UNITED STATES
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FORM
CURRENT REPORT
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Item 7.01. Regulation FD Disclosure.
On Wednesday, January 15, 2020 at 8:30 am PT at the 38th Annual J.P. Morgan Healthcare Conference (the “Conference”), PTC Therapeutics, Inc. (the “Company”) presented pursuant to advance notice its 2020 strategic priorities, preliminary 2019 financial results, and 2020 financial guidance. The Company’s presentation has been made available on the Events and Presentations page under the Investors section of the Company’s website. A copy of the slide deck, which the Company presented to investors at the Conference, is attached as Exhibit 99.1.
The information in this Item 7.01 of this Current Report on Form 8-K, including Exhibit 99.1, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
Item 8.01 Other Events
At the Conference, the Company announced certain preliminary (unaudited) financial information for its fiscal year ending December 31, 2019, including that the Company expects to report (i) total unaudited revenue of approximately $306 million, including net product revenue for the Duchenne muscular dystrophy franchise of approximately $291 million and a $15 million milestone payment from F. Hoffmann La Roche Ltd and Hoffmann La Roche Inc. for the risdiplam New Drug Application (“NDA”) acceptance; (ii) net product revenue for Translarna™ of approximately $190 million, (iii) net product revenue for Emflaza® of approximately $101 million and (iv) ending cash and cash equivalents of approximately $686 million. Final results are subject to completion of the Company’s year-end audit and are subject to revision.
The Company also announced certain corporate updates, including that (i) the Company submitted a Marketing Authorization Application for the potential approval of a gene therapy treatment, PTC-AADC, for AADC deficiency with the European Medicines Agency and the Company expects the Committee for Medicinal Products for Human Use opinion in the second half of 2020, (ii) in a recent interaction with the U.S. Food and Drug Administration (the “FDA”) there was a request for additional information concerning the use of the commercial delivery system for PTC-AADC in young patients and the Company anticipates the submission of a Biologics License Application to the FDA in the second quarter of 2020, (iii) the Prescription Drug User Fee Act date for a decision by the FDA on the risdiplam NDA is May 24, 2020 and (iv) in 2020, the Company plans to initiate three clinical trials in its newly acquired redox platform including potential registrational trials in mitochondrial epilepsy and Friedreich ataxia with PTC743 and a Phase 1 trial with PTC857 targeting GBA Parkinson's disease.
Forward Looking Statements: All statements, other than those of historical fact, contained in this Current Report on Form 8-K, are forward-looking statements, including preliminary (unaudited) financial information for fiscal year 2019, expectations with respect to future financial results and statements regarding: expectations with respect to the Company's gene therapy platform, including any potential regulatory submissions and manufacturing capabilities; and advancement of the Company's joint collaboration program in spinal muscular atrophy (“SMA”), including any potential regulatory submissions, commercialization or royalty or milestone payments. The Company's actual results, performance or achievements could differ materially from those expressed or implied by forward-looking statements it makes as a result of a variety of risks and uncertainties, including those related to: the preliminary nature of the Company's 2019 financial information, which is subject to completion of the Company's year-end audit; expectations with respect to the Company’s gene therapy platform, including any potential regulatory submissions and potential approvals, manufacturing capabilities and the potential financial impact and benefits of its leased biologics facility and the potential achievement of development, regulatory and sales milestones and contingent payments that the Company may be obligated to make; the enrollment, conduct, and results of studies under the SMA collaboration and events during, or as a result of, the studies that could delay or prevent further development under the program, including any potential regulatory submissions and potential commercialization with regards to risdiplam; and the factors discussed in the “Risk Factors” section of the Company's Annual Report on Form 10-K for the year ended December 31, 2018, Quarterly Reports on Form 10-Q for the periods ended March 31, 2019, June 30, 2019 and September 30, 2019 as well as any updates to these risk factors filed from time to time in the Company's other filings with the Securities and Exchange Commission. You are urged to carefully consider all such factors. The forward-looking statements contained herein and the exhibit hereto represent the Company's views only as of the date of this Current Report on Form 8-K and the Company does not undertake or plan to update or revise any such forward-looking statements to reflect actual results or changes in plans, prospects, assumptions, estimates or projections, or other circumstances occurring after the date of this Current Report on Form 8-K except as required by law. All website addresses given in this Current Report on Form 8-K or incorporated herein by reference are for information only and are not intended to be an active link or to incorporate any website information into this Report.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits
| Exhibit No. | Description | |
| 99.1 | Corporate Presentation - 38th Annual J.P. Morgan Healthcare Conference | |
| 104 | The cover page from this Current Report on Form 8-K, formatted in Inline XBRL |
Signature
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this Report to be signed on its behalf by the undersigned hereunto duly authorized.
