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December 2019
2
Disclaimer This presentation contains forward-looking statements that include information about possible or assumed future
results of the business, financial condition, liquidity, results of operation, clinical program, plans and objectives of
Pharma Mar, S.A. ("PharmaMar" or the "Company"). These forward-looking statements can be identified by the
use of forward-looking terminology such as “may,” “will,” “should,” “expect,” “endeavor,” “anticipate,” “project,”
“estimate,” “intend,” “continue” or “believe” or the negatives thereof or other variations thereon or comparable
terminology. These forward-looking statements are based on the expectations of management under current
assumptions at the time of this presentation, are not guarantees of future performance and are subject to risks
and uncertainties that could cause actual results to materially differ from those contained in the forward-looking
statements. All forward-looking statements in this presentation apply only as of the date made. Except as required
by law, the Company is not obligated to, and does not intend to, update or revise any forward-looking statements,
whether as a result of new information, future events or otherwise. To the extent that this presentation contains
market data, industry statistics and other data that have been obtained from, or compiled from, information made
available by third parties, the Company has not independently verified their data.
This presentation is made pursuant to Section 5(d) of the U.S. Securities Act of 1933, as amended, and is
intended solely for investors that are either qualified institutional buyers or institutions that are accredited
investors (as such terms are defined under U.S. Securities and Exchange Commission ("SEC") rules) solely for
the purpose of determining whether such investors might have an interest in a securities offering contemplated by
the Company. Any such offering of securities will only be made by means of a registration statement (including a
prospectus) to be filed with the SEC, after such registration statement has become effective. This presentation
shall not constitute an offer to sell or the solicitation of an offer to buy these securities, nor shall there be any sale
of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.
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INVESTMENT H IGHLIGHTS
Leader in development & commercialization of marine derived oncology drugs
Global integrated biotech developing marine-derived and novel MoA oncology drugs
Established oncology sales force in Europe
Late stage pipeline: Transformative time for PharmaMar
Revenue generating company
• Strong partners in the US (Jazz and Janssen), Japan (Taiho), Australia (STA),
• Zepsyre® (lurbinectedin) relapsed small cell lung cancer (“SCLC”) monotherapy NDA filed Dec. 17th 2019
• Zepsyre® ATLANTIS combo with Doxo randomized trial to read out ~2020
• FY'18 revenues € 108.8mm
• ~ € 540mn market cap. (~ $600mn)1
• Shares listed on the Spanish Stock Exchanges under the symbol “PHM”
1. As of December 18th 2019
• 2 approved oncology drugs, Yondelis® and Aplidin ®
• 1 oncology candidate, Zepsyre® filed FDA December 17th 2019
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PharmaMar & Jaz z Pharmaceut ica ls
• PharmaMar to receive an up-front payment of US $200 million
• An additional US $250 million through full regulatory approval in the US for SCLC
• PharmaMar is eligible to receive tiered royalties on net sales ranging from the high
teens up to 30%
• In addition, sales milestones of up to US $550 million
• This income may be further increased, if other therapeutic indications are approved
• PharmaMar also retains production rights and will supply the product to Jazz
Sign a license and distribution agreement for lurbinectedin in US, 19th December 2019
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TRANSFORMATIVE T IME FOR PHARMAMAR
Transformative
time
Lurbinectedin: Pipeline within a drug (e.g.
ovarian, sarcoma, Pan-small cell, etc.
