Dr Francisco Javier Hevia U
Gastroenteroacutelogo-Hepatoacutelogo
Costa Rica
Nombre del gen ATP7B
Proteiacutena Proteiacutena Transportadora de Cobre ATPasa 2
Localizacioacuten 13q143
Exones 21 exones traducidos
Herencia Autosoacutemica Recesiva
- MUNDIAL
bull 1955 Walshe D-P
bull 1970 Hoogenraad - Zinc
bull 1981 Walshe Trietilen tetramina
Dra Mildred Jimeacutenez HBT Indira Chaves G
MSc Jessica Arroyo H
fheviaugmailcom
2015 Dec 18 7(29) 2859ndash2870
Wilsonrsquos disease A review of what we have learnedKryssia Isabel Rodriguez-Castro1 Francisco Javier Hevia-Urrutia2 and Giacomo Carlo Sturniolo3
Policlinico Abano Terme Padua Italy 1
Hospital San Juan de Dios Hospital CIMA San Joseacute Costa Rica2
Padua University Hospital Padua Italy3
National alliance for Wilsonrsquos disease health policy in Costa Rica(2017) 25
Francisco Hevia-Urrutia1 Ileana Alvarado-Echeverriacutea1 Alfredo Sanabria-Castro1 Marta Saacutenchez-Molina Luis Meza-Sierra1 Alexander Parajeles-Vindas1 Oscar Meacutendez-Blanca1 Aacutelvaro Saacutenchez-Siles2 Manuel Saboriacuteo-Rocafort3 Marcela Barguil-Gallardo1 Iliana Chavarriacutea-Quiroacutes1 and Cecilia Monge-Bonilla1
1Hospital San Juan de Dios Caja Costarricense del Seguro Social 4917-1000 San Jose Costa Rica 2Hospital Mexico Caja Costarricense del Seguro Social San Jose Costa Rica 3Hospital Nacional de Ninos Caja Costarricense del Seguro Social San Jose Costa Rica
EPIDEMIOLOGIacuteA EN CENTROAMEacuteRICA Y EL CARIBE
bull Guatemala El Salvador Honduras Panamaacute Rep Dominicana casos aislados
bull Nicaragua 2 casos neuroloacutegicos y 1 Wilson Fulminante (Costa Rica)
bull Cuba mutacioacuten N41S en 130 pts
SURAMEacuteRICAbull BRASIL mutaciones maacutes frecuentes
3402delC 308L708P 167
Enf Wilson en el sur de Brasil 40 antildeos de seguimientoClinics (Sao Paulo) 2011 Mar 66(3) 411ndash416
36 pts 1970-2010 75 origen Europeo
bull ARGENTINA El exjugador de Gimnasia La Plata sufre la enfermedad de Wilson y necesita ayuda del mundo del fuacutetbol para poder seguir luchando por su vida
bull PERUacute Enfermedad de Wilson forma nueropsiquiaacutetrica dominante presentacioacuten de un caso
bull CHILE La enfermedad de Wilson es infrecuente en Chile aunque existen comunicaciones de casos y series cliacutenicas en nuestro medio (Dr Marco Arrese)
Revista medica de ChileRev meacuted Chile v138 n10 Santiago oct 2010rtamento de Neurologiacutea Cliacutenica Las Condes Santiago de ChileMiranda M Brinck P Roessler JL Troncoso M Gonzaacutelez M Villagra R Enfermedad de Wilson Experiencia Cliacutenica en 16 pacientes Rev Med Chile 1995 123 1098-107
bull URUGUAY Comunicacioacuten de un caso cliacutenico y su evolucioacuten a los 8 antildeos Forma de presentacioacuten neurosiquiaacutetrica Drs Tarigo H Legnani E
Med Int Mex 200723(5)458-63
Enfermedad de Wilson reporte de un caso y
revision de la literatura
Marco Antonio Lopez Hernandez Marlene Serrano Rufino
MEacuteXICO
bull Costa Rica 49 100000 h (1989)
HEPAacuteTICONEUROLOacuteGICO Y OTROS
-COSTA RICA
bull mutante Asn 1270 Ser
bull Insuficiencia hepaacutetica fulminante con hemoacutelisis
COSTA RICA ndash DRA MARIacuteA A MATAMOROS
bull 92
(15)
( 21)
EW357
bull Tx con chaperones 4 fenil-butirato (4-PBA) y curcumina
bull Antioxidante
Quelante de Cu
Wilson Therapeutics ndash Improved treatment for Wilson DiseaseSeptember 2016
36
Wilson Therapeutics in brief
Founded in 2012 based in Stockholm
Develops novel therapies for rare diseases with high unmet medical needs
Current focus on Wilson Disease
Orphan indication
Approximately 25000 patients in EU and US combined
Lead program WTX101 ndash Decupratereg (bis-choline-tetrathiomolybdate)
Global Phase II study ongoing
gt500 patients exposed to tetrathiomolybdate for up to 8 years adds to the knowledge around safety
Public company listed on Nasdaq Stockholm
37
DrugRecommended
daily doseFrequenc
yIllustration
(daily dosage)
Trientine(Syprinetrade)
~1000 mg
250 mg caps
2-4 times day
Penicillamine(Cupriminetrade)
~1000 mg
250 mg caps
2-4 times day
Zinc (Galzintrade) 150 mg50 mg
caps3-5 times
day
Decupratereg ~30 mg30 mg tablet
1 time day
Capsules (L=19mm) and tablet (D=64mm) drawn to scale
Convenient dosing expected to improve treatment compliance
Decupratereg ndash once daily ndash one tablet ndash small size
Iron
B6
38
Decupratereg is being developed as a monotherapy for Wilson Disease
Phase 2 is ongoing
Trial sites
28 Wilson Disease patients in US and EUPatient population
Open label non-comparator evaluating free Cu and clinical outcomes for 24 weeks
Trial design
Fully recruited
Status 14 out of 14 patients have enrolled in extension phase
Top line data expected late 2016early 2017
Note Status as of August 3 2016
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
Nombre del gen ATP7B
Proteiacutena Proteiacutena Transportadora de Cobre ATPasa 2
Localizacioacuten 13q143
Exones 21 exones traducidos
Herencia Autosoacutemica Recesiva
- MUNDIAL
bull 1955 Walshe D-P
bull 1970 Hoogenraad - Zinc
bull 1981 Walshe Trietilen tetramina
Dra Mildred Jimeacutenez HBT Indira Chaves G
MSc Jessica Arroyo H
fheviaugmailcom
2015 Dec 18 7(29) 2859ndash2870
Wilsonrsquos disease A review of what we have learnedKryssia Isabel Rodriguez-Castro1 Francisco Javier Hevia-Urrutia2 and Giacomo Carlo Sturniolo3
Policlinico Abano Terme Padua Italy 1
Hospital San Juan de Dios Hospital CIMA San Joseacute Costa Rica2
Padua University Hospital Padua Italy3
National alliance for Wilsonrsquos disease health policy in Costa Rica(2017) 25
Francisco Hevia-Urrutia1 Ileana Alvarado-Echeverriacutea1 Alfredo Sanabria-Castro1 Marta Saacutenchez-Molina Luis Meza-Sierra1 Alexander Parajeles-Vindas1 Oscar Meacutendez-Blanca1 Aacutelvaro Saacutenchez-Siles2 Manuel Saboriacuteo-Rocafort3 Marcela Barguil-Gallardo1 Iliana Chavarriacutea-Quiroacutes1 and Cecilia Monge-Bonilla1
1Hospital San Juan de Dios Caja Costarricense del Seguro Social 4917-1000 San Jose Costa Rica 2Hospital Mexico Caja Costarricense del Seguro Social San Jose Costa Rica 3Hospital Nacional de Ninos Caja Costarricense del Seguro Social San Jose Costa Rica
EPIDEMIOLOGIacuteA EN CENTROAMEacuteRICA Y EL CARIBE
bull Guatemala El Salvador Honduras Panamaacute Rep Dominicana casos aislados
bull Nicaragua 2 casos neuroloacutegicos y 1 Wilson Fulminante (Costa Rica)
bull Cuba mutacioacuten N41S en 130 pts
SURAMEacuteRICAbull BRASIL mutaciones maacutes frecuentes
3402delC 308L708P 167
Enf Wilson en el sur de Brasil 40 antildeos de seguimientoClinics (Sao Paulo) 2011 Mar 66(3) 411ndash416
36 pts 1970-2010 75 origen Europeo
bull ARGENTINA El exjugador de Gimnasia La Plata sufre la enfermedad de Wilson y necesita ayuda del mundo del fuacutetbol para poder seguir luchando por su vida
bull PERUacute Enfermedad de Wilson forma nueropsiquiaacutetrica dominante presentacioacuten de un caso