| PTC Therapeutics, Inc. | ||
| Date: January 17, 2020 | By: | /s/ Emily Hill |
| Name: | Emily Hill | |
| Title: | Chief Financial Officer | |
Exhibit 99.1
PTC 2020 JP Morgan Healthcare Conference Stuart W. Peltz, Ph.D., CEO
Forwar lookingstatement Th i s pr e s en tat i o n co n ta i ns for w ar d - lo o k in g s ta tem en t s wi t h in the m ean i ng o f T he P r i va te S e c u r i ti e s Li ti g a ti o n R efor m Ac t o f 1995 . Al l s ta tem en t s c on ta i ned in t h is pr e s en tat i on , o ther than s ta tem en ts of h i s tor i c f a c t, ar e for w ar d - l oo k i ng s t at em ent s , i nc l ud i ng s t at em ent s r e l a ted to pr el i m i n ar y unau d i ted 2019 f i nan c i al i nfor m ati on wi t h r e sp e ct to 2019 ne t pr odu c t r e v enue of T r ans l ar na f or the tr eatm ent of n mD MD and E MFL A Z A f or the tr eatm ent of D u c he nne m u sc u l a r dy s tr o ph y , s tatem en t s wi t h r e sp e ct to 202 0 ne t pr odu c t r e v enue gu i da nc e, s tatem ent s wi t h r e s pec t to the 2020 oper a t i ng e x pend i tur e gu i dan c e and s tatem en t s r egar di ng : the futur e e x pe c tat i on s , p l a ns an d pr o s pec t s for PT C ; e x p e c ta ti o ns wi t h r e sp e ct to P T C' s gene ther ap y p l atf or m , i n cl ud i n g an y p oten t i al r eg u l ator y s ubm i s s i on s and m an ufa c t ur i ng c ap ab i l i t i es ; ad v a nc em en t o f P T C' s j o i n t c o l l abor a t i on pr ogr am in SM A, i ncl u d i n g an y p o t e nti al r egu l a tor y s ubm i s s i on s , co m m e r c ia l i za t io n or r oy a l ty or m i le st o n e p a y m e nts ; PT C ' s e x p e ct a ti o n s wi t h r e s p ect to the l i c e ns i ng, r e gu l at or y s ubm i s s i on s a nd po tent i a l co m m e r c ia l i za t io n o f T e gs e di and Wa y liv r a ; e x pa ns i on o f c om m er c i a l i z ati on o f T r ans l ar na and E m fl a z a and r e l a ted r eg ul a tor y su b m i ssi o ns ; P T C' s s tr ateg y , fu tur e o per at i on s , fu tur e fi n a n ci al po s i t i on, fut ur e r e v enu es , pr o j e c ted cos ts ; and the o b j e cti v es of m anag em en t . Ot her for w ar d - lo o k in g s ta tem en t s ma y be id e n t if ie d by th e wo r d s " gu i danc e " , " p l a n," " a n ti ci p at e ," " b e l i ev e," " e s ti m a t e," " e x p e ct ," " i n tend ," "m a y, " " t a r ge t," " p ote n t i a l ," "w ill, " " w o ul d ," " co ul d ," " sh ou l d , " " co nti n u e ," a nd s im ila r e x p r e ssi o n s . P T C' s a c t u a l r e s u l t s, per for m an c e or a c h i ev e m e n ts c oul d d i ffer m a t e r ia lly fr om th os e e x p r e ss e d or im p lie d by for w ar d - lo o ki n g s tatem en ts it m a ke s as a r e su l t of a v ar i ety of r i s ks and u n c e r tai n ti es , i ncl u d i n g th o s e r e l a ted to : the ou tc om e o f pr i c i ng , c o v er age an d re i mb u rs e me n t negot i at i on s wi t h t h ir d par t y pa y or s for P T C’s pr o duc t s or pr odu c t c and i date s that PT C co m m e r c ia l i ze s or ma y co m m e r c ia l i ze in t he fu tur e ; e x pe c tat i on s wi t h r e sp e ct to P T C’s gen e ther apy p l a tfor m , i ncl u di n g an y p o t e nti al r egu l ator y s ubm i s s i ons a nd p o t e nti al appr ov a l s , m anu fa c t ur i ng c a p a bi l i ti e s and th e p o t e nti al fi n a n ci a l im p a ct and bene f i t s of it s le a se d b i o l og i c s f a ci l i ty and th e po ten t i al a ch ie ve m e n t o f de v e l opm en t, r