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): February 22, 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.
Attached hereto as Exhibit 99.1 and incorporated by reference herein is an investor presentation of Pieris Pharmaceuticals, Inc.
The information set forth under this “Item 7.01. Regulation FD Disclosure,” including the exhibit 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: February 22, 2018 | /s/ Allan Reine | |
Allan Reine | ||
Chief Financial Officer | ||
Investor Presentation
February 2018
(Nasdaq: PIRS)
Forward Looking Statements
Statements in this presentation that are not descriptions of historical facts are forward-looking statements that are based on management’s
current expectations and assumptions and are subject to risks and uncertainties. In some cases, you can identify forward-looking statements
by terminology including “anticipates,” “believes,” “can,” “continue,” “could,” “estimates,” “expects,” “intends,” “may,” “plans,” “potential,”
“predicts,” “projects,” “should,” “will,” “would” or the negative of these terms or other comparable terminology. Factors that could cause actual
results to differ materially from those currently anticipated include, without limitation, risks relating to the results of our research and
development activities, including uncertainties relating to the discovery of potential drug candidates and the preclinical and clinical testing of
our drug candidates; the early stage of our drug candidates presently under development; our ability to obtain and, if obtained, maintain
regulatory approval of our current drug candidates and any of our other future drug candidates; our need for substantial additional funds in
order to continue our operations and the uncertainty of whether we will be able to obtain the funding we need; our future financial performance;
our ability to retain or hire key scientific or management personnel; our ability to protect our intellectual property rights that are valuable to our
business, including patent and other intellectual property rights; our dependence on third-party manufacturers, suppliers, research
organizations, testing laboratories and other potential collaborators; our ability to successfully market and sell our drug candidates in the future
as needed; the size and growth of the potential markets for any of our approved drug candidates, and the rate and degree of market
acceptance of any of our approved drug candidates; developments and projections relating to our competitors and our industry; our ability to
establish collaborations; our expectations regarding the time which we will be an emerging growth company under the JOBS Act; our use of
proceeds from this offering; regulatory developments in the U.S. and foreign countries; and other factors that are described more fully in our
Annual Report on form 10-K filed with the SEC on March 30, 2017. In light of these risks, uncertainties and assumptions, the forward-looking
statements regarding future events and circumstances discussed in this report may not occur and actual results could differ materially and
adversely from those anticipated or implied in the forward-looking statements. You should not rely upon forward-looking statements as
predictions of future events. The forward-looking statements included in this presentation speak only as of the date hereof, and except as
required by law, we undertake no obligation to update publicly any forward-looking statements for any reason after the date of this presentation
to conform these statements to actual results or to changes in our expectations.
2
Anticalin Proteins – A Novel Therapeutic Class
3
BenefitsFeatures
Small size (1/8th the size of a mAb)
Engineerable scaffold
Derived from lipocalins
(human epithelial proteins)
Engineerable binding pocket
No observed
immunogenicity to date
Potent target engagement
Unique bi/multispecific fusion
proteins
Enhanced delivery, e.g.,
Inhaled therapeutics
Our pipeline addresses clinically-validated targets in new ways by leveraging unique
features of the Anticalin® protein drug class, effectively taking reduced target biology risk
Pieris Investment Opportunity
• An industry-validated class of novel therapeutics
- Anticalin proteins
- $120+M in upfront payments and milestones since January
2017
• Potentially transformative, wholly owned IO program
- Clinical-stage, tumor-targeted 4-1BB bispecific
