© Polyphor Ltd Presentation title11/4/2019
November, 2019
Corporate Presentation
This presentation (the “Presentation”) has been prepared by Polyphor Ltd. (“the Company” and together with itssubsidiary, “we”, “us” or the “Group”) solely for informational purposes.
Certain statements in this Presentation are forward-looking statements, beliefs or opinions, including statementsrelating to, among other things, the Company's business, financial condition, future performance, results of operation,potential new market opportunities, growth strategies, and expected growth in the markets in which the Groupoperates. In some cases, these forward-looking statements may be identified by the use of forward-lookingterminology, including the terms “targets”, “believes”, “estimates”, “anticipates”, expects”, “intends”, “may”, “will” or“should” or, in each case, their negative or other variations or similar expressions. By their nature, forward-lookingstatements involve a number of risks, uncertainties and assumptions that could cause actual results or events to differmaterially from those expressed or implied by the forward-looking statements. These risks, uncertainties andassumptions could adversely affect the outcome and financial consequences of the plans and events described herein.Actual results may differ materially from those set forth in the forward-looking statements as a result of various factors(including, but not limited to, future global economic conditions, changed market conditions, intense competition in themarkets in which the Group operates, costs of compliance with applicable laws, regulations and standards, diversepolitical, legal, economic and other conditions affecting the Group’s markets, and other factors beyond the control ofthe Group). Neither the Company nor any of its respective directors, officers, employees, agents, affiliates, advisors orany other person is under any obligation to update or revise any forward-looking statements, whether as a result ofnew information, future events or otherwise. You should not place undue reliance on forward-looking statements,which speak of the date of this Presentation. Statements contained in this Presentation regarding past trends or eventsshould not be taken as a representation that such trends or events will continue in the future. Some of the informationpresented herein is based on statements by third parties, and no representation or warranty, express or implied, ismade as to, and no reliance should be placed on, the fairness, accuracy, completeness or correctness of thisinformation or any other information or opinions contained herein, for any purpose whatsoever.
Forward-looking statement
2
Investment highlights
Immuno-Oncology
Cystic Fibrosis and Hospital Infections
Financials
Outlook
3
Agenda
1
2
3
4
5
Investment Highlights
2 Proprietary Macrocycle Technology Platform – discovery engine in oncology & antibiotics
5 Antibiotic pipeline : Inhaled murepavadin aimed at CF and OMPTAs, the first new class of antibiotics against gram negative pathogens in 50 years - both largely externally financed. In addition, POL6014 (respiratory-outlicensed)
Polyphor: Innovative biopharmaceutical company with a Phase III immuno-oncology compound with fast path to market and a strong pipeline
1
4
3 Balixafortide: Potentially best in class CXCR4 inhibitor. Phase III in HER2-negative metastatic breast cancer in combination with eribulin, based on strong PoC data. First readout (ORR) expected around end of Q121
Market potential USD 1.3+ bn in combination with eribulin; up to 6-7bn if expanded to combinations with taxanes in breast cancer - and more if to other combinations/ indications
4
6 Experienced management team with strong support from leading investor base
7 Financed to achieve the next value inflection points
4
5
Proprietary Macrocycle Technology PlatformUnique discovery engine in oncology & infectious disease
Can make druggable targets previously thought undruggable
Polyphor Pipeline
ProgramFunding /
CollaborationResearch Preclinical Phase I Phase II Phase III
Next Inflection
Point
Balixafortide
mBC HER2-
FORTRESS
ORR Readout
~ end Q1 2021
Balixafortide
other combos/
indic’ns
First
Experiments’
results
~ Q2 2020
Inhaled
Murepavadin
CTA (auth. To
Phase 1a Start)
~ Q2 2020
OMPTA
- POL7306
- Murepavadin
IV
POL7306 CTA
(auth. To Phase
1a Start)
~H2 2020
Murepavdin IV
