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DNA FUNCTIONS TOMORROWS NEW HOPE AGAINST RESISTANT CANCER LISTED - - PowerPoint PPT Presentation
TODAYS SCIENCE TARGETING TUMOR DNA FUNCTIONS TOMORROWS NEW HOPE AGAINST RESISTANT CANCER LISTED EURONEXT Paris NASDAQ Copenhagen EPA: ONXEO Important Information IMPORTANT: You must read the following before continuing. In
EURONEXT │ Paris NASDAQ │ Copenhagen EPA: ONXEO
IMPORTANT: You must read the following before continuing. In accessing this document, you agree to be bound by the following terms and conditions. This document has been prepared by Onxeo SA (together with its subsidiaries, the "Group") and is for information purposes only. The content of this document is provisional and for information purposes only and is not to be construed as providing investment advice. The information, statements and opinions contained in this document (the “Information”) are provided as of the date of this document only and may be subject to significant changes at any time without notice. Neither the Group, nor its advisors, nor any other person is under any obligation to update the Information. Subject to applicable law, none of the Company or its advisors accepts any responsibility whatsoever and makes no representation or warranty, express or implied, as to the fairness, accuracy, completeness or correctness of the Information. 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April 2020
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NEXT KEY MILESTONES FUNDED
Financial visibility to Q3 2020 supports strategic plan to deliver key near-term clinical milestones
A highly skilled team of 30, with strong translational & clinical expertise, led by experienced management and board of directors with demonstrated track record in product & business development
DIFFERENTIATED SCIENCE IN DNA DAMAGE RESPONSE
PlatON™, proprietary chemistry platform of decoy
AsiDNA™, lead candidate at clinical stage, a first-in-class decoy agonist showing unique anti-tumoral properties OX401, a newly optimized next-gen PARPi*
A WELL-DEFINED BUSINESS MODEL
Create value by bringing drug candidates from preclinical stage to proof-of concept in man, the best inflection points to monetize these assets and generate revenues.
EURONEXT │ Paris NASDAQ │ Copenhagen EPA: ONXEO
* PARP inhibitors (PARPi) are a leading class of targeted therapies, the first approved and marketed in the field of DDR
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OPTIMIZATION PRECLINICAL PHASE I PHASE Ib PHASE II
platON™ Proprietary Platform of Decoy Oligonucleotides OX401
Next-gen PARPi + STING pathway activation
AsiDNA™ IT + radiotherapy AsiDNA™ IV AsiDNA™ IV + chemotherapy AsiDNA™ IV + PARPi
DRIIV -1b
DRIIV study in solid tumors
GENERATION OF NEW COMPOUNDS TARGETING DNA FUNCTIONS
DNA Damage Response
1 IT: intratumoral – IV: intravenous
DRIIM study in metastatic melanoma
Ongoing proof-of concept
DDR + IO
REVocan
Completed or ongoing
Legend
Planned short-term
April 2020
5
2019
OX401 presented at the European ESMO-TAT Congress 2020 in Paris
Jan Mar
5 abstracts presented at AACR on AsiDNA™
Apr
2020
AsiDNA™ OX401
Sep
Pipeline expansion w/OX401, a next-gen PARPi: no resistance and immune response activation Positive interim results from DRIIV-1b study FPI in DRIIV-1b study of AsiDNA™ in combination w/chemotherapy
May
Agreement with Gustave Roussy to conduct REVOCAN, a phase 1b/2 study of AsiDNA™ & niraparib for treatment of relapsed ovarian cancer
Apr
$6.6m exclusive agreement with Acrotech on belinostat New equity line started with Nice & Green – Total
Kepler Cheuvreux initiates coverage w/ “Buy” recommendation
Oct
€495,000 grant as part of the Innov'up Leader program PIA
Feb
Agreement to settle the remaining actions in the litigation with SpePharm and SpeBio Corporate
Jun
Final results of DRIIV-1 study: strong activity via IV route,
