UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
WASHINGTON, D.C. 20549
FORM
CURRENT REPORT
Pursuant to Section 13 or 15(d) of the Securities Exchange Act of 1934
Date of Report (Date of earliest event reported):
(Exact Name of Company as Specified in Charter)
|
| |||
(State or Other Jurisdiction | (Commission | (IRS Employer | ||
of Incorporation) | File Number) | Identification No.) |
| ||
(Address of Principal Executive Offices) | (Zip Code) |
Registrant’s telephone number, including area code: (
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):
Securities registered pursuant to Section 12(b) of the Act:
Title of each class |
| Trading Symbol(s) |
| Name of each exchange on which registered |
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.
PTC Therapeutics, Inc. (the “Company”) will host a conference call on May 17, 2023 at 8:00 a.m. eastern time. During this conference call, the Company expects to discuss the results from its Phase 3 registration-directed clinical trial of sepiapterin for phenylketonuria. Directions on how to access the conference call are included in the press release furnished as Exhibit 99.1 hereto. A copy of the slide deck that will be presented during the conference call is furnished as Exhibit 99.2 hereto.
The information in this Item 7.01 of this Current Report on Form 8-K (“Report”), including Exhibits 99.1 and 99.2, 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 8.01. Other Events.
On May 17, 2023, the Company announced that the primary endpoint was achieved in its Phase 3 registration-directed clinical trial of sepiapterin in adult and pediatric patients with phenylketonuria.
Item 9.01. Financial Statements and Exhibits.
(d) Exhibits
Exhibit No. |
| Description |
99.1 | Press Release, dated May 17, 2023 issued by PTC Therapeutics, Inc. | |
99.2 | ||
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: May 17, 2023 | By: | /s/ Emily Hill |
Name: | Emily Hill | |
Title: | Chief Financial Officer | |
EXHIBIT 99.1
PTC Therapeutics Announces APHENITY Trial Achieved Primary Endpoint
with Sepiapterin in PKU Patients
- Highly statistically significant and clinically meaningful results -
- 63% mean blood Phe reduction in primary analysis population (p<0.0001) -
- Conference call and webcast to be held at 8:00 AM EDT -
SOUTH PLAINFIELD, N.J., May 17, 2023 -- PTC Therapeutics, Inc. (NASDAQ: PTCT) today announced that the primary endpoint was achieved in the APHENITY, Phase 3 registration-directed clinical trial of sepiapterin in adult and pediatric patients with phenylketonuria (PKU).
“The positive results from the APHENITY trial bring us one step closer to providing a therapy that could deliver meaningful benefit to PKU patients,” said Matthew B. Klein, M.D., Chief Executive Officer, PTC Therapeutics. “The Phe reductions observed in the placebo-controlled portion of the study are consistent with, and, in some cases, exceed the magnitude of Phe reductions recorded in the open label portion of the study. We look forward to meeting with regulatory authorities to discuss the path to approval.”
The placebo-controlled portion of the study included 98 patients in the primary analysis population. The mean percent Phe reduction in sepiapterin treated patients was 63%. In the subset of classical PKU patients, the mean percent Phe reduction was 69%. Minimal reductions in Phe levels were observed in the placebo treated patients resulting in a highly statistically significant sepiapterin treatment benefit (p<0.0001). Sepiapterin was generally well tolerated with no serious adverse events.
Today's Conference Call and Webcast
PTC will hold a conference call at 8 AM EDT today to discuss this news. To access the call by phone, please click here to register and you will be provided with dial-in details. To avoid delays, we recommend participants dial in to the conference call 15 minutes prior to the start of the call. The webcast conference call can be accessed on the Investor section of the PTC website at https://ir.ptcbio.com/events-presentations. A replay of the call will be available approximately two hours after completion of the call and will be archived on the company's website for 30 days following the call.
About APHENITY
APHENITY was a global double-blind, placebo-controlled, registration-directed study which enrolled 156 children and adults with PKU. Participants were randomized to receive sepiapterin or placebo for six weeks with the primary endpoint being reduction in blood phenylalanine levels. The trial consisted of two parts. Part 1 was a run-in phase, during which all screened subjects received sepiapterin for two weeks. Only those subjects who demonstrated a reduction in phenylalanine levels of 15% or more from baseline in Part 1 were randomized to receive either sepiapterin or placebo in Part 2 of the clinical trial. The primary analysis population consists of those who had greater than 30% reduction in phenylalanine levels from baseline during Part 1 of the trial. The primary outcome measure is the reduction of blood phenylalanine levels from baseline compared to Weeks 5 and 6 in patients from Part 2 of the clinical trial. All patients are eligible to enroll in an open label long term clinical trial designed to further evaluate the long-term safety and durable effect of sepiapterin.
