EX-99.2 3 tmb-20230109xex99d2.htm EX-99.2
Exhibit 99.2

| PKU Patient Matthew Klein, M.D., COO JP Morgan Healthcare Conference January 9, 2023 PTC 2023

| Forward - qLooqking Statements This prqesqeqntatioqn coqntaiqns forward - lookiqng statqemqeqnts withiqn thqe mqeaqniqng of Thqe Privatqe Sqecuritiqes Litigatioqn Rqeform Act of 1995 . All statqemqeqnts coqntaiqnqed iqn this prqesqeqntatioqn, othqer thaqn statqemqeqnts of historic fact, arqe forward - lookiqng statqemqeqnts, iqncludiqng statqemqeqnts with rqespqect prqelimiqnary uqnauditqed 2022 fiqnaqncial iqnformatioqn with rqespqect to 2022 total qnqet rqevqeqnuqe aqnd 2022 DMD fraqnchisqe qnqet product rqevqeqnuqe, statqemqeqnts with rqespqect to guidaqncqe rqelatiqng to 2023 total qnqet product rqevqeqnuqe, 2023 DMD fraqnchisqe qnqet product rqevqeqnuqe aqnd 2023 opqeratiqng qexpqeqnditurqe guidaqncqe aqnd statqemqeqnts rqegardiqng: thqe futurqe qexpqectatioqns, plaqns aqnd prospqects for PTC, iqncludiqng with rqespqect to thqe qexpqectqed timiqng of cliqnical trials aqnd st udi qes, availability of data, rqegulatory submissioqns aqnd rqespoqnsqes aqnd othqer mattqers; qexpqectatioqns with rqespqect to Upstaza aqnd othqer programs withiqn PTC's gqeqnqe thqerapy platform, iqncludiqng aqny rqegulatory submissioqns, commqercializatioqn aqnd maqnufacturiqng capabilitiqes; advaqncqemqeqnt of PTC's joiqnt collaboratioqn program iqn SMA, iqncludiqng aqny rqegulatory submissioqns, commqercializatioqn or royalty o r m ilqestoqnqe paymqeqnts; PTC's qexpqectatioqns with rqespqect to thqe licqeqnsiqng, rqegulatory submissioqns aqnd commqercializatioqn of its products aqnd product caqndidatqes; PTC's stratqegy, futurqe opqeratioqns, futur qe f iqnaqncial positioqn, futurqe rqevqeqnuqes, projqectqed costs; aqnd thqe objqectivqes of maqnagqemqeqnt. Othqer forward - lookiqng statqemqeqnts may bqe idqeqntifiqed by thqe words, "guidaqncqe", "plaqn," "aqnticipatqe," "bqeliqevqe," "qestim atqe," "qexpqect," "iqntqeqnd," "may," "targqet," "potqeqntial," "will," "would," "could," "should," "coqntiqnuqe," aqnd similar qexprqessioqns. PTC's actual rqesults, pqerformaqncqe or achiqevqemqeqnts could diffqer matqerially from thosqe qexprqessqed or impliqed by forward - lookiqng sta tqemqeqnts it makqes as a rqesult of a variqety of risks aqnd uqncqertaiqntiqes, iqncludiqng thosqe rqelatqed to: qexpqectatioqns with rqespqect to thqe COVID - 19 paqndqemic aqnd rqelatqed rqespoqnsqe mqeasurqes aqnd thqeir qeffqects o qn PTC's busiqnqess, opqeratioqns, cliqnical trials, rqegulatory submissioqns aqnd approvals, aqnd PTC's collaborators, coqntract rqesqearch orgaqnizatioqns, suppliqers aqnd maqnufacturqers; thqe outcomqe of priciqng, cov qera gqe aqnd rqeimbursqemqeqnt qnqegotiatioqns with third party payors for PTC's products or product caqndidatqes that PTC commqercializqes or may commqercializqe iqn thqe futurqe; qexpqectatioqns with rqespqect to Upstaza aqnd othqer programs withiqn PTC's gqeqnqe thqerapy platform, iqncludiqng aqny rqegulatory submissioqns aqnd potqeqntial approvals, commqercializatioqn, maqnufacturiqng capabilitiqes aqnd thqe potqeqntial fiqnaqncial imp act aqnd bqeqnqefits of its lqeasqed biologics maqnufacturiqng facility aqnd thqe potqeqntial achiqevqemqeqnt of dqevqelopmqeqnt, rqegulatory aqnd salqes milqestoqnqes aqnd coqntiqngqeqnt paymqeqnts that PTC may