8-K
PTC THERAPEUTICS, INC. (PTCT)
8-K
2021-09-23
For: 2021-09-23
View Original
Added on
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): September 23, 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.
As previously announced, PTC Therapeutics, Inc. (the “Company”) will host a conference call on September 23, 2021 at 8:00 a.m. eastern time. During this conference call, the Company expects to discuss the results from the PTC518 Phase 1 healthy volunteer study and provide an update on the PTC518 Phase 2 study, to be conducted in Huntington’s disease patients. A copy of the slide deck that will be presented during the conference call is attached as Exhibit 99.1.
The information in this Report (including Item 7.01 and 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
| | | |
|---|---|---|
| Exhibit No. | Description | |
| 99.1 | | Corporate Presentation – PTC518 Huntington’s Disease Program Update |
| 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: September 23, 2021 | By: | /s/ Emily Hill |
| | Name: | Emily Hill |
| | Title: | Chief Financial Officer |
Exhibit 99.1
| PTC518 Huntington’s<br>Disease Program<br>Update<br>September 23, 2021 |
|---|
| Forward Looking Statements:<br>This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements<br>contained in this release, other than statements of historic fact, are forward-looking statements, including statements regarding: the future<br>expectations, plans and prospects for PTC, including with respect to the expected timing of clinical trials and studies, availability of data and other<br>matters; PTC's strategy, future operations, future financial position, future revenues, projected costs; and the objectives of management. Other<br>forward-looking statements may be identified by the words "guidance", "plan," "anticipate," "believe," "estimate," "expect," "intend," "may," "target,"<br>"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<br>as a result of a variety of risks and uncertainties, including those related to: the outcome of pricing, coverage and reimbursement negotiations with<br>third party payors for PTC's products or product candidates that PTC commercializes or may commercialize in the future; the enrollment, conduct,<br>and results of PTC518 clinical studies for HD; 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 potential of PTC's products and<br>product candidates; PTC's scientific approach and general development progress; and the factors discussed in the "Risk Factors" section of PTC's<br>most recent Annual Report on 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<br>are urged to carefully consider all such factors.<br>As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new<br>products. There are no guarantees that any product will receive or maintain regulatory approval in any territory, or prove to be commercially<br>successful.<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<br>to update or revise any such forward-looking statements to reflect actual results or changes in plans, prospects, assumptions, estimates or<br>projections, or other circumstances occurring after the date of this presentation except as required by law.<br>2 |
| --- |
| MAPT-Tauopathies<br>ATXN3-SCA3<br>Undisclosed target 1<br>Undisclosed target 2<br>Undisclosed target 3<br>Undisclosed target 4<br>Undisclosed target 5<br>5’ Splice Site<br>3’ Splice Site<br>3<br>HTrnaSeq<br>HTSpliceoseq<br>Nanostring Plex Screen<br>Identify Splice<br>Site targets<br>Identification of<br>splicing compounds Preclinical Pipeline Clinical Target<br>Pipeline<br>Approved<br>Drug<br>Familial Dysautonomia<br>IKBKAP<br>Huntington’s Disease<br>HTT<br>Spinal Muscular<br>Atrophy - SMN<br>Small Molecule Splicing Modulation Platform |
| --- |
