8-K
PTC THERAPEUTICS, INC. (PTCT)
8-K
2021-11-30
For: 2021-11-30
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April 07, 2026
UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM 8-K
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported): November 30, 2021
PTC THERAPEUTICS, INC.
(Exact Name of Company as Specified in Charter)
| | | | | |
|---|---|---|---|---|
| Delaware | 001-35969 | 04-3416587 | ||
| (State or Other Jurisdiction | | (Commission | | (IRS Employer |
| of Incorporation) | | File Number) | | Identification No.) |
| | | |
|---|---|---|
| 100 Corporate Court | | |
| South Plainfield , NJ | | 07080 |
| (Address of Principal Executive Offices) | | (Zip Code) |
Registrant’s telephone number, including area code: (908) 222-7000
Not applicable
(Former Name or Former Address, if Changed Since Last Report)
Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):
☐Written communications pursuant to Rule 425 under the Securities Act (17 CFR 230.425)
☐Soliciting material pursuant to Rule 14a-12 under the Exchange Act (17 CFR 240.14a-12)
☐Pre-commencement communications pursuant to Rule 14d-2(b) under the Exchange Act (17 CFR 240.14d-2(b))
☐Pre-commencement communications pursuant to Rule 13e-4(c) under the Exchange Act (17 CFR 240.13e-4(c))
Securities registered pursuant to Section 12(b) of the Act:
| | | | | |
|---|---|---|---|---|
| Title of each class | **** | Trading Symbol(s) | **** | Name of each exchange on which registered |
| Common Stock, $0.001 par value per share | | PTCT | | Nasdaq Global Select Market |
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☐
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Item 7.01. Regulation FD Disclosure.
On November 30, 2021, the Company presented a company overview at the 4th Annual Evercore ISI HealthCONx Conference (the “Conference”). The Company’s corporate presentation slide deck, which includes updated regulatory timelines referenced at the Conference, has been posted on the Events and Presentations page under the Investors section of the Company’s website. A copy of the slide deck is also attached to this Current Report on Form 8-K (this “Report”) as Exhibit 99.1 and is incorporated by reference into this Item 7.01.
The information in 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. All website addresses given in this Report 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
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|---|---|---|
| Exhibit No. | Description | |
| 99.1 | | Corporate Presentation – 4th Annual Evercore ISI HealthCONx 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.
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| | PTC Therapeutics, Inc. | |
| | | |
| Date: November 30, 2021 | By: | /s/ Emily Hill |
| | Name: | Emily Hill |
| | Title: | Chief Financial Officer |
Exhibit 99.1
| PTC 2021<br>Corporate Deck<br>Updated Nov 30, 2021 |
|---|
| Forward Looking Statements<br>This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 199 5. All statements contained in this<br>release, other than statements of historic fact, are forward -looking statements, including statements with respect to 2021 net product revenue guidance, statements with<br>respect to the 2021 operating expenditure guidance and statements regarding: the future expectations, plans and prospects for PTC, including with respect to the<br>expected timing of clinical trials and studies, availability of data, regulatory submissions and responses and other matters; expectations with respect to PTC's gene<br>therapy platform, including any potential regulatory submissions and manufacturing capabilities; advancement of PTC's joint c ollaboration program in SMA, including any<br>potential regulatory submissions, commercialization or royalty or milestone payments; PTC's expectations with respect to the licensing, regulatory submissions and<br>commercialization of its products and product candidates; the timing with respect to orders for PTC's products; PTC's strategy, future operations, future financial position,<br>future revenues, projected costs; and the objectives of management. Other forward -looking statements may be identified by the words "guidance", "plan," "anticipate,"<br>"believe," "estimate," "expect," "intend," "may," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions.<br>PTC'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<br>of risks and uncertainties, including those related to: the outcome of pricing, coverage and reimbursement negotiations with third party payors for PTC's products or<br>product candidates that PTC commercializes or may commercialize in the future; expectations with respect to PTC's gene therap y platform, including any potential<br>regulatory submissions and potential approvals, manufacturing capabilities and the potential financial impact and benefits of its leased biologics manufacturing facility<br>and the potential achievement of development, regulatory and sales milestones and contingent payments that PTC may be obligat ed to make; the enrollment, conduct,<br>and results of ongoing studies under the SMA collaboration and events during, or as a result of, the studies that could delay or prevent further development under the<br>program, including any potential regulatory submissions and potential commercialization with respect to Evrysdi; PTC's ability to complete a dystrophin study necessary<br>to support a re-submission of its Translarna NDA for the treatment of nonsense mutation Duchenne muscular dystrophy (nmDMD) to t he FDA, and PTC's ability to perform<br>any necessary additional clinical trials, non-clinical studies, and CMC assessments or analyses at significant cost; PTC's abili ty to maintain its marketing authorization<br>of Translarna for the treatment of nmDMD in the European Economic Area (EEA), including whether the European Medicines Agency (E MA) determines in future annual<br>renewal cycles that the benefit-risk balance of Translarna authorization supports renewal of such authorization; PTC's ability t o enroll, fund, complete and timely submit<br>to the EMA the results of Study 041, a randomized, 18-month, placebo-controlled clinical trial of Translarna for the treatment of nmDMD followed by an 18-month open-<br>label extension, which is a specific obligation to continued marketing authorization in the EEA; expectations with respect to the commercialization<br>of Tegsedi and W aylivra™; the enrollment, conduct and results of PTC’s emvododstat clinical trial for COVID -19; expectations with respect to the COVID-19 pandemic<br>and related response measures and their effects on PTC's business, operations, clinical trials, potential regulatory submissi ons and approvals, and PTC's collaborators,<br>contract research organizations, suppliers and manufacturers; significant business effects, including the effects of industry , market, economic, political or regulatory<br>conditions; changes in tax and other laws, regulations, rates and policies; the eligible patient base and commercial potentia l of PTC's products and product candidates;<br>PTC's scientific approach and general development progress; PTC's ability to satisfy its obligations under the terms of the l ease agreement for its leased biologics<br>manufacturing facility; the sufficiency of PTC's cash resources and its ability to obtain adequate financing in the future fo r its foreseeable and unforeseeable operating<br>expenses and capital expenditures; and the factors discussed in the "Risk Factors" section of PTC's most recent Quarterly Rep ort on Form 10-Q and Annual Report on<br>Form 10-K, as well as any updates to these risk factors filed from time to time in PTC's other filings with the SEC. You are urg ed to carefully consider all such factors.<br>As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commerc ialization of new products. There are no<br>guarantees that any product will receive or maintain regulatory approval in any territory, or prove to be commercially succes sful,<br>including Translarna, Emflaza, Evrysdi, Tegsedi, W aylivra or PTC-AADC.<br>The forward-looking statements contained herein represent PTC's views only as of the date of this presentation and PTC does not undertake or plan to update or revise<br>any such forward-looking statements to reflect actual results or changes in plans, prospects, assumptions, estimates or projecti ons, or other circumstances occurring<br>after the date of this presentation except as required by law.<br>2 |