combo set at 600mg
May
April 2020
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* Timelines may be affected by Covid-19 pandemic
April 2020
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In € thousands 12/31/2019 12/31/2018 Recurring revenue from licensing agreements 3,455 2,310 Non-recurring revenue from licensing agreements 833 3,817 TOTAL REVENUES 4,289 6,127 Purchases (350) (215) Personnel expenses (4,808) (5,438) External expenses (7,857) (8,731) Taxes and duties (127) (346) Net depreciation, amortization and provisions (671) (92) Other current operating expenses (365) 622 OPERATING EXPENSES (14,178) (14,200) Other current operating income 95 4,546 CURRENT OPERATING INCOME (LOSS) (9,794) (3,527) Other operating income and expenses (24,543) (12,117) Share of profit from equity affiliates (39) 5,176 OPERATING LOSS AFTER SHARE OF PROFIT FROM EQUITY AFFILIATES (34,376) (10,468) Income from cash and cash equivalents 19 15 Gross cost of financial debt (1,037) (601) Other financial income and expenses (659) (104) FINANCIAL INCOME (LOSS) (1,677) (691) Income tax expense 2,324 1,760
2,330 1,764 CONSOLIDATED NET INCOME (LOSS) (33,728) (9,399)
Good performance of commercialization activities (notably by US partner Acrotech) Impairment of R&D assets + goodwill €14.9m / depreciation of SpeBio shares €3.7m / provision SpePharm €6m Cost of bond financing (proportional to royalties received from Acrotech) Decrease of deferred tax liability due to impairment of R&D assets
April 2020
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Assets in € thousands 12/31/2019 12/31/2018
Non-current assets
Intangible assets 23,358 38,573 Tangible assets 109 296 Right-of-use assets 2,718
20 3,701 Other financial fixed assets 141 304 TOTAL NON-CURRENT ASSETS 26,345 42,874
Current assets
Stocks and work in progress 64 47 Accounts receivable and related accounts 991 1,479 Other receivables 4,520 7,597 Cash and Cash equivalent 5,708 11,253 TOTAL CURRENT ASSETS 11,284 20,376 TOTAL ASSETS 37,629 63,250
Impairment of goodwill -€2m and belinostat-related R&D assets -€12.9m Rights of use relating to leases in the scope of IFRS 16 Depreciation of JV SpeBio shares sold at nominal value in Feb. 2020 within settlement with SpePharm Reduction of receivables in line with R&D activity
April 2020
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Liabilities and Shareholders’ Equity in € thousands 12/31/2019 12/31/2018
Shareholders’ equity
Share capital 15,329 13,344 Minus: treasury shares (189) (97) Share premium 44,924 48,824 Reserves (9,139) (270) Earnings (33,728) (9,399)
TOTAL EQUITY
17,197 45,402
Non-current liabilities
Deferred tax liabilities 2,330 Provisions 6,821 531 Other financial liabilities 7,412 6,593
TOTAL NON-CURRENT LIABILITIES
14,233 9,455 Current liabilities Short-term borrowings and financial debts 1,170 450 Trade payables and related accounts 3,672 4,145 Other liabilities 1,358 3,798
TOTAL CURRENT LIABILITIES
6,199 8,393
TOTAL LIABILITIES AND SHAREHOLDERS’ EQUITY
37,629 63,250
Capital increase from the equity line €4.8m Variation of deferred tax resulting from the €12.9m impairment of assets Provision of €6m payable to SpePharm before 01/31/24 Loan relating to leases (IFRS 16) +€2m / Repayment
Impact of SpeBio/SpePharm €2.8m penalty paid early 2019
(netted with the €1.5m current account)
April 2020
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5 708 (10 111) (2 729) 2 412 4 743 140 11 253
2 000 4 000 6 000 8 000 10 000 12 000
Cash January 1, 2019 Net operating income & expenses R&D tax credit Capital increase - equity line Repayment of loans Other Cash December 31, 2019
€7.3m in cash at March 31, 2020
$6.6m from Acrotech Biopharma
Post Q1 2020 information
April 2020
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Long IP (up to 2040) Clinical-stage asset
