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CORPORATE PRESENTATIONMarch 2021
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.
3
INVESTMENT HIGHLIGHTS
We are inspired by the sea, driven by science, and motivated by patients with serious diseases to improve their lives by delivering novel medicines to them. We intend to continue to be the world leader in marine medicinal discovery, development and innovation.
Global integrated commercial stage biotech developing marine-inspired and novel MoA oncology drugs
• 3 approved oncology drugs, Yondelis®, Aplidin® and Zepzelca®• Zepzelca® approved by FDA 15th June 2020; Launched in USA 7th July 2020
Established oncology sales force in Europe
• Strong partners in the US (Jazz, Janssen), Japan (Taiho), Australia (STA)• Active BDL in-licensing effort
Late-stage pipeline: Transformative time for PharmaMar
• Zepzelca® (lurbinectedin) development plan in SCLC and other solid tumor indications emerging• Pipeline drugs maturing; two new compounds to enter clinic in 2021
Revenue generating company
• FY’20 revenues €269.9 mm. • ~€2bn market cap. (~$ 2,4bn1)• Cash 2020 €216.5mm (~$260mm)• Shares listed on the Spanish Stock Exchanges under the symbol “PHM”
(1) As of 1st March 2021
THE PLAN FOR 2021 GROWTH
• 3 commercial products; Yondelis®, Aplidin®, Zepzelca®• Potential lurbinectedin approvals in other countries.
• 2 Phase III trials recruiting (confirmatory trial in 3rd line SCLC, relapsed mesothelioma)• 2 Phase II trials for PM14 recruiting and 2 new compounds entering phase I
• Looking for in-licensing products to market in EU, in 2021• Profitable, cash-flow positive, with significant cash
Transformative Time
INORGANIC
CLINICAL
ORGANIC
5
Expeditions & collection
UNIQUE FULLY INTEGRATED PLATFORM
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
Clinical trials
Post marketing trials
Oncology-focused sales force in Europe (n=~65)
Geographic licensing & partnering with
experienced companies
(~13 companies)
Regulatory inspections passed from FDA, AEMPS, PMDA (US, Spain/EU, Japan)
SIGNED A LICENSEAND DISTRIBUTION
AGREEMENT FOR ZEPZELCA® IN US
PHARMAMAR & JAZZ PHARMACEUTICALS
• PharmaMar received an up-front payment of $200 million in January 2020
• PharmaMar received accelerated approval regulatory milestone payment of
$100 million in June 2020 and can receive up to $150 million more for full
regulatory approval of Zepzelca® by FDA within certain timelines
• Jazz launched, and added to NCCN guidelines July 7th 2020
• PharmaMar is eligible to receive tiered royalties of between high teens and 30%
on net sales, and sales milestones of up to US $550 million
• Milestones & royalties may increase if other indications are approved
• PharmaMar retains production rights and will supply the product to Jazz
19TH DECEMBER 2019
JAZZ PHARMACEUTICALS LAUNCH METRICS1
• 72 total sales reps: ~100 total commercial infrastructure
• WAC: $6,633 per vial, annualized equals $227k assuming 2 vials per pt per cycle (3wks)
• Based on average BSA, a patient would require 2 vials per 21-day cycle
• Cost per course of therapy, based on median of 4 cycles, would be ~$53k
• 'Multi-hundred million dollar opportunity’ with 3-5 year route to peak in current indication
• 1st (incomplete) quarter of US net sales termed ‘successful’ ~$37mm2
1. Source: Jazz Zepzelca investor update slides, June 17 2020”2. November 2 2020 Jazz earnings report PR3. Source Jazz presentation 1/11/2021
ZEPZELCA®LAUNCHED AND AVAILABLE IN USA JULY 7th 2020;
Added to NCCN guidelines same day
OUR ONCOLOGY PORTFOLIO; SELECTED CLINICAL TRIALS
Yondelis®Soft 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+Dexa
Zepzelca®(Lurbinectedin)
Small cell lung cancer 2nd line Single agent
≥2nd line mesothelioma(Phase III planned start 2021)
Lurbi+IO
Confirmatory Phase III study for FDARegistration study for EMA
(Planned start 2021)Single agent
Small cell lung cancer 2nd line Lurbi+Iriontecan
IST Combos 2nd line SCLCLurbi+Atezo
Lurbi+Pemrbo
PM14Solid tumors 4 Single agent
Soft tissue sarcoma Combination radiation
Program / Indication Phase I Phase II Phase III Market
(1) Not approved in the USA(2) Pegylated liposomal doxorubicin (PLD)(3) Approved in Australia(4) Envisaged potential cohorts include Ewing’s sarcoma, relapsed ovarian, 2nd line endometrial, pan small-cell (ex lung)
PROMOTER
Cancer is frequently a transcriptional disease caused by deregulated oncogenic transcription factors
A Selective Inhibitor of Oncogenic Transcription
LURBINECTEDIN (ZEPZELCA®): MoA
TranscriptionFactors
SWI/SNFLurbinectedin
SWI/SNF
ARID 1A
ARID 1A
By inhibiting active transcription in Tumor Associated Macrophages (TAMs), lurbinectedin downregulates
IL-6, IL-8, CCL2 and VEGFSelectively 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.