Expand R&D vertically and horizontally
BD: seek synergistic
assets
MoA oncology drugs
5
>6
UNIQUE FULLY INTEGRATED PLATFORM
Regulatory inspections passed from FDA, AEMPS, PMDA (US, Spain/EU, Japan)
Expeditions
and Collection
Cell Biology
Chemistry &
Preclinical
Pharmaceutical
Development &
Operations
Clinical &
regulatory Commercial
• Marine derived leads
• Global expeditions
• Over 200,000 samples
• Screening of antitumoral
activity
• Synthesis & molecule
optimization
• Patent protection
• Preclinical studies
• FDA inspected production
facility
• GMP Production
• New drug candidates
• New ADC Payloads
• Clinical trials
• Post marketing
trials
• Oncology-focused
sales force in Europe
(~ 65 people)
• Geographic licensing
& partnering with
experienced companies
>7
YondelisSoft tissue sarcoma 2nd/3rd line Single agent
Ovarian cancer 2nd/3rd line (1) Yondelis+Doxil(2)
Aplidin R/R Multiple Myeloma 3th/4th line (3) Aplidin+Dexameth
Zepsyre
Small cell lung cancer relapsed Zepsyre+Doxo(4)
Basket trial (small cell lung cancer
expansion cohort)Single agent
Basket trial (other) (5) Single agent
Solid tumorsSingle agent
and combinations
PM184 Solid tumorsSingle agent
and combinations
PM14 Solid tumors Single agent
Program / Indication Phase I Phase II Phase III Market
ATLANTIS
(1) Not approved in the USA
(2) Pegylated liposomal doxorubicin (PLD)
(3) Approved in Australia
(4) Doxorubicin
(5) Breast BRCA+, Head & neck, Endometrial, Biliary tract, Ewing sarcoma, NET, Germ cell, CUP
OUR ONCOLOGY PORTFOLIO:
December 17th 2019:
filed monotherapy NDA
for Accelerated Approval
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LURBINECTEDIN: MoA
A Selective Inhibitor of Oncogenic Transcription
Harlow et al, 2016; Cancer Res 72: 6657-68
Harlow et al, 2019; Clin Cancer Res doi: 10.1158/1078-0432.CCR-18-3511
Santamaría et al, 2016. Mol Cancer Ther 15:2399-412
Cancer is frequently a transcriptional disease caused
by deregulated oncogenic transcription factors
Promoter
Lurbinectedin
ARID1A
Transcription
Factors
SWI/SNF
SWI/SNF
ARID1A
DNA
Induction of Tumor C<ell Proliferation
Inhibition of Immune Response
Activation of Immune Checkpoints
Induction of
angiogenesis
TAMs
VEGF
IL-8
IL-6
IL-8
CCL2
IL-6
By inhibiting active transcription in Tumor
Associated Macrophages (TAMs), lurbinectedin
downregulates IL-6, IL-8, CCL2 and VEGF
Selectively inhibits active transcription of protein-coding genes
through binding to promoters and irreversibly stalling elongating
RNA polymerase II on the DNA template, thereby leading to
double-stranded DNA breaks and apoptosis.
Dr. Luis Paz Ares
>
ZEPSYRE®
SCLC
Relapsed
Combo
Doxorubicin
Basket trial SCLC cohort Single agent
Basket trial (other) Single agent
Solid tumors
Single agent /
combinations
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PIPEL INE - ZEPSYRE ® (LURBINECTEDIN)
Development and commercial strategy
ATLANTIS
CLINICAL PROGRAM/ INDICATION PHASE I PHASE II PHASE III MARKETClinical Program / Indication Phase I Phase II Phase III Market
Commercialization Plans:
• EU: Utilize/expand existing Yondelis sales force and select regional distributors
• US: Licence and distribution agreement with Jazz
• ROW: Regional partnerships
December 17th 2019:
filed monotherapy NDA
for Accelerated Approval
>10
ZEPSYRE ®: SCLC
Market overview: Orphan drug designation granted in the United States and EU
Decision Resources, Inc. expects that in 2018,
there will be approximately 61,300 new cases
of small cell lung cancer in the EU2
The American Cancer Society expects that in 2018
there will be approximately 35,000 new cases of
small cell lung cancer in the United States1
• SCLC represents a significant unmet medical need with limited late stage options.