Re-engineering
~Q4 2019
POL6014 Phase 1b Results
6
On
co
log
yC
F/R
es-
pir
ato
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nti
in-
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Ou
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se
Metastatic Breast Cancer
Other Cancers/ Combos
CF Infections
MDR Bacteria
CF Elastase Inhibitor
Investment highlights
Immuno-Oncology
Cystic Fibrosis and Hospital Infections
Financials
Outlook
7
Agenda
1
2
3
4
5
Most advanced CXCR4 antagonist in clinical development for solid tumors - Phase III
Disruption of CXCR4 and SDF-1 axis renders cancer cells more susceptible to chemo
and increases immune cells infiltration into the tumor
Potentially best-in-class efficacy among CXCR4 inhibitors
Clear dose-response demonstrated
Potential to enhance activity of a range of chemo and immunotherapies
8
Potentially best-in-class CXCR4 inhibitorBalixafortide
CXCR4 overexpression is a key mechanism of cancer prognosis
CXCR4 promotes breast cancer growth through increased signalling pathways, angiogenesis, metastasis and immune cell modulation
Xu et al., 2015, modified
Tumor cells dissemination and
metastases formationPrimary Breast Tumor
Regulation of
immune cells
*
* SDF-1/CXCL12: CXCR4 Ligand
9
Tumor Cell and Stromal CXCR4 vs time to distant metastasis and survival
CXCR4 overexpression correlates with poor prognosis in breast cancer patients
Chen et al., PNAS 2019
10
Highest exposure among CXCR4 inhibitors – and importance of it shown by dose-response
Ple
rixa
for
1X4P
-001
2 BL-8
040
3
Bal
ixaf
ortid
e
4
0.1
1
10
100
1000
10000
noPPBinfo
fra
cti
on
un
bo
un
d
790x
211x106x
Ref
Cmax / IC50
Ple
rixa
for
1X4P
-001
2 BL-8
040
3
Bal
ixaf
ortid
e
4
0.1
1
10
100
1000
noPPBinfo fr
acti
on
u
nb
ou
nd
Ref
1060x
66x100x
AUC0-24h / IC50,24h
CXCR4 inhibitors: IC50 coverage by clinical exposure vs plerixafor (=1x)*
Balixafortide has potentially the best in class efficacy amongst CXCR4s
Balixafortide: potentially the Best in Class Efficacy
38%
63%
33%
47%
13%13%
0%
10%
20%
30%
40%
50%
60%
70%
ORRCBR
6.2
3.03.3
0
1
2
3
4
5
6
7
mPFS (mo)
18
11.29.4
mOS (mo)
0.5-2.0 mg/kg 2.5-4.5 mg/k 5.5 mg/kg(n=15) (n=15) (n=24)
Clear Dose Response Across all Efficacy Endpoints
Low Dose Medium Dose High Dose
* Compounds disclosed on company websites
1. FDA CDER Pharmacology Review: application number 22-311, FDA CDER Clinical Pharmacology Review: application number 22-311, mean of studies at 0.24 mg/kg dose
2. Wong, RS et al. Mol Pharmacol. 2008 Dec;74(6):1485-95. doi: 10.1124/mol.108.049775 Stone_Hendrix_2007, Antimicrob Agents Chemother 51(7):2351-2358
3. Tamamura H, et al. FEBS Lett. 2003 Aug 28;550(1-3):79-83, calculated from Abraham_Peled_2017, Clin Cancer Res 23(22); 6790–801 (supplemental table 2) From
ClincalTrials.gov, accesed 23 January 2018, ongoing trials, e.g. COMBATà (NCT02826486)
4. In-house unpublished study POL6326-07. Intra-experiment comparisons must always be interpreted with caution11
12
Balixafortide + eribulin: PoC demonstrated with strong results across all efficacy parameters
12
13
38
0
10
20
30
40
50
60
70
Balixafortide (Ph Ib / PoC) Proof of Concept1—Improving treatment of advanced HER2 negative mBC2 (Open label, n=24)
Notes:
1 Reflects an indirect comparison
2 Metastatic Breast Cancer
3 "Embrace” Registration Trial for Eribulin
4 Polyphor trial – results from dose expansion cohort
5 Eribulin alone was 53% in EMBRACE pivotal trial and 64% in Capecitabine trial; Twelves et al., 2014; Cortes et al., 2011
Eribulin3 Balixafortide +
Eribulin4
Overall Response Rate
%
Progression Free Survival
3.6
6.2
0
2
4
6
8
Eribulin3 Balixafortide +
Eribulin4
Me
dia
n, m
on
ths
28
63
0
10
20
30
40
50
60
70
Eribulin3 Balixafortide +
Eribulin4
Clinical Benefit Rate
%
13.1
18
0
2
4
6
8
10
12
14
16
18
20
Overall Survival
Balixafortide +
Eribulin4Eribulin3
Me
dia
n, m
on
ths
Kaplan-Meyer CurvesDose Response in Phase Ib Study
13
Progression Free Survival
KM by dose
Overall Survival
KM by dose
5.5 mg/kg 5.5 mg/kg
Balixafortide+ Eribulin vs EMBRACE studies – Rationale for Phase III
14
PFS and Overall Survival in Phase 1b Study
Progression Free Survival
High Dose patients
Overall Survival
High Dose patients
Eribulin (EMBRACE) (n=459)
TPC (EMBRACE) (n=216)
Balixafortide+ Eribulin Overall (Phase 1b) (n=24)
Balixafortide+ Eribulin Confidence Interval (Phase 1b)
NOTE: Indirect comparison between studies.