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| Translating Science to Transform Lives<br>3 |
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| Significant Execution and Value Creation in 2020<br>4<br>Clinical<br>Regulatory<br>Commercial<br>Financial<br>✓ Initiated two potential registrational trials with vatiquinone in Mitochondrial Disease Associated<br>Seizures & Friedreich ataxia<br>✓ Initiated Phase 1 trial of PTC518 in healthy volunteers for Huntington disease program<br>✓ Initiated one potential registrational trial with emvododstat in COVID-19<br>✓ Evrysdi™ approval in US and multiple additional countries<br>✓ Submitted MAA to EMA for gene therapy to treat AADC deficiency<br>✓ Translarna label modification related to non-ambulatory patients<br>✓ Broader patient access and continued geographic growth of Translarna<br>✓ Strong Emflaza growth; 38% YoY<br>✓ Evrysdi strong commercial launch<br>✓ Strengthened balance sheet; over $1B cash position<br>✓ 2020 Net Revenue: $333M Net Product Revenue; $331M DMD Franchise Net Product Revenue;<br>$42.5M Roche Collaboration Revenue associated with Evrysdi regulatory and sales milestones |
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| Diversified Platform Drives Strong Portfolio<br>5<br>Clinical<br>Commercial<br>Research<br>Nonsense<br>Mutation<br>LatAm<br>Commercial Deflazacort<br>Gene<br>Therapy Bio-e Metabolic Oncology<br>US Ataluren<br>PTC-AADC<br>Emvododstat<br>AML<br>Unesbulin DIPG<br>Unesbulin LMS<br>Vatiquinone<br>MDAS<br>Vatiquinone<br>FA<br>PTC923 PKU Emvododstat<br>COVID-19<br>SCA-3<br>Undisclosed<br>MAP-Tau<br>PTC857<br>GBA-PD<br>PTC518 HD<br>Splicing Virology<br>• AADC, aromatic L-amino acid decarboxylase deficiency; AML; acute myeloid leukemia; COVID-19, coronavirus disease 2019; DIPG, diffuse intrinsic pontine glioma; FA, Friedreich’s ataxia; GBA, glucocerebrosidase; HD, Huntington‘s disease; IRD, inherited retinal dystrophy;<br>LMS, leiomyosarcoma; ME, Mitochondrial Epilepsy; PD, Parkinson’s disease; PKU, phenylketonuria; SCA-3, spinocerebellar ataxia type 3.<br>SCIENTIFIC PLATFORMS and RESEARCH<br>Potential registrational studies<br>Angelman<br>IRDs<br>Cog Disorders<br>FA |
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| Enduring<br>Innovation<br>Engine<br>6 |
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| Diversified Platform Drives Strong Portfolio<br>7<br>Clinical<br>Commercial<br>Research<br>Nonsense<br>Mutation<br>LatAm<br>Commercial Deflazacort<br>Gene<br>Therapy Bio-e Metabolic Oncology<br>US Ataluren<br>PTC-AADC<br>Emvododstat<br>AML<br>Unesbulin DIPG<br>Unesbulin LMS<br>Vatiquinone<br>MDAS<br>Vatiquinone<br>FA<br>PTC923 PKU Emvododstat<br>COVID-19<br>SCA-3<br>Undisclosed MAP-Tau<br>PTC518 HD<br>Splicing Virology<br>• AADC-d, aromatic L-amino acid decarboxylase deficiency; AML; acute myeloid leukemia; COVID-19, coronavirus disease 2019; DIPG, diffuse intrinsic pontine glioma; FA, Friedreich’s ataxia; GBA, glucocerebrosidase; HD, Huntington‘s disease; IRD, inherited retinal dystrophy;<br>LMS, leiomyosarcoma; ME, Mitochondrial Epilepsy; PD, Parkinson’s disease; PKU, phenylketonuria; SCA-3, spinocerebellar ataxia type 3.<br>SCIENTIFIC PLATFORMS and RESEARCH<br>Potential registrational studies<br>Angelman<br>IRDs<br>Cog Disorders<br>FA<br>PTC857<br>GBA-PD |
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| 15-Lipoxygenase is a Key Regulator of Inflammation and<br>Oxidative Stress Pathways in CNS Diseases<br>Glial Cell<br>Activation &<br>Inflammation<br>Oxidative Stress<br>Mediated<br>Membrane<br>Damage<br>15-Lipoxygenase<br>Alpha-synuclein<br>Oxidation<br>& Aggregation<br>Glutathione<br>Oxidation &<br>Depletion<br>8<br>Lipid<br>signaling<br>molecule that<br>regulates<br>fundamental<br>disease<br>processes<br>O<br>OH<br>O<br>OH<br>O<br>OH<br>Arachidonic acid 15-OOH-Arachidonic acid 15(S)-HpETE*<br>15-lipoxygenase O2<br>- |