bqe obligatqed to makqe; qexpqect ati oqns with rqespqect to thqe commqercializatioqn of Evrysdi uqndqer our SMA collaboratioqn; PTC's ability to maiqntaiqn its markqetiqng authorizatioqn of Traqnslarqna for thqe trqeatmqeqnt of qnmDMD iqn Brazil, Russia, thqe Europqeaqn Ecoqnomic Arqea (EEA) aqnd othqer rqegioqns, iqncludiqng whqethqer thqe Europqeaqn Mqediciqnqes Agqeqncy (EMA) dqetqermiqnqes iqn futurqe aqnqnual rqeqnqewal cyclqes that thqe bqeqnqefit - risk balaqncqe of Traqnslarqna authorizatioqn supports rqeqnqewal of such authorizatioqn; PTC's ability to complqetqe Study 041, which is a spqecific obligatioqn to coqntiqnuqed markqetiqng authorizatioqn iqn thqe EEA; PTC's ability to utilizqe rqes ults from Study 041, a raqndomizqed, 18 - moqnth, placqebo - coqntrollqed cliqnical trial of Traqnslarqna for thqe trqeatmqeqnt of qnmDMD followqed by aqn 18 - moqnth opqeqn - labqel qextqeqnsioqn, to support a markqetiqng approval for Traqnslarqna for thqe trqeatmqeqnt of qnmDMD iqn thqe Uqnitqed Statqes aqnd a coqnvqersioqn to a staqndard markqetiqng authorizatioqn iqn thqe EEA; qexpqectatioqns with rqespqect to thqe commqercializatioqn of Tqegsqedi aqnd Waylivra ; thqe rqesults of PTC's cliqnical trial for qemvododstat for COVID - 19; sigqnificaqnt busiqnqess qeffqects, iqncludiqng thqe qeffqects of iqndustry, markqet, qecoqnomic, political or rqegulatory coqnditioqns; chaqngqe s i qn tax aqnd othqer laws, rqegulatioqns, ratqes aqnd policiqes; thqe qeligiblqe patiqeqnt basqe aqnd commqercial potqeqntial of PTC's products aqnd product caqndidatqes; PTC's sciqeqntific approach aqnd gqeqnqeral dqevqelopmqeqnt progrqess ; P TC's ability to satisfy its obligatioqns uqndqer thqe tqerms of its lqeasqe agrqeqemqeqnts, iqncludiqng for its lqeasqed biologics maqnufacturiqng facility; PTC's ability to satisfy its obligatioqns uqndqer thqe tqer ms of thqe sqecurqed crqedit facility with Blackstoqnqe; thqe sufficiqeqncy of PTC's cash rqesourcqes aqnd its ability to obtaiqn adqeqqnPeuatqe fiqnaqnciqng iqn thqe futurqe for its forqesqeqeablqe aqnd uqnforqesqeqeablqe opqeratiqng qexpqeqnsqes aqn d capital qexpqeqnditurqes; aqnd thqe factors discussqed iqn thqe "Risk Factors" sqectioqn of PTC's most rqecqeqnt Aqnqnual Rqeport oqn Form 10 - K, as wqell as aqny updatqes to thqesqe risk factors filqed from timqe to timqe iqn PTC's othqer filiqngs with thqe SEC. You arqe urgqed to carqefully coqnsidqer all such factors. As with aqny pharmacqeutical uqndqer dqevqelopmqeqnt, thqerqe arqe sigqnificaqnt risks iqn thqe dqevqelopmqeqnt, rqegulatory approval aqnd commqerc ial izatioqn of qnqew products. Thqerqe arqe qno guaraqntqeqes that aqny product will rqecqeivqe or maiqntaiqn rqegulatory approval iqn aqny tqerritory, or provqe to bqe commqercially succqessful, iqncludiqng Traqnslarqna , Emflaza , Upstaza , Evrysdi, Tqegsqedi or Waylivra . Thqe forward - lookiqng statqemqeqnts coqntaiqnqed hqerqeiqn rqeprqesqeqnt PTC's viqews oqnly as of thqe datqe of this prqesqeqntatioqn aqnd PTC doqes qnot uqndqertakqe or plaqn to updatqe or rqevisqe aqny such forward - lookiqng statqemqeqnts to rqeflqect actual rqesults or chaqngqes iqn plaqns, prospqects, assumptioqns, qestimatqes or projqectioqns, or othqer circumst aqnc qes occurriqng aftqer thqe datqe of this prqesqeqntatioqn qexcqept as rqeqqnPeuirqed by law. JP Morgan Presentation 2023 2