Over 5 Times Safety Margin
Balixafortide is very well tolerated and has a high safety margin
Safety Margin* of Balixafortide13-week NHP toxicity study
Cmax AUC0
1
2
3
4
5
6
7
8
Safe
ty m
arg
in
15
No dose limiting toxicities in any dose cohort
In the expanded dose cohort (n=24 , 5.5
mg/kg). median patient treatment = 178 days
Mild Infusion Related Reactions observed
(76% in the Expanded Cohort and 48% in the
overall study population)
Observations from PoC/ Phase Ib study
*Safety Margins are calculated as multiples of Balixafortide plasma concentration at No Observed Adverse Effect Level (NOAEL) in 13
week NHP toxicology study compared to balixafortide plasma concentration in humans at 5.5mg/kg dose, which is the dose in the
Phase 3 FORTRESS study.
Timelines:
Clear development path with accelerated approval potential
16
Development and regulatory strategy in HER2 negative mBCa
Source: Company information
1 Fast track status granted
2 Conditional approval based on accelerated approval, timelines based on current
estimates for recruitment
3 Being reviewed to take into account EMA advice
Balixafortide +
eribulin in mBC
EOP1 FDAApproval
Fast Track 1
Phase Ib / PoC US/EU pivotal trial
2017 2018 2019 2020 2021 2022
Potential for accelerated FDA approval based on interim
analysis and application for Breakthrough designation2/3
FilingStart
Target timeline Potential accelerated timeline
Agreed on a single pivotal study with FDA and EMA for registration and launch. Fast track (FDA)
Parallel comparative study: Balixafortide+ eribulin vs. eribulin - 320 patients in 3rd line+ 64 in 2nd line
First readout on ORR in ~18 months (~end of Q1 21) - could lead to an accelerated approval in the US
Primary endpoint PFS, supported by positive OS trend and favorable risk/benefit
Exploratory analysis for patients with high CXCR4 expression
Target Indication: HER2 negative metastatic breast cancer, 3rd line (US), 2nd and 3rd line (Europe)
ORR PFS* OS*
* Event Driven Outcomes; timelines are indicative only
• No SoC is established in the treatment of Her2 negative metastatic Breast Cancer
• Multiple treatment options - all with similar, and limited, benefit
• High medical need for more efficacious therapies, without increasing toxicity in this setting
• Balixafortide could offer the opportunity for establishing a new SoCbased on relevant clinical improvements across all endpoints
• Scientific and clinical rationale for further extending this opportunity in Breast Cancer with other combinations - besides with eribulin
• In addition, CXCR4 is becoming an important and recognized target across a spectrum of indications
• Further opportunity to expand beyond breast cancer in a number of solid and haematological tumors
Significant opportunity in mBC; further opportunity beyond BCSignificant Market Opportunity
17
Market Opportunity - metastatic breast cancer, in combination with eribulin
18
Subtypes of Breast Cancer (% of Patients)
HER2- Metastatic1 Breast Cancer Incidence (‘000 Patients, 2018)
54
8.8
74
12.1
0
20
40
60
80
100
120
140
Incident patients Eribulin treated
75%
10%
10%5%
HER2-/HR+ HER2-HR- (TNBC)
HER2+/HR+ HEr2+/HR-
Balixafortide Target population
128
~21
US EU152
Notes:
1 Includes unresectable, locoregionally recurrent
2 EU 15 consists of Austria, Belgium, Denmark, Finland, France, Germany, Greece, Ireland, Italy, Luxembourg, The Netherlands, Portugal, Spain, Sweden and the UK
