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| 8-K - 8-K - PIERIS PHARMACEUTICALS, INC. | d326324d8k.htm |
Exhibit 99.1
Exhibit 99.1
Pieris Pharmaceuticals, Inc.
Nasdaq:PIRS
27th Annual Oppenheimer Healthcare Conference
Stephen Yoder, President & CEO
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 23, 2016. 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.
Non-Confidential 2
Expanding the Playing Field for
Therapeutic Proteins
Anticalins® – A Novel Therapeutic Protein Drug Class
Novel Drug
Class • Fully proprietary and unique
| • |
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Excellent drug-like properties and clinical validation |
Multiple Paths for Success & Risk Diversification
Novel Modes of Action • Potentially transformative immuno-oncology multispecifics –PRS-343
- TME-targeted T cell agonists / Multi-checkpoint blockade
• Inhaled biologics may bring enormous benefits in respiratory disease –PRS-060
Partnerships and Capital to Pursue Clinical-based Inflection Points
Validation and Growth • Transformative alliance with Servier in Immuno-oncology with fully retained US rights
Capital on several novel multispecific drug candidates for immuno-oncology
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JP-market partnership with ASKA de-risks may accelerate time to market for PRS-080 |
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~$100 M in revenues since inception |
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$2.6 B in biodollar potential from partnerships + royalties |
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$60+ million in cash on hand provides runway into 2019 through key value inflection points on fully proprietary pipeline |
Non-Confidential 3
Diversified Immuno-Oncology (IO) and Non-IO Product Pipeline
IMMUNO?ONCOLOGY PROGRAMS
Our Commercial Preclinical IND?
Candidate Target Indication Partner Discovery Phase I Phase Ib/IIa
Rights enabling
4?1BB/HER2
PRS?343 Bispecific IO Worldwide 4?1BB/GPC3 PRS?342 IO Worldwide Bispecific
PRS?300s n.d. IO Worldwide
PD?1/n.d.
PRS?332 Bispecific IO U.S. Servier n.d./n.d. U.S./ Milestones Bispecific IO
4 Programs & Royalties Milestones &
Roche n.d. IO
Royalties
RESPIRATORY, ANEMIA AND OTHER DISEASE AREAS
Our Commercial Preclinical IND?
Candidate Target Indication Partner Discovery Phase I Phase Ib/IIa
Rights enabling
Major Markets
PRS?080 Hepcidin Anemia ex?Japan PRS?060 IL4Ra Asthma Worldwide
Milestones & DS?9001 PCSK9 Dyslipidemia Royalties Milestones & Daiichi Sankyo n.d. n.d. Royalties Infectious Milestones & Sanofi P. aeruginosa disease Royalties PRS?110 cMet Oncology Major Markets
Non-Confidential 4
Experiencing an Acceleration Phase
2017
Continued exploration of additional
Recent Value Drivers partnerships
2017
Clinical e
ntry of inhaled respiratory program, 2017 PRS-060
Near-Term Value Drivers Strategic, Multi-program
Co-development IO Alliance 2017
Retaining US rights on 4 programs Presentation of 2017
Phib data f
or Key data readout anemia program, (Hb) for PRS-080 2015 PRS-080
First IO Partnership
2014 2017
Focus on IO Clinical entry of Multispecifics and fully proprietary IO
Inhaled Biologics for program, PRS-343
2010-2011 Respiratory Disease 2015-2016
Multiple Large Lead IO and
Pharma Collaborations Respiratory Programs 2017 IND-enabling Studies Partnership for PRS-080 in Japan 2014-2015
Go Public
2008
2001 Set up Boston HQ $25M Series B
Founded in led by OrbiMed Munich, Germany
2010
Platform Improvements First Anticalin® Initial drug enters clinic discovery efforts
Growing
The Early Years Drug Class Validation Acceleration Phase Disease Focus
2001 – 2007 2008 – 2013 2014 – 2016 2017+
Projected events
Non-Confidential 5
Servier Immuno-Oncology Partnership is a Transformative Strategic Alliance
Strategic Alliance Highlights
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IO co-development alliance: ~$30M upfront, up to $1.8B in potential milestones and low double-digit royalties |
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5 committed bispecifics, including PRS-332 (PD-1-based) |
- Potential to expand to 3 additional bispecific programs
- Full US commercial rights on PRS-332 and up to 3 additional programs