About Sepiapterin
Sepiapterin (formerly PTC923) is an oral formulation of synthetic sepiapterin, a precursor to intracellular tetrahydrobiopterin, which is a critical enzymatic cofactor involved in the metabolism and synthesis of numerous metabolic products. Sepiapterin is a more bioavailable precursor than exogenously administered synthetic BH4 and has the potential to treat the broad range of PKU patients.
About Phenylketonuria
Phenylketonuria (PKU) is a rare, inherited metabolic disease, which affects the brain.1 It is caused by a defect in the gene that helps create the enzyme needed to break down phenylalanine.1 If left untreated or poorly managed, phenylalanine – an essential amino acid found in all proteins and most foods – can build up to harmful levels in the body. This causes severe and irreversible disabilities, such as permanent
intellectual disability, seizures, delayed development, memory loss, and behavioral and emotional problems.1 Newborns with phenylketonuria initially don’t have any symptoms, but symptoms are usually progressive, and damage caused by toxic levels of phenylalanine in the first few years of life is irreversible.2,3 Diagnosis of phenylketonuria usually takes place during newborn screening programs.4 There are an estimated 58,000 people with phenylketonuria globally.
About PTC Therapeutics, Inc.
PTC is a science-driven, global biopharmaceutical company focused on the discovery, development and commercialization of clinically differentiated medicines that provide benefits to patients with rare disorders. PTC's ability to innovate to identify new therapies and to globally commercialize products is the foundation that drives investment in a robust and diversified pipeline of transformative medicines. PTC's mission is to provide access to best-in-class treatments for patients who have little to no treatment options. PTC's strategy is to leverage its strong scientific and clinical expertise and global commercial infrastructure to bring therapies to patients. PTC believes this allows it to maximize value for all its stakeholders. To learn more about PTC, please visit us at www.ptcbio.com and follow us on Facebook, Instagram, LinkedIn and Twitter at @PTCBio.
For More Information:
Investors:
Kylie O'Keefe
+1 (908) 300-0691
kokeefe@ptcbio.com
Media:
Jeanine Clemente
+1 (908) 912-9406
jclemente@ptcbio.com
Forward-Looking Statement
This press release contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this press release, other than statements of historic fact, are forward-looking statements, including statements with respect to the future expectations, plans and prospects for PTC, including with respect to the expected timing of clinical trials and studies, availability of data, regulatory submissions and responses and other matters, future operations, future financial position, future revenues, projected costs; and the objectives of management. Other forward-looking statements may be identified by the words, "guidance", "plan," "anticipate," "believe," "estimate," "expect," "intend," "may," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions.
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 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 product candidates that PTC commercializes or may commercialize in the future; expectations with respect to potential regulatory submissions and commercialization of sepiapterin for phenylketonuria, or PKU, and potential development and regulatory milestone payments that PTC may be obligated to make with regards to sepiapterin, expectations with respect to the COVID-19 pandemic and related response measures and their effects on PTC's business, operations, clinical trials, regulatory submissions and approvals, and PTC's collaborators, contract research organizations, suppliers and manufacturers; significant business effects, including the effects of industry, market, economic, political or regulatory conditions; changes in tax and other laws, regulations, rates and policies; the eligible patient base and commercial potential of sepiapterin for PKU; PTC's scientific approach and general development progress; the sufficiency of PTC's cash resources and its ability to obtain adequate financing in the future for its foreseeable and unforeseeable operating expenses and capital expenditures; and the factors discussed in the "Risk Factors" section of PTC's 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 are urged to carefully consider all such factors.
As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. There are no guarantees that any product will receive or maintain regulatory approval in any territory, or prove to be commercially successful, including sepiapterin.
The forward-looking statements contained herein represent PTC's views only as of the date of this press release and PTC 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 presentation except as required by law.