bull CHILE La enfermedad de Wilson es infrecuente en Chile aunque existen comunicaciones de casos y series cliacutenicas en nuestro medio (Dr Marco Arrese)
Revista medica de ChileRev meacuted Chile v138 n10 Santiago oct 2010rtamento de Neurologiacutea Cliacutenica Las Condes Santiago de ChileMiranda M Brinck P Roessler JL Troncoso M Gonzaacutelez M Villagra R Enfermedad de Wilson Experiencia Cliacutenica en 16 pacientes Rev Med Chile 1995 123 1098-107
bull URUGUAY Comunicacioacuten de un caso cliacutenico y su evolucioacuten a los 8 antildeos Forma de presentacioacuten neurosiquiaacutetrica Drs Tarigo H Legnani E
Med Int Mex 200723(5)458-63
Enfermedad de Wilson reporte de un caso y
revision de la literatura
Marco Antonio Lopez Hernandez Marlene Serrano Rufino
MEacuteXICO
bull Costa Rica 49 100000 h (1989)
HEPAacuteTICONEUROLOacuteGICO Y OTROS
-COSTA RICA
bull mutante Asn 1270 Ser
bull Insuficiencia hepaacutetica fulminante con hemoacutelisis
COSTA RICA ndash DRA MARIacuteA A MATAMOROS
bull 92
(15)
( 21)
EW357
bull Tx con chaperones 4 fenil-butirato (4-PBA) y curcumina
bull Antioxidante
Quelante de Cu
Wilson Therapeutics ndash Improved treatment for Wilson DiseaseSeptember 2016
36
Wilson Therapeutics in brief
Founded in 2012 based in Stockholm
Develops novel therapies for rare diseases with high unmet medical needs
Current focus on Wilson Disease
Orphan indication
Approximately 25000 patients in EU and US combined
Lead program WTX101 ndash Decupratereg (bis-choline-tetrathiomolybdate)
Global Phase II study ongoing
gt500 patients exposed to tetrathiomolybdate for up to 8 years adds to the knowledge around safety
Public company listed on Nasdaq Stockholm
37
DrugRecommended
daily doseFrequenc
yIllustration
(daily dosage)
Trientine(Syprinetrade)
~1000 mg
250 mg caps
2-4 times day
Penicillamine(Cupriminetrade)
~1000 mg
250 mg caps
2-4 times day
Zinc (Galzintrade) 150 mg50 mg
caps3-5 times
day
Decupratereg ~30 mg30 mg tablet
1 time day
Capsules (L=19mm) and tablet (D=64mm) drawn to scale
Convenient dosing expected to improve treatment compliance
Decupratereg ndash once daily ndash one tablet ndash small size
Iron
B6
38
Decupratereg is being developed as a monotherapy for Wilson Disease
Phase 2 is ongoing
Trial sites
28 Wilson Disease patients in US and EUPatient population
Open label non-comparator evaluating free Cu and clinical outcomes for 24 weeks
Trial design
Fully recruited
Status 14 out of 14 patients have enrolled in extension phase
Top line data expected late 2016early 2017
Note Status as of August 3 2016
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
- MUNDIAL
bull 1955 Walshe D-P
bull 1970 Hoogenraad - Zinc
bull 1981 Walshe Trietilen tetramina
Dra Mildred Jimeacutenez HBT Indira Chaves G
MSc Jessica Arroyo H
fheviaugmailcom
2015 Dec 18 7(29) 2859ndash2870
Wilsonrsquos disease A review of what we have learnedKryssia Isabel Rodriguez-Castro1 Francisco Javier Hevia-Urrutia2 and Giacomo Carlo Sturniolo3
Policlinico Abano Terme Padua Italy 1
Hospital San Juan de Dios Hospital CIMA San Joseacute Costa Rica2
Padua University Hospital Padua Italy3
National alliance for Wilsonrsquos disease health policy in Costa Rica(2017) 25
Francisco Hevia-Urrutia1 Ileana Alvarado-Echeverriacutea1 Alfredo Sanabria-Castro1 Marta Saacutenchez-Molina Luis Meza-Sierra1 Alexander Parajeles-Vindas1 Oscar Meacutendez-Blanca1 Aacutelvaro Saacutenchez-Siles2 Manuel Saboriacuteo-Rocafort3 Marcela Barguil-Gallardo1 Iliana Chavarriacutea-Quiroacutes1 and Cecilia Monge-Bonilla1
1Hospital San Juan de Dios Caja Costarricense del Seguro Social 4917-1000 San Jose Costa Rica 2Hospital Mexico Caja Costarricense del Seguro Social San Jose Costa Rica 3Hospital Nacional de Ninos Caja Costarricense del Seguro Social San Jose Costa Rica
EPIDEMIOLOGIacuteA EN CENTROAMEacuteRICA Y EL CARIBE
bull Guatemala El Salvador Honduras Panamaacute Rep Dominicana casos aislados
bull Nicaragua 2 casos neuroloacutegicos y 1 Wilson Fulminante (Costa Rica)
bull Cuba mutacioacuten N41S en 130 pts
SURAMEacuteRICAbull BRASIL mutaciones maacutes frecuentes
3402delC 308L708P 167
Enf Wilson en el sur de Brasil 40 antildeos de seguimientoClinics (Sao Paulo) 2011 Mar 66(3) 411ndash416
36 pts 1970-2010 75 origen Europeo
bull ARGENTINA El exjugador de Gimnasia La Plata sufre la enfermedad de Wilson y necesita ayuda del mundo del fuacutetbol para poder seguir luchando por su vida
bull PERUacute Enfermedad de Wilson forma nueropsiquiaacutetrica dominante presentacioacuten de un caso
bull CHILE La enfermedad de Wilson es infrecuente en Chile aunque existen comunicaciones de casos y series cliacutenicas en nuestro medio (Dr Marco Arrese)
Revista medica de ChileRev meacuted Chile v138 n10 Santiago oct 2010rtamento de Neurologiacutea Cliacutenica Las Condes Santiago de ChileMiranda M Brinck P Roessler JL Troncoso M Gonzaacutelez M Villagra R Enfermedad de Wilson Experiencia Cliacutenica en 16 pacientes Rev Med Chile 1995 123 1098-107
bull URUGUAY Comunicacioacuten de un caso cliacutenico y su evolucioacuten a los 8 antildeos Forma de presentacioacuten neurosiquiaacutetrica Drs Tarigo H Legnani E
Med Int Mex 200723(5)458-63
Enfermedad de Wilson reporte de un caso y
revision de la literatura
Marco Antonio Lopez Hernandez Marlene Serrano Rufino
MEacuteXICO
bull Costa Rica 49 100000 h (1989)
HEPAacuteTICONEUROLOacuteGICO Y OTROS
-COSTA RICA
bull mutante Asn 1270 Ser
bull Insuficiencia hepaacutetica fulminante con hemoacutelisis
COSTA RICA ndash DRA MARIacuteA A MATAMOROS
bull 92
(15)
( 21)
EW357
bull Tx con chaperones 4 fenil-butirato (4-PBA) y curcumina
bull Antioxidante
Quelante de Cu
Wilson Therapeutics ndash Improved treatment for Wilson DiseaseSeptember 2016
36
Wilson Therapeutics in brief
Founded in 2012 based in Stockholm
Develops novel therapies for rare diseases with high unmet medical needs
Current focus on Wilson Disease
Orphan indication
Approximately 25000 patients in EU and US combined
Lead program WTX101 ndash Decupratereg (bis-choline-tetrathiomolybdate)
Global Phase II study ongoing
gt500 patients exposed to tetrathiomolybdate for up to 8 years adds to the knowledge around safety
Public company listed on Nasdaq Stockholm
37
DrugRecommended
daily doseFrequenc
yIllustration
(daily dosage)
Trientine(Syprinetrade)
~1000 mg
250 mg caps
2-4 times day
Penicillamine(Cupriminetrade)
~1000 mg
250 mg caps
2-4 times day
Zinc (Galzintrade) 150 mg50 mg
caps3-5 times
day
Decupratereg ~30 mg30 mg tablet
1 time day
Capsules (L=19mm) and tablet (D=64mm) drawn to scale
Convenient dosing expected to improve treatment compliance
Decupratereg ndash once daily ndash one tablet ndash small size
Iron
B6
38
Decupratereg is being developed as a monotherapy for Wilson Disease
Phase 2 is ongoing
Trial sites
28 Wilson Disease patients in US and EUPatient population
