Pharma Mar S A : Institutional Presentation 2021

CORPORATE PRESENTATION

January 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.

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.

INVESTMENT HIGHTLIGHTS

Global integrated commercial stage biotech developing marine-inspired and novel MoA oncology drugs

• 3 approved oncology drugs, Yondelis®, Aplidin® and ZepzelcaTM

• ZepzelcaTM 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

• ZepzelcaTM (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'19 revenues €85.8 mm.). First 9m 2020 €222mm

• ~€1.3bn market cap. (~$ 1.6bn1)
• Cash (as of Sep 30 2020) €218mm (~$265mm)
• Shares listed on the Spanish Stock Exchanges under the symbol "PHM"

(1) As of 31 December 2020

3

UNIQUE FULLY INTEGRATED PLATFORM

Expeditions	Cell biology	Pharmaceutical	Clinical &
Chemistry &	development &	Commercial
& collection	Regulatory
Preclinical	operations

Marine derived leads	Screening of	FDA inspected	Clinical trials	Oncology-focused sales
Global expeditions	antitumoral activity	production facility	Post marketing trials	force in Europe (n=~65)
		Geographic licensing &
Over 200,000 samples	Synthesis & molecule	GMP Production
optimization			partnering with
	New drug candidates
			experienced companies
	Patent protection
			(~13 companies)
	Preclinical studies

Regulatory inspections passed from FDA, AEMPS, PMDA (US, Spain/EU, Japan)	4

TRANSFORMATIVE TIME FOR PHARMAMAR

Discovery oncology drugs

Expand R&D verticaly and horizontally

Lurbinectedin: Pipeline within a drug e.g. SCLC expansion, mesothelioma, etc.

BD: seek synergistic, late stage or commercial assets in oncology

TRANSFORMATIVE

TIME

PHARMAMAR & JAZZ PHARMACEUTICALS

19TH DECEMBER

2019

SIGNED A LICENSE AND DISTRIBUTION AGREEMENT FOR ZEPZELCATM

IN US

• 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 ZepzelcaTM 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

ZEPZELCATM

LAUNCHED AND

AVAILABLE IN

USA JULY 7 2020;

Added to NCCN guidelines same day

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-hundredmillion 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", except: (2) November 2 2020 Jazz earnings report PR

OUR ONCOLOGY PORTFOLIO

	Program / Indication	Phase I	Phase II	Phase III	Market
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
	Small cell lung cancer 2nd line	Single agent
	(expansion cohort Basket trial)
ZepzelcaTM	Small cell lung cancer 2nd line	Lurbi+Doxorubicin	ATLANTIS
	Lurbi+Atezolizumab
(Lurbinectedin)	≥2nd line mesothelioma
	Basket trial (other) (4)	Single agent
	Small cell lung cancer 2nd line	Lurbi+Iriontecan
PM184	Solid tumors	Single agent
and combinations
PM14	Solid tumors	Single agent

1. Not approved in the USA
2. Pegylated liposomal doxorubicin (PLD)
3. Approved in Australia
4. Breast BRCA+, Head & neck, Endometrial, Biliary tract, Ewing sarcoma, NET, Germ cell, CUP

LURBINECTEDIN (ZEPZELCATM): MoA

A Selective Inhibitor of Oncogenic Transcription

Cancer is frequently a transcriptional disease caused	By inhibiting active transcription in Tumor Associated
by deregulated oncogenic transcription factors	Macrophages (TAMs), lurbinectedin downregulates
	IL-6,IL-8, CCL2 and VEGF

Transcription

Factors

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.

SWI/SNF	Lurbinectedin	IL-6		VEGF
ARID 1A	TAMs
	SWI/SNF	IL-8	IL-8
	ARID 1A		CCL
		INDUCTION OF	IL-6	INDUCTION OF
			ANGIOGENESIS
		TUMOR CELL
		PROLIFERATION	INHIBITION OF
	DNA		IMMUNE
		RESPONSE
			ACTIVATION OF
	Harlow et al, 2016; Cancer Res 72: 6657-68		IMMUNE
		CHECKPOINTS
	Harlow et al, 2019; Clin Cancer Res doi: 10.1158/1078-0432.CCR-18-3511
PROMOTER
Santamaría et al, 2016. Mol Cancer Ther 15:2399-412

Dr. Luis Paz Ares

PIPELINE- ZEPZELCATM (lurbinectedin)

Development and Commercial Strategy

Clinical Program / Indication	Phase I	Phase II	Phase III	Market
Zepzelca (Lurbinectedin)
SCLC 2nd line (Basket trial)	Single agent
SCLC 2nd line	Combo	ATLANTIS
Doxorubicin
	Combo
≥2nd line mesothelioma	Atezolizumab
Basket trial (other)	Single agent
SCLC 2nd line	Combo
irinotecan