• High-value, inhaled targeted respiratory program
- Clinical-stage inhaled IL-4Ra antagonist
- partnered with AstraZeneca – retained US co-dev/comm rights
• All three anchor partnerships include US-focused
commercialization rights
• Robust IND engine that has yielded several clinical-stage
candidates with excellent drug-like properties
4
Respiratory
Immuno-oncology
ANCHOR PARTNERSHIPS
DISCOVERY PRECLINICAL PHASE I PHASE II
PRS-080
PRS-343
PRS-060
Servier
PRS-300’s
AZ
SeaGen
• PRS-343: Initial safety and PD data in 2H18
• PRS-060: First-in-human data in 2H18
• Advance multiple programs in immuno-oncology
and respiratory
• PRS-080: Phase IIa data in 2H18 (safety, PK,
hemoglobin change post 5QW dosing)
Financial Update (9/30/17)
5
Cash & Cash Equivalents $89.9M
Debt $0.0M
YTD Opex (as of 9/30) $29.1M
CSO 44.4M
2018 Anticipated Milestones
Pipeline Highlights
Core Clinical
Next-Generation
Pipeline
Non-Core
Clinical
Anticipate two IO IND filings in 2019
Advance additional respiratory programs under the AstraZeneca alliance in 2018
Servier Alliance
• 5-program deal (all bispecific fusion proteins)
• Pieris retains full U.S. rights for 3 out of 5 programs
• $31M upfront payment, $1.8B milestone potential
• Up to low double-digit royalties on non-codev products
Immuno-oncology Franchise
6
Proprietary Clinical
• PRS-343: First-in-class bispecific to preferentially activate
T cells in the tumor microenvironment (TME)
• Committed to advancing several additional tumor-localized
costimulatory bispecific fusion proteins
Seattle Genetics Collaboration
• 3-program partnership based on tumor-localized costimulatory bispecific
fusion proteins
• Pieris retains opt-in rights for 50/50 global profit split and US
commercialization rights on one of the programs
• $30 upfront payment, $1.2B milestone potential
• Up to double-digit royalties on non-codev products
PRS-343: Why did we Design This?
4-1BB systemically agonizing antibody has shown
mono-therapy efficacy yet significant toxicity in the clinic
(narrow therapeutic window)
PRS-343 preferentially agonizes 4-1BB in the TME by
using its anti-HER2 component to drive drug clustering
and, therefore, 4-1BB cross-linking
7
4-1BB-targeting
Anticalin proteins
HER2-targeting
antibody
PRS-343 Targets Local Biology
4-1BB (CD137) – Key Costimulatory Target
• Marker for tumor-specific T cells in TME
• Ameliorates T cell exhaustion
• Critical for T cell expansion
• Induces anti-tumor cytolytic activity
• Drives central memory T cell differentiation for
sustained response
8
HER2 – Strongly Validated Tumor Target
• Restricted expression on normal tissue
• Multiple HER2+ tumors with high-unmet need
- Bladder, Gastric, Breast and several others
- Mediates drug mobilization and immune receptor
activation within the tumor bed
High HER2
Expression
Clustering &
T cell Activation
T cell costimulation in TME
Tumor-specific
T cell
PRS-343 Shows Bifunctional Activity – Dose-dependent Tumor Growth
Inhibition & CD8(+)TIL Expansion in HER2+ Ovarian Cancer Model
• PRS-343 shows dose-dependent tumor growth inhibition in HER2-sensitive model
• PRS-343 leads to strong and dose-dependent lymphocyte infiltration in tumors; monospecific anti-HER2
mAb (IgG4 backbone) inhibits tumor growth but lacks this immuno-stimulatory activity
• Monospecific anti-4-1BB benchmark mAb shows insignificant response compared to isotype control and no
significant tumor infiltration of lymphocytes
9
Tumor growth (median)
SK-OV-3 tumor model
Incomplete
group due to
mortality
100µg
Isotype Ctrl
100µg
PRS-343
100µg
Anti-4-1BB
0
10
20
30
F
re
q
u
en
cy
[
%
] C
D
3
C
D
45
C
D
4
C
D
8
0
10
20
30
F
re
q
u
en
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[
%
]
C
D
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C
D
45
C
D
4
C
D
8
0
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20
30
F
re
q
u
en
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[
%
] C
D
3
C
D
45
C
D
4
C
D
8
hCD4hCD3 hCD8 Plot
TIL phenotyping by IHC
PRS-343 Avoids Unwanted Effect of Peripheral T Cell Activation,
Unlike Systemically Agonistic 4-1BB Antibody
• Toxicity observed with anti-4-1BB mAb likely corresponds to indiscriminate peripheral T cell
activation
• Unlike PRS-343, anti-4-1BB benchmark mAb shows accelerated graft-versus-host-disease with
significant mortality in line with literature data1
10
Survival
% CD8+
of CD45+
1Sanmamed et al., Cancer Res. 2015 Sep 1;75(17):3466-78.