egu l a tor y and sal e s m i l es to ne s and c on t i ngen t p a y m e nts tha t PT C m ay be ob l i g ated to m ak e ; th e e nr o l l m en t, c ondu c t , and r es u l ts o f s tudi es un der th e SM A c o l l abor a t i on and ev ent s dur i ng , or a s a r e su l t of , the s tud i es tha t co u ld d e l ay or pr e v en t fur ther de v e l opm en t u nder the pr ogr am , i ncl u d i n g an y poten ti al r egu l ator y s ubm i s s i ons and poten t i a l co m m e r ci al i z ati o n wi t h r eg ar d s to r i sd ip la m ; P T C' s a b ili t y to c om p l ete a d y s tr oph i n s tud y nec e s s ar y to s upp or t a re - s ubm i s s i on of it s T r ans l ar na NDA for the tr eatm en t of non s en s e m uta ti on D u c henne m us c u l ar d y s tr oph y ( n mD MD ) to th e FD A , and P T C' s a b ilit y to per for m an y n e c e ss a r y add i t i ona l c lin ic a l tr i al s , non - cl i n i ca l st u di e s , and CM C ass e ss m e nt s or a n al yses at s i gn i f i c ant co s t ; P T C' s a b ilit y to m a i n t a i n i ts m ar k et i ng a uthor i z at i on of Tra n s l a rn a for the tr e atm en t of n mD MD in the E ur opean E co n o m ic A r ea ( EE A) , i nc l ud i ng w h et her the E ur opean M e di ci n e s A gen c y ( EM A) de ter m i ne s in f ut ur e annu a l r e n ew a l cy c l es that the be nef i t - ri s k ba l an c e of T r an s l ar na au thor i z at i on s u ppor t s r ene w a l o f su ch a uthor i z at i on ; P T C' s a b ilit y to e n r ol l , fund , co m p le t e a nd ti m el y s ubm i t to the EM A the r e su lt s of S tu dy 041 , a r an dom i z ed , 18 - m ont h, p l ac ebo - c ontr o l l ed c lin ic a l t r ia l o f T r ans l ar na for the tr e atm en t of n mD MD fo l l o w ed b y an 18 - m onth o pen - l abe l e x t e n s i o n, wh i ch is a sp e ci fi c ob l i ga t i on to c on t i nued m ar k et i ng au thor i z at i on in th e EE A ; ex p e ct a ti o ns wi t h r es pe c t to the co m m e r c ia l i za t io n of T eg s ed i and Wa y liv r a ; si g n i f i ca n t b us i nes s e f f e c ts, i nc l ud i ng the ef f e c ts o f i nd us tr y , m ar k et , ec onom i c , p o l i ti cal or r e gu l a tor y c ond i t i on s ; c hange s in tax an d o ther la ws , r e g ul a ti o ns , r ate s and p o l i ci es ; the e li g ib le p a ti e nt b a se and co m m e r c ia l p o t e nti al of T r an s l ar n a, E m f l az a, P TC - AAD C , T e g s e d i , Wa y liv r a , r i sd ip la m or an y of P T C' s ot her pr odu c t c and i d ates ; P T C' s sc i e nti fi c appr oa c h an d gen er a l de v e l opm en t pr ogr e s s ; P T C’s a b il it y to s at i s fy it s ob l i gati on s under t he ter m s of th e le a se agr eem ent f or it s l ea s ed b io lo g ics f a ci l i ty ; P T C' s a b ilit y to s ati s fy i ts ob l i gat i on s under the t e rms of the se n io r s ec ur ed ter m l oan f a c ilit y wi t h M id C a p F in a n ci a l ; the su f fi ci e nc y o f P T C' s cas h r e s o u r c es an d i ts a b il it y to ob ta i n adequate f i nan c i ng in th e fut ur e f or it s for e s ee ab l e and un for e s eeab l e o per at i ng ex p e n s e s and c ap i ta l e x p end i tur e s ; a nd the fa c tor s d i sc u ss e d in the "Ris k F a c tor s " se cti o n of P T C' s m o st r ec ent Quar t er l y R e por t o n Fo r m 10 - Q and A nnua l R e por t on Fo r m 1 0 - K, as we l l as an y updat es to th e s e r i sk fa c tor s f i le d fr om t im e to t im e in P T C' s o ther f ili n g s wi t h the SEC . Yo u a r e ur ge d