| Evrysdi™ (risdiplam) Roadmap to Success<br>4<br>Highly selective<br>Orally bioavailable<br>and penetrates<br>blood brain barrier<br>Broad tissue<br>distribution in<br>animal models<br>Defined blood<br>to brain<br>exposure ratio<br>Proof of splicing<br>mechanism<br>demonstrated<br>in P1 HV<br>Evrysdi™<br>clinical benefit<br>established |
| --- |
| PTC518 Huntington’s Disease Program Update Agenda<br>5<br>Huntington’s<br>Disease<br>Program<br>PTC518 Phase 2 Study Design<br>Splicing and Huntington’s<br>Disease<br>PTC518 Phase 1 Study Results |
| --- |
| Huntington’s Disease Is a Debilitating Neurodegenerative<br>Disorder with No Available Disease Modifying Treatments<br>Huntington’s Disease<br>• Caused by a monogenic defect;<br>autosomal dominant inheritance<br>• Leads to movement, psychiatric<br>and cognitive disorders<br>• 135,000 patients worldwide<br>Current Treatments<br>• No approved disease<br>modifying therapies |
| --- |
| HD Is a Monogenic Gain of Function Disorder and<br>Lowering HTT Targets The Root Cause of Pathogenesis<br>Modified from Tabrizi,S. Cell.2019. 7<br>Toxic gain of function mutation<br>Expansion of CAG repeat in<br>huntingtin (HTT) gene<br>Huntington’s disease<br>Whole brain atrophy<br>HTT protein aggregates<br>Therapeutic approach:<br>Make less HTT<br>NUCLEUS CYTOSOL<br>HTT<br>DNA<br>HTT<br>mRNA<br>HTT<br>pre-mRNA<br>Transcription Splicing Nuclear<br>export<br>Translation<br>mHTT<br>protein |
| --- |
| Multiple models demonstrate<br>partial reduction of wild type<br>HTT is well tolerated<br>HTT reduction correlates with<br>clinical benefit<br>Modified from Tabrizi,S. Cell.2019. 8<br>Toxic gain of function mutation<br>Expansion of CAG repeat in<br>huntingtin (HTT) gene<br>Huntington’s disease<br>Whole brain atrophy<br>HTT protein aggregates<br>Therapeutic approach:<br>Make less HTT<br>HD Is a Monogenic Gain of Function Disorder and<br>Lowering HTT Targets The Root Cause of Pathogenesis |
| --- |
| Identification of a Novel Splicing Mechanism that Leads to<br>Degradation of Mutant HTT mRNA<br>9<br>With PTC518<br>Pseudoexon is spliced in;<br>Nonsense mutation leads<br>to mRNA degradation<br>No compound<br>Pseudoexon is not spliced in;<br>full length HTT protein is produced<br>Exon 49 Exon 50 psiExon<br>5’ss 3’ss<br>Exon 49 Exon 50<br>STOP<br>Exon 49 Exon 50 psiExon<br>Nonsense-mediated HTT mRNA decay |
| --- |
| Characteristics of PTC518 Were Demonstrated in<br>Preclinical Studies<br>10<br>Orally bioavailable and<br>penetrates blood brain barrier<br>Reduces HTT mRNA and<br>protein in the CNS and periphery<br>Reversible and titratable<br>Uniform lowering in key<br>regions of the brain<br>Not effluxed<br>Highly selective |
| --- |
| PTC518 Phase 1<br>Healthy<br>Volunteer Study |
| --- |
| The PTC518 Phase 1 Trial Was a 4-Part Study<br>12<br>Phase 1 trial<br>in healthy<br>volunteers<br>Multiple ascending dose longer duration:<br>HTT mRNA splicing & protein lowering<br>CSF sampling:<br>Evaluate pharmacokinetics of PTC518 in the CSF<br>Compare drug levels in CSF with plasma compartment<br>Food effect:<br>Evaluate the effects of food on PTC518 pharmacokinetics<br>Preliminary Results:<br>Single and multiple ascending dose:<br>Evaluate safety & tolerability; HTT mRNA splicing |
| --- |
| Data on file PTC518- CNS- 001- HD 13<br>Proof of Mechanism of PTC518 Was Confirmed By Dose-<br>Dependent HTT mRNA Splicing in Healthy Volunteers<br>• Whole blood HTT splicing in humans<br>• Doses evaluated = 15 mg and 30 mg<br>• Time – Day 14; multiple doses;<br>splicing evaluated 6h post dose on day 14<br>MAD Study<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>• Whole blood HTT splicing in humans<br>• Doses evaluated = 5mg, 15mg, 45 mg, 90 mg, and 135 mg<br>• Time – one day; single dose; splicing evaluated 24h post dose<br>SAD Study<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 |