Commercialization Plans:

• EU:

Utilize/expand existing Yondelis sales force and select regional distributors

• US: License and distribution agreement with Jazz
• ROW: Regional partnerships

SCLC MARKET OVERVIEW

Orphan Drug Designation granted

in the United States and EU

In 2019 there were approximately 30,000 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
• Prior to ZepzelcaTM last FDA approved NCE for 2nd line Topotecan (iv) 1996, (only sensitive patients). Median TTP ~3m; OS ~6m4

Sources:

1, American Cancer Society and SEER Cancer Stat Facts https://seer.cancer.gov/statfacts/html/lungb.html

1. Data Monitor: Small cell lung cancer (SCLC) Market Spotlight, May 1 2018
2. http://www.cancer.gov/types/lung/hp/small-cell-lung-treatment-pdq
3. https://www.accessdata.fda.gov/drugsatfda_docs/label/2014/022453s002lbl.pdf

Estimated that in 2018, there were approximately 61,300 new cases of small cell lung cancer in the EU2

SCLC OVER THE YEARS;

FAR LESS PROGRESS THAN IN NSCLC

S C L C

	Cisplatin+	Carboplatin+	Durv or Atezo+
First line	Carboplatin+
Etoposide	Etoposide
	Etoposide
	1985	1999
	2019
Second line		Topotecan	ZepzelcaTM
	1996	2020
Third line			Pembrolizumab
		2019
Adapted from ; Sabari et al, Clinical Oncology; September 2017	FDA approval

1985

1990

1995

2000

2015

2018

2019

2020

N S C L C

Alkylating

Antimetabolites

Antiangiogenesis

Microtubule

IO

EGFR

TKI

TRK

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

ZEPZELCATM LURBINECTEDIN: SCLC

USA: Current and Emerging Disease Treatment

Paradigm

FDA APPROVED

NCCN Guidelines

(not FDA appvd)

P3 trials#*

****

1st LINE

Platinum/Etoposide + Atezolizumab or Durvalumab

Pembro*

Nivo*

Tiragolumab*

2nd LINE

ZepzelcaTM

Topotecan (sensitive)

Bendamustine1*	Oral etopoide@ 1*
CAV 1*	Paclitaxel 1*
Docetaxel 1*	Pembro 1*@
Gemcitabine 1*	Rechallenge 1*2
Irinotecan 1*	Temozolomide1*
Nivo 1* @	Vinorelbine 1*

Onivyde4*

Data expected Dec 2022

3rd LINE

Pembro

Nivolumab5*

RRx-001*

• Investigational drug or not approved for this indication/line

1. All drugs listed in NCCN guidelines v1.2021 alphabetically
2. 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 relapse
3. @ 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 Durv
4. Source:https://clinicaltrials.gov/ct2/show/NCT03088813?term=Onivyde&recrs=ab&draw=2&rank=2
5. Nivo received FDA approval for 3rd line Aug 2018; Volutarily withdawn by BMS 12/29/2020

# Completed or recruiting disease treating trials for NCEs in US and /or EU

LURBINECTEDIN 2ND LINE SCLC:

2 TRIALS, 2 DOSES, 2 PROTOCOLS, 2

POPULATIONS

COMBO ATLANTIS:

• Combo with Doxorubicin (in NCCN guidelines within CAV)
• Phase III ATLANTIS n=613, CTFI*>30d
• Primary endpoint OS not met however no 'adverse effect'
• Dosing Lurbi 2mg/m2 + 40mg Doxo/m2

Top-line data reported December 3rd 2020

MONO(2):

• Mono 57% sensitive, 21% resistant, 22% refractory
• 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-CSFuse 22%

Monotherapy approved FDA for relapsed SCLC June 15 2020

1. Source: IASLC 2018
2. Source: ASCO 2019

• Chemotherapy free interval: time in days from progression on prior chemotherapy

MONOTHERAPY: BASIS OF FDA APPROVAL

JUNE 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%
LURBINECTEDIN	•	ITT OS 9.3m
	•	No brain mets
	•	Lurbi dose 3.2mg/m2
	•	G-CSF use (22%)

MONOTHERAPY LURBINECTEDIN

FINAL DATA: ASCO 2019

Efficacy

	Overall	Decrease in tumor size in 65% patients
	(n=105)
ORR, %	35.2
(95% CI) (confirmed responses) # ^	(26.2-45.2)
ORR, %	22.2
Resistant CTFI< 90 days (n=45)	(11.2-37.1)
ORR, %	45.0
Sensitive CTFI = 90 days (n=60)	(32.1-58.4)
Duration of response (months), median	5.3
(95% CI)	(4.1-6.4)
Disease Control Rate *, %	68.6
(95% CI)	(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