Open label non-comparator evaluating free Cu and clinical outcomes for 24 weeks
Trial design
Fully recruited
Status 14 out of 14 patients have enrolled in extension phase
Top line data expected late 2016early 2017
Note Status as of August 3 2016
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
Dra Mildred Jimeacutenez HBT Indira Chaves G
MSc Jessica Arroyo H
fheviaugmailcom
2015 Dec 18 7(29) 2859ndash2870
Wilsonrsquos disease A review of what we have learnedKryssia Isabel Rodriguez-Castro1 Francisco Javier Hevia-Urrutia2 and Giacomo Carlo Sturniolo3
Policlinico Abano Terme Padua Italy 1
Hospital San Juan de Dios Hospital CIMA San Joseacute Costa Rica2
Padua University Hospital Padua Italy3
National alliance for Wilsonrsquos disease health policy in Costa Rica(2017) 25
Francisco Hevia-Urrutia1 Ileana Alvarado-Echeverriacutea1 Alfredo Sanabria-Castro1 Marta Saacutenchez-Molina Luis Meza-Sierra1 Alexander Parajeles-Vindas1 Oscar Meacutendez-Blanca1 Aacutelvaro Saacutenchez-Siles2 Manuel Saboriacuteo-Rocafort3 Marcela Barguil-Gallardo1 Iliana Chavarriacutea-Quiroacutes1 and Cecilia Monge-Bonilla1
1Hospital San Juan de Dios Caja Costarricense del Seguro Social 4917-1000 San Jose Costa Rica 2Hospital Mexico Caja Costarricense del Seguro Social San Jose Costa Rica 3Hospital Nacional de Ninos Caja Costarricense del Seguro Social San Jose Costa Rica
EPIDEMIOLOGIacuteA EN CENTROAMEacuteRICA Y EL CARIBE
bull Guatemala El Salvador Honduras Panamaacute Rep Dominicana casos aislados
bull Nicaragua 2 casos neuroloacutegicos y 1 Wilson Fulminante (Costa Rica)
bull Cuba mutacioacuten N41S en 130 pts
SURAMEacuteRICAbull BRASIL mutaciones maacutes frecuentes
3402delC 308L708P 167
Enf Wilson en el sur de Brasil 40 antildeos de seguimientoClinics (Sao Paulo) 2011 Mar 66(3) 411ndash416
36 pts 1970-2010 75 origen Europeo
bull ARGENTINA El exjugador de Gimnasia La Plata sufre la enfermedad de Wilson y necesita ayuda del mundo del fuacutetbol para poder seguir luchando por su vida
bull PERUacute Enfermedad de Wilson forma nueropsiquiaacutetrica dominante presentacioacuten de un caso
bull CHILE La enfermedad de Wilson es infrecuente en Chile aunque existen comunicaciones de casos y series cliacutenicas en nuestro medio (Dr Marco Arrese)
Revista medica de ChileRev meacuted Chile v138 n10 Santiago oct 2010rtamento de Neurologiacutea Cliacutenica Las Condes Santiago de ChileMiranda M Brinck P Roessler JL Troncoso M Gonzaacutelez M Villagra R Enfermedad de Wilson Experiencia Cliacutenica en 16 pacientes Rev Med Chile 1995 123 1098-107
bull URUGUAY Comunicacioacuten de un caso cliacutenico y su evolucioacuten a los 8 antildeos Forma de presentacioacuten neurosiquiaacutetrica Drs Tarigo H Legnani E
Med Int Mex 200723(5)458-63
Enfermedad de Wilson reporte de un caso y
revision de la literatura
Marco Antonio Lopez Hernandez Marlene Serrano Rufino
MEacuteXICO
bull Costa Rica 49 100000 h (1989)
HEPAacuteTICONEUROLOacuteGICO Y OTROS
-COSTA RICA
bull mutante Asn 1270 Ser
bull Insuficiencia hepaacutetica fulminante con hemoacutelisis
COSTA RICA ndash DRA MARIacuteA A MATAMOROS
bull 92
(15)
( 21)
EW357
bull Tx con chaperones 4 fenil-butirato (4-PBA) y curcumina
bull Antioxidante
Quelante de Cu
Wilson Therapeutics ndash Improved treatment for Wilson DiseaseSeptember 2016
36
Wilson Therapeutics in brief
Founded in 2012 based in Stockholm
Develops novel therapies for rare diseases with high unmet medical needs
Current focus on Wilson Disease
Orphan indication
Approximately 25000 patients in EU and US combined
Lead program WTX101 ndash Decupratereg (bis-choline-tetrathiomolybdate)
Global Phase II study ongoing
gt500 patients exposed to tetrathiomolybdate for up to 8 years adds to the knowledge around safety
Public company listed on Nasdaq Stockholm
37
DrugRecommended
daily doseFrequenc
yIllustration
(daily dosage)
Trientine(Syprinetrade)
~1000 mg
250 mg caps
2-4 times day
Penicillamine(Cupriminetrade)
~1000 mg
250 mg caps
2-4 times day
Zinc (Galzintrade) 150 mg50 mg
caps3-5 times
day
Decupratereg ~30 mg30 mg tablet
1 time day
Capsules (L=19mm) and tablet (D=64mm) drawn to scale
Convenient dosing expected to improve treatment compliance
Decupratereg ndash once daily ndash one tablet ndash small size
Iron
B6
38
Decupratereg is being developed as a monotherapy for Wilson Disease
Phase 2 is ongoing
Trial sites
28 Wilson Disease patients in US and EUPatient population
Open label non-comparator evaluating free Cu and clinical outcomes for 24 weeks
Trial design
Fully recruited
Status 14 out of 14 patients have enrolled in extension phase
Top line data expected late 2016early 2017
Note Status as of August 3 2016
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
fheviaugmailcom
2015 Dec 18 7(29) 2859ndash2870
Wilsonrsquos disease A review of what we have learnedKryssia Isabel Rodriguez-Castro1 Francisco Javier Hevia-Urrutia2 and Giacomo Carlo Sturniolo3
Policlinico Abano Terme Padua Italy 1
Hospital San Juan de Dios Hospital CIMA San Joseacute Costa Rica2
Padua University Hospital Padua Italy3
National alliance for Wilsonrsquos disease health policy in Costa Rica(2017) 25
Francisco Hevia-Urrutia1 Ileana Alvarado-Echeverriacutea1 Alfredo Sanabria-Castro1 Marta Saacutenchez-Molina Luis Meza-Sierra1 Alexander Parajeles-Vindas1 Oscar Meacutendez-Blanca1 Aacutelvaro Saacutenchez-Siles2 Manuel Saboriacuteo-Rocafort3 Marcela Barguil-Gallardo1 Iliana Chavarriacutea-Quiroacutes1 and Cecilia Monge-Bonilla1
1Hospital San Juan de Dios Caja Costarricense del Seguro Social 4917-1000 San Jose Costa Rica 2Hospital Mexico Caja Costarricense del Seguro Social San Jose Costa Rica 3Hospital Nacional de Ninos Caja Costarricense del Seguro Social San Jose Costa Rica
EPIDEMIOLOGIacuteA EN CENTROAMEacuteRICA Y EL CARIBE
bull Guatemala El Salvador Honduras Panamaacute Rep Dominicana casos aislados
bull Nicaragua 2 casos neuroloacutegicos y 1 Wilson Fulminante (Costa Rica)
bull Cuba mutacioacuten N41S en 130 pts
SURAMEacuteRICAbull BRASIL mutaciones maacutes frecuentes
3402delC 308L708P 167
Enf Wilson en el sur de Brasil 40 antildeos de seguimientoClinics (Sao Paulo) 2011 Mar 66(3) 411ndash416
36 pts 1970-2010 75 origen Europeo
bull ARGENTINA El exjugador de Gimnasia La Plata sufre la enfermedad de Wilson y necesita ayuda del mundo del fuacutetbol para poder seguir luchando por su vida
bull PERUacute Enfermedad de Wilson forma nueropsiquiaacutetrica dominante presentacioacuten de un caso
bull CHILE La enfermedad de Wilson es infrecuente en Chile aunque existen comunicaciones de casos y series cliacutenicas en nuestro medio (Dr Marco Arrese)
Revista medica de ChileRev meacuted Chile v138 n10 Santiago oct 2010rtamento de Neurologiacutea Cliacutenica Las Condes Santiago de ChileMiranda M Brinck P Roessler JL Troncoso M Gonzaacutelez M Villagra R Enfermedad de Wilson Experiencia Cliacutenica en 16 pacientes Rev Med Chile 1995 123 1098-107