References:
| 1. | de Groot MJ, Hoeksma M, Blau N, et al. Mol Genet Metab 2010;99:S86–S89. |
| 2. | Phenylketonuria (PKU). Available at: https://www.mayoclinic.org/diseases-conditions/phenylketonuria/symptoms-causes/syc-20376302. Accessed October 2021. |
| 3. | Blau N, van Spronsen FJ, Levy HL. Lancet 2010;376:1417–1427. |
| 4. | Al Hafid N, Christodoulou J. Transl Pediatr 2015;4(4):304–317. |
| Patient Living with PKU Matthew Klein, M.D. CEO May, 2023 APHENITY Topline Results |
| Forward-Looking Statements 2 This presentation contains forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. All statements contained in this presentation, other than statements of historic fact, are forward-looking statements, including statements with respect to the future expectations, plans and prospects for PTC, including with respect to the expected timing of clinical trials and studies, availability of data, regulatory submissions and responses and other matters, future operations, future financial position, future revenues, projected costs; and the objectives of management. Other forward-looking statements may be identified by the words, "guidance", "plan," "anticipate," "believe," "estimate," "expect," "intend," "may," "target," "potential," "will," "would," "could," "should," "continue," and similar expressions. 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 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 product candidates that PTC commercializes or may commercialize in the future; expectations with respect to potential regulatory submissions and commercialization of sepiapterin for phenylketonuria, or PKU, and potential development and regulatory milestone payments that PTC may be obligated to make with regards to sepiapterin, expectations with respect to the COVID-19 pandemic and related response measures and their effects on PTC's business, operations, clinical trials, regulatory submissions and approvals, and PTC's collaborators, contract research organizations, suppliers and manufacturers; significant business effects, including the effects of industry, market, economic, political or regulatory conditions; changes in tax and other laws, regulations, rates and policies; the eligible patient base and commercial potential of sepiapterin for PKU; PTC's scientific approach and general development progress; the sufficiency of PTC's cash resources and its ability to obtain adequate financing in the future for its foreseeable and unforeseeable operating expenses and capital expenditures; and the factors discussed in the "Risk Factors" section of PTC's 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 are urged to carefully consider all such factors. As with any pharmaceutical under development, there are significant risks in the development, regulatory approval and commercialization of new products. There are no guarantees that any product will receive or maintain regulatory approval in any territory, or prove to be commercially successful, including sepiapterin. 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 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 presentation except as required by law. APHENITY Topline Results |
| APHENITY Topline Results Demonstrate Clinical and Statistically Significant Benefit 3 Achieved primary endpoint in placebo-controlled portion of study with statistically significant (p<0.0001) blood phenylalanine (Phe) reduction Demonstrated substantial Phe reduction in both the overall primary analysis population (63%) and the subset of classical PKU patients (69%) Achieved Phe reduction sufficient to bring 84% of study patients within US guidelines for Phe reduction <360 µmol/L Well tolerated with no serious adverse events APHENITY Topline Results |
| APHENITY Global Registration-Directed Trial of Sepiapterin Study Design 4 Primary Endpoint Reduction in blood phenylalanine levels Primary Endpoint Sepiapterin Placebo 42 Days Placebo-Controlled Sepiapterin Run-in Part 1 Part 2 R 14 Days APHENITY Topline Results |
| -70% -60% -50% -40% -30% -20% -10% 0% Overall Classical PKU APHENITY Part 1 Results Demonstrated Marked Blood Phe Reductions 5 Mean Absolute Blood Phe Reduction (µmol/L) ≥30% responders Mean % Blood Phe Reduction ≥30% responders Mean % Blood Phe Reduction Mean Absolute Blood Phe Reduction (µmol/L) N=103 N=16 60% 66% -600 -500 -400 -300 -200 -100 0 Overall Classical PKU N=103 N=16 586 464 APHENITY Topline Results |
| APHENITY Study Population 6 Sepiapterin-Responsiveness Evaluated in 156 patients Patients <2 age 2 patients* Not randomized 3 patients Primary Analysis Population 98 patients 12 Patients with ≥15 – <30% Reduction 110 randomized patients Responders ≥30% Reduction in Blood Phe from Baseline 103 patients 66% APHENITY Topline Results *As per protocol this population entered directly into open label extension |