to car ef ul l y co nsi d e r a ll such facto r s . As wi t h any ph ar m ac eu t i c a l und er de v e l opm en t, ther e ar e si gn i fi c a nt r i sk s in the de v e l opm en t, r e gu l a tor y appr o v a l a nd c om m er c i a l i z at i on o f ne w pr odu c ts . T her e a re no gu ar antee s t hat an y pr odu c t w ill r e ce i ve or m a i n t a i n r egu l ator y appr o v a l in an y t er r i tor y , or p r o ve to be co m m e r ci al l y s ucc ess f u l , i ncl u d i n g T r an s l ar n a, E m f l az a, PT C - AAD C , T e gse d i , Wa y liv r a o r r i sd i p l am . T he for w ar d - l o o ki n g s ta tem ent s c on ta i ne d her e i n r epr e s en t P T C' s vi e ws on l y as of the d ate o f th i s pr e s en tat i on an d PT C doe s no t und er ta k e or p la n to upd ate or r e v i s e any suc h for w ar d - l o o ki n g s ta tem ent s to r e fl e c t a c tua l r e s u l ts or c h ange s in pl a ns , p r o s p ec ts, as s um pt i on s , es ti m at es or p r o j ec ti o n s, or other c ir cu m st a n ce s o c cu r r in g after the d ate of thi s pr ese nt a ti o n e x ce pt as r e q ui r ed b y la w . 2
A global, commercial, diversified, biopharmaceutical company focused on innovative therapies for rare genetic disorders 3
Global commercial capabilities & infrastructure Offices in 20 countries Footprint in >50 countries 800+ employees 4
Strong financial performance supports future growth ~$306M 2019 Unaudited Net Revenue New product launches and approvals could also contribute 2020 revenue to $291M 2019 DMD Franchise Net Product Unaudited Net Revenue (e.g.,Tegsedi, commercial Waylivra EAP, PTC-AADC and risdiplam) $320–$340M 2020 DMD Franchise Net Product Revenue Guidance $545–$575M 2020 Opex Guidance PTC Therapeutics Provides Corporate Update and Highlights Pipeline Progress at 2020 J.P. Morgan Healthcare Conference 5
Significant success-based revenue through remaining risdiplam milestones and royalties Total remaining regulatory milestone-based payments Potential 2020 risdiplam milestone payments to PTC $72.5M Milestone Payment Up to NDA Filing in Japan $ 7,500,000 mid-teen royalties Total sales-threshold-based payments Annual, tiered potential royalties-based on net sales PTC Therapeutics Provides Corporate Update and Highlights Pipeline Progress at 2020 J.P. Morgan Healthcare Conference 6 First US Commercial Sale$ 20,000,000 Total$ 42,500,000 MAA Filing with EMA$ 15,000,000
Multiplatform approach builds diversified pipeline SCIENTIFIC PLATFORMS & RESEARCH * Investigator-initiated study with NYU 7 Potential registrational studies Commercial SMA AADC Clinical HD FA PTC857 GBA-PD Angelman Undisclosed IRDs Research Cog Disorders Undisclosed PTC299 AML PTC596 LMS PTC596 DIPG PTC743 MEDS PTC743 FA US Dystrophin Aniridia CDKL5/Dravet* LGMD2i Oncology Deflazacort Nonsense Mutation LatAm Commercial Redox Gene Therapy Splicing
Sustainable innovation drives continuous value creation 2023 DMD Franchise, PTC-AADC, risdiplam, Tegsedi™, Waylivra® 2020* DMD Franchise (risdiplam, Tegsedi™, Waylivra®, PTC-AADC) REVENUE Beyond 2023 Nonsense Mutation Gene Therapy Splicing Redox 2019 DMD Franchise (unaudited) $1.5B 2016 Translarna™ $320 – $340M 2015 Translarna™ $291M $81M $34M Angelman, ataluren (aniridia), FA, GBA-PD, HD, LGMD2i, MEDS, PTC-FA, undisclosed redox, gene therapy, and splicing Angelman, ataluren (US DMD, aniridia), FA, GBA-PD, HD, LGMD2i, MEDS, PTC-FA Emflaza® HD, PTC-AADC, PTC-FA, risdiplam, HD, risdiplam Risdiplam Tegsedi™, Waylivra® INNOVATION 8