bull URUGUAY Comunicacioacuten de un caso cliacutenico y su evolucioacuten a los 8 antildeos Forma de presentacioacuten neurosiquiaacutetrica Drs Tarigo H Legnani E
Med Int Mex 200723(5)458-63
Enfermedad de Wilson reporte de un caso y
revision de la literatura
Marco Antonio Lopez Hernandez Marlene Serrano Rufino
MEacuteXICO
bull Costa Rica 49 100000 h (1989)
HEPAacuteTICONEUROLOacuteGICO Y OTROS
-COSTA RICA
bull mutante Asn 1270 Ser
bull Insuficiencia hepaacutetica fulminante con hemoacutelisis
COSTA RICA ndash DRA MARIacuteA A MATAMOROS
bull 92
(15)
( 21)
EW357
bull Tx con chaperones 4 fenil-butirato (4-PBA) y curcumina
bull Antioxidante
Quelante de Cu
Wilson Therapeutics ndash Improved treatment for Wilson DiseaseSeptember 2016
36
Wilson Therapeutics in brief
Founded in 2012 based in Stockholm
Develops novel therapies for rare diseases with high unmet medical needs
Current focus on Wilson Disease
Orphan indication
Approximately 25000 patients in EU and US combined
Lead program WTX101 ndash Decupratereg (bis-choline-tetrathiomolybdate)
Global Phase II study ongoing
gt500 patients exposed to tetrathiomolybdate for up to 8 years adds to the knowledge around safety
Public company listed on Nasdaq Stockholm
37
DrugRecommended
daily doseFrequenc
yIllustration
(daily dosage)
Trientine(Syprinetrade)
~1000 mg
250 mg caps
2-4 times day
Penicillamine(Cupriminetrade)
~1000 mg
250 mg caps
2-4 times day
Zinc (Galzintrade) 150 mg50 mg
caps3-5 times
day
Decupratereg ~30 mg30 mg tablet
1 time day
Capsules (L=19mm) and tablet (D=64mm) drawn to scale
Convenient dosing expected to improve treatment compliance
Decupratereg ndash once daily ndash one tablet ndash small size
Iron
B6
38
Decupratereg is being developed as a monotherapy for Wilson Disease
Phase 2 is ongoing
Trial sites
28 Wilson Disease patients in US and EUPatient population
Open label non-comparator evaluating free Cu and clinical outcomes for 24 weeks
Trial design
Fully recruited
Status 14 out of 14 patients have enrolled in extension phase
Top line data expected late 2016early 2017
Note Status as of August 3 2016
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
2015 Dec 18 7(29) 2859ndash2870
Wilsonrsquos disease A review of what we have learnedKryssia Isabel Rodriguez-Castro1 Francisco Javier Hevia-Urrutia2 and Giacomo Carlo Sturniolo3
Policlinico Abano Terme Padua Italy 1
Hospital San Juan de Dios Hospital CIMA San Joseacute Costa Rica2
Padua University Hospital Padua Italy3
National alliance for Wilsonrsquos disease health policy in Costa Rica(2017) 25
Francisco Hevia-Urrutia1 Ileana Alvarado-Echeverriacutea1 Alfredo Sanabria-Castro1 Marta Saacutenchez-Molina Luis Meza-Sierra1 Alexander Parajeles-Vindas1 Oscar Meacutendez-Blanca1 Aacutelvaro Saacutenchez-Siles2 Manuel Saboriacuteo-Rocafort3 Marcela Barguil-Gallardo1 Iliana Chavarriacutea-Quiroacutes1 and Cecilia Monge-Bonilla1
1Hospital San Juan de Dios Caja Costarricense del Seguro Social 4917-1000 San Jose Costa Rica 2Hospital Mexico Caja Costarricense del Seguro Social San Jose Costa Rica 3Hospital Nacional de Ninos Caja Costarricense del Seguro Social San Jose Costa Rica
EPIDEMIOLOGIacuteA EN CENTROAMEacuteRICA Y EL CARIBE
bull Guatemala El Salvador Honduras Panamaacute Rep Dominicana casos aislados
bull Nicaragua 2 casos neuroloacutegicos y 1 Wilson Fulminante (Costa Rica)
bull Cuba mutacioacuten N41S en 130 pts
SURAMEacuteRICAbull BRASIL mutaciones maacutes frecuentes
3402delC 308L708P 167
Enf Wilson en el sur de Brasil 40 antildeos de seguimientoClinics (Sao Paulo) 2011 Mar 66(3) 411ndash416
36 pts 1970-2010 75 origen Europeo
bull ARGENTINA El exjugador de Gimnasia La Plata sufre la enfermedad de Wilson y necesita ayuda del mundo del fuacutetbol para poder seguir luchando por su vida
bull PERUacute Enfermedad de Wilson forma nueropsiquiaacutetrica dominante presentacioacuten de un caso
bull CHILE La enfermedad de Wilson es infrecuente en Chile aunque existen comunicaciones de casos y series cliacutenicas en nuestro medio (Dr Marco Arrese)
Revista medica de ChileRev meacuted Chile v138 n10 Santiago oct 2010rtamento de Neurologiacutea Cliacutenica Las Condes Santiago de ChileMiranda M Brinck P Roessler JL Troncoso M Gonzaacutelez M Villagra R Enfermedad de Wilson Experiencia Cliacutenica en 16 pacientes Rev Med Chile 1995 123 1098-107
bull URUGUAY Comunicacioacuten de un caso cliacutenico y su evolucioacuten a los 8 antildeos Forma de presentacioacuten neurosiquiaacutetrica Drs Tarigo H Legnani E
Med Int Mex 200723(5)458-63
Enfermedad de Wilson reporte de un caso y
revision de la literatura
Marco Antonio Lopez Hernandez Marlene Serrano Rufino
MEacuteXICO
bull Costa Rica 49 100000 h (1989)
HEPAacuteTICONEUROLOacuteGICO Y OTROS
-COSTA RICA
bull mutante Asn 1270 Ser
bull Insuficiencia hepaacutetica fulminante con hemoacutelisis
COSTA RICA ndash DRA MARIacuteA A MATAMOROS
bull 92
(15)
( 21)
EW357
bull Tx con chaperones 4 fenil-butirato (4-PBA) y curcumina
bull Antioxidante
Quelante de Cu
Wilson Therapeutics ndash Improved treatment for Wilson DiseaseSeptember 2016
36
Wilson Therapeutics in brief
Founded in 2012 based in Stockholm
Develops novel therapies for rare diseases with high unmet medical needs
Current focus on Wilson Disease
Orphan indication
Approximately 25000 patients in EU and US combined
Lead program WTX101 ndash Decupratereg (bis-choline-tetrathiomolybdate)
Global Phase II study ongoing
gt500 patients exposed to tetrathiomolybdate for up to 8 years adds to the knowledge around safety
Public company listed on Nasdaq Stockholm
37
DrugRecommended
daily doseFrequenc
yIllustration
(daily dosage)
Trientine(Syprinetrade)
~1000 mg
250 mg caps
2-4 times day
Penicillamine(Cupriminetrade)
~1000 mg
250 mg caps
2-4 times day
Zinc (Galzintrade) 150 mg50 mg
caps3-5 times
day
Decupratereg ~30 mg30 mg tablet
1 time day
Capsules (L=19mm) and tablet (D=64mm) drawn to scale
Convenient dosing expected to improve treatment compliance
Decupratereg ndash once daily ndash one tablet ndash small size
Iron
B6
38
Decupratereg is being developed as a monotherapy for Wilson Disease
Phase 2 is ongoing
Trial sites
28 Wilson Disease patients in US and EUPatient population
Open label non-comparator evaluating free Cu and clinical outcomes for 24 weeks
Trial design
Fully recruited
Status 14 out of 14 patients have enrolled in extension phase
Top line data expected late 2016early 2017
Note Status as of August 3 2016
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
EPIDEMIOLOGIacuteA EN CENTROAMEacuteRICA Y EL CARIBE
bull Guatemala El Salvador Honduras Panamaacute Rep Dominicana casos aislados
bull Nicaragua 2 casos neuroloacutegicos y 1 Wilson Fulminante (Costa Rica)
bull Cuba mutacioacuten N41S en 130 pts
SURAMEacuteRICAbull BRASIL mutaciones maacutes frecuentes
