solely to Samumed’s internal research and development programs that are not licensed to United Therapeutics Corporation, and reflects the views of Samumed, LLC. These views are not endorsed by United Therapeutics Corporation.


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OSTEOARTHRITIS

SUBJECT: Patient knee X-rays

STATUS: Completed Phase 1, Phase 2a, Phase 2b

NEXT STEP:Initiate Phase 3 (1Q19)

Osteoarthritic Knee - Baseline Osteoarthritic Knee - Treated

1-2 mmdecreased 1-2 mm

increased



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REPAIR TENDON > TENDINOPATHY

SUBJECT: Rat Achilles tendon, once-daily lotion, at 3 weeks

STATUS:Completed Phase 1, RIPT (skin sensitization)

NEXT STEP:Initiate Phase 2 (4Q18)

Healthy Adult Tendon

Damaged/Untreated Tendon

Treated Tendon



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ELIMINATE WNT+ CANCERS

–200 400 600 800

1,000 1,200 1,400 1,600 1,800 2,000

0 3 6 10 13 17 21Day of Treatment

Tum

or V

olum

e (m

m³)

WNT+ Prevalence: 93%

Colorectal

untreated

treated

–200 400 600 800

1,000 1,200 1,400 1,600 1,800 2,000

0 3 6 10 13 17 21Day of Treatment

Tum

or V

olum

e (m

m³)


Colorectal

untreated

treated

–200400600800

1,0001,2001,4001,6001,8002,000

0 2 5 8 12 15 20

Day of Treatment

PancreaticWNT+ Prevalence: 65%

untreated

treated

–200400600800

1,0001,2001,4001,6001,8002,000

0 2 4 10 13 16 19 23

Day of Treatment

Triple-Negative BreastWNT+ Prevalence: 50%

untreated

treated

–

500

1,000

1,500

2,000

2,500

0 4 7 11 14 18 21

Day of Treatment

LiverWNT+ Prevalence: 90%

untreated

treated

–50

100 150 200 250 300 350 400 450

0 4 7 11 14 18 21 Day of Treatment

Gastric

Tum

or V

olum

e (m

m³)


untreated

treated

Colorectal Pancreatic Triple-Negative Breast Liver

0

500

1,000

1,500

2,000

2,500

0 4 7 11 14 18

Day of Treatment

Endometrial (Uterus)WNT+ Prevalence: 28%

untreated

treated

Endometrial (Uterus)

–

500

1,000

1,500

2,000

2,500

3,000

3,500

4,000

0 4 7 11 14

Day of Treatment

OvarianWNT+ Prevalence: 30%

untreated

treated

Ovarian

–500

1,000 1,500 2,000 2,500 3,000 3,500 4,000 4,500

0 4 7 11 14 Day of Treatment

LungWNT+ Prevalence: 50%

untreated

treated

Lung

SUBJECT: Human tumors in mouse xenografts

STATUS:Phase 1 dose escalation safety study on-going

NEXT STEP:Initiate Phase 2/3 in select indications (‘19)



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ONCOLOGY

SUBJECT: Terminal Pancreatic Cancer Patient, Before and After

Day 0 Month 3 Month 6



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REVERSE DEMENTIA >ALZHEIMER’S DISEASE

HealthySUBJECT: Transgenic mice, once-daily pill, at 3 months

STATUS:Initiating Phase 1 SAD and MAD (3Q18)

NEXT STEP:Complete Phase 1 (‘19)

Untreated Treated with SM Drug

Neurofibrillary Tangles(mouse brain stem)



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IDIOPATHIC PULMONARY FIBROSIS (IPF)


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REVERSE SCARRING IN LUNGS >PULMONARY FIBROSIS

SUBJECT: Rat lungs, once-daily nebulizer, at 4 weeks

STATUS:Completed Phase 1; Phase 1b on-going

Healthy / Normal Lung Tissue

Untreated / Fibrotic Lung

Treated with SM Drug


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IPF: INCREASED WNT AND TGFβ >EMT + INFLAMATION + FIBROSIS

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Healthy Pathway Aberrant Pathway

Abnormal ‘wound healing’

Injury to the alveolar epithelium

Epithelial-mesenchymal transition (EMT)

Epithelial cells abnormally activated

(via Wnt & TGF-β)

Differentiation of fibroblasts to myofibroblasts

Induce migration of fibroblasts

Fibrosis

Promote secretion of excessive ECM

proteins from myofibroblasts


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SM04646: A SMALL MOLECULE WNT INHIBITOR TO TREAT IPF

TRIPLE MOA: Anti-fibrosisAnti-InflammatoryInhibition of EMT

OPTIMAL pK: FIC inhaled therapyUniform lung concentrationLow systemic exposure

BLEOMYCIN- INDUCED LUNG FIBROSIS IN MICE

PBS + no dosing BLEO + Vehicle BLEO + SM04646


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SM04646CLINICAL OVERVIEW

17 9-18

1 3-64 + DOSE DOSE

SINGLE-ASCENDING DOSE 28-DAY MULTI-ASCENDING DOSE

VEHICLE PATIENTS PER COHORT

SUBJECTS EACH IN 4 COHORTS ACTIVE

No SAEs23 AEs in 11 of 17 subjects (all AEs Grade 1/2, deemed not/unlikely related per PI, except 2)

No SAEs3 AEs in 2 of 7 subjects (no respiratory AEs, 2 AEs possibly related)

0.7 mg | 2 mg | 7 mg | 20 mg 2 mg | 7 mg | 20 mg | Ongoing

SM04646-IPF-01 (SAD) STUDY SM04646-IPF-02 (MAD) STUDY

pK ConfirmedPlasma concentrations dose-dependent, below clinically relevant levels

ORPHAN DRUG DESIGNATION GRANTED BY FDA JULY 2017


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PARTNERING WITH UNITED THERAPEUTICS

LICENSING TRANSACTION:» Entered into on September 14, 2018» Exlusivity in the US and Canada» UT in charge of all development and

commercialization

WHY UT:» Expertise: Pulmonology; Drug/Device Combos» Commitment: IPF non-compete; Increasing minimum

annual spending» Integrity: Simplified governance structure

THANK YOU

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RESTORATIVE MEDICINE PLATFORM FOR - ir …ir-scienceday.unither.com/...SAMUMED_IPF_Osman_Kibar_Final_0924.pdf · > degenerative diseases > oncology and other proliferative indications