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A “True Partnership” – equal voice with a collaborator having a shared strategic vision and resources to develop several novel IO bispecifics |
Strategic Implications of Partnership
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Underscores the value of Pieris’ powerful multispecifics platform in IO |
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Extends financial runway into 2019, through several clinical-stage value inflection points |
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Fully retained rights on lead IO bispecific, PRS-343 (4-1BB/HER2) |
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Several assets within partnership provide US commercialization opportunity |
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Ability to enter into additional partnerships |
Non-Confidential 6
Regional Partnership with ASKA Derisks and Accelerates Development of PRS-080
Alliance Highlights ASKA Company Overview
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Option deal for Japan, S. Korea and a Independent Japanese pharma company few smaller Asian countries Founded 1920, >800 employees |
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Exercisable after completion of Phase 2a Annual revenues: ~$400M study to be conducted by Pieris |
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Listed on Tokyo Stock exchange |
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Option Fee of $2.75M |
- Market Cap: ~$470M1
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>$80M in Option Exercise Fee & Milestones—Largest shareholder: Takeda Pharmaceutical for 1st indication in Japan (CKD HD patients) |
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Main therapeutic areas: Internal Medicine, |
- Additional Milestones in other indications
Urology & Woman’s Health and other Asian countries
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Double-digit royalties up to mid- to high-teens Products distributed through |
Strategic Implications of Partnership
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Further validates Anticalin® drug class and value of PRS-080, addressing a high medical need in Japan |
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Enables immediate investment into manufacturing efficiencies and future drug supply |
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Monetizes non-core asset in a key market (JP), improves probability of finding US/EU partner after P2a |
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Facilitates Company focus on clinical development of high-value immunology assets |
1: as of Feb 24, 2017
Non-Confidential 7
Anticalins® Share Several Features with mAbs yet are Highly Differentiated
? Monoclonal Antibodies (mAbs) are highly successful drugs
? Anticalins share many of the beneficial properties of mAbs yet are highly differentiated
Differentiating Features
Antibody Anticalin
Human-derived ?? Natural binding molecule ? ? Non-immunogenic ? ? High affinity and specificity ? ? Systemic delivery ? ? Tunable pharmacokinetics (?) ? Valent- and geometry-versatile multispecifics ? Inhalable ? Protein class exclusivity ? Positive freedom to operate landscape ? Safety Related Efficacy Related IP Related
Non-Confidential 8
Anticalins in Immuno-Oncology
Non-Confidential
Valent- and Geometry-Versatile Multi-specifics to Achieve Optimal Biology
Pure Anticalins Multispecif
ic Fc-Anticalins Building bloc
ks
Ac
Fc
mAb
linker
Multispecific mAb-
Anticalins
? Potent Multi-target Engagement ?Novel MoA ? Excellent Drug-like Properties
Non-Confidential 10
pieris
PRS-343 is a First-in-Class TME-activated Co-stim Agonist
4-1BB (CD137) – Key Costimulatory Target Tumor-specific T Cell
? 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
4-1BB
differentiation for sustained response TcR
(CD137)
MHC-peptide
HER2
HER2 – Strongly Validated Tumor Target
? Restricted expression on normal tissue
? Multiple HER2+ tumors with high-unmet need? Breast, Gastric & Bladder; several others? Mediates drug mobilization and immune receptor activation within the tumor bed
Tumor Cell
Non-Confidential 12
PRS-343 is a First-in-Class TME-activated Co-stim Agonist
Tumor Target: HER2
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A highly validated tumor target |