Multiple potential value driving 1Q20 events in 2020 4Q19 2Q20 3Q20 4Q20 ales through early access program Clinical Regulatory Commercial 9 Analyst Day Nonsense Mutation Aniridia data US dystrophin data Splicing Risdiplam NDA filed SUNFISH Part 2 topline SUNFISH Part 2 data FIREFISH Part 2 topline Risdiplam MAA filing Risdiplam PDUFA Risdiplam US launch HD IND filed Gene Therapy AADC MAA submitted AADC BLA submitted FA enters clinic Redox Initiate PTC743 MEDS trial Initiate PTC857 Ph1 trial Initiate PTC743 FA trial LGMD2i data ANVISA approval hATTR launch FCS s ANVISA approval
Multiplatform approach builds diversified pipeline SCIENTIFIC PLATFORMS & RESEARCH * Investigator-initiated study with NYU 1 0 Potential registrational studies Commercial SMA AADC Clinical HD FA PTC857 GBA-PD Angelman Undisclosed IRDs Research Cog Disorders Undisclosed PTC299 AML PTC596 LMS PTC596 DIPG PTC743 MEDS PTC743 FA US Dystrophin Aniridia CDKL5/Dravet* LGMD2i Oncology Deflazacort Nonsense Mutation LatAm Commercial Redox Gene Therapy Splicing
Translarna™ demonstrates long-term benefit in DMD patients EU5 nmDMD patients treated with Translarna Compliance STRIDE is a real-world, long-term registry of patients receiving Translarna Translarna treatment slowed disease progression in nmDMD compared to matched natural history patients 2.2% Translarna-treated pts had an FVC<50% compared to 32.1% 3 years Extension in ability to stand from supine in less than 5 seconds 3.5 years Delay in loss of ambulation 1 1
Growth opportunities in DMD franchise Translarna • Increased penetration in existing territories Geographic expansion into new territories Increased awareness and earlier diagnosis Potential US NDA submission in 2020 2020 net DMD Franchise revenue guidance 2019 net DMD Franchise revenue • • $190M (unaudited) • $320-340M $291M (unaudited) Emflaza $101M (unaudited) • • • Growth in 2-5 year olds from label expansion Optimize dosing in both new and existing pts Publications showing the benefit of Emflaza over prednisone • • Reduced payer restrictions Benefit of switching 1 2
Multiplatform approach builds diversified pipeline SCIENTIFIC PLATFORMS & RESEARCH * Investigator-initiated study with NYU 1 3 Potential registrational studies Commercial SMA AADC Clinical HD FA PTC857 GBA-PD Angelman Undisclosed IRDs Research Cog Disorders Undisclosed PTC299 AML PTC596 LMS PTC596 DIPG PTC743 MEDS PTC743 FA US Dystrophin Aniridia CDKL5/Dravet* LGMD2i Oncology Deflazacort Nonsense Mutation LatAm Commercial Redox Gene Therapy Splicing
Splicing is highly selective with broad applicability Isoform plex Proprietary RNA-targeted small molecule library HTSpliceseq Transcriptome mRNA isoform detection platforms Exploiting U1-noncanonical exons 2020 and beyond Risdiplam SMN2 exon 7 inclusion Alternative splicing Familial dysautonomia ELP1 exon 20 inclusion Exon skipping >5 additional undisclosed targets Stop exon inclusion Huntington disease Stop exon inclusion 1 4 2019
Risdiplam: An modifier oral small molecule selective SMA splicing SMN1 SMN2 DNA 6 6 7 8 7 8 pre-mRNA 6 7 8 6 7 8 Risdiplam mRNA 6 7 8 6 8 Protein 2b 7 1 2a 2b 3 4 5 6 1 2a 3 4 5 6 8 Functional Unstable 1 5