INDUCTION OFTUMOR CELL
PROLIFERATION INHIBITION OF IMMUNE
RESPONSE ACTIVATION OF
IMMUNE CHECKPOINTS
INDUCTION OFANGIOGENESIS
Harlow et al, 2016; Cancer Res 72: 6657-68Harlow et al, 2019; Clin Cancer Res doi: 10.1158/1078-0432.CCR-18-3511Santamaría et al, 2016. Mol Cancer Ther 15:2399-412
Dr. Luis Paz Ares
IL-6IL-8
VEGFIL-8
CCLIL-6
TAMs
DNA
In 2019 there were approximately 30,000
new cases of small cell lung cancer in the
United States1
Orphan Drug Designation grantedin the United States and EU
SCLC MARKET OVERVIEW
Estimated that in 2018, there were approximately
61,300 new cases of small cell lung cancer
in the EU2
• SCLC represents a significant unmet medical need with limited late-stage options.
• The 5-year survival rate is about 5%-10%3
• Prior to Zepzelca® last FDA approved NCE for 2nd line Topotecan (iv) 1996,
(only sensitive patients). Median TTP ~3m; OS ~6m4
1, American Cancer Society and SEER Cancer Stat Facts https://seer.cancer.gov/statfacts/html/lungb.html
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
Sources:
NSCLC
AlkylatingAntimetabolitesAntiangiogenesisMicrotubuleIOEGFRTKITRK
Adapted from ; Sabari et al, Clinical Oncology; September 2017 FDA approval
Carboplatin+Etoposide
1999
Topotecan1996
Cisplatin+Etoposide
1985
First line
Second line
Third line
SCLC
Durv or Atezo+ Carboplatin+
Etoposide2019
1985 1990 1995 2000 2015 2018 2019 2020
Zepzelca®2020
SCLC OVER THE YEARS; FAR LESS PROGRESS THAN IN NSCLC
WHY IS SCLC SO HARD TARGET?
Drug class failures 2nd line SCLC
• Aurora Kinase• BCL2• C-Kit• DLL-3• EGFR• FLT3• HDAC• IGF• mTOR• PD1 • Proteosome inhibitor• VEGF• GD2
"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
ZEPZELCA® LURBINECTEDIN: SCLCUSA: Disease Targeting Treatment Paradigm
1st LINE 3rd LINE
Bendamustine1*
CAV 1*
Docetaxel 1*
Gemcitabine 1*
Irinotecan 1*
Nivo 1* @
Onivyde4*
Data expected Dec 2022
2nd LINE
P3 trials#*****
FDA APPROVED
NCCNGuidelines(not FDA appvd)
Oral etopoide@ 1*
Paclitaxel 1*
Pembro 1*@
Rechallenge 1*2
Temozolomide1*Vinorelbine 1*
Platinum/Etoposide +Atezolizumab or Durvalumab
Zepzelca®Topotecan (sensitive)
RRx-001*
Pembro-Olaparib*
Nivo*
Tiragolumab*
• Investigational drug or not approved for this indication/line1. All drugs listed in NCCN guidelines v1.2021 alphabetically2. Only with relapse >6m; for pts who relapse >6m after Atezo or Durv maintenance, but who are not on maintenance atezo or durv at time of relapse3. @ Not recommended for pts who relapse while on maintenance Atezo or Durv. For those who relapse after >6m, recommendation is re-treatment with original regimen ex Atezo or Durv4. Source: https://clinicaltrials.gov/ct2/show/NCT03088813?term=Onivyde&recrs=ab&draw=2&rank=2
ATLANTIS REFLECTIONS
• Did not meet primary endpoint, however was arm numerically greater on OS
• Showed efficacy and safety advantages over control
• Topo introduces a patient selection bias that did not help lurbi arm
• Mandatory primary GCSF helped control arm more than lurbi arm
• Lower dose of 2.0mg/m2 vs. 3.2 not justified by addition of doxorubicin
• Will not serve as confirmatory trial
• Planning to submit to medical meeting for 2nd half of 2021
• Reinforces the clinical utility of lurbinectedin in relapsed SCLC, especially compared to alternatives
• US launch and EU reimbursed EAP programs underline the large unmet medical need and clinical utility, especially during COVID due to once every 3wk dosing