• The 5-year survival rate is about 5%-10%3
• 2nd line Standard of Care: Topotecan; Median TTP ~3m; OS ~6m4
• Last FDA approved NCE for 2nd line, Topotecan (iv) 1996, (only sensitive patients)
• PHM internal market research estimates ~75% of patients get treated in 2nd line
Sources:
1, American Cancer Society
2. Data Monitor: Small cell lung cancer (SCLC) Market Spotlight, May 1 2018
3. http://www.cancer.gov/types/lung/hp/small-cell-lung-treatment-pdq
4. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022453s002lbl.pdf
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SC LC OVER TH E YEA R S; FA R LESS PR OGR ESS TH A N IN N SC LC
NSCLC
AlkylatingAntimetabolitesAntiangiogenesisMicrotubuleIOEGFRTKITRK
11
Adapted from ; Sabari et al, Clinical Oncology; September 2017 FDA approval
1985 1990 1995 2000 2005 2015 2018 2019
Carboplatin+Etoposide
1999
Topotecan1996
Cisplatin+Etoposide
1985
First line
Second line
Third line
SCLC
Nivolumab2018
Atezolizumab+
Carboplatin+Etoposide
2019
Pembrolizumab
2019
>12
"SCLC is difficult to treat in part because you can’t target an absent protein the way you can target a mutant protein—there’s
nothing against which a drug can be directed“
Rudin C. Looking Ahead to New Therapies in Small Cell Lung Cancer. Clinical Advances to Hematology & Oncology 2018:16 (4): 269-272
Drug class failures 2nd line SCLC
• Aurora Kinase
• BCL2
• C-Kit
• DLL-3
• EGFR
• FLT3
• HDAC
• IGF
• mTOR
• PD1
• Proteosome inhibitor
• VEGF
>13
ZEPSYRE ®: SCLC
USA: Current and emerging treatment paradigm#
1st LINE 3rd LINE
Durv/Trem*
Pembro*
Irinotecan1*
Paclitaxel1*
Docetaxel1*
Temozolomide1*
Nivo*+/-Ipi1*
Pembro1*
Lurbinectedin* RRx-001*
Dinutuximab*
Onivyde*
Nivolumab
Pembro
2nd LINE
• Investigational drug or not approved for this indication/line
1. All drugs listed in NCCN guidelines v1.2020
2. Only with relapse >6m; for pts who relapse >6m after Atezo maintenance, recommendation is to rechallenge with carbo/etoposide without Atezo
** Durvalumab filed with FDA ~Q4 2019
# Recruitung trials for NCEs in US and /or EU
13
Durv/Trem*P3 trials#
FDA APPROVEDDRUGS SCLC
NCCNGuidelines
Vinorelbine1*
Oral etopoide1*
Gemcitabine1*
CAV1*
Bendamustine1*
Rechallenge2
Platinum/Etoposide/
AtezolizumabTopotecan
MAINTENANCE
Durvalumab1*
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IMMUNOTHERAPY GRAVITAT ING TO F IRST AND TH IRD L INE
First-Line +maintenance
• Atezolizumab (Impower 133)
• Durvalumab (CASPIAN)
First-Line Maintenance
• Nivolumab +/- Ipilimumab (CheckMate 451)
Second-Line
• Nivolumab vs chemo (CheckMate 331)
• Atezolizumab vs chemo (IFCT-1603)
Third-Line
• Nivolumab +/- ipilimumab (CheckMate 032)
• Pembrolizumab (Keynote 028 & 158)
Negative trials
Single arm studies
?