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| 15-Lipoxygenase is a Key Regulator of Inflammation and<br>Oxidative Stress Pathways in Refractory Epilepsies<br>9<br>O<br>OH<br>O<br>OH<br>O<br>OH Polyunsaturated Fatty<br>Acids<br>Oxidized Fatty<br>Acids<br>Activated<br>Enzyme 15-LO<br>Oxidative stress<br>activates enzyme<br>e<br>e e e<br>ee<br>e<br>e<br>ee e e<br>e<br>e<br>e<br>e e e e<br>e<br>e e e e e e e<br>ee<br>XX<br>O2<br>-<br>Diseased<br>Mitochondria<br>Healthy<br>Mitochondria<br>Increased<br>inflammation &<br>oxidative stress<br>Decreased<br>cellular viability &<br>neurological<br>function |
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| O<br>OH<br>O<br>OH<br>Oxidized Fatty Acids<br>Enzyme<br>Polyunsaturated Fatty<br>Acids<br>O<br>OH<br>Bio-e Platform is a Novel Approach to Treating Rare<br>Disorders<br>Polyunsaturated<br>Fatty Acids<br>Oxidized<br>Fatty Acids Activated<br>Enzyme<br>Oxidative stress<br>cellular viability &<br>neurological<br>function<br>inflammation &<br>oxidative stress<br>decreased increased<br>10<br>• Bio-e platform targets a<br>family of oxidoreductase<br>enzymes critical to<br>generation and regulation<br>of energy key to disease<br>pathology<br>• Dysregulation of this<br>pathway results in several<br>CNS disease pathologies<br>including epilepsy<br>• 15-lipoxygenase is a well-<br>known regulator key to<br>CNS and other diseases |
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| Enzyme<br>Polyunsaturated Fatty<br>Acids<br>O<br>OH<br>Bio-e Platform is a Novel Approach to Treating Rare<br>Disorders<br>Polyunsaturated<br>Fatty Acids<br>Oxidized<br>Fatty Acids Activated<br>Enzyme<br>Oxidative stress<br>Inhibited<br>11<br>PTC Compounds<br>O<br>O<br>HO<br>• Bio-e platform targets a<br>family of oxidoreductase<br>enzymes critical to<br>generation and regulation<br>of energy key to disease<br>pathology<br>• Dysregulation of this<br>pathway results in several<br>CNS disease pathologies<br>including epilepsy<br>• 15-lipoxygenase is a well-<br>known regulator key to<br>CNS and other diseases cellular viability &<br>neurological<br>function<br>inflammation &<br>oxidative stress<br>increased decreased |
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| 12<br>MIT-E:<br>Registrational trial of<br>vatiquinone<br>for Mitochondrial<br>Disease Associated<br>Seizures |
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| Mitochondrial Disease Associated Seizures is a Highly<br>Morbid Disorder with High Unmet Medical Need<br>Disease<br>• Mitochondrial disease associated seizures is the highly morbid<br>condition of refractory seizures in patients with inherited<br>mitochondrial disease<br>Current Treatments<br>• No approved disease modifying treatments for mitochondrial<br>disease associated seizures<br>Opportunity<br>• Vatiquinone targets the energetic and oxidative stress pathways<br>that underpin seizures in these patients<br>~20,000<br>Global<br>Prevalence<br>13 |
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| Vatiquinone Reduced Seizure Frequency and Improved<br>Neurological Function in Mitochondrial Disease<br>Associated Seizures Patients<br>14<br>Disruption of refractory status epilepticus<br>Reduction in seizure frequency<br>Decrease in seizure-related<br>hospitalizations<br>Decrease in disease-related mortality<br>risk<br>Data from previous<br>studies<br>demonstrate a<br>positive effect on<br>seizures and<br>seizure related-<br>morbidity across<br>multiple disease<br>subtypes |
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| Vatiquinone has Potential to Show Clinically<br>Differentiated Improvement for Mitochondrial<br>Disease Associated Seizures Patients<br>15<br>Primary Endpoint<br>Change from baseline in<br>frequency of observable motor<br>seizures<br>PTC743 (vatiquinone)<br>Placebo<br>N = 30 (planned)<br>24 weeks<br>R<br>N = 30 (planned)<br>48 weeks<br>PTC743 (vatiquinone)<br>N = 60 (planned)<br>Open-Label Extension Placebo-Controlled<br>~15 sites globally<br>Primary Endpoint<br>Trial Status<br>• Enrolling<br>• Data expected 3Q 2022 |
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| 16<br>MOVE-FA:<br>Registrational trial<br>of vatiquinone for<br>Friedreich Ataxia |