Phase III Lurbi+ doxorubicin vs. Physician’s choice of Topo or CAV
LURBINECTEDIN MONOTHERAPY
• Phase II basket trial expansion n=105 in 2nd line SCLC, with CTFI*>0
• Population: Mono 57% sensitive, 21% resistant, 22% refractory
• Primary endpoint ORR (investigator) 35%
• ITT OS 9.3m
• No brain mets
• Lurbi dose 3.2mg/m2
• G-CSF use 22% (not primary)
• AEs leading to death or discontinuation 2%
• Convenience of once every 3wk dosing a positive differentiator
1. FDA label https://www.accessdata.fda.gov/drugsatfda_docs/label/2020/213702s000lbl.pdf2. Source: ASCO 2019* Chemotherapy free interval: time in days from progression on prior chemotherapy
Approved by FDA for relapsed SCLC June 15 20201
MONOTHERAPY COHORT FROM BASKET TRIAL2
LURBINECTEDIN
MONOTHERAPY: BASIS OF FDA APPROVALJUNE 15TH 2020
• Monotherapy for SCLC
• Phase II basket trial expansion n=105 with CTFI>0
• 57% sensitive, 21% resistant; 22% refractory
• Primary endpoint ORR (investigator) 35%
• ITT OS 9.3m
• No brain mets
• Lurbi dose 3.2mg/m2
• G-CSF use (22%)
MONOTHERAPY LURBINECTEDINFINAL DATA: ASCO 2019
Efficacy
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)
# 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
PFS TO PRIOR IO AND PFS AFTER LURBINECTEDIN
PFS prior IO PFS Lurbinectedin
Dr. Luis Paz Ares
MONOTHERAPY FINAL DATA: ASCO 2019Safety
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 3-4
n (%) 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 aminotransferaseincreased *
. 2 (1.9)
Skin ulcer . 1 (1.0)
* Per protocol: dose had to be reduced in case of grade 4 neutropenia * Lab abnormalities associated with a specific treatment, were considered a SAE, or were reasons for dose reduction or treatment delay
Safety: Related or Unknown Adverse Events Treatment Related (or Unknown) Adverse Events (AEs) ( >5% or Gr 3-4)
LURBIDECTEDIN 2ND/3RD LINE IN MALIGNANT PLEURAL MESOTHELIOMA
An international, multi-centre, single-arm, phase II trial
• Swiss cooperative group SAKK trial N=42
• Progression on one prior platinum line; one additional line IO also allowed
• No CNS mets
• Primary endpoint PFS at 12 wks; null hypothesis ≤35%; alternate hypothesis 55% (corresponds to PFS 3.5m)
• ORR 5%; DCR 52%
• PFS 52%, 4.1m
• DCR 6.6m
• OS 11.1m
• G3-4 AEs (>10%): Neutropenia 24%, Fatigue 17%, FN 10%)
Presented ESMO 20191
Source: 1. Metaxas et al. Annals of Oncology, https://pubmed.ncbi.nlm.nih.gov/32085891/
In 2019 there were approximately 2,500
new cases of MPM in the United States1
MALIGNANT PLEURAL MESOTHELIOMA MARKET OVERVIEW
Estimated that in 2018, there were approximately
10,000 new cases of MPM
in the EU282
• MPM represents a significant unmet medical need with limited late-stage options.
• Average latency period 35-40 years3
• Treatment rate in 2nd line 67%4; 3rd line 38%5
• Median OS ~12m from diagnosis
1. https://www.cancer.org/content/dam/CRC/PDF/Public/8733.00.pdf
2. RARECARENET applying the EU crude incidence 2000-2007 to the EU28 population of 2014; main countries UK, Italy, Germany, France
3. https://www.mesothelioma.com/mesothelioma/latency-period/
4. Zalcman et al ; Bevacizumab for newly diagnosed pleural mesothelioma in the Mesothelioma Avastin Cisplatin Pemetrexed Study (MAPS): The Lancet. December 2015
5. Hassan et al: Efficacy and Safety of Avelumab Treatment in Patients With Advanced Unresectable Mesothelioma. Phase 1b Results From the JAVELIN Solid Tumor Trial. JAMA Oncol. 2019;5(3):351-357.
