restorative medicine platform for - ir...
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> 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
PROGENITOR STEM CELLS
Mesenchymal Stem Cells
Dermal Stem Cells
Bone Cartilage
Epithelial Stem Cells
EpendymalStem Cells Etc.
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
PROGENITOR STEM CELLS
Etc.ADULT CELLS Hair ColonSkin Neurons
Mesenchymal Stem Cells
Dermal Stem Cells
Epithelial Stem Cells
EpendymalStem Cells Etc.
Wnt x
Wnt x
Bone Cartilage
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SAMUMED PLATFORM:WE’RE HEALTHY AGAIN
TISSUE REPAIR & REGENERATION > HEALTH RESTORED
PROGENITOR STEM CELLS
Etc.ADULT CELLS Hair ColonSkin Neurons
Mesenchymal Stem Cells
Dermal Stem Cells
Epithelial Stem Cells
EpendymalStem Cells Etc.
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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RESTORATIVE MEDICINE PLATFORM
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
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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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
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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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)
WNT+ Prevalence: 93%
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)
WNT+ Prevalence: 30%
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)
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.
UTHR Science Day 2018 / IPF / Osman Kibar
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ONCOLOGY
SUBJECT: Terminal Pancreatic Cancer Patient, Before and After
Day 0 Month 3 Month 6
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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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)
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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RESTORATIVE MEDICINE PLATFORM
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