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): October 2, 2019
PIERIS PHARMACEUTICALS, INC.
(Exact Name of Registrant as Specified in its Charter)
Nevada | 001-37471 | EIN 30-0784346 | ||
(State or other jurisdiction of Incorporation) | (Commission File Number) | (IRS Employer Identification No.) | ||
225 State Street, 9th Floor Boston, MA | 02109 | |
(Address of principal executive offices) | (Zip Code) | |
Registrant’s telephone number, including area code: 857-246-8998
N/A
(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:
☐ | 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 | PIRS | The Nasdaq Capital Market | ||
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (17 CFR §230.405) or Rule 12b-2 of the Securities Exchange Act of 1934 (17 CFR §240.12b-2).
Emerging Growth Company ý
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 October 2, 2019, Pieris Pharmaceuticals, Inc. presented its phase 1 single ascending dose study of PRS-060 entitled Phase 1 evaluation of the inhaled IL-4Ra antagonist, AZD1402/PRS-060, a potent and selective blocker of IL-4Ra. The presentation is furnished as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference.
The information set forth under this “Item 7.01. Regulation FD Disclosure,” including Exhibit 99.1 attached hereto, shall not be deemed “filed” for any purpose, and shall not be deemed incorporated by reference into any filing under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended, regardless of any general incorporation language in any such filing. except as shall be expressly set forth by specific reference in such filing.
Item 9.01 Financial Statements and Exhibits
(d) Exhibits.
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.
PIERIS PHARMACEUTICALS, INC. | ||
Dated: October 2, 2019 | /s/ Tom Bures | |
Tom Bures | ||
Vice President, Finance | ||
Phase 1 evaluation of the inhaled IL‐4Rα antagonist, AZD1402/PRS‐060, a potent and selective blocker of IL‐4Rα Abstract: OA5336 Bruns IB,1 Fitzgerald MF,1 Pardali K,2 Gardiner P,3 Keeling DJ,2 Axelsson LT,2 Jiang F,2 Lickliter J,4 Close DR5 1Pieris Pharmaceuticals, Boston, MA, USA; 2Early Research and Development, Respiratory, Inflammation and Autoimmune, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden; 3Clinical Pharmacology and Safety Sciences, BioPharmaceuticals R&D, AstraZeneca, Gothenburg, Sweden; 4Nucleus Network, Melbourne, Australia; 5Early Research and Development, Respiratory, Inflammation and Autoimmune, BioPharmaceuticals R&D, AstraZeneca, Cambridge, UK
Conflict of interest disclosure I have no real or perceived conflicts of interest that relate to this presentation. I have the following real or perceived conflicts of interest that relate to this presentation: Affiliation / Financial interest Commercial Company Grants/research support: • This study was sponsored by Pieris Pharmaceuticals and funded by AstraZeneca • Lickliter J is an employee of Nucleus Network; AstraZeneca provided funding to Nucleus Network for conducting this study Honoraria or consultation fees: • Fitzgerald MF is a consultant of Pieris Pharmaceuticals Participation in a company sponsored bureau: Stock shareholder: • Bruns IB is a paid employee and shareholder of Pieris Pharmaceuticals • Fitzgerald MF is a shareholder of Pieris Pharmaceuticals • Pardali K, Gardiner P, Keeling DJ, Axelsson LT, Jiang F and Close DR are employees of AstraZeneca, and may own stock or stock options Spouse / partner: Other support / potential conflict of interest: This event is accredited for CME credits by EBAP and EACCME and speakers are required to disclose their potential conflict of interest. The intent of this disclosure is not to prevent a speaker with a conflict of interest (any significant financial relationship a speaker has with manufacturers or providers of any commercial products or services relevant to the talk) from making a presentation, but rather to provide listeners with information on which they can make their own judgments. It remains for audience members to determine whether the speaker’s interests, or relationships may influence the presentation. The ERS does not view the existence of these interests or commitments as necessarily implying bias or decreasing the value of the speaker’s presentation. Drug or device advertisement is forbidden.