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Restricted expression on normal |
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Several HER2+ tumors with high- |
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Mediates drug mobilization and activation within the tumor bed |
Tumor Cell
PRS-343 Engages HER2 on Tumor Cells
PRS-343 binds to HER2 expressed on tumor cells
Non-Confidential 14
PRS-343 is a First-in-Class TME-activated Co-stim Agonist
Anti-4-1BB T cell Target: 4-1BB
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Key Costimulatory Target |
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Marker for tumor-specific T cells in TME |
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Critical for T cell expansion |
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Induces anti-tumor cytolytic activity |
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Drives central memory T cell differentiation for sustained response |
Tumor Target: HER2
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A highly validated tumor target |
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Restricted expression on normal tissue |
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Multiple HER2+ tumors with high-unmet |
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Mediates drug mobilization and immune receptor activation within the tumor bed |
Tumor Cell
Non-Confidential 15
4-1BB Engagement by PRS-343, Alone, Does Not Cause T Cell Activation
T Cell
PRS-343 binds to 4-1BB expressed on T cells (including, as desired, tumor-specific T cells)
By design, PRS-343 requires an additional factor to activate T cells
Non-Confidential 16
PRS-343 is a First-in-Class TME-activated Co-stim Agonist
Anti-4-1BB
Potential Benefits of Pieris’ Approach
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Localized T cell activation |
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Reduced T cell-mediated systemic toxicity |
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Increased therapeutic index in patients unresponsive to standard of care |
Tumor Cell
Non-Confidential 17
HER2-mediated Clustering of PRS-343 Causes 4-1BB-mediated T Cell Activation
T Cell
With this approach, toxicity from systemic activation of the immune system may be avoided
…while a robust, localized immune response is induced Tumor Cell
Non-Confidential 18
PRS-343 –In Vivo Data Show High Differentiation Over mAbs (1/2)
Tumor growth (Median) TIL frequency (hCD45) Tras-IgG4 80µg IHC
40 of 35 [%] area 30 IHC 25 20 positive hCD45 15
— 10 PRS-343 100µg IHC
DAB anti 5 0
y C r l 3 3 3 4 7 l 4 4 4 3 n M ct 3 3 343 3 G 1 o — — Ig
B S S S S—D
P s C
MC o type R R R i -nPPRPP ra
B o g g gT ant
P Is 0 µ 0 µ 4 µ g
µg
0 20µg µ
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10 80 0 |
Incomplete group 10 due to mortality
SK-OV-3 tumor model TIL phenotyping by IHC
hCD3 hCD4 hCD8 Plot
? PRS-343 shows dose-dependent tumor growth
CD45 CD3 CD4 CD8
inhibition, which is dominated by anti-HER2 activity [%] 30
100µg PRS-343 20
? PRS-343 leads to strong, dose-dependent Frequency 10
0
lymphocyte infiltration in tumors; monospecific anti-
[%]
30 CD45 CD3 CD4 CD8
100µg
HER2 mAb (IgG4 backbone) lacks this activity 20
Isotype Ctrl Frequency 10
? Monospecific anti-4-1BB benchmark mAb shows 0
[%] 30 CD45 CD3 CD4 CD8
insignificant response compared to isotype control 100µg
20
Anti-4-1BB
and no significant tumor infiltration of lymphocytes Frequency 10
0
Non-Confidential 19
PRS-343 –In Vivo Data Show High Differentiation Over mAbs (2/2)
Mortality at study end PBMC phenotyping at day 19
(Day 20)
% CD45+ of PBMC
? Anti-CD137 benchmark mAb shows % CD8+ accelerated GvHD with significant mortality of CD45+ at day 20 in line with literature data2? Toxicity corresponds with expansion of CD8-positive T cells in PBMC for this group
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GvHD = graft vs host disease |
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Sanmamed et al., Cancer Res. 2015 Sep 1;75(17):3466-78. |
Non-Confidential 20
PRS-343 Phase 1 Initiation
Planned for 1H17
2016 2017 2018
Ph I mono
PRS-343
4-1BB/HER2 IND-enabling
combo w/ PD-1 mAb
? Lead drug candidate progressing through IND enabling
studies
