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 16, 2018
PIERIS PHARMACEUTICALS, INC.
(Exact Name of Registrant as Specified in its Charter)
Nevada | 001-37471 | EIN 30-0784346 | ||
(State of Incorporation) | (Commission File Number) | (IRS Employer Identification No.) | ||
255 State Street, 9th Floor
Boston, MA 02109
United States
(Address of principal executive offices, including zip code)
Registrant’s telephone number, including area code: 857-246-8998
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)) |
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 September 16, 2018, Pieris Pharmaceuticals, Inc. presented preclinical data regarding PRS-060. The poster is furnished as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated by reference herein.
The information set forth under this “Item 7.01. Regulation FD Disclosure,” including the exhibits attached hereto, shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended, nor shall it be deemed incorporated by reference into any filing under the Securities Act of 1933, as amended, 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: September 17, 2018 | /s/ Allan Reine | |
Allan Reine | ||
Chief Financial Officer | ||
The Discovery and Development of AZD1402/PRS-060 a Potent and Selective Blocker of the IL-4 Receptor alpha G. Matschiner±, S. Huang+, S. Constant+, B. Rattenstetter±, H. Gille#, A.M. Hohlbaum§, B.H. Koller**, D. Keeling* & M. Fitzgerald± ± Pieris Pharmaceuticals, 255 State St, 9th Floor, Boston, MA 02109, USA; + Epithelix Sàrl, Geneva, Switzerland; *Respiratory, Inflammation and Autoimmunity, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden; # Iason Consulting, Niederzier, Germany; §Ablynx, Ghent, Belgium; * Department of Genetics, UNC at Chapel Hill, USA Introduction Results 1 Results 2 Results 3 ▪ TM In 5-10% of asthma patients control of disease is not achieved with Table 1. Dual inhibition of hIL-4 and hIL-13 induced STAT6 In a human airway epithelium culture system (3D MucilAir ), PRS- Figure 5. Effect of PRS-060/AZD1402 on OVA induced standard of care therapies (inhaled corticosteroids in combination with phosphorylation in TF1 cells by PRS-060/AZD1402 060/AZD1402 effectively inhibits IL-13 induced goblet cell metaplasia with a inflammation 48 hours post challenge in a murine asthma long-acting beta-2 agonists). This inability to achieve asthma control similar potency to AMG317, an anti-IL-4 receptor alpha (IL-4Ra) monoclonal IL-13 [10nM] induced TF-1 IL-4 [0.1nM] induced TF-1 antibody, and a greater potency than pitrakinra (figure 2). model significantly impacts patients’ quality of life and healthcare costs. Type 2 Test substance (T2) cytokines, specifically interleukin (IL)-4, IL-5, and IL-13, play crucial roles pSTAT6 IC50 (mean ± SD) pSTAT6 IC50 (mean ± SD) in asthma pathogenesis1,2. Dupilumab, a fully human anti-IL-4 receptor PRS-060 0.097 nM ± 0.007 0.14 nM ± 0.04 alpha (IL-4Ra) monoclonal antibody given by subcutaneous injection, Figure 3. Effect of PRS-060/AZD1402 on IL-13-induced inhibits IL-4 and IL-13 signalling, key drivers of T2-mediated inflammation, IL-4 mutein increases in eotaxin gene expression in murine PD model 9.1 nM ± 1.088 7.12 nM ± 0.06 and has been shown to reduce exacerbations and improve lung function in (Pitrakinra) moderate to severe asthma subjects3. Pitrakinra, an inhaled IL-4 mutein that ▪ antagonises IL-4Ra, has also been shown to have beneficial effects in a In an in vitro assay using TF-1 cells, PRS-060/AZD1402 showed dual subset of asthma patients5. PRS-060/AZD1402, is a human tear lipocalin inhibition of IL-4R and IL-13R signalling by inhibiting both the IL-4 and derived Anticalin antagonist that has a high potency and selectivity for the IL-13 induced STAT6 phosphorylation with 50 - 90 fold greater potency human IL-4 receptor alpha. Selectivity has been established by testing compared to pitrakinra (table 1), respectively. against a range of cytokine receptors. PRS-060/AZD1402 is being developed Figure 1. Inhibition of a) IL-4 and b) IL-13 induced TF1 cell ▪ as an inhaled treatment for moderate to severe asthma. In an in vivo pharmacodynamic model developed in humanised mice, pre- proliferation by PRS-060/AZD1402 treatment with PRS-060/AZD1402 given via the i.t. route, inhibited IL-13- induced eotaxin gene expression. A dose of 2µg/mouse inhibited this response over a 24-hour period (figure 3). Methods ▪ In a murine asthma model developed in the humanised mouse, PRS- 060/AZD1402 given i.t. (30µg/mouse) twice, 0.5 hours prior to and 24 TF1 cells, known to express IL-4Ra4, were used in a FACS assay measuring hours post OVA challenge, inhibited antigen-induced pulmonary the signal transducer and activator of transcription 6 (STAT6) inflammation in the BAL 48 hours post challenge (figure 