Anticalin® proteins – a new class of biopharmaceuticals Building blocks Mono‐/multispecific Pure Anticalin® proteins Anticalin® Multispecific Protein Fc‐Anticalin® proteins Antibody AZD1402/ PRS‐060 Fc Multispecific mAb‐Anticalin® proteins Potent multi‐target engagement • Novel inhaled and multispecific MoA • Favorable drug‐like properties Adapted from Rothe C, Skerra A1 Fc, fragment crystallizable; mAb, monoclonal antibody; MoA, mechanism of action 1. Rothe C, Skerra A. BioDrugs 2018;32:233–43 3
AZD1402/PRS‐060 – a first‐in‐class asthma therapy 1 IL, interleukin; IL‐4Rα, IL‐4 receptor α Adapted from Bagnasco D et al. 2016 1. Bagnasco D et al. Intl Arch Allerg Immunol 2016;170:122–31 4
AZD1402/PRS‐060 – a first‐in‐class asthma therapy • Despite the availability of standard‐of‐care therapies, disease control is not achieved in 5–10% of patients with asthma1 • Type 2 cytokines IL‐4 and IL‐13 signal through IL‐4Rα, and play crucial roles in asthma pathogenesis2–4 • AZD1402/PRS‐060 is a tear lipocalin‐derived Anticalin protein antagonist of IL‐4Rα that is being developed as an inhaled treatment for moderate‐to‐severe asthma • This presentation details the results of a phase 1, single‐blind, randomized, first‐in‐human dose‐escalation study of AZD1402/PRS‐060 in healthy volunteers (NCT03384290) IL, interleukin; IL‐4Rα, IL‐4 receptor α 1. Murphy AC et al. Thorax 2012;67:751–53; 2. Voehringer D et al. J Exp Med 2006;203:1435–46; 3. Locksley RM. Cell 2010;140:777–83; 4. Wenzel S et al. Lancet 2016;388:31–44 5
NCT03384290 – study design and subject disposition Cohort 1 Cohort 2 Cohort 3 Cohort 4 Cohort 5 Study endpoints 0.25 (0.1) 1.25 (0.5) 5.00 (2.0) 20.0 (8.0) 60 (24.0) Safety PK Inhalation device dose • Serial blood samples were drawn (up to 48 hours Cohort 6 Cohort 7 Cohort 8 Cohort 9 (delivered dose), mg after administration of each dose) 180 (72.0) 400 (160.0) 1.0 2.0 Intravenous dose, mg • Standard PK parameters were derived for evaluation PD to establish systemic target engagement Dose 2 Single dose 1 • Blood was drawn from subjects after dosing with Sentinel subjects Sentinel subjects inhaled AZD1402/PRS‐060 or placebo, and was stimulated with IL‐4 10 ng/mL for 15 minutes • pSTAT6 was assessed by FACS in the CD3+ Dose modified T‐cell subpopulation Safety review Study population • 72 healthy volunteers were enrolled Acceptable findings • 54 received AZD1402/PRS‐060 The same process No is repeated • 18 received placebo Yes • Sex: 100% male Single dose 1 • Mean age: 26.4 years 8 subjects • Mean BMI: 24.5 kg/m2 BMI, body mass index; FACS, fluorescence‐activated cell sorting; IL, interleukin; PD, pharmacodynamic; PK, pharmacokinetic; pSTAT6, phosphorylated signal transducer and activator of transcription 6 6