3 Calculation assumptions (2031): Price US as per comparators (8.8K EUR/Cycle), 2% increase; EU 3.6K EUR; incident patients growth 1.4%; 8 cycles/patient; US access
adjustment ~25%; EUR/US$= 1.145
Sources: Estimates as per leading management consulting firm commissioned by the company (2018) and calculated using data from Global Data, SEER, German Centre for Cancer
Registry, Institut National du Cancer, REDECAN, AIRTUM. Extrapolation from EU 5 to EU 15 based on population
HER2-85%
• Few Treatment Options
• Substantial unmet medical need
• Market opportunity US + EU153 – based on eribulin patients only:
USD 1.3B
• Potential further increased by establishing a new SoC and expanding use beyond eribulinpatients only
Notes:
1 Eribulin share of treatments lower than patients’ share because used in later lines (shorter duration) and use of combos
2 Assumes US split=Europe split and HER2-/HR+split equal to HER2-/HR+split
3 Includes new products mono/combination
Sources: Global data, analysis of a leading management consulting firm commissioned by the company (2018/9)
27.1%
11.5%
8.9%
5.3%
4.2%
2.0%
7.9%
33.1%
Taxanes+ Abraxane CapcitabineGemcitabine EribulinAntracyclines IxabepiloneOther monotherapies ³ Combinations
19
Market opportunity – metastatic breast cancer, other combinations
Split of total HER2-/HR+ chemo-therapy treatments by regimen
(US, 2018, % of total treatments1)
Preclinical program to validate possibility to expand use in breast cancer
FOR EXAMPLE
If balixafortide combination
could be expanded from
eribulin to taxanes/
Abraxane
MARKET POTENTIAL
USD 1.3+
6-7bn2
Rationale for the combination of CXCR4 inhibitors and taxanes
Wang Y et al., 2018
NT21MP negatively regulates paclitaxel-resistant cells by targeting miR-155-3p and miR-155-5p via the CXCR4 pathway in breast cancer.
Rationale for the combination of CXCR4
inhibitors and anthracyclines
Mahjoub MA et al., 2017
Combination treatment with dendrosomalnanocurcumin and doxorubicin improves anticancer effects on breast cancer cells through modulating CXCR4/NF-kB/Smoregulatory network.
Rationale for use of
Balixafortide in additional
combinations in breast cancer
Even without a biomarker, Balixafortide with Eribulin could generate a sizable
opportunity in mBC, based on superior outcomes
A biomarker specific strategy aimed at CXCR4 high expressers is being explored
CXCR4 expressers may have a substantially higher benefit
CXCR4 subpopulation is an exploratory end point in the Phase 3 study
New CXCR4 biomarker assay under development
A high CXCR4 expression targeting approach could further expand commercial potential
Bigger market: eribulin patients all CXCR4 expressers across chemos
Easier development of other indications
Better commercial sustainability: easier patient targeting, higher pricing/ better
access, further IP
20
With a CXCR4 expression biomarker Balixafortide could compete in a larger market with further
differentiation
Biomarker opportunity
21
Balixafortide in combination with Cytarabine (Ara-C)
Beyond Breast Cancer. CXCR4 correlates with poor outcomes in several cancers; Balixafortide showing positive results in AML
CXCR4 overexpression and PFS across cancer types
MD Anderson Cancer Center
Objective: CXCR4 and subtypes of breast cancer
Investigator: Prof. Debasish Tripathy
August, 2019
University of L’ Aquila, Italy
Objective: Balixafortide and solid cancer indication other than
breast cancer
Investigators: Dr. Claudio Festuccia and Prof. Roberto Giacomelli
June, 2019
University of Michigan
Objective: CXCR4-dependent signaling pathways.