5). In this model, phosphorylation following IL-4 or IL-13 stimulation in the presence and Figure 4. Effect of PRS-060/AZD1402 on OVA induced treatment with PRS-060/AZD1402 was associated with histologically absence of PRS-060/AZD1402. To demonstrate functional activity of PRS- histopathological outcomes 48 hours post challenge in a significant reductions in bronchiolar and alveolar inflammation, 060/AZD1402, a proliferation assay using hGM-CSF starved TF1 cells murine asthma model eosinophil, neutrophil, macrophage infiltration, bronchiolar epithelial stimulated with a low dose of IL-4 (0.1 nM) or IL-13 (10 nM) was set up, hyperplasia and fibroplasia (figure 4). using as readout the release of ATP by living cells. In a human airway epithelium culture system (3D MucilAirTM)6, incubation with Summary IL-13 (10 ng/ml, every 2 days for a total of 14 days) induced a goblet cell ▪ PRS-060/AZD1402 is a potent and selective antagonist of the IL-4Rα that metaplasia as assessed by in situ Alcian blue staining. has a comparable profile to the monoclonal antibody to this receptor, dupilumab, and 50-90 fold greater potency than the inhaled IL-4 mutein, As PRS-060/AZD1402 does not cross react with IL-4Rα from species pitrakinra. commonly used for in vivo efficacy studies, a syntenic (humanised) mouse ▪ PRS-060/AZD1402 effectively inhibits IL-13 induced goblet cell was generated by Dr. Beverly Koller at UNC-Chapel Hill and the mouse metaplasia in vitro supporting the concept that treatment will reduce studies were performed in her laboratory. In this mouse the genes for IL- mucus hypersecretion in moderate to severe asthma patients. 4Ra and IL-4/13 were replaced with the respective human orthologues. ▪ In a murine PD model a single intra-tracheal dose of PRS-060/AZD1402 This mouse both responds to human IL-4 and IL-13 but also generates potently inhibited an IL-13 induced response and had a 24-hour duration human IL-4 and IL-13 when the T2 cytokine pathway is activated. of action. ▪ In a murine asthma model, intra-tracheal PRS-060/AZD1402 reduced A pharmacodynamic murine model for the evaluation of the potency and pulmonary inflammation as assessed by an inhibition of BAL cell duration of action of PRS-060/AZD1402 was developed in this mouse. recruitment and via a reduction in antigen-induced histopathological Human IL-13 (1µg) was given via the intra-tracheal (i.t.) route and the ▪ In a functional cell-based assay, PRS-060/AZD1402 inhibited IL-4 and IL-13 changes. expression of Ccl11 (eotaxin-1) was quantified in lung tissue by qPCR 24- induced proliferation of TF-1 cells with similar potency to dupilumab (figure 1). hour post challenge. Figure 2. Inhibition of IL-13-induced goblet cell metaplasia by Conclusions An ovalbumin (OVA) model of asthma was also developed in these mice. Mice were sensitised to OVA (20µg OVA in Alum i.p.) on day 0 and day 7 PRS-060/AZD1402 The overall profile of PRS-060/AZD1402 supports its development as an and were challenged with an aerosol of OVA on day 14. Animals were inhaled therapy for moderate to severe asthma. Non-clinical safety studies e 1 0 0 c suggest that this inhaled Anticalin therapeutic is safe and well tolerated and sacrificed 24 and 48hr later and the inflammatory response was assessed a f r it is currently being evaluated clinically for safety, tolerability and efficacy in in the bronchoalveolar lavage fluid by performing total and differential cell u 7 5 P R S -0 6 0 /A Z D 1 4 0 2 s two Phase 1 studies (NCT03384290 and NCT03574805). counts. In separate animals, lungs were perfused with PBS/ heparin e W ild ty p e lip o c a lin u l b P itra k in ra followed by 4% PFA in PBS. Lungs were then inflated with 4% PFA/ PBS at a 5 0 n i A M G 317 constant head pressure of 20 cm H20, and then maintained in the inflation a References c solution until fixation. Three serial sagittal lung sections were then l 2 5 A 1. Voehringer et al. J Exp Med. 2006;203:1435-46. prepared from formalin fixed, paraffin blocked lung tissue and stained for % 2. Locksley Cell. 2010; 140:777-83. 0 haematoxylin and eosin, Periodic-acid Schiff and trichrome 3. Wenzel et al. Lancet. 2016; 388:31-44. 1 1 0 0 demonstrations, respectively. . 1 0 4. Lefort et al. FEBS Letters 1995; 366: 122-12. 0 1 C o n c e n tr a tio n [n M ] 5. Slager et al. JACI 2012; 130: 516-522. 6. http://www.epithelix.com/products/mucilair Disclosure of Commercial Support and Relevant Financial Interests: Dr. Matschiner is an ® employee of Pieris Pharmaceuticals, Dr. Fitzgerald is a consultant for Pieris Pharmaceuticals, Anticalin Proteins for Respiratory Disease and Dr. Keeling is an employee of AstraZeneca; Professor Koller has provided scientific support and advice on the development of mouse models and the testing of novel Anticalin proteins.