AZD1402/PRS‐060 was well tolerated after intravenous and inhaled administration • Single inhaled doses and single intravenous doses System organ class Placebo AZD1402/PRS‐060 Overall of AZD1402/PRS‐060 were well tolerated Preferred termb (n = 18) (n = 54) (N = 72) n (%) m n (%) m n (%) m • Twenty‐five subjects (35%) experienced 28 TEAEs Subjects with TEAEs 6 (33) 8 19 (35) 20 25 (35) 28 • Nervous system disorders 1 (6)1 5 (9)6 6 (8)7 Most TEAEs (80%) were mild and no subjects reported Headache 1 (6)1 5 (9)5 6 (8)6 severe TEAEs Somnolence 0 1 (2)1 1 (1)1 • No clinically significant abnormalities or change from Infections and infestations 2 (11) 2 5 (9) 5 7 (10) 7 URTI 2 (11) 2 3 (6) 3 5 (7) 5 a baseline in hematology, clinical chemistry laboratory Respiratory tract infection 0 1 (2) 1 1 (1) 1 results, urinalysis results, vital signs or 12‐lead Tonsillitis 0 1 (2) 1 1 (1) 1 electrocardiogram values were noted in any subjects Respiratory, thoracic and 2 (11) 2 3 (6) 3 5 (7) 5 mediastinal disorders • No notable changes in pulmonary function Dry throat 0 2 (4) 2 2 (3) 2 Pleuritic pain 0 1 (2) 1 1 (1) 1 parameters were observed in any of the subjects Throat irritation 2 (11) 2 0 2 (3) 2 General disorders 1 (6) 1 2 (4) 2 3 (4) 3 Exploratory analysis Fatigue 0 1 (2) 1 1 (1) 1 Influenza‐like illness 0 1 (2) 1 1 (1) 1 • There was no significant taste or smell associated Gastrointestinal disorders 0 1 (2) 1 1 (1) 1 with the study drug or placebo Nausea 0 1 (2) 1 1 (1) 1 aThe laboratory tests analyzed hemoglobin, hematocrit, red blood cells, platelets, white blood cells, neutrophils, lymphocytes, eosinophils, basophils and monocytes bMedDRA 20.1 m, number of events, n, number of subjects in the specified category; TEAE, treatment‐emergent adverse event; URTI, upper respiratory tract infection 7
AZD1402/PRS‐060 was absorbed after inhalation resulting in dose‐dependent increases in Cmax and AUCinf Serum PK profile of AZD1402/PRS‐060 after inhalation Serum PK profile of AZD1402/PRS‐060 after intravenous infusion • After intravenous infusion, AZD1402/PRS‐060 had a terminal t ½ of 2 hours, clearance of 6 L/hour and volume of distribution of 9 L, consistent with limited tissue distribution and clearance via renal filtration • A longer t½ observed after inhalation (4.1–6.2 hours) than after intravenous infusion (2.2–2.3 hours) indicated involvement of an absorption lag time • There were no confirmed positive anti‐AZD1402/PRS‐060 antibodies in any of the dose groups AUCinf, area under the serum concentration time curve from time 0 to infinity; Cmax, maximum observed serum concentration; PK, pharmacokinetics; t½, terminal half‐life 8
Inhaled AZD1402/PRS‐060 shows systemic target engagement correlating with serum exposure pSTAT6 levels after inhalation of AZD1402/PRS-060 pSTAT6 levels versus systemic exposure of AZD1402/PRS-060 • Inhibition of pSTAT6 was observed from cohort 4 onwards (delivered dose 8 mg) • Inhibition of systemic pSTAT6 was dose‐dependent and aligned with systemic levels of AZD1402/PRS‐060 • Near complete and sustained inhibition was observed at higher inhaled doses +/‐ IL‐4 Ex vivo FACS heparinized Fix cells Stain with CD3 and CD3+ and pSTAT6+ whole blood 15 minutes pSTAT6 antibodies @ 37oC FACS, fluorescence‐activated cell sorting; IC50, half maximal inhibitory concentration; pSTAT6, phosphorylated signal transducer and activator of transcription 6 9