| --- |
| MAD showed long<br>drug half-life with<br>maintenance of<br>splicing up to 72 hours<br>following last dose<br>Dose-dependent<br>splicing of<br>HTT mRNA<br>Predictable<br>pharmacology<br>Well tolerated<br>Phase 1 SAD & MAD Interim Results Showed That PTC518<br>Reduced HTT mRNA in a Dose-Dependent Manner<br>14 |
| --- |
| Decay Rates Can Be Modeled To Predict Drug-Dependent<br>Decrease in mRNA and Protein Concentration Over Time<br>15<br>time<br>concentration<br>1 Initial steady state:<br>100% HTT mRNA & protein<br>4 New steady state reached:<br>50% HTT mRNA & protein<br>3 50% HTT protein produced:<br>HTT protein T½ is longer<br>than T½ HTT mRNA<br>2 Add splicing<br>drug [PTC518]:<br>target dose where 50% of new<br>mRNA will contain STOP-exon<br>50% HTT mRNA<br>+<br>50% STOP-exon (degraded) |
| --- |
| PTC518 Is Predicted to Achieve Equivalent HTT mRNA and Protein<br>Reduction at Steady-State<br>16<br>0 2 4 6 8 10 12 14 16 18 20 22<br>0<br>20<br>40<br>60<br>80<br>100<br>HTT mRNA abundance<br>Steady state lowering should reach within 1 week<br>Days<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>0 7 14 21 28 35 42<br>0<br>20<br>40<br>60<br>80<br>100<br>HTT protein abundance<br>Steady state lowering should take ≥6 weeks<br>Days<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>P<br>r<br>o<br>t<br>e<br>i<br>n<br>Data on file |
| --- |
| 0 7 14 21 28 35 42<br>0<br>20<br>40<br>60<br>80<br>100<br>HTT protein abundance<br>Steady state lowering should take ≥6 weeks<br>Days<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>P<br>r<br>o<br>t<br>e<br>i<br>n<br>PTC518<br>Simulation<br>PTC518 Is Predicted to Achieve Equivalent HTT mRNA and Protein<br>Reduction at Steady-State<br>Data on file 17<br>0 2 4 6 8 10 12 14 16 18 20 22<br>0<br>20<br>40<br>60<br>80<br>100<br>HTT mRNA abundance<br>Steady state lowering reached within 1 week<br>Days<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>PTC518<br>Simulation |
| --- |
| The PTC518 Phase 1 Trial Was a 4-Part Study<br>18<br>Phase 1 trial<br>in healthy<br>volunteers<br>Multiple ascending dose longer duration:<br>HTT mRNA splicing & protein lowering<br>CSF sampling:<br>Evaluate pharmacokinetics of PTC518 in the CSF<br>Compare drug levels in CSF with plasma compartment<br>Food effect:<br>Evaluate the effects of food on PTC518 pharmacokinetics<br>Preliminary Results:<br>Single and multiple ascending dose:<br>Evaluate safety & tolerability; HTT mRNA splicing |
| --- |
| PTC518 Crosses the Blood Brain Barrier in<br>Non-Human Primates and Humans<br>Data on file 19<br>1.0 1.5 2.0 2.5<br>2<br>4<br>6<br>8<br>10<br>Human plasma-CSF correlation<br>Free drug plasma concentration (ng/mL)<br>C<br>S<br>F<br><br>(<br>n<br>g<br>/<br>m<br>L<br>)<br>0 5 10 15 20 25<br>0<br>5<br>10<br>15<br>20<br>25<br>Monkey plasma-CSF correlation<br>Free drug plasma concentration (ng/mL)<br>C<br>S<br>F<br><br>(<br>n<br>g<br>/<br>m<br>L<br>) |
| --- |
| The PTC518 Phase 1 Trial Was a 4-Part Study<br>20<br>Phase 1 trial<br>in healthy<br>volunteers<br>Multiple ascending dose longer duration:<br>HTT mRNA splicing & protein lowering<br>CSF sampling:<br>Evaluate pharmacokinetics of PTC518 in the CSF<br>Compare drug levels in CSF with plasma compartment<br>Food effect:<br>Evaluate the effects of food on PTC518 pharmacokinetics<br>Preliminary Results:<br>Single and multiple ascending dose:<br>Evaluate safety & tolerability; HTT mRNA splicing |
| --- |