? Demonstrated ability to activate human T cells consistent with
desired mode of action
? Potent, tumor-dependent activation
? Differentiation over anti-4-1BB (CD137) mAbs
? Desired drug-like properties
? CMC / manufacturing: robust titers and long-term stability
? Low risk of immunogenicity observed ex vivo
? Antibody-like half-life in mouse and cynomolgus monkey
? Clean cynomolgus monkey GLP toxicity study
? First-in-Patient Clinical Trial planned for 1H17
? HER2+ solid tumor patients unresponsive to SOC
Non-Confidential 21
PRS-343 Prioritized Indications Address High-need, Large Markets
Muscle- Resistant Advanced invasive Metastatic
Targeted Indication Characteristics Gastric
Bladder HER2+Breast Cancer Cancer Cancer
Known Immune Component
? Existing tumor-infiltrating lymphocyte (TIL) repertoire? Validated role of CD137
High Medical Need
? Populations where current HER2 therapies don’t work
Straightforward Registration Path
? Manageable trial size and duration with clear endpoints
Total Prevalence (2012, in .000s) Prevalence (2012, in .000s)
Main Indication 7MM US EU5 JP Relevant Patient subset* 7MM US EU5 JP
Bladder cancer 837 520 247 70 Muscle-invasive 1st line, HER2+ 108 67 32 9 Recurrent, platinum-failed muscle-invasive, HER2+ 58 36 17 5 Gastric cancer 514 105 78 331 Advanced gastric cancer, HER2+ 23 5 3 15 Breast cancer 4.221 2.975 1.000 246 Recurrent or metastatic 2nd line, HER2+ 143 101 34 8 Recurrent or metastatic 3rd line, HER2+ 77 54 18 4
Total 5.572 3.600 1.325 647 * ex US stage distribution based on US data 409 263 105 42
Non-Confidential 22
Anticalins in Respiratory Disease & Anemia
PRS-060: First-in-Class Inhaled IL-4Ra Antagonist For Uncontrolled Asthma
First inhaled biologic 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
hIL-13-induced increases in eotaxin gene expression Lung Total and differential cell counts in OVA model Histopathology
06 Percentage inhibition of lung inflammatory cells Control 48-hr
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10 48hr after OVA challenge |
78% 71% 79% 66% eotaxin 5 1006 in
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1006 |
Change expression differential 3 1006
Cell 2 1006
Fold ** ** PRS-060 48-hr
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1006 |
**
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0
Total Macrophages Eosinophils Lymphocytes
48hr timepoint
Anticaln control *p<0.
05, **p<0.001 compared with control TLPC134, (TLPC134) unpaired tw
o-tailed t test (n=9-10); data are Mean SEM PRS-060
24-hr duration of action at Inhibits the influx of key inflammatory cells doses feasible for inhalation both in lavage fluid and lung tissue
Non-Confidential 24
PRS-060: Phase 1 to Start Mid 2017
First-in-man study initiation planned for mid 2017
2017 2018 2019
IND-Enabling Phase I Ph IIa
? Clear biomarker strategy and pathway to clinical PoC? ~12 M moderate to severe uncontrolled asthma patients in US/EU
PRS-060 progressing through IND-enabling activities
? High affinity to human IL-4Ra: 20 pM
? Based on a protein found in lung epithelial cells (tear lipocalin)? CMC / Manufacturing: microbial production with robust titers? Ph I trial with a nebulized formulation? Nebulization and spray drying feasibility demonstrated
Projected Timing
Non-Confidential 25
PRS-060: Transformational & Blockbuster Potential
PRS-060 has the potential to transform the use of biologics in uncontrolled asthma
? A fraction of uncontrolled asthmatics are currently treated Physician preference in
administration route in asthma with biologics (% of responders citing “preferred” or “most preferred” r.o.a.)*
? Uptake of biologics limited by 80% 75% several factors including; inconvenient in-office dosing, high
60%
price & biomarker restrictions
? PRS-060 as an inhaled biologic is 40% positioned to overcome these challenges 20% 16%
8%
? An inhaled IL4Ra blocker has the 0% potential to become market leader IV SQ Inhaled and create new markets
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Primary market research with prescribing physicians by Artisan Healthcare Consulting (on behalf of Pieris) in 2016 |
Non-Confidential 26
PRS-080 Offers Further Drug Class Validation & Niche Opportunity in Anemia