Conclusions • The novel IL‐4Rα antagonist AZD1402/PRS‐060 was well tolerated when given as single inhaled or intravenous doses to healthy volunteers • The overall profile of AZD1402/PRS‐060 supports its further development as an inhaled drug for the treatment of asthma • Systemic target engagement (pSTAT6) will be compared with local lung target engagement in the ongoing, multiple ascending dose study in patients with mild asthma (NCT03574805) • This study determined the local lung effects and dose relationship by measuring FeNO, a validated biomarker of asthma • Results presented on Tuesday October 1: Multiple ascending dose study of the inhaled IL‐4Rα antagonist, AZD1402/PRS‐060, in mild asthmatics demonstrates robust FeNO reduction and a promising clinical profile for the treatment of asthma (poster number: PA3709) • The outcome of this study will help to determine the inhaled dose levels for evaluation in future studies of this first‐in‐class, inhaled anticalin molecule PRS‐060 protein structure FeNO, fractional concentration of exhaled nitric oxide; IL‐4Rα, IL‐4 receptor α; pSTAT6, phosphorylated signal transducer and activator of transcription 6 10
Acknowledgments Pieris Pharmaceuticals AstraZeneca • Kayti Aviano • AstraZeneca and Pieris Pharmaceuticals thank the volunteers and site staff who • Jen Tsung participated in this study • George Mensing • Medical writing support was provided • All the phase 1 site staff at Nucleus by Kelly Soady, PhD, of PharmaGenesis Network (Melbourne, Australia) London, London UK, with funding from AstraZeneca 360BioLabs • Deidre Cournane • Jonathan Ferrand • Melinda Pryor 11
Back‐up slides 12
Doses of AZD1402/PRS‐060 Cohort Inhalation device doses (delivered doses), mg 1 0.25 (0.1) 2 1.25 (0.5) 3 5.00 (2.0) 4 20.0 (8.0) 5 60 (24.0) 6 180 (72.0) 7 400 (160.0) Intravenous doses, mg 81.0 92.0 13
Serum PK parameters after AZD1402/PRS‐060 inhalation at the delivered dose for cohorts 4–7 (PK population) and after intravenous administration for cohorts 8 and 9 Parameter Inhalation dose Intravenous dose Cohort 4 Cohort 5 Cohort 6 Cohort 7 Cohort 8 Cohort 9 8 mg (n = 6) 24 mg (n = 6) 72 mg (n = 6) 160 mg (n = 6) 1 mg (n = 6) 2 mg (n = 5) a b AUCinf, h.ng/mL 87.2 (27.8) 261.5 (125.6) 1252.1 (398.9) 3446.0 (2314.9) 187.3 (32.5) 311.6 (23.1) Cmax, ng/mL 8.3 (4.8) 21.2 (9.8) 93.0 (33.8) 266.8 (232.5) 123.3 (13.1) 201.5 (9.0) MRT, h 7.8 (2.9)a 8.9 (2.1)b 10.9 (1.6) 11.5 (1.3) 1.4 (0.2) 1.5 (0.1) Tmax, h (min, max) 4.6 (2.1, 5.1) 4.7 (4.1, 8.2) 4.6 (1.7, 8.1) 8.2 (1.7, 8.3) 1.0 (0.97, 1.1) 1.0 (0.97, 1.0) a b t½, h 4.2 (1.7) 4.1 (0.9) 6.2 (0.7) 6.0 (0.7) 2.2 (0.75) 2.3 (0.1) BA, % 7.0 7.0 11.2 13.8 CL, L/h 5.5 (0.96) 6.4 (0.5) Vss, L 7.6 (0.69) 9.7 (0.7) Vz, L 17.0 (4.0) 21.5 (2.4) • Urinary excretion of unchanged AZD1402/PRS‐060 was not detected after intravenous administration or inhalation, except in three individuals in the high‐dose inhalation cohorts • There were no confirmed positive anti‐AZD1402/PRS‐060 antibodies in any of the dose groups an = 2; bn = 5 AUCinf, area under the serum concentration time curve from time 0 to infinity; BA, bioavailability; CL, clearance; Cmax, maximum observed serum concentration; h, hour; max, maximum; min, minimum; 14 MRT, mean residence time; PK, pharmacokinetic; t½, terminal half‐life; Tmax, time to maximum serum concentration; Vss, volume of distribution at steady state; Vz, volume of distribution at terminal phase