PRS-343 First-in-Patient Clinical Trial
11
Phase I Trial (Initiated 3Q17)
Dose Escalation Phase
Enrolling HER2+ cancer patients
Starting with single patient cohorts (modified 3+3 design)
Determine maximum tolerated and/or efficacious dose level
Initial safety and PD data 2H18
Expansion Phase
Gastric Bladder Other
Novel Inhaled Biologics Platform: Targeting Lung Diseases Locally
• PRS-060 (Part of AstraZeneca alliance)
- First-in-class inhaled IL-4Ra antagonist for asthma
- Phase I initiated in 4Q17
- Pieris retains opt-in for co-development/co-
commercialization rights in the US
• Proprietary inhaled discovery programs ongoing
12
Alliance Highlights
5 committed novel inhaled
Anticalin protein programs
Including lead asthma program
PRS-060 (IL-4Ra)
Retained co-development and
co-commercialization (US) options on
PRS-060 and up to 2 additional
programs
$57.5M upfront & Phase I MS in 2017;
up to ~$2.1B in milestones,
plus double-digit royalties
Access to complementary
formulation and device know-how
for inhaled delivery
PRS-060 for Uncontrolled Asthma: Why did we Design This?
13
What We Know
Regeneron/Sanofi’s dupilumab (systemically administered anti-IL-4Ra antibody) has demonstrated the following:
67%
reduction in
high-eosinophil
patients
What We Are Testing
• Is this a local phenomenon?
• First-in-man study underway
Reduction in FeNO Exacerbation Reduction Steroid Sparing
80%
avg. reduction
in corticosteroid
use
Improved lung function
PRS-080 for Anemia – Why did we Design This?
14
What We Know
Hepcidin is up-regulated in
functional iron deficiency anemia
Antagonizing hepcidin with
single-dose PRS-080 in CKD5
patients led to Fe mobilization
What We Are Testing
Will antagonizing hepcidin
with PRS-080 lead to a
hemoglobin increase after
5 q/wk. doses?
0
10
20
30
40
50
60
0 48 96 144
Mean Iron Concentrations
Se
ru
m
Ir
on
[µ
M
]
Ph Ib SAD in CKD5 patients
• Phase IIa study
underway testing two
dose cohorts: 4mg/kg
and 8mg/kg vs. placebo
• Data expected 2H18
Pieris Pharmaceuticals, Inc.
Corporate HQ: 255 State Street, 9th Floor, Boston, MA 02109, USA
R&D Hub: Freising, Germany (Munich)
info@pieris.com
www.pieris.com
Back Up Slides
Bispecific Geometry Impacts Immune Synapse, Efficacy
A Varied Immune Synapse...
~15nm
C-terminal Heavy chain fusion
~8nm
C-terminal Light chain fusion
~5nm
N-terminal Light chain fusion
N-terminal Heavy chain fusion
~5nm
...But Impacts Efficacy
α-CD3
antibody
α-CD3 Antibody
IL-2
IFN-γ
T Cell
HER-2+
Tumor Cell
Signal 1 Signal 2
Activation
Culture Dish
17Stand-alone building
block affinity
Bispecific-based
building block affinity
... Does Not Materially Impact Target Engagement...