? PRS-080 is a PEGylated Anticalin that potently neutralizes Hepcidin? Hepcidin is a peptide hormone that regulates iron entry into plasma from the three main sources of iron:
- Dietary absorption in the duodenum
- Release of recycled iron from macrophages
- Release of stored iron from hepatocytes
? Chronic inflammation drives increased hepcidin production
- Prevents transferrin-mediated transport to the bone marrow for erythropoiesis
- Causes anemia of chronic disease
- “functional” iron deficiency (FID), as opposed to absolute iron deficient anemia
Haematologica 2
013 98:11
Non-Confidential 27
PRS-080 Drives Iron Mobilization in Healthy Subjects; Ongoing Development in FID ESRD Patients
2016 2017
Ph Ib (SAD) Ph 2? Excellent Ph I results (ASH 2015)
(Hemoglobin e.p.)? Safe, well tolerated in HV (36 drug + 12 placebo)? Mode of action (iron mobilization) confirmed
Mean Iron Concentrations [µM]? Increase in serum iron mobilization (p = 0.005)
Healthy subjects achieving iron response > 34.5 µM
60? First-in-patient trial (dialysis-dependent anemia)
50? Single Ascending Dosing completed [µM]? Drug well tolerated – encouraging activity
40 1.2 mg/kg Iron 4.0 mg/kg
30? Disclosing unblinded data in 2Q17
Serum 8.0 mg/kg
20? Multi-dose trial initiation expected April 2017
16.0 mg/kg
10? Hemoglobin (Hb), reticulocyte concentration of Hb as endpoints
0
?60 40 140 240? Planning to disclose data in 2H17
Time after start of infusion [hours]
NEW: Regional partnership with ASKA Pharmaceutical in Japan
? First Anticalin projected to achieve clinical Proof of Concept (increased hemoglobin)
? Will address FID anemia patients poorly responsive to ESAs and iron therapies? Within ESRD, among highest economic burden patient population? Est. 90k patients in the US and 80k patients in JP
? Significant Commercial opportunity = report data
Non-Confidential 28
Senior Management Financials & Milestones
Management and Board Profile
Senior Management Team
Stephen Yoder, J.D. Louis Matis, M.D. Lance Thibault Claude Knopf
President & CEO SVP, Chief Development Officer Interim CFO SVP, Chief Business Officer
CGI Pharmaceuticals
Board of Directors
Stephen Yoder Michael Richman Jean-Pierre Bizzari, M.D. Christopher Kiritsy
President & CEO CEO, NextCure, Inc. Celgene, Servier, Rhone- CEO, Arisaph Pharmaceuticals Amplimune, Chiron, Poulenc, Sanofi-Aventis Kos Pharmaceuticals MedImmune, Macrogenics
Chau Khuong (Chairman) Steven Prelack Julian Adams, PH.D.
Partner, OrbiMed Advisors SVP, COO, VetCor Clal Biotechnology, Infinity, Velquest Corp., Galectin Millennium Pharm., Therapeutics, BioVex Group LeukoSite Inc.
Non-Confidential 30
Financial Highlights – As of 9/30/16
Cash & Cash Equivalents* $36.6M Total Debt $0.0M Revenue Since Inception (license & collaborations) $54.0M Grant Revenue Since Inception $14.2M
9 Months 2016 Net Loss ($16.2M)
9 Months 2016 Cash Burn
(less cash received from PIPE financing & Roche Up Front payment) $14.5M
Common Shares Outstanding 43.1M
Preferred Shares Outstanding (as converted) 4.9M Options Outstanding 4.8M
| * |
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Does not include upfront payment of ~$ 31.3M from Servier collaboration or $2.75M ASKA option fee |
Non-Confidential 31
2016 Achievements and 2017 Expected Milestones
2016: Significant Achievements 2017: a Year of Transformation
Immuno-Oncology Immuno-Oncology
? Generated our first PD-1 based bispecific? Cornerstone IO Servier Strategic Alliance incl. (PRS-332) PRS-332. Runway into 2019 with PRS-343? In vivo POC for 4-1BB bispecific immune unencumbered costimulatory (PRS-343)? PRS 343: First-in-patient clinical trial initiation? Progressing PRS-343 trough IND-enabling planned for 1H17 studies? Several preclinical-stage, highly differentiated multispecifics
Respiratory Respiratory
? PRS-060 (asthma) through IND-enabling? PRS-060: Initiate First-in-human trial Mid-2017 studies Anemia Anemia
? PRS-080
? Conducting first-in-patient study for PRS-080
? Regional partnership in Japan with ASKA in targeted patient population (FID in ESRD)
? Phase 1b dosing completed early Q1 2017
- Phase 1b results disclosure by end of Q2 2017
- Phase 2a results 2H 2017
Non-Confidential 32
Pieris Pharmaceuticals, Inc.
255 State Street, 9th Floor Boston, MA 02109 USA info@pieris.com www.pieris.com
Non-Confidential 33