(Preparatory study to be followed by 3-4 specific studies)
Investigator: Prof. Gary Luker
January, 2019
22
Preclinical Studies already started with top institutionsOther indications/ combinations
23
Opportunity to build a very significant franchise by expanding in broader mBC and to other indications
Long Term Balixafortide Strategy
2. Balixa – Eribulinin mBCA high
CXCR4 expressers
Breakthrough designation
3. Expansion to mBCA+ Taxanes
New Dosage/ administration
4. Expansion to other
indications/ Other
combination
‘Treatment paradigm for
CXCR4 related
disease’
1. Balixa– Eribulinin mBCA
Advantage:
Expand Balixafortide+
erib outside the currently
eribulin tx patients in later
lines
Breakthrough designation
could help in setting
balixafortide+ eribulin as
standard of care in 2nd/3rd
line
Advantage:
Would move from a large
indication into a ‘large MoA’-
as many successful oncology
and immunology drugs have
done
Increasing Potential
Advantage:
Would directly tap into the
‘king of chemos’ and
further drive earlier lines of
Tx in mBCA
Would further enlarge
population with a more
convenient scheme
BREAST BEYOND BREAST
Investment highlights
Immuno-Oncology
Cystic Fibrosis and Hospital Infections
Financials
Outlook
24
Agenda
1
2
3
4
5
Inhaled Murepavadin could change the treatment paradigm for CF patients
2/3 of CF patients have a Pseudomonas infection
Introduction of CFTR modulators has not changed the need for effective Pseudomonas control
Murepavadin exhibits strong preclinical efficacy, incl. resistant strains, and exposure
A mono-pathogen would be the most rational treatment vs broad spectrum agents (e.g microbiome impact)
Kidney organ toxicity not expected at inhaled dose strength -supported by first safety studies in mice and NHP
Low dose vs. IV (est.~1/10th)
Low systemic penetration (>5 fold)
Targeted, attractive orphan opportunity
Attractive orphan pricing
Comparators’ ** peak sales (200-400m USD)
Can be expanded from CF to NCFB*** and beyond
Substantial external financing and First Value Inflection point ~9 months form now
IMI Contribution up to Ph I included
CTA (Clinical Trial Application) by H1 20
* ACRCCM 2017, 195 ; 12:1617-28** Tobi and Cayston*** Non Cystic Fibrosis Bronchiectasis
25
Cystic FibrosisInhaled murepavadin: an attractive opportunity
Evolution of PA colonization after
ivacaftor treatment*
Up to EUR 5M
26
Strong in-vivo efficacy of murepavadin IT* in MDR/XDR strainsEfficacy in neutropenic lung infection models
* Intra Tracheal, proxy of inhaled
Antibiotics
New Mechanism of Action —
targets specifically outer-membrane proteins of gram-negative pathogens.
27
Source: Compound Interest (2014)
Antibiotics class active against gram-negative pathogens by year of discovery
β-Lactams
All contain a beta-lactam ring
Examples
Penicillins (shown) such as amoxicillin and
flucloxacillin; Cephalosporins such as cefalexin
Mode of action
Inhibit bacteria cell wall biosynthesis
Most widely used antibiotics
in the NHS
Aminoglycosides
Family of over 20 antibiotics
All contain aminosugar substructures
Examples
Streptomycin (shown), neomycin,
kanamycin, paromomycin
Mode of action
Inhibit the synthesis of proteins
by bacteria, leading to cell death
Tetracyclines
Becoming less popular due to
development of resistance
All contain 4 adjacent cyclic hydrocarbon rings
Examples
Tetracycline (shown), doxycycline,
limecycline, oxytetracycline
Mode of action
Inhibit synthesis of proteins
by bacteria, preventing growth
Macrolides
All contain a 14-, 15-, or
16-membered macrolide ring
Examples
Erythromycin (shown), clarithromycin,
azithromycin.
