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 | |||
- Not approved in the USA
- Pegylated liposomal doxorubicin (PLD)
- Approved in Australia
- 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
- Data Monitor: Small cell lung cancer (SCLC) Market Spotlight, May 1 2018
- http://www.cancer.gov/types/lung/hp/small-cell-lung-treatment-pdq
- 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
- All drugs listed in NCCN guidelines v1.2021 alphabetically
- 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
- @ 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
- Source:https://clinicaltrials.gov/ct2/show/NCT03088813?term=Onivyde&recrs=ab&draw=2&rank=2
- 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
- Source: IASLC 2018
- 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% |
- G-CSFgive as rescue in 71%, 43% and 18% respectively, Phase III using prophylaxis
- 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
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Pharma Mar SA published this content on 05 January 2021 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 05 January 2021 15:03:03 UTC