Risdiplam – Most population competitive commercial profile across broadest FIREFISH – Type 1 SMA • Studied in Type 1,2,3 patients from newborns to 60 years of age • No treatment-related safety findings leading to withdrawal 82% on high dose had a CHOP-INTEND ≥ 40 48% of all infants were able to maintain head control 33% of all infants were able to sit independently 12% on high dose achieved bouncing, the first HINE-2 walking milestone • Systemic and central mode of action • Demonstrated increases in full-length SMN2 mRNA SUNFISH – Type 2 and 3 SMA • Ability to measure full-length mRNA and protein in blood 58% achieved improvements of ≥ 3 in MFM32 scores Part 2 study demonstrated statistically significant improvement for patients • PDUFA: May 24, 2020 SUNFISH Part 2 data presentation expected in Q1 2020 1 6 FIREFISH Part 2 topline data expected in Q1 2020
Risdiplam – Most competitive commercial profile population across broadest SMN protein in blood of SMA patients and healthy subjects • Studied in Type 1,2,3 patients from newborns to 60 years of age before and after 4 weeks of treatment 8 • No treatment-related safety findings leading to withdrawal 6 • Systemic and central mode of action 4 • Demonstrated increases in full-length SMN2 mRNA 2 • Ability to measure full-length mRNA and protein in blood 0 • PDUFA: May 24, 2020 Baseline Sunfish =<11yrs Week 4 Firefish Sunfish >11yrs Jewelfish Healthy Volunteers 1 7 SMN Protein (ng/ml)
Toxic HTT death protein aggregation causes extensive neuronal cell Healthy HD Goh et al. Aus Psychiatry. 2018 1 8
Splicing modifiers reduce HTT protein in Huntington disease Healthy HD HD is a neurodegenerative disease caused by a toxic gain-of-function triplet repeat (CAG) expansion in the huntingtin gene (CAG)>35 (CAG)>35 Stop exon Stop exon Treatment with splicing modifier Untreated Ex 1 Ex X Ex Y Ex 1 Ex X Ex Y R3 Stop exon R1 Ex 1 Ex X Ex Y Ex 1 Ex X Ex Y HET1 R2 Ar Degraded through translation-linked mRNA decay Splicing modifiers potentiate stop exon inclusion Toxic HTT protein Toxic HTT protein 1 9
HD splicing small molecules have broad tissue distribution Dose dependent HTT lowering in the brain in BACHD mice HD IND expected late 2020 • • • • Oral, crosses BBB Titratable Development candidate selected Ability to measure mRNA and protein in blood in healthy volunteers Brain 120 100 80 60 40 20 0 Vehicle 1 3 7 21 63 Treated (mg/kg) Uniform HTT lowering with ~1:1 brain and blood concentrations* Striatum Cortex Cerebellum Brain and blood HTT lowering 120 100 80 60 40 20 0 120 100 80 60 40 20 0 120 100 80 60 40 20 0 Vehicle 7 mg/kg Vehicle 7 mg/kg Vehicle 7 mg/kg *Data on file from multiple studies 2 0 % HTT Remaining % HTT Remaining % HTT Remaining % HTT Remaining
Multiplatform approach builds diversified pipeline SCIENTIFIC PLATFORMS & RESEARCH * Investigator-initiated study with NYU 2 1 Potential registrational studies Commercial SMA AADC Clinical HD FA PTC857 GBA-PD Angelman Undisclosed IRDs Research Cog Disorders Undisclosed PTC299 AML PTC596 LMS PTC596 DIPG PTC743 MEDS PTC743 FA US Dystrophin Aniridia CDKL5/Dravet* LGMD2i Oncology Deflazacort Nonsense Mutation LatAm Commercial Redox Gene Therapy Splicing
Treating rare monogenic disorders with targeted gene therapy Potential advantages of targeted therapy • Local administration lowers systemic immunogenicity and exposure Low turnover cells may lead to improved durability • • Micro-dosing lowers manufacturing and patient burden Pipeline • • • • • PTC-AADC MAA submitted PTC-AADC BLA now expected in 2Q20 PTC-FA expected to enter clinic in 3Q20 Angelman syndrome IND anticipated 1H 2021 >5 nonclinical development candidates 2 2