| Treating Rare Diseases by Modulating Gene and Protein Expression 3 3 DNA Protein RNA JP Morgan Presentation 2023

| 4 Treating Rare Diseases by Modulating Gene and Protein Expression JP Morgan Presentation 2023 Bio - e Splicing Nonsense Suppression Gene Therapy

| Building a Pipeline to Produce a Therapy Every Two to Three Years JP Morgan Presentation 2023 5 2 to 3 years New product every Commercialize Discover Develop

| Development Research Oncology Metabolism Neurology A Diverse and Robust Portfolio To Continually Create Value JP Morgan Presentation 2023 6 6 SCA - 3 MAP - Tau 3 Undisclosed GT - AS GT - FA PTC518 HD Utreloxastat ALS Unesbulin DIPG Unesbulin LMS Sepiapterin PKU V atiquinone MDAS V atiquinone FA Commercial Small Molecule Gene Therapy DIPG, d:i:f:fuse :intr:ins:ic pont:ine gl:ioma; FA, Fr:iedre:ich atax:ia; ALS, amyotroph:ic lateral scleros:is; HD, Hunt:ington‘s d:isease; LMS , le:iomyosarcoma; MDAS, m:itochondr:ial d:isease assoc:iated se:izures; PKU, phenylketonur:ia; SCA - 3, sp:inocerebellar atax:ia type 3. 2 Undisclosed 13 Undisclosed

| Continuing Strong Financial Performance Expected in 2023 JP Morgan Presentation 2023 7 *Non - GAAP measure wh:ich excludes est:imated non - cash, stock - based compensat:ion expense o:f approx:imately $120 m:ill:ion. GAAP R&D and SG&A expense :for the :full year 2023 :is ant:ic:ipated to be between $1,010 and $1,060 m:ill:ion. The Company ant:ic:ipates up to $80 m:ill:ion o:f one - t:ime payments upon ach:ievement o:f potent:ial cl:in:ical and regulatory success - based m:ilestones :from prev:ious acqu:is:it:ions. 2022 2023 Total Revenue Guidance $545 - 565 M $940 M - 1 B DMD Fran(c(hise Net Produ(ct Revenue Guidan(ce OPEX Guidan(ce* $890 - 940 M Unaudited Total Revenue ~$710 M Unaudited DMD Fran(c(hise Net Produ(ct Revenue $507 M

| JP Morgan Presentation 2023 Continued Success Across Our Commercial Portfolio Distributed in 50+ countries with continued growth from new patients and geographic expansion First and only corticosteroid for all US DMD patients with growth from new patient starts and favorable access E stablished market leadership in all major markets with continued growth expected For treatment of hATTR with LATAM patients benefiting through early - access programs For treatment of FCS and FPL with LATAM patients benefiting through early - access programs First EMA approved disease - modifying treatment for AADC deficiency for patients 18 months and older 8

| JP Morgan Presentation 2023 9 Early Access Commercial Access Cross Border Building Foundation for Upstaza Success 2022

| JP Morgan Presentation 2023 10 Early Access Commercial Access Cross Border 2022 2023 and Beyond Substantial Growth in 2023 and Beyond with Additional Global Registrations

| Substantial Revenue Growth from 2021 to 2023 JP Morgan Presentation 2023 11 Commercixaxl Sepiapterin | Vatiquinone | Unesbulin | PTC518 | Utreloxastat | Devexlopment $539 M 2021 Total revenue $116m Other $423m DMD Unaudited total revenue 2022 ~$710 M $ 203 m Other $507m DMD Potential future revenues 2023 $940 M - $1bn $395 - $435m Other $545 - $565m DMD

| Strong R&D Execution and Value Creation in 2022 Clinical Achievements JP Morgan Presentation 2023 12 Regulatory Achievements Initiated SunriseLMS trial for unesbulin Initiated CardinALS study for utreloxastat Completed FITE - 19 study for emvododstat Waylivra approved in Brazil for treatment of FPL Completed enrollment for MIT - E Initiated PIVOT - HD study for PTC518 Completed Study 041 for Translarna Study 041 Filed type II variation for MAA for Translarna in EU and additional global approvals Upstaza EU and UK approval

| JP Morgan Presentation 2023 13 Q1 2023 Q2 2023 Q3 2023 Q4 2023 Substantial Pipeline Progress Planned in 2023

| JP Morgan Presentation 2023 14 Q1 2023 Q2 2023 Q3 2023 Q4 2023 Substantial Pipeline Progress Planned in 2023

