Presentación de PowerPointpharmamar.com/wp-content/uploads/2020/04/Corp-Pres-april-2020-v2.pdf ·...

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April 2020 Corporate Presentation

Transcript of Presentación de PowerPointpharmamar.com/wp-content/uploads/2020/04/Corp-Pres-april-2020-v2.pdf ·...

April 2020

Corporate Presentation

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.

>3

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, Janssen), Japan (Taiho), Australia (STA)

• Lurbinectedin relapsed small cell lung cancer (“SCLC”) monotherapy NDA Aug 16th 2020 PDUFA date

• Lurbinectedin ATLANTIS combo with Doxo randomized trial top line data 2H 2020

• FY’19 revenues €85.8mm

• ~ € 1000 mn market cap.;(~$1.1 Bn1)

• Shares listed on the Spanish Stock Exchanges under the symbol “PHM”

1. As of April 9 2020

• 2 approved oncology drugs, Yondelis® and Aplidin ®

• 1 oncology candidate, Lurbinectedin filed FDA December 16th 2019

>

PharmaMar & Jaz z Pharmaceut ica ls

• PharmaMar received an up-front payment of $200 million in January 2020

• Eligible to receive potential regulatory milestone payments of up to $250 million upon the achievement

of accelerated and/or full regulatory approval of Lurbinectedin by FDA within certain timelines

• PharmaMar is eligible to receive tiered royalties of between high teens and 30% on net sales

• 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

4

>

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

Lurbinectedin

Small cell lung cancer relapsed Lurbin+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:

August 16th 2020 FDA

PDUFA date

8

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 Cell 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

>

LURBINECTEDIN

SCLC

Relapsed

Combo

Doxorubicin

Basket trial SCLC cohort Single agent

Basket trial (other) Single agent

Solid tumors

Single agent /

combinations

9

PIPEL INE - 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: License and distribution agreement with Jazz

• ROW: Regional partnerships

August 16th 2020 FDA

PDUFA date

>10

LURBINECTEDIN: 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 2019

there will be 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

• 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 ~60% of patients get treated in 2nd line

Sources:

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

>

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

• GD2

>13

LURBINECTEDIN: SCLC

USA: Current and emerging treatment paradigm#

1st LINE 3rd LINE

Tiragolumab*

Irinotecan1*

Paclitaxel1*

Docetaxel1*

Temozolomide1*

Nivo*+/-Ipi1*@

Pembro1*@

Lurbinectedin* RRx-001*

Onivyde*

Nivolumab

Pembro

2nd LINE

• Investigational drug or not approved for this indication/line

1. All drugs listed in NCCN guidelines v232020

2. Only with relapse >6m; for pts who relapse >6m after Atezo maintenance, recommendation is to re-challenge with carbo/etoposide without Atezo

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

** Durvalumab filed with FDA ~Q4 2019

# Recruitung trials for NCEs in US and /or EU

13

P3 trials#

FDA APPROVEDDRUGS SCLC

NCCNGuidelines

Vinorelbine1*

Oral etopoide1*

Gemcitabine1*

CAV1*

Bendamustine1*

Rechallenge2

Platinum/Etoposide/

AtezolizumabTopotecan

MAINTENANCE

Durvalumab1*

>14

IMMUNOTHERAPY GRAVITAT ING TO 1s t AND 3 rd L INE

Solebury Trout KOL Day 11/15/19

>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%)

LURBINECTEDIN SCLC: 2 TR IALS, 2 PROTOCOLS, 2 POPULATIONS

1. Source: ASCO 2019

2. Source: IASLC 2018

Monotherapy NDA PDUFA date 16th Aug 2020

for Accelerated Approval for relapsed SCLC

Combo top-line data expected 2H 2020 for

relapsed SCLC

>16

COMBINATION: Lurb inected in + Doxorub ic in

>17

LU R B INEC TEDIN: 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

Lurb inec ted in : PHASE I I I RELAPSED SMALL CELL LUNG CANCERATLANTIS Trial Design SCLC (Trial initiated August 2016)

Arm A:

Lurbinectedin (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

- Monotherapy filed 12/16/2019

- 5 Safety analyses passed (IDMC)

- PharmaMar announced ATLANTIS reached target enrollment July 2018

- Data anticipated 2H 2020

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

Lurbinectedin mono (after 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

>21

PFS TO PR IOR IO AND PFS AFTER LURBINECTEDIN

Prior IO

PFS prior IO PFS Lurbinectedin

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

22

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)

>23

NON HEAD -TO-HEAD COMPARISONS

Adverse EventsGrade 3-4

Monotherapy

n=105CTFI>0

Topotecan label

n=107 CTFI>60

Topotecan von Pawel2014 n=167

CAV (from Topo label)

n=104CTFI>60

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-CSF give as rescue in 71%, 43% and 18% respectively, Phase III using prophylaxis

2. Treatment-emergent abnormalities

Safety

>24

EU

New per year1 ~60000

% treated 2nd line2 ~60%

DOR3 5.3m

Annual Px IO front line5 $62-63k

Annual Px IO 3rd line5 $53-54k

Market Share ?

USA

New per year1 ~30000

% 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 102. Internal estimates3. From ASCO 2019 data4. WAC USA5. Assumed EU average price ~35% USA

>25

LURBINECTEDIN: 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 2024*

Protection until 2031#

*Subject to potential patent term extension

#Pending patent

>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 2026

Japan

Manufacturing

2022 Sarcoma

Protection until 2030

Protection until 2022

Protection until 2021

>27

Covid -19: Apl id in® (pl i t idepsin )

Slides show a Coronavirus HCoV-229E

infected cell culture on the right hand side

(the “white” spots indicate virus presence),

and, on the left hand side is the image of

the same virus infected cell culture when treated

with 5 μM Aplidin.

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

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

• Approved in Australia for R/R =3L multiple myeloma

• Moa: Inhibits of EF1A, a host protein, which Covid-19 infected

human cells needs to reproduce and/or spread1

• In vitro preliminary work, potency against Covid-19 seen at the

order of 0.5µM

• Multi-center Phase II APLICOV might start in April to see

efficacy and safety of two dose levels. Efficacy measured in

terms of non-evolution to Acute Respiratory Distress Syndrome

(ARDS).

• Intend to speak with regulators about path forward regarding

clinical trials, compassionate use etc.

Aplidin®

>28

Covid-19:

Genomica

• GENOMICA, founded in 1990 is a 100% owned subsidiary of PharmaMar.

• Molecular diagnostics tools including kits for SAR and Covid-19

• CE mark and commercial availability March 2020 for Covid-19 diagnostic kits

• Able to analyze up to 96 samples in under 5hrs

• Highly sensitive and specific in detecting the coronavirus Covid-19

• The virus could be detected even before the patient shows symptoms

• Currently manufacturing ~2000 test per day; ability to scale up

• Potential for more countries to come on board

>29

0,0

10,0

20,0

30,0

40,0

50,0

60,0

70,0

80,0

90,0

100,0

2016 2017 2018 2019

16.9 16.7

28.6

7.0

80.2 78.8

0

10

20

30

40

50

60

70

80

2016 2017 2018 2019

72,3 7163,7

48,7

4,9 5,3

5,1

2,9

2,41,9

4,9

2

73.7

78.290.6

94.3 79.6

53.6

>

KEY EVENTSCatalyst calendar

• Lurbinectedin monotherapy SCLC basket trial oral presentation ASCO June 1st 2019

• Lurbinectedin monotherapy FDA grants Accelerated Approval path

• Lurbinectedin monotherapy filed Accelerated Approval USA December 16th 2019

• Partnership agreement for US rights signed with Jazz Pharma

• USA EAP open Q1 2020

• Lurbinectedin monotherapy NDA accepted 2/14/20 for priority review

• Lurbinectedin SCLC monotherapy published Lancet Oncology

• Lurbinectedin monotherapy PDUFA 8/16/2020

• Lurbinectedin ATLANTIS top-line data 2H 2020

• Lurbinectedin potential US launch 2H 2020

• File Lurbinectedin with EMA30