Mode of action
Inhibit protein synthesis by bacteria,
occasionally leading to cell death
Second most prescribed antibiotics in the NHS
Quinolones
All contain fused aromatic rings with a
carboxylic acid group attached
Examples
Ciprofloxacin (shown),
levofloxacin, trovafloxacin
Mode of action
Interfere with bacteria DNA
replication and transcription
Resistance evolves rapidly
198019701960195019401930Discovery
Commonly act as bacteriostatic agents, restricting growth and reproduction Commonly act as bactericidal agents, causing bacterial cell deathKey:
2010
O
R
O
O
OH
N
SH
HO
HO
HN
OO
OO
HOHO
N
N
NH2
H2N NH2
O
OH
OH
NH2
HO
O O
FOH
NNHN
HO
O OH
NH2
OH
OHOH OOH
N
NCH3
O
O
OHHO
C2H5 OCH3OOH
HOO
CH3
OH
O
O
OMPTA
Targets critical
gram negative pathogens
O
“OMPTA”* could become first gram negative antibiotics to be introduced in the last 50 years
*Outer Membrane Protein Targeting Antibiotics
28
Targeting the most resistant gram-negative ESKAPE1 pathogens
New OMPTAs – Strong efficacy, low resistance and largely externally financed
Gram-negative infections with limited treatment options
28
Notes:
1 ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.
Up to CHF 11.5M+ Up to
USD 5.6M
MICs (μg/ml) against resistant isolates POL7306 vs. Other antibiotics -Serial Passage on select strains
Investment highlights
Immuno-Oncology
Cystic Fibrosis and Hospital Infections
Financials
Outlook
29
Agenda
1
2
3
4
5
CHF 97.2 million in cash and cash equivalents as of June 30, 2019
Net cash used in operating activities of CHF 36.8 million in H1 2019,reflecting significant clinical trial investments
Operating Cost Guidance for the FY 2019 60-65 million. End of year Cash68-72 million
Company funded until the next value inflection points
Timelines and potential milestone payments for existing and potential newpartnerships are not disclosed.
30
Financial highlights
Investment highlights
Immuno-Oncology
Cystic Fibrosis and Hospital Infections
Financials
Outlook
31
Agenda
1
2
3
4
5
2019 2020 2021 2022
3232
Overview
Overall plan
Notes:
1 Fast track status granted
2 ORR: Overall Response Rate
3 PFS: Progression Free Survival
4 OS: Overall Survival
5 AML: Acute Myeloid Leukemia
6 CTA= Clinical Trial Application (similar to IND, for Europe)
Balixafortide
Eribulin combo
Other combo/
indicationsOther combination studies (eg AML5)
Target timeline
Approval
accelerated
ORR2
readout
Fast Track 1
Antibio
tics
Imm
uno-O
ncolo
gy
Potential accelerated timeline
PoC7CTA6
US/ EU pivotal trial
PFS3
readout
OS4
readout
Approval
standard process
Filing
accelerated
Inhaled
murepavadin (CF)Preclinical studies Phase Ia Phase Ib/2a (CF)
Preclinical studies Phase I Phase II
CTA6 Phase II
results
Preclinical studies
OMPTA8
7. PoC= Proof of Concept
8. Timelines refer to lead candidate, POL7306
Investment Highlights
2 Proprietary Macrocycle Technology Platform – discovery engine in oncology & antibiotics
5 Antibiotic pipeline : Inhaled murepavadin aimed at CF and OMPTAs, the first new class of antibiotics against gram negative pathogens in 50 years - both largely externally financed. In addition, POL6014 (respiratory-outlicensed)
Polyphor: Innovative biopharmaceutical company with a Phase III immuno-oncology compound with fast path to market and a strong pipeline
1
33
3 Balixafortide: Potentially best in class CXCR4 inhibitor. Phase III in HER2-negative metastatic breast cancer in combination with eribulin, based on strong PoC data. First readout (ORR) expected around end of Q121
Market potential USD 1.3+ bn in combination with eribulin; up to 6-7bn if expanded to combinations with taxanes in breast cancer - and more if to other combinations/ indications
4
6 Experienced management team with strong support from leading investor base
7 Financed to achieve the next value inflection points
33
Polyphor Ltd | Hegenheimermattweg 125 | 4123 Allschwil | SwitzerlandT +41 61 567 16 00 | [email protected] | www.polyphor.com
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