3402delC 308L708P 167
Enf Wilson en el sur de Brasil 40 antildeos de seguimientoClinics (Sao Paulo) 2011 Mar 66(3) 411ndash416
36 pts 1970-2010 75 origen Europeo
bull ARGENTINA El exjugador de Gimnasia La Plata sufre la enfermedad de Wilson y necesita ayuda del mundo del fuacutetbol para poder seguir luchando por su vida
bull PERUacute Enfermedad de Wilson forma nueropsiquiaacutetrica dominante presentacioacuten de un caso
bull CHILE La enfermedad de Wilson es infrecuente en Chile aunque existen comunicaciones de casos y series cliacutenicas en nuestro medio (Dr Marco Arrese)
Revista medica de ChileRev meacuted Chile v138 n10 Santiago oct 2010rtamento de Neurologiacutea Cliacutenica Las Condes Santiago de ChileMiranda M Brinck P Roessler JL Troncoso M Gonzaacutelez M Villagra R Enfermedad de Wilson Experiencia Cliacutenica en 16 pacientes Rev Med Chile 1995 123 1098-107
bull URUGUAY Comunicacioacuten de un caso cliacutenico y su evolucioacuten a los 8 antildeos Forma de presentacioacuten neurosiquiaacutetrica Drs Tarigo H Legnani E
Med Int Mex 200723(5)458-63
Enfermedad de Wilson reporte de un caso y
revision de la literatura
Marco Antonio Lopez Hernandez Marlene Serrano Rufino
MEacuteXICO
bull Costa Rica 49 100000 h (1989)
HEPAacuteTICONEUROLOacuteGICO Y OTROS
-COSTA RICA
bull mutante Asn 1270 Ser
bull Insuficiencia hepaacutetica fulminante con hemoacutelisis
COSTA RICA ndash DRA MARIacuteA A MATAMOROS
bull 92
(15)
( 21)
EW357
bull Tx con chaperones 4 fenil-butirato (4-PBA) y curcumina
bull Antioxidante
Quelante de Cu
Wilson Therapeutics ndash Improved treatment for Wilson DiseaseSeptember 2016
36
Wilson Therapeutics in brief
Founded in 2012 based in Stockholm
Develops novel therapies for rare diseases with high unmet medical needs
Current focus on Wilson Disease
Orphan indication
Approximately 25000 patients in EU and US combined
Lead program WTX101 ndash Decupratereg (bis-choline-tetrathiomolybdate)
Global Phase II study ongoing
gt500 patients exposed to tetrathiomolybdate for up to 8 years adds to the knowledge around safety
Public company listed on Nasdaq Stockholm
37
DrugRecommended
daily doseFrequenc
yIllustration
(daily dosage)
Trientine(Syprinetrade)
~1000 mg
250 mg caps
2-4 times day
Penicillamine(Cupriminetrade)
~1000 mg
250 mg caps
2-4 times day
Zinc (Galzintrade) 150 mg50 mg
caps3-5 times
day
Decupratereg ~30 mg30 mg tablet
1 time day
Capsules (L=19mm) and tablet (D=64mm) drawn to scale
Convenient dosing expected to improve treatment compliance
Decupratereg ndash once daily ndash one tablet ndash small size
Iron
B6
38
Decupratereg is being developed as a monotherapy for Wilson Disease
Phase 2 is ongoing
Trial sites
28 Wilson Disease patients in US and EUPatient population
Open label non-comparator evaluating free Cu and clinical outcomes for 24 weeks
Trial design
Fully recruited
Status 14 out of 14 patients have enrolled in extension phase
Top line data expected late 2016early 2017
Note Status as of August 3 2016
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
SURAMEacuteRICAbull BRASIL mutaciones maacutes frecuentes
3402delC 308L708P 167
Enf Wilson en el sur de Brasil 40 antildeos de seguimientoClinics (Sao Paulo) 2011 Mar 66(3) 411ndash416
36 pts 1970-2010 75 origen Europeo
bull ARGENTINA El exjugador de Gimnasia La Plata sufre la enfermedad de Wilson y necesita ayuda del mundo del fuacutetbol para poder seguir luchando por su vida
bull PERUacute Enfermedad de Wilson forma nueropsiquiaacutetrica dominante presentacioacuten de un caso
bull CHILE La enfermedad de Wilson es infrecuente en Chile aunque existen comunicaciones de casos y series cliacutenicas en nuestro medio (Dr Marco Arrese)
Revista medica de ChileRev meacuted Chile v138 n10 Santiago oct 2010rtamento de Neurologiacutea Cliacutenica Las Condes Santiago de ChileMiranda M Brinck P Roessler JL Troncoso M Gonzaacutelez M Villagra R Enfermedad de Wilson Experiencia Cliacutenica en 16 pacientes Rev Med Chile 1995 123 1098-107
bull URUGUAY Comunicacioacuten de un caso cliacutenico y su evolucioacuten a los 8 antildeos Forma de presentacioacuten neurosiquiaacutetrica Drs Tarigo H Legnani E
Med Int Mex 200723(5)458-63
Enfermedad de Wilson reporte de un caso y
revision de la literatura
Marco Antonio Lopez Hernandez Marlene Serrano Rufino
MEacuteXICO
bull Costa Rica 49 100000 h (1989)
HEPAacuteTICONEUROLOacuteGICO Y OTROS
-COSTA RICA
bull mutante Asn 1270 Ser
bull Insuficiencia hepaacutetica fulminante con hemoacutelisis
COSTA RICA ndash DRA MARIacuteA A MATAMOROS
bull 92
(15)
( 21)
EW357
bull Tx con chaperones 4 fenil-butirato (4-PBA) y curcumina
bull Antioxidante
Quelante de Cu
Wilson Therapeutics ndash Improved treatment for Wilson DiseaseSeptember 2016
36
Wilson Therapeutics in brief
Founded in 2012 based in Stockholm
Develops novel therapies for rare diseases with high unmet medical needs
Current focus on Wilson Disease
Orphan indication
Approximately 25000 patients in EU and US combined
Lead program WTX101 ndash Decupratereg (bis-choline-tetrathiomolybdate)
Global Phase II study ongoing
gt500 patients exposed to tetrathiomolybdate for up to 8 years adds to the knowledge around safety
Public company listed on Nasdaq Stockholm
37
DrugRecommended
daily doseFrequenc
yIllustration
(daily dosage)
Trientine(Syprinetrade)
~1000 mg
250 mg caps
2-4 times day
Penicillamine(Cupriminetrade)
~1000 mg
250 mg caps
2-4 times day
Zinc (Galzintrade) 150 mg50 mg
caps3-5 times
day
Decupratereg ~30 mg30 mg tablet
1 time day
Capsules (L=19mm) and tablet (D=64mm) drawn to scale
Convenient dosing expected to improve treatment compliance
Decupratereg ndash once daily ndash one tablet ndash small size
Iron
B6
38
Decupratereg is being developed as a monotherapy for Wilson Disease
Phase 2 is ongoing
Trial sites
28 Wilson Disease patients in US and EUPatient population
Open label non-comparator evaluating free Cu and clinical outcomes for 24 weeks
Trial design
Fully recruited
Status 14 out of 14 patients have enrolled in extension phase
Top line data expected late 2016early 2017
Note Status as of August 3 2016
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
Med Int Mex 200723(5)458-63
Enfermedad de Wilson reporte de un caso y
revision de la literatura
Marco Antonio Lopez Hernandez Marlene Serrano Rufino
MEacuteXICO
bull Costa Rica 49 100000 h (1989)
HEPAacuteTICONEUROLOacuteGICO Y OTROS
-COSTA RICA
bull mutante Asn 1270 Ser
bull Insuficiencia hepaacutetica fulminante con hemoacutelisis
COSTA RICA ndash DRA MARIacuteA A MATAMOROS
bull 92
(15)
( 21)
EW357
bull Tx con chaperones 4 fenil-butirato (4-PBA) y curcumina
bull Antioxidante
Quelante de Cu
Wilson Therapeutics ndash Improved treatment for Wilson DiseaseSeptember 2016
36
Wilson Therapeutics in brief
Founded in 2012 based in Stockholm
Develops novel therapies for rare diseases with high unmet medical needs