| APHENITY Global Registration-Directed Trial of Sepiapterin Study Design 7 Primary Endpoint Sepiapterin Placebo 42 Days Placebo-Controlled Sepiapterin Run-In Part 1 Part 2 R 14 Days Stratification Mean percent reduction in blood Phe levels from Part 1 (≥30% or ≥15 - <30% ) Baseline blood Phe level (<600 µmol/L or ≥600 µmol/L) APHENITY Topline Results |
| 8 APHENITY Primary Analysis Population Includes Full Spectrum of PKU Patients APHENITY Topline Results Baseline Characteristic Sepiapterin (N=49) Placebo (N=49) Mean age at enrollment (yrs) [min, max] 16.3 [2, 47] 18.1 [4, 54] 2-17 (%) 34 (69.4) 31 (63.3) ≥18 years (%) 15 (30.6) 18 (36.7) Sex: %F, %M F: 46.9 M: 53.1 F: 55.1 M: 44.9 Mean Baseline Blood Phe (µmol/L) (min, max) 646.1 (179.5, 1350.0) 654.0 (289.5, 1650.0) Mean Baseline Blood Phe in Classical PKU (µmol/L) (min, max) 761.25 (452.0, 1350.0) 771.56 (317.0, 1240.0) |
| Sepiapterin Treatment Resulted in Clinically Significant Blood Phe Reduction 9 APHENITY Topline Results Mean % Blood Phe Reduction -70 -60 -50 -40 -30 -20 -10 0 10 Sepiapterin Overall Primary Analysis Population Classical PKU Patients Mean % Blood Phe Reduction Mean % Blood Phe Reduction N=49 63% 586 464 1% N=49 -70 -60 -50 -40 -30 -20 -10 0 10 Sepiapterin Placebo N=6 69% 3% N=9 (p<0.0001) (p<0.001) Placebo |
| -600 -500 -400 -300 -200 -100 0 Sepiapterin Placebo Sepiapterin Treatment Resulted in Clinically Significant Blood Phe Reduction 10 -600 -500 -400 -300 -200 -100 0 Sepiapterin Placebo Overall Primary Analysis Population Classical PKU Patients Mean Absolute Blood Phe Reduction (µmol/L) Mean Absolute Blood Phe Reduction (µmol/L) N=49 410 586 16 N=49 -416 523 42 N=9 APHENITY Topline Results Mean Absolute Blood Phe Reduction (µmol/L) N=6 (p<0.0001) (p<0.001) |
| EU guidelines: ≥12 years of age Vast Majority of Patients Achieved Guidelines Target Blood Phe Levels 11 93% Achieved <600µmol/L Blood Phe US guidelines: all ages EU guidelines: <12 years of age 84% Achieved <360µmol/L Blood Phe APHENITY Topline Results |
| Sepiapterin Part 1 Treatment Effect in Patients Receiving Sapropterin at Study Entry 12 800 700 600 500 400 300 200 100 0 Mean Blood Phe (µmol/L) (N=27 patients) Mean blood Phe on sapropterin (µmol/L) at study entry Mean blood Phe (µmol/L) following 7-day washout Mean blood Phe (µmol/L) on sepiapterin in Part 1 APHENITY Topline Results 48% lower Phe levels following sepiapterin treatment in those patients receiving sapropterin at study entry Guideline Target |
| Sepiapterin Demonstrated to be Well Tolerated 13 Most common adverse events were headache and diarrhea Sepiapterin was well tolerated with no serious adverse events Similar related adverse event frequency between sepiapterin and placebo treatment groups APHENITY Topline Results |
| APHENITY Open-Label Extension Assesses Long Term Safety and Phe Tolerance 14 R Sepiapterin Placebo 42 Days Placebo-Controlled Open-Label Extension Sepiapterin 1 Year Sepiapterin Run-in Part 1 Part 2 Study Objectives Long-term safety Change in dietary Phe/protein consumption 14 Days APHENITY Topline Results |
| 0 20 40 60 80 100 120 140 M1 W1-W2 (BL) M2 W1-W2 M2 W3-W4 M3 W5-W6 M3 W7-W8 M4 W9-W10 M4 W11-W12 M5 W13-W14 M5 W15-W16 M6 W17-W18 M6 W19-W20 M7 W21-W22 Initial Phe Tolerance Data in Open-Label Extension 15 APHENITY Topline Results Prescribed Phe Consumption (mg/kg/day) Adult recommended Phe intake (N=12) (N=4) 0 50 100 150 200 250 300 M1 W1-W2 (BL) M1 W3-W4 M2 W1-W2 M3 W5-W6 M4 W9-W10 M5 W13-W14 M6 W17-W18 M7 W21-W22 Mean Blood Phe (µmol/L) (N=12) (N=4) Increase in Dietary Phe Intake Blood Phe Levels |
| Commercial Pillars for Success Already Established 16 Newborn screening with ~58,000 patients worldwide1,2,3 Well-known metabolic centers of excellence worldwide Connected and coordinated patient advocacy community Disease pathology well understood and documented APHENITY Topline Results 1. NPKUA; https://www.npkua.org/, 2. Shoraka et. Al, Clin Exp Pediatr. 2020; 63(2): 34–43., 3. Borrajo G., Acta Ped Mex. 2012; 33(6): 279-287. |
| APHENITY Results Support Potential for Sepiapterin to Address Majority of PKU Segments 17 APHENITY Topline Results Sepiapterin Market Opportunity Therapy Naive Patients Including Classical PKU Patients Who Are Not Well Controlled Patients Who Have Failed on Current Therapies |
| PTC Global Commercial Infrastructure Will Allow for Rapid Worldwide Launch 18 KOL/ Payor Relationships PAG Relationships Patient Support Dedicated Customer Facing Teams EAP/ Access & Reimbursement Plug and Play in PKU APHENITY Topline Results |
| APHENITY Results Support Next Steps in Regulatory Process and Commercial Planning 19 Pre-Submission Meetings Regulatory Submissions APHENITY Topline Results Initiate Launch Preparation |