Internal gene therapy manufacturing capabilities • • In-house manufacturing begins in 2020 15-year lease on ~185,000 sq. ft. which includes a state-of-the-art biologics production facility with supporting research and operations buildings in NJ • Highly qualified staff in biologics manufacturing joining PTC • Facility to support gene therapy production & continued development of investigational medicines 2 3
AADC deficiency – Rare disorder with significant unmet need Normal AADC • Rare progressive childhood disease, affecting approximately 5,000 patients globally Head Position 3-4 months Up • Children with severe AADC deficiency never achieve motor development milestones • Profound development failure with shortened life expectancy in severe forms (4 - 8 yrs) Sitting 6-9 months • Patients identified in Asia, US, Europe and LatAm > 50 disease causing variants described in AADC deficiency Standing 10-12 months • Wassenberg T et al. Orphanet J Rare Dis. 2017;12(1):12 2 4
PTC-AADC patients make significant and sustainable progress Untreated Post-Treatment Age 2 Age 3 Age 4.5 2 5
PTC-AADC demonstrates significant and durable motor improvements across patient population 1-Year Results of Motor Development PDMS-21 through 12 months – Studies 1 & 2 5-Year Results of Motor Development PDMS-21 through 60 months - Study 1 150 150 100 100 50 50 0 60 0 20 40 60 80 100 120 20 40 80 100 120 Chronological Age (Months) Chronological Age (Months) 1 Peabody Developmental Motor Scale Chien et al. Presented at Child Neurology Society October 23-26 2019, Charlotte, NC 2 6 Score Score
Expertise in patient identification Early diagnosis Increased awareness Genotyping 2 7 AADC US efforts: No-cost testing via whole blood 3-OMD newborn screening test; reflex to AADC enzyme activity and DDC gene sequencing AADC Ex-US efforts: No-cost testing via dried blood spot cards 3-OMD screening; reflex to DDC gene sequencing 200 AADC patients identified Newborn Screening More than 1 million newborns expected to be screened by the end of 2021 in the US Prevalence Screening Study in Patients with Cerebral Palsy (CP) Protocol driven study to identify prevalence of AADC in CP patients of unknown etiology
Expertise in patient identification Early diagnosis Increased awareness Genotyping 2 8 AADC US efforts: No-cost testing via whole blood 3-OMD newborn screening test; reflex to AADC enzyme activity and DDC gene sequencing AADC Ex-US efforts: No-cost testing via dried blood spot cards 3-OMD screening; reflex to DDC gene sequencing 300+ AADC patients by launch Newborn Screening More than 1 million newborns expected to be screened by the end of 2021 in the US Prevalence Screening Study in Patients with Cerebral Palsy (CP) Protocol driven study to identify prevalence of AADC in CP patients of unknown etiology
Friedreich Ataxia (FA) is a severe neuromuscular disorder amenable to gene therapy Larger repeat expansion Lower protein levels • Inherited, monogenic disease arising from triplet repeat expansion Mutation in frataxin gene limits protein production • • Most common hereditary ataxia (~25,000 patients globally) Childhood onset Debilitating, life shortening neuromuscular disorder Only palliative treatments available currently Dentate nucleus • • • Reduced mitochondrial function Koeppen A. J Neurol Sci. 2011 April 15; 303(1-2): 1–12 2 9