PFS TO PRIOR IO AND PFS AFTER

LURBINECTEDIN

PFS prior IO

PFS Lurbinectedin

MONOTHERAPY FINAL DATA: ASCO 2019

Safety

Safety: Related or Unknown Adverse Events

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	2	(1.9)
discontinuation
Dose delays treatment related	21 (22.1*)
Dose reductions #	25 (26.3*)
G-CSF	23	(21.9)
Transfusions (red blood cells and/or	10 (9.5)
platelets)

Treatment Related (or Unknown) Adverse Events (AEs) ( >5% or Gr 3-4)

	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)
	Febrile neutropenia		.	5	(4.8)
	Fatigue	54	(51.4)	7	(6.7)
	Nausea	34	(32.4)		.
	Decreased appetite	22	(21.0)		.
Non-Hematological	Vomiting	19	(18.1)		.
AEs	Diarrhea	13	(12.4)	1	(1.0)
	Constipation	10 (9.5)		.
	Pneumonia		.	2	(1.9)
	Alanine aminotransferase		.	2	(1.9)
	increased *
	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

Dr. Luis Paz Ares

NON HEAD-TO-HEAD SELECTED COMPARISONS

Safety

	Monotherapy	Topotecan label	Topotecan von	CAV (from Topo label)
Adverse Events		Pawel 2014
		n=167
Grade 3-4		n=107	n=104
n=105
	CTFI>60		CTFI>60
	CTFI>0
Febrile Neutropenia	4.8%	28%	3%	26%
Anemia	6.7%	42%	30.5%	20%
Thrombocytopenia	4.8%	29% (G4)	54.3%2	5% (G4)
Neutropenia	22.9%	70% (G4)	53.8%2	72% (G4)
Sepsis	NR	5%1	NR	5%1
Pneumonia	1.9%	8%	3%	6%

1. G-CSFgive as rescue in 71%, 43% and 18% respectively, Phase III using prophylaxis
2. Treatment-emergentabnormalities

ZEPZELCATM : KEY IP AND BARRIERS TO ENTRY

Orphan drug	Exclusivity in SCLC	Exclusivity in SCLC for
June 14 2027	10 years from approval

Composition of matter	Protection until 2024*	Protection until 2022*

NCE Protection

Protection until 2025

*Subject to potential patent term extension #Pending patent

YONDELIS® : KEY IP AND BARRIERS TO ENTRY

Orphan drug

2023 Sarcoma

2022 Sarcoma

Formulation

Protection until 2028

Protection until 2025

Protection until 2030

Use Patent

Protection until 2022

COVID-19: Plitidepsin

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-centerclinical 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

1. Sources: Zhou et al; The Nucleocapsid Protein of Severe Acute Respiratory Syndrome Coronavirus Inhibits Cell Cytokinesis and Proliferation by Interacting with

Translation Elongation Factor 1α; Journal if Virology, July 2008, p. 6962-6971, and

Losada et al; Translation Elongation Factor eEF1A2 is a Novel Anticancer Target for the Marine Natural Product Plitidepsin; Scientific Reports 6:35100 10/7/16

GROUP REVENUES AND R&D EXPENSES

Revenues: € millions		R&D: € millions
						137.8
140,0							79.6	78.2
							2,4				73.7
120,0						80	1,9
							4,9	5,3	4,9
	90.6				70							53.6
100,0										5,1
		80.2			83.9
				78.8	60
80,0																2
						50										2,9
60,0						40	72,3	71
							63,7
						30
40,0			28.6											48,7
	16.7				20
20,0					7	10
0,0						0	2016	2017	2018	2019
	2017	2018		2019	9m 2020
		Royalties & Milestones		Sales				Diagnostic			RNAi			Oncology
		Biopharma			Biopharma

KEY EVENTS

CATALYST CALENDAR

Partnership agreement for US rights signed with Jazz Pharma ZepzelcaTM monotherapy approved 15th June 2020 ZepzelcaTM launched in USA 7thJuly 2020

ZepzelcaTM added to NCCN guidelines 7thJuly 2020 Aplidin POC trial in Covid-19 data October 2020

ATLANTIS: did not meet primary endpoint. Exploratory secondary endpoints of interest IASLC 1/31/21 oral presentation lurbi+irinotecan in relapsed SCLC

ATLANTIS data discussions FDA/EMA/UK 2021

ZepzelcaTM (lurbinectedin) development plan to emerge 2021

Lurbinectedin regulatory updates (e.g. Australia, Canada, Switzerland, Israel, S. Korea)

www.pharmamar.com