14Source: Dr. Jacob Sands, Solebruy Trout KOL day Nov 15 2019
>15
COMBO(2):
• Combo with Doxorubicin (in NCCN guidelines within CAV)
• Phase II n=27 saw OS 10.2m in CTFI 30+ (n=21)
• Phase III ATLANTIS fully accrued 613 pts;
OS endpoint expected 2020
• Stable brain mets allowed
• Dosing Lurbi 2mg/m2 + 40mg Doxo/m2
• Phase III prophylaxis G-CSF
MONO(1):
• Mono 57% sensitive, 21% resistant
• Phase II basket trial expansion n=105 with CTFI>0
• Primary endpoint ORR (investigator) 35%
• ITT OS 9.3m
• No brain mets
• Lurbi dose 3.2mg/m2
• G-CSF (22%)
ZEPSYRE® SCLC: 2 TR IALS, 2 PROTOCOLS, 2 POPULATIONS
1. Source: ASCO 2019
2. Source: IASLC 2018
Monotherapy NDA filed 17th Dec. 2019 for
Accelerated Approval for relapsed SCLC
Combo read out data expected during 2020 for
relapsed SCLC
>16
COMBINATION: Lurb inected in + Doxorub ic in
>17
ZEPSYR E®: PH A SE I / I I 2nd L IN E SMA LL C ELL LU N G C A N C ER
Combination Doxorubicin:
Source: Forster et al IASLC 2018 “Overall Survival with Lurbinectedin Plus Doxorubicin in Relapsed SCLC. Results from an Expansion Cohort of a Phase Ib Trial”; except *DOR data from ESMO 2017
n=27L2 mg/m2 D1
+ DOX 40 mg/m2 D1
4%
33%
37%
37%
26%
74%
5.2m
3.4m
7.9m
Response
Evaluable patients
CR
PR
ORR
SD
PD
Disease Control Rate
Duration of Response*
PFS
Overall Survival
Lurbinectedin + DOX (q3wk)
n=21CTFI>30d
5%
43%
48%
33%
19%
81%
n/a
5.3
10.2
Lurbinectedin + DOX (q3wk)
>18
ZEPSYRE ®: PHASE I I I RELAPSED SMALL CELL LUNG CANCERATLANTIS Trial Design SCLC (Trial initiated August 2016); Anticipate data ~ 2020
Arm A:
Zepsyre (2mg/m2) & Doxo (40 mg/m2)
(up to 10 cycles)
Arm B:
Topotocan or CAV
(42%/58%)
R
(1:1)
• Primary endpoint: median OS HR ≤ 0.75 with 90% power at ~510 events.
Control arm modelled for ~7.5m
613 patients recruited in >150 centers; 20 countries; EU & N. Am accounts ~ 90%
• Registration Strategy
- 5 Safety analyses passed (IDMC)
- PharmaMar announced ATLANTIS reached target enrollment July 2018
- Data anticipated 2020
- Trial supported by ongoing monotherapy trial (n=105).
Stratification by prior PD1/PD-L1, CTFI, and CNS mets .
Eligible SCLC pts
1prior platinum
N=613
No Crossover
Primary GCSF required in both arms
Zepsyre mono (following doxo
maximum cumulative dose) at
3.2 mg/m2 q3w until PD
>19
MONOTHERAPY: Lurb inected in
Overall
(n=105)
ORR, %
(95% CI) (confirmed responses) # ^
35.2
(26.2-45.2)
ORR, %
Resistant CTFI< 90 days (n=45)
22.2
(11.2-37.1)
ORR, %
Sensitive CTFI = 90 days (n=60)
45.0
(32.1-58.4)
Duration of response (months), median
(95% CI)
5.3
(4.1-6.4)
Disease Control Rate *, %
(95% CI)
68.6
(58.8-77.3)
MONOTHERAPY FINAL DATA: ASCO 2019
# 5 of 8 patients who failed prior immunotherapy had confirmed response
^ Tumor assessments performed every 2cycles until cycle 6 and every 3 cycles thereafter
* Disease Control Rate: Response or SD
Dr. Luis Paz Ares
Decrease in tumor size in 65% patients
Efficacy
20
Safety: Related or Unknown Adverse Events
* Per protocol: dose had to be reduced in case of grade 4 neutropenia
Dr. Luis Paz Ares
Treatment Related (or Unknown) Adverse Events (AEs) ( >5% or Gr 3-4)
* Lab abnormalities associated with a specific treatment, were considered a SAE, or were reasons for dose reduction or treatment delay
MONOTHERAPY FINAL DATA: ASCO 2019Safety
21
n=105 n (%)
AEs 89 (84.8)
- Gr ≥3 36 (34.3)
SAEs 11 (10.5)
AEs leading to death 0 (0.0)
AEs leading to treatment
discontinuation2 (1.9)
Dose delays treatment related 21 (22.1*)
Dose reductions # 25 (26.3*)
G-CSF 23 (21.9)
Transfusions (red blood cells
and/or platelets)10 (9.5)
n=105 Gr 1-2 Gr 3-4n (%) n (%)
Hematological AEs *Neutropenia 6 (5.7) 24 (22.9)
Anemia 2 (1.9) 7 (6.7)
Thrombocytopenia 2 (1.9) 5 (4.8)
Non-Hematological AEs
Febrile neutropenia . 5 (4.8)
Fatigue 54 (51.4) 7 (6.7)
Nausea 34 (32.4) .