Current focus on Wilson Disease
Orphan indication
Approximately 25000 patients in EU and US combined
Lead program WTX101 ndash Decupratereg (bis-choline-tetrathiomolybdate)
Global Phase II study ongoing
gt500 patients exposed to tetrathiomolybdate for up to 8 years adds to the knowledge around safety
Public company listed on Nasdaq Stockholm
37
DrugRecommended
daily doseFrequenc
yIllustration
(daily dosage)
Trientine(Syprinetrade)
~1000 mg
250 mg caps
2-4 times day
Penicillamine(Cupriminetrade)
~1000 mg
250 mg caps
2-4 times day
Zinc (Galzintrade) 150 mg50 mg
caps3-5 times
day
Decupratereg ~30 mg30 mg tablet
1 time day
Capsules (L=19mm) and tablet (D=64mm) drawn to scale
Convenient dosing expected to improve treatment compliance
Decupratereg ndash once daily ndash one tablet ndash small size
Iron
B6
38
Decupratereg is being developed as a monotherapy for Wilson Disease
Phase 2 is ongoing
Trial sites
28 Wilson Disease patients in US and EUPatient population
Open label non-comparator evaluating free Cu and clinical outcomes for 24 weeks
Trial design
Fully recruited
Status 14 out of 14 patients have enrolled in extension phase
Top line data expected late 2016early 2017
Note Status as of August 3 2016
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
bull Costa Rica 49 100000 h (1989)
HEPAacuteTICONEUROLOacuteGICO Y OTROS
-COSTA RICA
bull mutante Asn 1270 Ser
bull Insuficiencia hepaacutetica fulminante con hemoacutelisis
COSTA RICA ndash DRA MARIacuteA A MATAMOROS
bull 92
(15)
( 21)
EW357
bull Tx con chaperones 4 fenil-butirato (4-PBA) y curcumina
bull Antioxidante
Quelante de Cu
Wilson Therapeutics ndash Improved treatment for Wilson DiseaseSeptember 2016
36
Wilson Therapeutics in brief
Founded in 2012 based in Stockholm
Develops novel therapies for rare diseases with high unmet medical needs
Current focus on Wilson Disease
Orphan indication
Approximately 25000 patients in EU and US combined
Lead program WTX101 ndash Decupratereg (bis-choline-tetrathiomolybdate)
Global Phase II study ongoing
gt500 patients exposed to tetrathiomolybdate for up to 8 years adds to the knowledge around safety
Public company listed on Nasdaq Stockholm
37
DrugRecommended
daily doseFrequenc
yIllustration
(daily dosage)
Trientine(Syprinetrade)
~1000 mg
250 mg caps
2-4 times day
Penicillamine(Cupriminetrade)
~1000 mg
250 mg caps
2-4 times day
Zinc (Galzintrade) 150 mg50 mg
caps3-5 times
day
Decupratereg ~30 mg30 mg tablet
1 time day
Capsules (L=19mm) and tablet (D=64mm) drawn to scale
Convenient dosing expected to improve treatment compliance
Decupratereg ndash once daily ndash one tablet ndash small size
Iron
B6
38
Decupratereg is being developed as a monotherapy for Wilson Disease
Phase 2 is ongoing
Trial sites
28 Wilson Disease patients in US and EUPatient population
Open label non-comparator evaluating free Cu and clinical outcomes for 24 weeks
Trial design
Fully recruited
Status 14 out of 14 patients have enrolled in extension phase
Top line data expected late 2016early 2017
Note Status as of August 3 2016
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
HEPAacuteTICONEUROLOacuteGICO Y OTROS
-COSTA RICA
bull mutante Asn 1270 Ser
bull Insuficiencia hepaacutetica fulminante con hemoacutelisis
COSTA RICA ndash DRA MARIacuteA A MATAMOROS
bull 92
(15)
( 21)
EW357
bull Tx con chaperones 4 fenil-butirato (4-PBA) y curcumina
bull Antioxidante
Quelante de Cu
Wilson Therapeutics ndash Improved treatment for Wilson DiseaseSeptember 2016
36
Wilson Therapeutics in brief
Founded in 2012 based in Stockholm
Develops novel therapies for rare diseases with high unmet medical needs
Current focus on Wilson Disease
Orphan indication
Approximately 25000 patients in EU and US combined
Lead program WTX101 ndash Decupratereg (bis-choline-tetrathiomolybdate)
Global Phase II study ongoing
gt500 patients exposed to tetrathiomolybdate for up to 8 years adds to the knowledge around safety
Public company listed on Nasdaq Stockholm
37
DrugRecommended
daily doseFrequenc
yIllustration
(daily dosage)
Trientine(Syprinetrade)
~1000 mg
250 mg caps
2-4 times day
Penicillamine(Cupriminetrade)
~1000 mg
250 mg caps
2-4 times day
Zinc (Galzintrade) 150 mg50 mg
caps3-5 times
day
Decupratereg ~30 mg30 mg tablet
1 time day
Capsules (L=19mm) and tablet (D=64mm) drawn to scale
Convenient dosing expected to improve treatment compliance
Decupratereg ndash once daily ndash one tablet ndash small size
Iron
B6
38
Decupratereg is being developed as a monotherapy for Wilson Disease
Phase 2 is ongoing
Trial sites
28 Wilson Disease patients in US and EUPatient population
Open label non-comparator evaluating free Cu and clinical outcomes for 24 weeks
Trial design
Fully recruited
Status 14 out of 14 patients have enrolled in extension phase
Top line data expected late 2016early 2017
Note Status as of August 3 2016
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
-COSTA RICA
bull mutante Asn 1270 Ser
bull Insuficiencia hepaacutetica fulminante con hemoacutelisis
COSTA RICA ndash DRA MARIacuteA A MATAMOROS
bull 92
(15)
( 21)
EW357
bull Tx con chaperones 4 fenil-butirato (4-PBA) y curcumina
bull Antioxidante
Quelante de Cu
Wilson Therapeutics ndash Improved treatment for Wilson DiseaseSeptember 2016
36
Wilson Therapeutics in brief
Founded in 2012 based in Stockholm
Develops novel therapies for rare diseases with high unmet medical needs
Current focus on Wilson Disease
Orphan indication
Approximately 25000 patients in EU and US combined
Lead program WTX101 ndash Decupratereg (bis-choline-tetrathiomolybdate)
Global Phase II study ongoing
gt500 patients exposed to tetrathiomolybdate for up to 8 years adds to the knowledge around safety
Public company listed on Nasdaq Stockholm
37
DrugRecommended
daily doseFrequenc
yIllustration
(daily dosage)
Trientine(Syprinetrade)
~1000 mg
250 mg caps
2-4 times day
Penicillamine(Cupriminetrade)
~1000 mg
250 mg caps
2-4 times day
Zinc (Galzintrade) 150 mg50 mg
caps3-5 times
day
Decupratereg ~30 mg30 mg tablet
1 time day
Capsules (L=19mm) and tablet (D=64mm) drawn to scale
Convenient dosing expected to improve treatment compliance
Decupratereg ndash once daily ndash one tablet ndash small size
Iron
B6
38
Decupratereg is being developed as a monotherapy for Wilson Disease
Phase 2 is ongoing
Trial sites
28 Wilson Disease patients in US and EUPatient population
Open label non-comparator evaluating free Cu and clinical outcomes for 24 weeks
Trial design
Fully recruited
Status 14 out of 14 patients have enrolled in extension phase
Top line data expected late 2016early 2017
Note Status as of August 3 2016
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
bull Insuficiencia hepaacutetica fulminante con hemoacutelisis
COSTA RICA ndash DRA MARIacuteA A MATAMOROS
bull 92
(15)
( 21)
EW357
bull Tx con chaperones 4 fenil-butirato (4-PBA) y curcumina