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| Friedreich Ataxia is a Highly Morbid, Neuromuscular<br>Disorder with no Approved Therapy<br>Disease<br>• Friedreich ataxia (FA) is a rare, inherited, progressive disease<br>resulting from mitochondrial dysfunction that mainly affects<br>the central nervous system and the heart<br>Current Treatments<br>• No approved disease modifying therapies<br>Opportunity<br>• Vatiquinone is a potent protector of oxidative stress-mediated cell<br>death in FA patients<br>~25,000<br>Global<br>prevalence<br>17 |
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| Vatiquinone Demonstrated Significant Improvement in<br>Long-term Disease Severity & Neurological Function in<br>Friedreich Ataxia Patients<br>Clinical Study Summary<br>• Double-blind, placebo-controlled with<br>delayed start<br>• N=63 subjects<br>• Three US clinical sites<br>• Key endpoint: FA disease rating scale<br>(FARS)<br>18<br>-1<br>-2<br>-3<br>2<br>1<br>0<br>4<br>3<br>5<br>6<br>Natural History<br>Cohort<br>Vatiquinone<br>p<0.001<br>24<br>-<br>month change in FARS score<br>18 |
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| Vatiquinone has the Potential to Provide<br>Improvement in Neurological Function<br>19<br>Primary and Key Secondary<br>Endpoints<br>Change from baseline in the<br>Modified FA Rating Scale<br>(mFARS) Score at Week 72<br>Improvement in activities of<br>daily living (FA-ADL)<br>Open-Label Extension Placebo-Controlled<br>PTC743 (vatiquinone)<br>Placebo<br>N = ~60<br>72 weeks<br>R<br>N = ~60<br>24 weeks<br>PTC743 (vatiquinone)<br>N = ~120<br>Primary Endpoint<br>~10 sites globally<br>Trial Status<br>• Enrolling<br>• Data expected in 2023 |
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| Diversified Platform Drives Strong Portfolio<br>20<br>Clinical<br>Commercial<br>Research<br>Nonsense<br>Mutation<br>LatAm<br>Commercial Deflazacort<br>Gene<br>Therapy Bio-e Metabolic Oncology<br>US Ataluren<br>PTC-AADC<br>Emvododstat<br>AML<br>Unesbulin DIPG<br>Unesbulin LMS<br>Vatiquinone<br>MDAS<br>Vatiquinone<br>FA<br>PTC923 PKU Emvododstat<br>COVID-19<br>SCA-3<br>Undisclosed<br>MAP-Tau<br>PTC857<br>GBA-PD<br>PTC518 HD<br>Splicing Virology<br>• AADC, aromatic L-amino acid decarboxylase deficiency; AML; acute myeloid leukemia; COVID-19, coronavirus disease 2019; DIPG, diffuse intrinsic pontine glioma; FA, Friedreich’s ataxia; GBA, glucocerebrosidase; HD, Huntington‘s disease; IRD, inherited retinal dystrophy;<br>LMS, leiomyosarcoma; ME, Mitochondrial Epilepsy; PD, Parkinson’s disease; PKU, phenylketonuria; SCA-3, spinocerebellar ataxia type 3.<br>SCIENTIFIC PLATFORMS and RESEARCH<br>Potential registrational studies<br>Angelman<br>IRDs<br>Cog Disorders<br>FA |
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| 21<br>APHENITY:<br>Registrational trial<br>of PTC923 for<br>Phenylketonuria<br>(PKU) |
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| Phenylketonuria is a Serious Metabolic Condition with<br>High Unmet Medical Need<br>~58,000<br>Global<br>prevalence<br>Disease<br>• Phenylketonuria is a metabolic condition caused by mutations to<br>phenylalanine hydroxylase that can lead to cognitive disabilities and seizures<br>Current Treatments<br>• Majority of patients do not initially respond or are not well controlled by<br>standard of care<br>Opportunity<br>• PTC923 can potentially treat a broad population and is more effective than<br>exogenously administered synthetic BH4 in increasing the intracellular levels<br>of natural tetrahydrobiopterin<br>22 |
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| Majority of PKU Patients not Addressed by Current<br>Therapies<br>23<br>~ 25-30%<br>of<br>diagnosed<br>patients<br>~60-75%<br>of<br>diagnosed<br>patients<br>Up to 70% of<br>Kuvan<br>Failure<br>Up to 60% of<br>Initial<br>Responders<br>Are Poorly<br>controlled on<br>Kuvan<br>Up to<br>30% of<br>diagnosed<br>patients |
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| PTC923 Demonstrated Statistically Significant Differences<br>in Reduction of Phenylalanine (Phe) Compared to Kuvan in<br>Phase 2 Study<br>24<br>p< 0.0001 |