Efficacy Experimental Design
13.4 nm
TNFRS
(e.g. 4-1BB)
TNFRSL
(e.g. 4-1BB Ligand)
The Natural Immune Synapse
4-1BB/HER-2
bispecific
4-1BB
HER-2
PRS-060 is a Localized IL-4Ra Antagonist for Uncontrolled Asthma
• First inhaled Anticalin protein to potently engage the highly validated asthma target, IL-4Ra
• Localized target engagement in lung tissue supports a rationale for a convenient, low-dose, low-cost
alternative to systemically administered antibodies
• Preclinical in vivo POC for pulmonary delivery at doses supportive of daily administration
18
24-hr duration of action at doses
feasible for inhalation
F
o
ld
C
h
a
n
g
e
i
n
e
o
ta
x
in
e
x
p
re
s
s
io
n
0 .0
0 .5
1 .0
1 .5
h IL -1 3
T re a t: V e h 5 0 µ g 2 µ g
P re (h r): 0 .5 4 8 2 4
***
***
***
***
**
* * p < 0 .0 1 , * * *p < 0 .0 0 1 c o m p a re d to a n tic a lin c o n tro l,
u n p a ire d tw o -ta ile d t- te s t (n = 5 -6 ); d a ta a re M e a n ± S E M
P e rc e n ta g e in h ib itio n
9 7 % 8 6 % 7 3 % 5 8 % 4 7 %
hIL-13-induced increases in eotaxin
gene expression
Total and differential cell counts in OVA model
Control 48-hr
PRS-060 48-hr
Lung
Histopathology
T o ta l M a c r o p h a g e s E o s in o p h ils L ym p h o c yte s
0
1×1 0 0 6
2×1 0 0 6
3×1 0 0 6
4×1 0 0 6
5×1 0 0 6
6×1 0 0 6
A n tic a ln c o n tro l
(T L P C 1 3 4 )
P R S -0 6 0
* *
* *
* *
*
*p < 0 .0 5 , * *p < 0 .0 0 1 c o m p a re d w ith c o n tro l T L P C 1 3 4 ,
u n p a ire d tw o -ta ile d t te s t (n = 9 -1 0 ); d a ta a re M ean ±S E M
4 8 h r t im e p o in t
C
e
ll
d
if
fe
re
n
ti
a
l
P e rc e n ta g e in h ib itio n o f lu n g in fla m m a to ry c e lls
4 8 h r a fte r O V A c h a lle n g e
7 8 % 7 1 % 7 9 % 6 6 %
Inhibits the influx of key inflammatory cells
both in lavage fluid and lung tissue
PRS-080 Shows Consistent Effects in Healthy Volunteers
& CKD5 Patients – Ongoing Ph IIa Study will Evaluate Hemoglobin
• In both healthy volunteers and CKD5
patients, PRS-080
o Was safe and well-tolerated
o Showed a dose-proportional increase of PK
parameters (data not shown)
o Demonstrated dose-dependent PD effects on
serum iron and TSAT
o Led to an immediate dose-dependent
decrease in circulating free Hepcidin (data
not shown)
• A Phase IIa trial is underway in Germany
and Czech Republic
• Planning 5 QW infusions in ESRD FID
anemia patients
• Two dose cohorts: 4 mg/kg and 8 mg/kg
body weigh (4 drug; 2 placebo per cohort)
• Safety, tolerability hemoglobin (Hb) and
reticulocyte concentration of Hb as endpoints
• If data are positive, Pieris will seek to out-
license beyond Japan
19
0
10
20
30
40
50
60
0 48 96 144 192 240
Se
ru
m
Ir
on
[µ
M
]
Mean Iron Concentrations†
Time after start of infusion [hours]
Mean TSAT (%)†
TS
A
T
(%
)
Mean TSAT (%)
Time after start of infusion [hours]
TS
A
T
(%
)
0
10
20
30
40
50
60
0 48 96 144
Mean Iron Concentrations
Se
ru
m
Ir
on
[µ
M
]
0
20
40
60
80
100
0 48 96 144
0
20
40
60
80
100
0 48 96 144 192 240
Ph I SAD in Healthy Volunteers* Ph Ib SAD in CKD5 patients**
** Presented at 54th ERA-EDTA Conference June 2017
N=24 (6 patients per dose cohort, 6 patients on placebo)
• Presented at 57th ASH Conference December 2015
† Subjects achieving iron response > 34.5 µM
(avg. 3 out of 6 subjects / dose cohort)
Management and Board
20
Board of Directors
Michael Richman
CEO, NextCure
Amplimune, Chiron,
MedImmune, Macrogenics
Steven Prelack
SVP & COO, VetCor
Aerpio, Galectin Therapeutics,
BioVex Group
Jean-Pierre Bizzari, M.D.
Director
Celgene, Servier, Rhone-Poulenc,
Sanofi-Aventis
Julian Adams, Ph.D.
President & CEO, Gamida Cell
Clal BioTech Industries,Ltd., Infinity,
Millennium Pharm., LeukoSite Inc.
Christopher Kiritsy
CEO, Arisaph Pharmaceuticals
Kos Pharmaceuticals
James Geraghty
Director
Third Rock Ventures, Sanofi, Genzyme,
Bain and Company
Stephen Yoder
President & CEO
Executive Management Team
Allan Reine, M.D.
SVP, Chief Financial Officer
CGI Pharmaceuticals
Louis Matis, M.D.
SVP, Chief Development Officer
Stephen Yoder, J.D.
President & CEO