LURBINECTEDIN: MESOTHELIOMAUSA and EU: Main Current and Emerging Disease Treatment Paradigm
1st LINE
Atezo*
Durv*
Pembro*
Avastin
Pemetrexed (sensitive)VinorelbineGemcitabinePembro
2nd LINE
P3 trials#*****
FDAAPPROVED
NCCNGuidelines#
Nivo/Ipi2
Pemetrexed + PlatinumGemcitabine + Cisplatin
Pembro (TMB high)
# Investigational drug or not approved for this indication/line1. All drugs listed in NCCN guidelines v1.2021 2. Under review by EMA as of Sep 15 2020
EMA APPROVED
ESMOGuidelines#
1st LINE
Nothing inESMO guidelines
2nd LINE
Pemetrexed + Platinum
Atezo*
Durv*
Pembro*
COVID-19: Plitidepsin
1. Sources: Zhou et al; The Nucleocapsid Protein of Severe Acute Respiratory Syndrome Coronavirus Inhibits Cell Cytokinesis and Proliferation by Interacting withTranslation Elongation Factor 1α; Journal if Virology, July 2008, p. 6962–6971, andLosada et al; Translation Elongation Factor eEF1A2 is a Novel Anticancer Target for the Marine Natural Product Plitidepsin; Scientific Reports 6:35100 10/7/16
Slides show a Coronavirus HCoV-229E infected cell culture on the bottom (the “white” spots indicate virus presence), and, on the top side is the image of the same virus infected cell culture when treated with 5nM plitidepsin.
• Aplidin® (plitidepsin) approved in Australia for R/R ≥3L multiple myeloma
• MoA: Inhibits EF1A, a host protein, which Covid-19 infected human cells need to reproduce and/or spread1
• In vitro potency vs. Covid-19 seen at ~0.5nM
• Multi-center clinical trial APLICOV-PC finished in October to see safety and efficacy of three dose levels 1.5 mg x 3 days; 2 mg x 3 days; 2.5 mg x 3 days
• The study met the primary safety endpoint
• Trial saw reductions in viral load and CRP
• 81% of the patients were discharged before the 15th day of hospitalization, and 38% before the 8th (according to the protocol, they must be in hospital for a minimum of 7 days)
• Company in conversations with the regulatory agencies to define the next phase III pivotal study
ZEPZELCA® : KEY IP AND BARRIERS TO ENTRY
NCE Protection
Exclusivity in SCLC
June 14 2027
Protection until 2024*
Protection until 2025
Composition of matter Protection until 2022*
Orphan drugExclusivity in SCLC for
10 years from approval
*Subject to potential patent term extension#Pending patent
YONDELIS® : KEY IP AND BARRIERS TO ENTRY
Use Patent
2023 Sarcoma
Protection until 2028
2022 Sarcoma
Protection until 2030Formulation Protection until 2025
Protection until 2022
Orphan drug
BUSINESS DEVELOPMENT: IN-LICENSING PARTNER OF CHOICE
• Existing 75 person commercial infrastructure covering 10 Western European countries from 6 local offices
• Experience navigating EMA, Swiss Medicines Authority, MHRA (UK)
• Experience with multi-lingual labeling issues
• Experience with reimbursement
• Logistics in place for distribution
• Experience with niche solid tumor products and a brand name in the hospitals
• Relationships with KOLs in many tumors
• 13 Partners and other local distributors
GROUP REVENUES AND R&D EXPENSES
0,0
20,0
40,0
60,0
80,0
100,0
120,0
140,0
160,0
2017 2018 2019 2020
16.7
28.6
7
80.2
113.9
90.6
Revenues: € millions R&D: € millions
0
10
20
30
40
50
60
70
80
2017 2018 2019 2020
7163.7
48.7 49.2
5.3
5.1
2.9 3.8
1.9
4.9
2 0.7
73.7
78.2
53.853.6
Royalties & Milestones Biopharma
SalesBiopharma Diagnostic RNAi Oncology
156
78.8
CATALYSTCALENDAR
KEY EVENTS
Partnership agreement for US rights signed with Jazz Pharma
Zepzelca® monotherapy approved 15th June 2020
Zepzelca® launched in USA 7thJuly 2020
Zepzelca® added to NCCN guidelines 7thJuly 2020
Aplidin POC trial in Covid-19 data October 2020
IASLC 1/31/21 oral presentation lurbi+irinotecan in relapsed SCLC
Mesothelioma phase III trial start 2021
PM14 start two Phase II in 2021
Zepzelca® (lurbinectedin) confirmatory trial and development plan to emerge 2021
Lurbinectedin regulatory updates
www.pharmamar.com