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| APHENITY is a Global Registrational<br>Trial of PTC923 for Phenylketonuria<br>25<br>R<br>PTC923<br>Placebo<br>Primary Endpoint<br>Reduction in blood of<br>phenylalanine levels<br>42 Days<br>~12 sites in 15-19 countries<br>Open-Label Extension Placebo-Controlled<br>PTC923<br>12<br>Months<br>Primary Endpoint<br>Trial Status<br>• Initiated in 3Q 2021<br>• Data expected YE 2022 |
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| Diversified Platform Drives Strong Portfolio<br>26<br>Clinical<br>Commercial<br>Research<br>Nonsense<br>Mutation<br>LatAm<br>Commercial Deflazacort<br>Gene<br>Therapy Bio-e Metabolic Oncology<br>US Ataluren<br>PTC-AADC<br>Emvododstat<br>AML<br>Unesbulin DIPG<br>Unesbulin LMS<br>Vatiquinone<br>MDAS<br>Vatiquinone<br>FA<br>PTC923 PKU Emvododstat<br>COVID-19<br>SCA-3<br>Undisclosed<br>MAP-Tau<br>PTC857<br>GBA-PD<br>PTC518 HD<br>Splicing Virology<br>• AADC, aromatic L-amino acid decarboxylase deficiency; AML; acute myeloid leukemia; COVID-19, coronavirus disease 2019; DIPG, diffuse intrinsic pontine glioma; FA, Friedreich’s ataxia; GBA, glucocerebrosidase; HD, Huntington‘s disease; IRD, inherited retinal dystrophy;<br>LMS, leiomyosarcoma; ME, Mitochondrial Epilepsy; PD, Parkinson’s disease; PKU, phenylketonuria; SCA-3, spinocerebellar ataxia type 3.<br>SCIENTIFIC PLATFORMS and RESEARCH<br>Potential registrational studies<br>Angelman<br>IRDs<br>Cog Disorders<br>FA |
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| 27<br>PTC518:<br>Program for<br>Huntington<br>Disease |
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| Huntington Disease is a Debilitating Neurological<br>Disorder with No Available Disease Modifying Treatments<br>Disease<br>• Huntington disease is a progressive brain disorder that causes<br>uncontrolled movements and cognitive loss<br>Current Treatments<br>• No approved disease modifying therapies<br>Opportunity<br>• PTC518 reduces HTT protein in Huntington disease<br>~135,000<br>Global<br>prevalence<br>28 |
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| Small Molecules Have a Critical Advantage for Pan Brain<br>Distribution<br>29<br>HD Healthy<br>Goh et al. Aus Psychiatry. 2018 |
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| Identification of a Novel Approach to Lower HTT<br>30<br>HTT patient<br>Ex 1 Ex Y Ex X<br>Favored mRNA<br>Ex 1 Ex Y Ex X<br>Leads to toxic HTT protein<br>(CAG)>35 |
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| Identification of a Novel Approach to Lower HTT<br>31<br>HTT patient<br>Ex 1 Ex Y Ex X<br>Favored mRNA<br>Ex 1 Ex Y Ex X<br>Leads to toxic HTT protein<br>(CAG)>35<br>Degraded through<br>translation-linked<br>mRNA decay<br>Ex 1 Ex Y Ex X<br>Mutant toxic<br>HTT protein lowering<br>Ex 1 Ex Y Ex X<br>(CAG)>35<br>Small molecule assisted<br>exon definition |
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| PTC518 Has Broad Tissue Distribution with Strong<br>Correlation between Brain and Blood<br>32<br>120<br>100<br>80<br>60<br>40<br>20<br>0<br>Vehicle 1 3 7 21 63<br>Brain<br>% HTT Remaining<br>Dose dependent HTT lowering in the brain in BACHD mice<br>Brain and blood HTT lowering<br>Dose (mg/kg)<br>*Data on file from multiple studies<br>Measurements demonstrate uniform HTT lowering across brain regions with ~1:1 brain and blood concentrations*<br>120<br>100<br>80<br>60<br>40<br>20<br>0<br>Vehicle 7 mg/kg<br>120<br>100<br>80<br>60<br>40<br>20<br>0<br>Vehicle 7 mg/kg<br>120<br>100<br>80<br>60<br>40<br>20<br>0<br>Vehicle 7 mg/kg<br>Striatum Cortex Cerebellum<br>% HTT Remaining<br>% HTT Remaining<br>% HTT Remaining<br>Vehicle Brain WBC<br>0<br>20<br>40<br>60<br>80<br>100<br>120<br>%<br><br>H<br>T<br>T<br><br>R<br>e<br>m<br>a<br>i<br>n<br>i<br>n<br>g<br>Treated |
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| The Phase 1 Trial is a 4-Part Study<br>33<br>Phase 1 trial<br>in healthy<br>volunteers is<br>ongoing<br>Multiple ascending dose<br>• Up to 5 cohorts of 8 healthy volunteers (6 active and 2 placebo)<br>• Evaluate safety & tolerability; HTT mRNA splicing & protein<br>lowering<br>Food effect<br>• Evaluate the effects of food on PTC518 pharmacokinetics<br>CSF sampling<br>• Evaluate pharmacokinetics of PTC518 in the CSF<br>• Compare drug levels in CSF with plasma compartment<br>Single ascending dose<br>• Five cohorts of 8 healthy volunteers (6 active and 2 placebo)<br>• Evaluate safety & tolerability; HTT mRNA splicing |
