Travere Therapeutics, Inc. · NASDAQ:TVTX
Travere Therapeutics — Retrophin — Investor Presentation (August 2013)
20 slides from Travere Therapeutics's investor presentation, Aug 19, 2013
Slide 1: Retrophin
Retrophin August 2013
Slide 2: Forward-Looking Statements
Forward-Looking Statements This presentation contains forward-looking statements, including statements about urr Prospects, competitive position, regulatory filings and agency actions, and the anticipated development, timing, data readouts and therapeutic scope of programs in our clinical pipeline.
Slide 3: Retrophin 2013 Goals
Retrophin 2013 Goals «Advance RE-024 to IND-enabling toxicology or IND filing «Initiate enrollment for the RE-021 FONT-3 trial eConsummate a transformative business development transaction
Slide 4: Pantothenate Kinase Associated Neurodegeneration (PKAN)
Pantothenate Kinase Associat Neurodegeneration (PKAN) + Lethal, autosomal recessive neurodegenerative disorder « Caused by mutations in PANK2, a kinase » Cause discovered in 2001 by Dr. Hayflick + Previously referred to as Hallervorden-Spatz Syndrome + Dystonia is the cardinal symptom of PKAN + Atyp
Slide 5: PKAN - Why Retrophin?
PKAN —- Why Retrophin? “Brute-Force” Disease Screening * 2000+ orphan diseases » Ranked by prevalence, pharmacoeconomics/QOL, monogenicity, treatment need, pathogenesis complexity Example: Gaucher Disease + Very severe, monogenic, difficult to improve on Cerezyme Decision: PASS. Example: Cystic Fibr
Slide 6: Retrophin's R&D Approach
Retrophin’s R&D Approach Catastrophic Properties Understood Properties * Not always rare * Often monogenic » Lethal * Traditional treatment . modality » Pediatric R e * Scientific consensus + High cost to system and patient + IND within 24 months » Low QOL, inability to » Defined target engaged have
Slide 7: PANK (pantothenate kinase)
PANK (pantothenate kinase) » Four human pantothenate kinase isoforms (E.C.2.7.1.33) PANK1, 2, 3, 4 - Isoforms of proteins expressed according to cell type & intracellular location + Pantothenate kinase phosphorylates its substrate, pantothenate, into phosphopantothenate PANK Pantothenate Phosphopant
Slide 8: Coenzyme A Biosynthesis
Coenzyme A Biosynthesis pantothenate rye pantothenate kinase (PANK) ~sT 9 phosphopantothenate odio: phosphopantothenate cysteine ligase (PPCL) ~ i ” phosphopantothenoylcysteine t wy phosphopantothenyolcysteine decarboxylase (PPC-DC) ia oa . i J phosphopantetheine egyey: phosphopantetheine adenyl tra
Slide 9: Coenzyme A Plays A Central Role in Metabolism
Coenzyme A Plays A Central Role in Metabolism Slycogen eam | Glucose of} a ied Pyruvate a -@ == i Amino Acids cond
Slide 10: Pantothenate Phosphopantothenate
Pantothenate Phosphopantothenate + Patients with PANK2 deficiency cannot phosphorylate x pantothenate (vitamin B5) into phosphopantothenate i “f Yo » The human PANK2 isoform is expressed in the brain - oe - We believe there are cell types which rely exclusively & on PANK2 for CoA production in the b
Slide 11: RE-024
RE-O24 yy fi AK <—=[RE-024 Vv v v Pantothenate: dietary supply of Vitamin B5 PANK2 gene: mutated and defective Even though PANK2 is mutated and cannot create phosphopantothenate, RE-024 can replace phosphopantothenate... ..and as a result, the rest of the Coenzyme A production chain can continue, as
Slide 12: RE-024
RE-O24 » Retrophin developed a library of phosphopantothenate molecules which serve as replacement therapy » Naked phosphopantothenate was predicted to not be viable » Unique “Pro-tide” chemistry used to overcome this challenge » NCEs with no prior art or similar disclosure of structure in literatur
Slide 13: RE-024 In Vitro
RE-024 In Vitro » Mouse cells with PANK1 knockout show limited or no restoration of CoA with pantothenate or phosphopantothenate » RE-024 species demonstrated profound CoA restoration Coitevels IniMEFs HEUG CoA Levels in MEFs - HPLC 24-hr w/Control Cmpnds wes 3
Slide 14: RE-024 In Vivo
RE-024 In Vivo » PANK1 knockout mice have profound liver CoA decrease relative to wild-type Pantothenate does not rescue this ~ RE-024 rescues this phenotype back to wild-type (or slightly above) » RE-024 has drug-like solubility, cell permeability = Predicted to be non-toxic CoA Levels in Liver —-
Slide 15: RE-024 Survival
RE-024 Survival « Healthy mice were given hopantenate, a pan-pantothenate kinase inhibitor which induces death in mice ~ We starved mice of Vitamin B5 to ensure rapid death » 93% of mice on RE-024 survived » 0% of mice on placebo survived » P<0.0001 100% 12345678 9 1 1213 14 15 18 17 15
Slide 16: RE-024 Next Steps
RE-024 Next Steps « Launching RE-024 toxicology program imminently « Urging regulators to allow for early access to RE-024 given limited likelihood of toxicity given metabolic fate Planning pivotal Phase I/II trial for 2014 + Will continue working on RE-024 library and backups 16
Slide 17: Autism: >1% of the U.S. population
+ >1% of the U.S. population (3,000,000+ people) have autism ~ 70% male 70% with severe cognitive impairment (IQ<70) Similar patient pool size and economic opportunity to Alzheimer’s 90% cannot hold regular job in adulthood (Mottron et al., 2011) 1 in 50-88 children born with autism (CDC) ~ Was 1 in
Slide 18: Schizophrenia
Schizophrenia + No new mechanism of action in schizophrenia in decades + All drugs are dopamine antagonists with some serotonin interaction + Schizophrenia is one of the largest pharmaceutical markets and still represents a market of unmet medical need + Zyprexa $5 billion peak sales + Abilify $6 bi
Slide 19: 2013 Milestones
2013 Milestones Initiate “FONT-3” study (potential pivotal) H2 2013 PKAN IND-enabling toxicology H2 2013 IND/CTA filing Q4 2013 Autism & Schizophrenia fo Close transaction Q3/Q4 2013 19
Slide 20: Retrophin
Retrophin August 2013