| The PTC518 Phase 1 Trial Was a 4-Part Study<br>21<br>Phase 1 trial<br>in healthy<br>volunteers<br>Multiple ascending dose longer duration:<br>HTT mRNA splicing & protein lowering<br>CSF sampling:<br>Evaluate pharmacokinetics of PTC518 in the CSF<br>Compare drug levels in CSF with plasma compartment<br>Food effect:<br>Evaluate the effects of food on PTC518 pharmacokinetics<br>Preliminary Results:<br>Single and multiple ascending dose:<br>Evaluate safety & tolerability; HTT mRNA splicing |
| --- |
| PTC518 levels in the<br>CSF are equal to or<br>greater than levels<br>observed in blood<br>Dose-dependent<br>reduction of<br>HTT mRNA<br>and Protein<br>Phase 1 Results Showed That PTC518 Reduced HTT mRNA<br>and Protein in a Dose-Dependent Manner and Passed<br>the Blood Brain Barrier<br>22<br>Predictable<br>pharmacology<br>Well tolerated |
| --- |
| Results Confirm Exposure of PTC518 Can Lead to<br>Clinically Meaningful HTT Reduction mRNA and Protein<br>23<br>What is the Dose? What is the<br>Exposure?<br>What is the<br>Level of HTT<br>Reduction?<br>Demonstrate<br>Clinical Benefit |
| --- |
| PTC518<br>Phase 2 Study<br>Design |
| --- |
| Phase 2 study objectives<br>25<br>Demonstrate safety, tolerability<br>and pharmacology of PTC518<br>and HTT mRNA and protein<br>reduction in HD patients<br>Demonstrate PTC518 effect on blood<br>based, CSF-based and radiographic<br>biomarkers of Huntington’s disease to<br>support potential accelerated approval |
| --- |
| Strategies For Potential FDA Approval<br>26<br>Sub Part H<br>Part D<br>Biomarker Path<br>Clinical Data Path |
| --- |
| 27<br>PTC518 Phase 2 Study –<br>PIVOT HD Planned Study Design<br>12 weeks 1 year Open<br>Label Extension<br>• Double blind, multiple<br>dose, 12-week placebo-<br>controlled study with a<br>long-term open label<br>extension<br>• Global clinical trial<br>• N~100-150 patients<br>• Trial to initiate by<br>YE2021<br>Placebo<br>Dose Level 1<br>Dose Level 2<br>Dose Level 1<br>Dose Level 2<br>Randomized<br>to PTC518<br>Alternative Dose Level<br>R<br>R |
| --- |
| PIVOT HD Endpoint Strategy<br>28<br>• Safety and tolerability of<br>PTC518 in Huntington’s<br>disease patients<br>• Percent reduction in HTT<br>mRNA and protein in blood<br>Primary endpoints<br>• Percent reduction in HTT<br>protein in CSF<br>• Changes in neurofilament<br>light chain (NfL) in plasma<br>and CSF<br>• Change in caudate,<br>putamenal, ventricular<br>volume on volumetric<br>MRI imaging<br>Biomarker endpoints<br>• Changes in clinical<br>scales of motor and<br>cognitive function<br>Clinical endpoints |
| --- |
| Identifying Optimal Clinical Trial Population<br>Finding the Goldilocks Population<br>29<br>• Use natural history to analyze<br>markers of disease progression<br>• Identify best indicators of earlier<br>stage/modifiable disease<br>• Determine target patient population<br>• Select endpoints to capture<br>meaningful clinical benefit |
| --- |
| 30<br>Optimal Endpoints Vary by Disease Stage<br>Percentile of measurement relative to controls<br>TFC<br>Stage 1<br>0<br>50<br>100<br>5<br>SDMT<br>TMS<br>Stage 3 Stage 2<br>Schematic adapted from Natural History Analyses<br>Brain Volume<br>Target<br>Population<br>Too<br>Advanced |
| --- |
| 31<br>PIVOT HD Inclusion Criteria<br>Age 25 years and older<br>Ambulatory<br>CAG repeat 42-50 inclusive<br>Specific clinical and radiographic parameters<br>o Brain volumetric MRI values<br>o Total motor score (TMS)<br>o Cognitive score<br>o Prognostic index of Huntington’s disease<br>(PINHD) |
| --- |
| 32<br>Summary<br>Phase 1 completed with<br>achievement of all study<br>objectives including<br>protein reduction and<br>projected CSF exposure<br>Phase 2 trial to be initiated by YE 2021<br>• Multiple dose placebo-controlled trial of<br>PTC518 in HD patients<br>• Study designed to capture biomarker<br>effects that could potentially support<br>accelerated approval<br>• Inclusion criteria optimized based on<br>extensive natural history data analyses |
| --- |
| Questions |
| --- |