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| 34<br>SAD Study: Proof of Mechanism of PTC518 Demonstrated<br>By Dose-Dependent HTT Splicing<br>Placebo<br>PTC518_45 m<br>g<br>PTC518_90 m<br>g<br>PTC518_135 m<br>g<br>0<br>20<br>40<br>60<br>80<br>100<br>120<br>%<br><br>o<br>f<br><br>b<br>a<br>s<br>e<br>l<br>i<br>n<br>e<br><br>H<br>T<br>T<br><br>R<br>N<br>A<br>➢ Whole blood HTT splicing in humans<br>➢ Doses evaluated = 45 mg, 90 mg, and 135 mg<br>➢ Time – one day; single dose; splicing evaluated 24h post dose<br>Data on file PTC518 -CNS- 001- HD |
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| 35<br>MAD Study: Proof of Mechanism of PTC518 Confirmed By<br>Dose-Dependent HTT Splicing<br>➢ Whole blood HTT splicing in humans<br>➢ Doses evaluated = 15 mg and 30 mg<br>➢ Time – Day 14; multiple doses; splicing evaluated 6h post dose on day 14<br>Placebo<br>PTC518_15 m<br>g<br>PTC518_30 m<br>g<br>0<br>20<br>40<br>60<br>80<br>100<br>120<br>%<br><br>o<br>f<br><br>b<br>a<br>s<br>e<br>l<br>i<br>n<br>e<br><br>H<br>T<br>T<br><br>R<br>N<br>A<br>Data on file PTC518 -CNS- 001- HD |
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| Diversified Platform Drives Strong Portfolio<br>36<br>Clinical<br>Commercial<br>Research<br>Nonsense<br>Mutation<br>LatAm<br>Commercial Deflazacort<br>Gene<br>Therapy Bio-e Metabolic Oncology<br>US Ataluren<br>PTC-AADC<br>Emvododstat<br>AML<br>Unesbulin DIPG<br>Unesbulin LMS<br>Vatiquinone<br>MDAS<br>Vatiquinone<br>FA<br>PTC923 PKU Emvododstat<br>COVID-19<br>SCA-3<br>Undisclosed MAP-Tau<br>PTC857<br>GBA-PD<br>PTC518 HD<br>Splicing Virology<br>• AADC, aromatic L-amino acid decarboxylase deficiency; AML; acute myeloid leukemia; COVID-19, coronavirus disease 2019; DIPG, diffuse intrinsic pontine glioma; FA, Friedreich’s ataxia; GBA, glucocerebrosidase; HD, Huntington‘s disease; IRD, inherited retinal dystrophy;<br>LMS, leiomyosarcoma; ME, Mitochondrial Epilepsy; PD, Parkinson’s disease; PKU, phenylketonuria; SCA-3, spinocerebellar ataxia type 3.<br>SCIENTIFIC PLATFORMS and RESEARCH<br>Potential registrational studies<br>Angelman<br>IRDs<br>Cog Disorders<br>FA |
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| Treating Rare Monogenic Disorders<br>with Targeted Gene Therapy<br>37<br>Potential advantages of targeted<br>therapy<br>• Local administration lowers systemic<br>immunogenicity and exposure<br>• Low turnover cells may lead to improved<br>durability<br>• Leveraging stereotactic neurosurgery<br>technologies to enable precise and accurate<br>delivery<br>• Lead treatment for AADC-d, pipeline includes<br>FA and AS |
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| Gene Therapy Has the Potential to Provide Significant<br>Benefit to AADC Patients<br>Disease<br>• Aromatic L-amino acid decarboxylase deficiency (AADC-d) is a<br>rare highly morbid and fatal childhood disease. Children with<br>severe AADC deficiency never achieve motor development<br>milestones<br>Current Treatments<br>• No disease modifying therapies approved<br>Opportunity<br>• Potential for AADC gene therapy to become standard of care.<br>Patients can achieve motor and cognitive long-term improvement<br>~5,000<br>Global<br>prevalence<br>38 |
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| PTC-AADC Treated Patients Make Significant and Sustainable<br>Progress<br>39<br>Age 2 Age 3 Age 4.5<br>Untreated Post-Treatment |
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| Preparing for PTC’s First Gene Therapy Launch<br>40<br>US Regulatory<br>PTC-AADC BLA<br>submission expected<br>in 1Q22<br>Treatment Centers<br>Identification and<br>preparation of expert<br>pediatric<br>neurosurgical centers<br>Patient Finding<br>Ongoing patient<br>finding targeting 300<br>patients identified at<br>launch<br>EU Regulatory<br>The CHMP has recently<br>asked for additional<br>manufacturing<br>bioanalytical data in<br>support of the MAA. We<br>expect to provide the<br>additional data in the first<br>quarter of 2022 and now<br>expect an opinion from the<br>CHMP shortly after that. |