Decreased appetite 22 (21.0) .
Vomiting 19 (18.1) .
Diarrhea 13 (12.4) 1 (1.0)
Constipation 10 (9.5) .
Pneumonia . 2 (1.9)
Alanine aminotransferase increased *
. 2 (1.9)
Skin ulcer . 1 (1.0)
>22
PFS TO PR IOR IO AND PFS AFTER LURBINECTEDIN
Prior IO
PFS prior IO PFS Lurbinectedin
>23
NDA F IL ING – A C C ELER ATED A PPR OVA L MILESTONES
D0
Request
Priority Review
SUBMIT
Filing
Orientation
Meeting
D30 D60
6-months Priority Review
90-day
Safety Update
Month 3
Mid-cycle
Review
ACTION
LETTER
Month 5
Late-cycle
Review
Month 8
PDUFA
target date
NDA
FILED
16th Dec 2019 16th Jan 2020 mid May 2020 mid August 2020
30-day
CMC
Approval
mid March 2020
D74
Notification
>24
EU
New per year1 ~60000
% treated 2nd line2 ~40%
DOR3 5.3m
Annual Px IO front line5 $62-63k
Annual Px IO 3rd line5 $53-54k
Market Share ?
USA
New per year1 ~35000
% treated 2nd line2 ~60%
DOR3 5.3m
Annual Px IO front line4 $177-180k
Annual Px IO 3rd line4 $150-153k
Market Share ?
MODELLING BASICS: FOR ILLUSTRATIVE PURPOSES ONLY
1. See slide 92. Internal estimates3. From ASCO 2019 data4. WAC USA5. Assumed EU average price ~35% USA
>25
ZEPSYRE ®: KEY IP AND BARRIERS TO ENTRY
US EU
25
Use patent
Orphan drug
Composition of matter
Grants exclusivity in SCLC
for 7 years from approvalGrants exclusivity in SCLC
for 10 years from approval
Protection until 2022*
Protection until 2031#
Protection until 2025*
Protection until 2031#
*Subject to potential patent term extension
#Pending patent
Formulation Protection until 2025Protection until 2028
>26
YONDELIS ®: KEY IP AND BARRIERS TO ENTRY
US EU
26
Use patent
Orphan drug
Formulation
2023 Sarcoma 2019 Ovarian cancer
Protection until 2025
Protection until 2021
Protection until 2028
Protection until 2021
Japan
Manufacturing
2022 Sarcoma
Protection until 2030
Protection until 2022
Protection until 2021
>27
0,0
20,0
40,0
60,0
80,0
100,0
120,0
2015 2016 2017 2018
64,6
94,3 90,680,2
30,8
16,916,7
28,6
107.3 108.7
0
10
20
30
40
50
60
70
80
2015 2016 2017 2018
55,6
72,3 7163,7
5,7
4,9 5,3
5,12,2
2,4 1,9
4,9
73.7
78.2
Net Operating cash flow
2015: €-11mn
2016: €-8.4mn
2017: €-1.4mn
2018: €-16.3mn
111.2
95.4
79.6
63.5
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KEY EVENTSCatalyst calendar
• Zepsyre® monotherapy SCLC basket trial oral presentation ASCO June 1st 2019
• Zepsyre® monotherapy FDA grants Accelerated Approval path
• Zepsyre® monotherapy filed Accelerated Approval USA December17th 2019
• Partnership agreement for US rights signed with Jazz Pharma
• USA EAP open year-end 2019
• Zepsyre® monotherapy NDA accept q1 2020
• Zepsyre® monotherapy PDUFA ~q3 2020
• Zepsyre® ATLANTIS data (2020)
• Zepsyre® potential US launch 2H 2020
• File Zepsyre® with EMA
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