bull Antioxidante
Quelante de Cu
Wilson Therapeutics ndash Improved treatment for Wilson DiseaseSeptember 2016
36
Wilson Therapeutics in brief
Founded in 2012 based in Stockholm
Develops novel therapies for rare diseases with high unmet medical needs
Current focus on Wilson Disease
Orphan indication
Approximately 25000 patients in EU and US combined
Lead program WTX101 ndash Decupratereg (bis-choline-tetrathiomolybdate)
Global Phase II study ongoing
gt500 patients exposed to tetrathiomolybdate for up to 8 years adds to the knowledge around safety
Public company listed on Nasdaq Stockholm
37
DrugRecommended
daily doseFrequenc
yIllustration
(daily dosage)
Trientine(Syprinetrade)
~1000 mg
250 mg caps
2-4 times day
Penicillamine(Cupriminetrade)
~1000 mg
250 mg caps
2-4 times day
Zinc (Galzintrade) 150 mg50 mg
caps3-5 times
day
Decupratereg ~30 mg30 mg tablet
1 time day
Capsules (L=19mm) and tablet (D=64mm) drawn to scale
Convenient dosing expected to improve treatment compliance
Decupratereg ndash once daily ndash one tablet ndash small size
Iron
B6
38
Decupratereg is being developed as a monotherapy for Wilson Disease
Phase 2 is ongoing
Trial sites
28 Wilson Disease patients in US and EUPatient population
Open label non-comparator evaluating free Cu and clinical outcomes for 24 weeks
Trial design
Fully recruited
Status 14 out of 14 patients have enrolled in extension phase
Top line data expected late 2016early 2017
Note Status as of August 3 2016
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
COSTA RICA ndash DRA MARIacuteA A MATAMOROS
bull 92
(15)
( 21)
EW357
bull Tx con chaperones 4 fenil-butirato (4-PBA) y curcumina
bull Antioxidante
Quelante de Cu
Wilson Therapeutics ndash Improved treatment for Wilson DiseaseSeptember 2016
36
Wilson Therapeutics in brief
Founded in 2012 based in Stockholm
Develops novel therapies for rare diseases with high unmet medical needs
Current focus on Wilson Disease
Orphan indication
Approximately 25000 patients in EU and US combined
Lead program WTX101 ndash Decupratereg (bis-choline-tetrathiomolybdate)
Global Phase II study ongoing
gt500 patients exposed to tetrathiomolybdate for up to 8 years adds to the knowledge around safety
Public company listed on Nasdaq Stockholm
37
DrugRecommended
daily doseFrequenc
yIllustration
(daily dosage)
Trientine(Syprinetrade)
~1000 mg
250 mg caps
2-4 times day
Penicillamine(Cupriminetrade)
~1000 mg
250 mg caps
2-4 times day
Zinc (Galzintrade) 150 mg50 mg
caps3-5 times
day
Decupratereg ~30 mg30 mg tablet
1 time day
Capsules (L=19mm) and tablet (D=64mm) drawn to scale
Convenient dosing expected to improve treatment compliance
Decupratereg ndash once daily ndash one tablet ndash small size
Iron
B6
38
Decupratereg is being developed as a monotherapy for Wilson Disease
Phase 2 is ongoing
Trial sites
28 Wilson Disease patients in US and EUPatient population
Open label non-comparator evaluating free Cu and clinical outcomes for 24 weeks
Trial design
Fully recruited
Status 14 out of 14 patients have enrolled in extension phase
Top line data expected late 2016early 2017
Note Status as of August 3 2016
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
EW357
bull Tx con chaperones 4 fenil-butirato (4-PBA) y curcumina
bull Antioxidante
Quelante de Cu
Wilson Therapeutics ndash Improved treatment for Wilson DiseaseSeptember 2016
36
Wilson Therapeutics in brief
Founded in 2012 based in Stockholm
Develops novel therapies for rare diseases with high unmet medical needs
Current focus on Wilson Disease
Orphan indication
Approximately 25000 patients in EU and US combined
Lead program WTX101 ndash Decupratereg (bis-choline-tetrathiomolybdate)
Global Phase II study ongoing
gt500 patients exposed to tetrathiomolybdate for up to 8 years adds to the knowledge around safety
Public company listed on Nasdaq Stockholm
37
DrugRecommended
daily doseFrequenc
yIllustration
(daily dosage)
Trientine(Syprinetrade)
~1000 mg
250 mg caps
2-4 times day
Penicillamine(Cupriminetrade)
~1000 mg
250 mg caps
2-4 times day
Zinc (Galzintrade) 150 mg50 mg
caps3-5 times
day
Decupratereg ~30 mg30 mg tablet
1 time day
Capsules (L=19mm) and tablet (D=64mm) drawn to scale
Convenient dosing expected to improve treatment compliance
Decupratereg ndash once daily ndash one tablet ndash small size
Iron
B6
38
Decupratereg is being developed as a monotherapy for Wilson Disease
Phase 2 is ongoing
Trial sites
28 Wilson Disease patients in US and EUPatient population
Open label non-comparator evaluating free Cu and clinical outcomes for 24 weeks
Trial design
Fully recruited
Status 14 out of 14 patients have enrolled in extension phase
Top line data expected late 2016early 2017
Note Status as of August 3 2016
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
bull Tx con chaperones 4 fenil-butirato (4-PBA) y curcumina
bull Antioxidante
Quelante de Cu
Wilson Therapeutics ndash Improved treatment for Wilson DiseaseSeptember 2016
36
Wilson Therapeutics in brief
Founded in 2012 based in Stockholm
Develops novel therapies for rare diseases with high unmet medical needs
Current focus on Wilson Disease
Orphan indication
Approximately 25000 patients in EU and US combined
Lead program WTX101 ndash Decupratereg (bis-choline-tetrathiomolybdate)
Global Phase II study ongoing
gt500 patients exposed to tetrathiomolybdate for up to 8 years adds to the knowledge around safety
Public company listed on Nasdaq Stockholm
37
DrugRecommended
daily doseFrequenc
yIllustration
(daily dosage)
Trientine(Syprinetrade)
~1000 mg
250 mg caps
2-4 times day
Penicillamine(Cupriminetrade)
~1000 mg
250 mg caps
2-4 times day
Zinc (Galzintrade) 150 mg50 mg
caps3-5 times
day
Decupratereg ~30 mg30 mg tablet
1 time day
Capsules (L=19mm) and tablet (D=64mm) drawn to scale
Convenient dosing expected to improve treatment compliance
Decupratereg ndash once daily ndash one tablet ndash small size
Iron
B6
38
Decupratereg is being developed as a monotherapy for Wilson Disease
Phase 2 is ongoing
Trial sites
28 Wilson Disease patients in US and EUPatient population
Open label non-comparator evaluating free Cu and clinical outcomes for 24 weeks
Trial design
Fully recruited
Status 14 out of 14 patients have enrolled in extension phase
Top line data expected late 2016early 2017
Note Status as of August 3 2016
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
bull Antioxidante
Quelante de Cu
Wilson Therapeutics ndash Improved treatment for Wilson DiseaseSeptember 2016
36
Wilson Therapeutics in brief
Founded in 2012 based in Stockholm
Develops novel therapies for rare diseases with high unmet medical needs
Current focus on Wilson Disease
Orphan indication
Approximately 25000 patients in EU and US combined
Lead program WTX101 ndash Decupratereg (bis-choline-tetrathiomolybdate)
Global Phase II study ongoing