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| Providing<br>Patients<br>Access to<br>Transformative<br>Treatments<br>41 |
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| Global Geographic Presence Supports Growing Product<br>Portfolio<br>42<br>>1,000<br>employees<br>Offices in<br>20 countries<br>Footprint in<br>>50 countries |
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| DMD Commercial Franchise – A Growing Global Business<br>43 |
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| DMD Commercial Franchise – A Growing Global Business<br>44<br>• YE 2020 net product<br>revenue of $192M<br>• Treatment for nonsense<br>mutation DMD for ages 2<br>and older<br>• Distributed in over 50<br>countries worldwide<br>• Data from Study 041<br>expected 3Q22 |
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| DMD Commercial Franchise – A Growing Global Business<br>45<br>• YE 2020 net product<br>revenue of $192M<br>• Treatment for nonsense<br>mutation DMD for ages 2<br>and older<br>• Distributed in over 50<br>countries worldwide<br>• Data from Study 041<br>expected 3Q22<br>• YE 2020 net product<br>revenue of $139M<br>• First and only corticosteroid<br>approved for DMD<br>• Approved for all DMD<br>patients in the US >2yrs<br>• Data from multiple<br>publications demonstrate<br>Emflaza’s clinical benefit<br>over prednisone |
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| Continued Strong DMD Franchise Growth<br>USD millions<br>34<br>81<br>145 171 190<br>29<br>92<br>101<br>2019 2020 2017 2015 2016 2018<br>263<br>174<br>331 +58% 291<br>Emflaza Net Sales<br>Translarna Net Sales<br>139<br>192<br>46 |
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| Evrysdi’s Strong Global Launch Brings Therapy to SMA<br>Patients with High Unmet Need<br>47<br>Patients treated across all SMA types<br>Patients are treatment-naïve or switching<br>from both Spinraza and Zolgensma<br>Broadest range of age treated<br>Differentiated product for SMA patients<br>• The first at-home, oral treatment for SMA<br>• Global approvals and regulatory<br>submissions<br>• EMA approval in 1Q21<br>• Japanese approval in 2Q21<br>Significant milestones ahead<br>• Potential $300 million in sales milestones<br>• ~15% tiered royalty on global sales |
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| Multiple Platforms Provide Opportunity to Treat Over<br>500,000 Patients by 2030<br>48<br>DMD<br>SMA<br>AADC<br>~50K<br>ME<br>~20K<br>PKU<br>~58K<br>FA<br>~25K<br>HD<br>~135K<br>GBA-PD<br>~190K<br>AS<br>~75K<br>2021 2030<br>AADC |
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| Strong Financial Performance Supports Future Growth<br>49<br>Net Product<br>Revenue<br>$333M<br>DMD Franchise<br>Net Product Net<br>Revenue<br>$331M $1.1B<br>Year-end Cash<br>Position<br>2020 |
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| Strong Financial Performance Supports Future Growth<br>50<br>DMD Franchise<br>Net Product<br>Revenue Guidance<br>$400-420M<br>OPEX<br>Guidance*<br>$715-735M<br>Net Product<br>Revenue<br>$333M<br>DMD Franchise<br>Net Product Net<br>Revenue<br>$331M<br>2020 2021<br>$1.1B<br>Year-end Cash<br>Position<br>*Non-GAAP measure which excludes estimated non-cash, stock-based compensation expense of approximately $100 million. GAAP R&D<br>and SG&A expense for the full year 2021 is anticipated to be between $815 and $835 million. |
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| 2021 Potential Milestones to Generate Value<br>51<br>PTC857<br>Data<br>PTC518<br>Data<br>Evrysdi<br>CHMP<br>Opinion<br>PTC518<br>Phase 2<br>Study<br>Initiation<br>Unesbulin<br>LMS and<br>DIPG<br>Data<br>PTC923<br>PKU P3<br>Trial<br>Emvododstat<br>COVID-19<br>Enrollment<br>Complete<br>1H 2021 2H 2021 |
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| PTC has Built a Strong, Sustainable Company to Execute<br>on our Mission<br>52<br>Proven<br>groundbreaking<br>science<br>Enduring<br>innovation<br>engine<br>Providing<br>patients access<br>to<br>transformative<br>treatments<br>Culture<br>Operational Excellence |
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| Translating Science to Transform Lives<br>53 |
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