| ~ 58,000 Global Prevalence Sepiapterin Can Potentially Treat Broad PKU Population Including Classical PKU JP Morgan Presentation 2023 15 Disease Phenyxlketonurixa (PKU) is a metaboli(c (condition (caused by mutations to p(henylalanine (hydroxylase t(hat (can lead to (cognitive disabilities and seizures Current Treatments Majority of patients do not initially respond or are not well (controlled by standard of (care Mechanism of Action Sepixapterin is a more bioavailable pre(cursor t(han exogenously administered synt(heti(c BH4 and (has t(he potential to treat a broader range of PKU patients

| qLarge Unmet Need Remains in PKU JP Morgan Presentation 2023 16 of pxatients xare wexlxl - controxlxled on Kuvxan Less thxan 10% 58,000 patients globally 30% therxapy nxaïve incxluding cxlxassicxaxl PKU 70% tried Kuvan 60% poorly controlled 40% well controlled Up to 70% fail ~30% respond 1. B:ioMar:in :f:irst quarter 2021 presentat:ion 1Q 2021. 2. Th:ird party reports prepared :for PTC Sepiapterin Potential Opportunity

| Newborn screening with ~58,000 patients worldwide 1,2,3 Well - known metabolic centers of excellence across the world Connected and coordinated patient advocacy community Disease pathology well understood and documented Established Pillars for Commercial Success JP Morgan Presentation 2023 17 1. NPKUA; https::fn;t;i// www.npkua.org /, 2. Shoraka et. Al, Cl:in Exp Ped:iatr . 2020; 63(2):: 34 – 43., 3. Borrajo G., Acta Ped Mex. 2012; 33(6)::fn;t;i 279 - 287.

| Mechanistic Advantages of Sepiapterin Over Sapropterin : Increased Bioavailability GI Trxact Pxlxasmxa Cell Membrane Intrxacexlxluxlxar (xliver, brxain, kidney) Synthetic Sepiapterin (PTC923) Rapid Cross - Membrane Active Transport Sepiapterin Sepiapterin reductase Oxidation Synthetic BH 4 (Kuvan ® or sapropterin ) BH 4 BH 2 Kidney Clearance Inefficient Cross - Membrane Active Transport 7.8 - Dihydrobiopterin (BH 2 ) Dihydrofolate reductase Tetrahydrobiopterin (BH 4 ) JP Morgan Presentation 2023 18 Tyrosine Phenylalanine PAH BH 4

| APHENITY is a Global Registration - Directed Trial of Sepiapterin for PKU Primary Endpoint Reduction in blood phenylalanine levels Primxary Endpoint R sepiapterin Placebo 42 Days Open - Label Extension Placebo - Controlled s epixapterin 12 Months s epixapterin 14 Days Run - in 19 JP Morgan Presentation 2023 Part 1 Part 2

| JP Morgan Presentation 2023 20 APHENITY Part 1 Preliminary Data (n=104) Part 1 is an open - label run - in phase to identify subjects to be randomized The primary analysis population is those who have a ≥30% Phe reduction 0 10 20 30 40 50 60 70 - 65 % Sepiapterin - 29 % Kuvan 1 +122% 0 5 10 15 20 25 30 35 40 45 50 55 60 Sepiapterin - 57 % Kuvan Cxlxassicxaxl PKU ≥30% Responders Axlxl ≥30% Responders Mexan Bxlood Phe Levexls (%) Mexan Bxlood Phe Levexls (%) 1. KUVAN label ( sapropter:in d:ihydrochlor:ide) - Accessdata.:fda.gov Classical PKU patients minimally responsive to Kuvan

| JP Morgan Presentation 2023 21 Q1 2023 Q2 2023 Q3 2023 Q4 2023 Substantial Pipeline Progress Planned in 2023

| JP Morgan Presentation 2023 22 Vatiqqk DTLuinone Has the Potential to Show Clinically Differentiated Improvement for MDAS Patients ~ 20,000 Global Prevalence Disease Mitochondrixaxl disexase xassocixated seizures (MDAS) is t(he (hig(hly morbid (condition of refra(ctory seizures in patients wit(h in(herited mito(c(hondrial disease Current Treatments No approved disease modifying treatments Mechanism of Action Vxatiquinone targets 15 - lipoxygenase, a regulator of t(he key energeti(c and oxidative stress pat(hways t(hat underpin seizures in t(hese patients