gt500 patients exposed to tetrathiomolybdate for up to 8 years adds to the knowledge around safety
Public company listed on Nasdaq Stockholm
37
DrugRecommended
daily doseFrequenc
yIllustration
(daily dosage)
Trientine(Syprinetrade)
~1000 mg
250 mg caps
2-4 times day
Penicillamine(Cupriminetrade)
~1000 mg
250 mg caps
2-4 times day
Zinc (Galzintrade) 150 mg50 mg
caps3-5 times
day
Decupratereg ~30 mg30 mg tablet
1 time day
Capsules (L=19mm) and tablet (D=64mm) drawn to scale
Convenient dosing expected to improve treatment compliance
Decupratereg ndash once daily ndash one tablet ndash small size
Iron
B6
38
Decupratereg is being developed as a monotherapy for Wilson Disease
Phase 2 is ongoing
Trial sites
28 Wilson Disease patients in US and EUPatient population
Open label non-comparator evaluating free Cu and clinical outcomes for 24 weeks
Trial design
Fully recruited
Status 14 out of 14 patients have enrolled in extension phase
Top line data expected late 2016early 2017
Note Status as of August 3 2016
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
Wilson Therapeutics ndash Improved treatment for Wilson DiseaseSeptember 2016
36
Wilson Therapeutics in brief
Founded in 2012 based in Stockholm
Develops novel therapies for rare diseases with high unmet medical needs
Current focus on Wilson Disease
Orphan indication
Approximately 25000 patients in EU and US combined
Lead program WTX101 ndash Decupratereg (bis-choline-tetrathiomolybdate)
Global Phase II study ongoing
gt500 patients exposed to tetrathiomolybdate for up to 8 years adds to the knowledge around safety
Public company listed on Nasdaq Stockholm
37
DrugRecommended
daily doseFrequenc
yIllustration
(daily dosage)
Trientine(Syprinetrade)
~1000 mg
250 mg caps
2-4 times day
Penicillamine(Cupriminetrade)
~1000 mg
250 mg caps
2-4 times day
Zinc (Galzintrade) 150 mg50 mg
caps3-5 times
day
Decupratereg ~30 mg30 mg tablet
1 time day
Capsules (L=19mm) and tablet (D=64mm) drawn to scale
Convenient dosing expected to improve treatment compliance
Decupratereg ndash once daily ndash one tablet ndash small size
Iron
B6
38
Decupratereg is being developed as a monotherapy for Wilson Disease
Phase 2 is ongoing
Trial sites
28 Wilson Disease patients in US and EUPatient population
Open label non-comparator evaluating free Cu and clinical outcomes for 24 weeks
Trial design
Fully recruited
Status 14 out of 14 patients have enrolled in extension phase
Top line data expected late 2016early 2017
Note Status as of August 3 2016
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
36
Wilson Therapeutics in brief
Founded in 2012 based in Stockholm
Develops novel therapies for rare diseases with high unmet medical needs
Current focus on Wilson Disease
Orphan indication
Approximately 25000 patients in EU and US combined
Lead program WTX101 ndash Decupratereg (bis-choline-tetrathiomolybdate)
Global Phase II study ongoing
gt500 patients exposed to tetrathiomolybdate for up to 8 years adds to the knowledge around safety
Public company listed on Nasdaq Stockholm
37
DrugRecommended
daily doseFrequenc
yIllustration
(daily dosage)
Trientine(Syprinetrade)
~1000 mg
250 mg caps
2-4 times day
Penicillamine(Cupriminetrade)
~1000 mg
250 mg caps
2-4 times day
Zinc (Galzintrade) 150 mg50 mg
caps3-5 times
day
Decupratereg ~30 mg30 mg tablet
1 time day
Capsules (L=19mm) and tablet (D=64mm) drawn to scale
Convenient dosing expected to improve treatment compliance
Decupratereg ndash once daily ndash one tablet ndash small size
Iron
B6
38
Decupratereg is being developed as a monotherapy for Wilson Disease
Phase 2 is ongoing
Trial sites
28 Wilson Disease patients in US and EUPatient population
Open label non-comparator evaluating free Cu and clinical outcomes for 24 weeks
Trial design
Fully recruited
Status 14 out of 14 patients have enrolled in extension phase
Top line data expected late 2016early 2017
Note Status as of August 3 2016
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
37
DrugRecommended
daily doseFrequenc
yIllustration
(daily dosage)
Trientine(Syprinetrade)
~1000 mg
250 mg caps
2-4 times day
Penicillamine(Cupriminetrade)
~1000 mg
250 mg caps
2-4 times day
Zinc (Galzintrade) 150 mg50 mg
caps3-5 times
day
Decupratereg ~30 mg30 mg tablet
1 time day
Capsules (L=19mm) and tablet (D=64mm) drawn to scale
Convenient dosing expected to improve treatment compliance
Decupratereg ndash once daily ndash one tablet ndash small size
Iron
B6
38
Decupratereg is being developed as a monotherapy for Wilson Disease
Phase 2 is ongoing
Trial sites
28 Wilson Disease patients in US and EUPatient population
Open label non-comparator evaluating free Cu and clinical outcomes for 24 weeks
Trial design
Fully recruited
Status 14 out of 14 patients have enrolled in extension phase
Top line data expected late 2016early 2017
Note Status as of August 3 2016
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
38
Decupratereg is being developed as a monotherapy for Wilson Disease
Phase 2 is ongoing
Trial sites
28 Wilson Disease patients in US and EUPatient population
Open label non-comparator evaluating free Cu and clinical outcomes for 24 weeks
Trial design
Fully recruited
Status 14 out of 14 patients have enrolled in extension phase
Top line data expected late 2016early 2017
Note Status as of August 3 2016
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
Terapia Geacutenica corrige a largo plazo metabolismo del Cu en modelo murino de EW
bull Patologiacutea primaria
bull Transportador de cobre ATP7B
bull Tx actuales
bull Problema
bull Trasplante
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
bull tx geacutenicos fallaron
bullNuevo vector de tx geacutenica
bullVectores AAV8
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
bullRatoacuten modelo EW Atp7b --
bullRevierte
bullPreviene
bullRestaura
bull Tx geacutenica realidad en la cliacutenica
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
Conclusiones
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
TUacute ERES EL MEacuteDICO QUE ME
DIAGNOSTICARAacute
ENFERMEDAD DE WILSON EN
AMEacuteRICA LATINAfheviaugmailcom
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
45
Bis-choline tetrathiomolybdate (WTX101) ndash New mode of action
Removes Cu from intracellular metallothionein (MT) copper stores by forming TTM-Cu complexes
TTM-Cu complexes are excreted into bile
TTM expands endogenous copper buffering capacity by forming stable TTM-Cu-Albumin complexes in blood
Specifically binds to copper (not iron or zinc) with high affinity
Active ingredient Tetrathiomolybdate
(TTM)
Bis-choline
tetrathiomolybdate
Ammonium TTM has been explored in Wilson Disease in the past The comparability of the two salt forms has been
established
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito
Modelo de funcionamiento de la ATPasa Wilson (ATP7B) en el hepatocito