Frataxin expression seen in large animal models PTC-FA Intracerebellar Dosing in Porcine Model* PTC-FA Intracerebellar Dosing in NHP Model* 3,000 1,000 Cerebellar Cortex Dentate Nucleus Cerebellar Cortex Dentate Nucleus 2,500 800 2,000 600 1,500 400 1,000 Target Frataxin Protein Healthy Human DN 200 Target Frataxin Protein Healthy Human DN 500 0 0 Unilateral dose of 3.0 x 1012 vg total - Day 28 - Mean (SEM) *Human-specific detection Bi-lateral Dose of 2.4 x 1012 vg total - Day 28 - Mean (SEM) *NHP background subtracted PTC-FA to enter 30 clinic 3Q20 3 0 ELISA for Human Frataxin (ng/g) ELISA for Human Frataxin (ng/g)
Multiplatform approach builds diversified pipeline SCIENTIFIC PLATFORMS & RESEARCH * Investigator-initiated study with NYU 3 1 Potential registrational studies Commercial SMA AADC Clinical HD FA PTC857 GBA-PD Angelman Undisclosed IRDs Research Cog Disorders Undisclosed PTC299 AML PTC596 LMS PTC596 DIPG PTC743 MEDS PTC743 FA US Dystrophin Aniridia CDKL5/Dravet* LGMD2i Oncology Deflazacort Nonsense Mutation LatAm Commercial Redox Gene Therapy Splicing
Redox platform is a novel approach focusing on inflammation and oxidative stress O OH Arachidonic acid 15-Lipoxygenase PTC743 & PTC857 15-lipoxygenase Lipid signaling molecule that regulates fundamental disease processes OH O O OH 15-OOH-Arachidonic acid 15(S)-HpETE* Glial Cell Activation & Inflammation Alpha-synuclein Oxidation & Aggregation Glutathione Oxidation & Depletion Oxidative Stress Mediated Membrane Damage Glutathione GPX4 Selenocysteine-dependent active site Glutathione disulfide HO O OH 15-OH-Arachidonic acid 3 2
Initiating three redox clinical trials in 2020 PTC743 PTC743 PTC857 Trial Starting 2Q20 Proof-of-concept in dozens of patients Clinical trials demonstrated reduction in hospitalizations and mortality risk in MEDS patients To enroll patients with 4 most common sub-types of MEDS Trial Starting 3Q20 Mechanism linked to FA pathology >60 subjects treated; Improvement in FARS compared to natural history Potentially complementary with FA gene therapy Trial Starting 2Q20 Targeting GBA Parkinson’s disease as first indication Inhibits alpha-synuclein oxidation and aggregate intensity in preclinical trials Protects dopamine-related motor function in MPTP mouse • • • • • • • • • 5-6K patients in the US and EU 25K patients WW ~50 – 90K patients in the US 3 3 Phase 1 Trial Friedreich Ataxia Trial Mitochondrial Epilepsy Trial
Multiplatform approach builds diversified pipeline SCIENTIFIC PLATFORMS & RESEARCH * Investigator-initiated study with NYU 3 4 Potential registrational studies Commercial SMA AADC Clinical HD FA PTC857 GBA-PD Angelman Undisclosed IRDs Research Cog Disorders Undisclosed PTC299 AML PTC596 LMS PTC596 DIPG PTC743 MEDS PTC743 FA US Dystrophin Aniridia CDKL5/Dravet* LGMD2i Oncology Deflazacort Nonsense Mutation LatAm Commercial Redox Gene Therapy Splicing
Leveraging our existing LatAm infrastructure to commercialize Tegsedi & Waylivra Waylivra to utilize our patient Best fit for Latin American hATTR market ANVISA approval granted in 2019 Only approved hATTR indication to include improvements in QoL hATTR most prevalent phenotype in Latin America with ~6,000 patients support in Latin America Potential ANVISA approval expected in 4Q20 Potential first FCS treatment Received EU conditional marketing approval FCS = familial chylomicronemia-syndrome 3 5
2020 Potential milestones to generate value Waylivra approval US Translarna NDA submission PTC857 GBA Parkinson’s PTC743 MEDS IND in Huntington Disease Aniridia data AADC gene therapy approval FA gene therapy to enter clinic PTC743 FA Risdiplam approval 3 6
A global, commercial, diversified, biopharmaceutical company focused on innovative therapies for rare genetic disorders 3 7