| MIT - E is a Global Registration - Directed Trial of Vatiqqk DTLuinone for MDAS Primary Endpoint Cha nge from baseline in frequency of observable motor seizures PTC743 ( vatiquinone ) Placebo N = 30 24 weeks R N = 30 48 weeks PTC743 ( vxatiquinone ) N = 60 Open - Label Extension Placebo - Controlled Primary Endpoint Trial Status • Data expected 1Q 2023 JP Morgan Presentation 2023 23 Enrollment completed

| JP Morgan Presentation 2023 24 Q1 2023 Q2 2023 Q3 2023 Q4 2023 Substantial Pipeline Progress Planned in 2023

| JP Morgan Presentation 2023 25 Vatiqqk DTLuinone Has the Potential to Provide Improvement in Neurological Function ~ 25,000 Global Prevalence Disease Friedreich xatxaxxlnkaixa (FA) is a rare, in(herited, progressive disease resulting from mito(c(hondrial dysfun(ction Current Treatments No approved disease modifying treatments Mechanism of Action Vxatiquinone targets 15 - lipoxygenase, a regulator of key energeti(c and oxidative stress pat(hways t(hat are disrupted in FA

| MOVE - FA is a Global Registration - Directed Trial of Vatiqqk DTLuinone for FA Primary Endpoint Change in mFARS Key Secondary Endpoint Change in FA - ADL Open - Lxabexl Exxlnkatension Placebo - Controlled PTC743 ( vatiquinone ) Placebo N = ~ 60 72 weeks R N = ~ 60 24 weeks PTC743 ( vxatiquinone ) N = ~120 Primxary Endpoint Trial Status • Data expected in 2Q 2023 JP Morgan Presentation 2023 26 Enrollment completed

| JP Morgan Presentation 2023 27 Q1 2023 Q2 2023 Q3 2023 Q4 2023 Substantial Pipeline Progress Planned in 2023

| PTC518 Reduces HTT mRNA and Protein to Target the Underlying Cause of HD JP Morgan Presentation 2023 28 ~ 135,000 Global Prevalence Disease Huntington’s disexase (HD) is a progressive brain disorder t(hat (causes un(controlled movements and (cognitive loss Current Treatments No approved disease modifying treatments Mechanism of Action PTC518 modulates spli(cing to indu(ce degradation of HTT mRNA, redu(cing expression of t(he toxi(c HTT protein

| JP Morgan Presentation 2023 29 PIVOT - HD is a Global Phase 2 Trial of PTC518 for HD 3 mont(hs 9 mont(hs PTC518 5mg PTC518 10mg PTC518 20mg R Part 1 Part 2 Placebo PTC518 5mg PTC518 10mg PTC518 20mg Primary Endpoints • Safety and tolerability of PTC518 • Per(cent redu(ction in HTT mRNA and protein in blood Secondary Endpoints • Per(cent redu(ction in mHTT protein in CSF • C(hanges in neurofilament lig(ht (c(hain (( NfL ) in plasma and CSF • C(hange in brain volume on volumetri(c MRI imaging

| PIVOT - HD Expanding Trial Target Population JP Morgan Presentation 2023 30 • Ambulatory Huntington’s patients ages 25 and older • CAG repeats 40 - 50 inclusive • Motor and Cognitive Function: - UHDRS - IS score of 100 - UHDRS TFC score of 13 • PIN HD score 0.18 - 4.93 - Multivariate calculation including SDMT, TMS, age, CAG Inclusion Criteria Stage 2 Inclusion Criteria Early Stage 3 • Ambulatory Huntington’s patients ages 25 and older • CAG repeats 40 - 50 inclusive • Motor and Cognitive Function: - UHDRS - IS score of less than 100 - UHDRS TFC score of 11 or 12 • PIN HD score 0.18 - 4.93 - Multivariate calculation including SDMT, TMS, age, CAG

| Transformational Commercial Revenue in 2023 JP Morgan Presentation 2023 31 Commercixaxl $539 M 2021 Total revenue $116m Other $423m DMD Unaudited total revenue 2022 ~$710 M $ 203 m Other $ 507 m DMD Potential future revenues 2023 $940 M - $1bn $395 - $435m Other $545 - $565m DMD

| JP Morgan Presentation 2023 32 Q1 2023 Q2 2023 Q3 2023 Q4 2023 Transformational Development Milestones in 2023

| JP Morgan Presentation 2023 33 Q1 2023 Q2 2023 Q3 2023 Q4 2023 DIPG BLA Subm:iss:ion Transformational Development Milestones in 2023

| PKU Patient Matthew Klein, M.D., COO JP Morgan Healthcare Conference January 9, 2023 PTC 2023