Favorable safety profile incl. in combination Proof of mechanism / signals of efficacy
Collaborations with top-academic centers
(Institut Curie - Gustave Roussy – Oncopole Toulouse…)
REVocan Phase 1b/2 to evaluate the addition of AsiDNA™ on the abrogation resistance to niraparib (to start H1 2020) Depletes the cells from which resistance to targeted therapy emerges
April 2020
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Strategic objectives Targeted Indications Opportunity Approval / Full Market Size
Optimal market access (fast, favorable P&R*)
2L with niraparib (PARPi) in ovarian cancer Short endpoint: PFS Expansion of maintenance treatment and delay new course of platinum
2024 $6,7B (1) 1st line treatment in a large WW market
1L with anti-EGFR TKI in EGFRm non-small cell lung cancer Target specific population with high risk of progression Address 1st line of treatment
2025 $16,9B (1) REVocan Combo w/ PARPi Combo w/ TKI
* P&R : pricing & reimbursement - (1) GlobalData (8MM)
April 2020
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UWB1.289 (Ovarian cancer model – BRCA1-/-)
10 20 30 40 50 4×104 8×104 1.2×105 1.6×105 2×105
Nira Nira+Asi at D34 Days post treatment Cell number niraparib Emergence of resistant cells Cell death
AsiDNA™ leads to niraparib-resistant cells eradication in ovarian cancer model, even if introduced only once resistance emerges (CA 125 increase) REVocan study (REVersion of resistance in ovarian cancer with AsiDNA™ and niraparib) ) was designed on the basis of these results
D17 D24 D31 D40 D17 D24 D31 D40 5 10 15 20 30 60 90 120 150
CA125 (pg/ml)
Introduction at CA125 increase (REVocan study protocol) Start of AsiDNA™ administration Start of AsiDNA™ administration
Source: Onxeo, data on file
April 2020
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MDAMB-436 (TNBC HR deficient - PARPi sensitive)
Source: Onxeo, data on file
April 2020
Non Small Cell Lung Cancer model – anti-EGFR sensitive
AsiDNA™ eradicates cells resistant to anti-EGFR and anti-ALK
15
3 5 6 7 10 12 13 14 17 21 24 27 34 38 41 46 49 52
20 40 60 80 100 120
Erlotinib Erlotinib+AsiDNA
Time (days) Surviving cells (%)
No surviving cells Emergence of resistant cells No surviving cells Emergence of resistant cells
PC9-3 (NSCLC EGFRmut)
Non Small Cell Lung Cancer model – anti-ALK sensitive
H3122 (NSCLC EML4-ALK)
Source: Onxeo, data on file
April 2020
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2nd line treatment : platinum-based chemotherapy (for patients sensitive to platinum) 2nd line maintenance : PARP inhibitors Median PFS 9,3 mo in non-BRCA mutated patients (86%
( vs. 21 mo in patients with BRCA mutation)(2) Development of resistance to PARPi limits duration of response(3) 3rd line with platinum-based CT in sensitive patients, but loss of sensitivity after subsequent relapses leads to lack
> 128,000 new incident cases in 2018(1)
Potential to extend maintenance / PFS, especially in non- BRCA mutated patients Potential to maintain sensitivity to platinum for subsequent lines of treatment
Current
Challenges Population
US 23,000 Japan 10,000 5 EU 31,000 China 64,000
(1) GlobalData (8MM = 5EU + US + JPN + Urban China) (2) NOVA study (3) Mweempwa A, Wilson MK. Mechanisms of resistance to
PARP inhibitors - an evolving challenge in oncology. Cancer Drug Resist2019;2:608-17.
AsiDNA™ opportunity
April 2020
17 Anti-EGFR TKIs now used in 1st line as well as in 2nd line treatment of EGFR-mutant NSCLC EGFRm NSCLC patients treated with anti-EGFR TKIs will inevitably develop acquired resistance to their treatment(2) Anti-EGFR TKIs now used as 1st line treatment, which limits further treatment options once resistance emerges Increasing progression free survival (PFS) and efficacy of 1st line treatment becomes critical NSCLC = 85% of all lung cancers 920,000 new incident cases in 2020(1) High occurrence of EGFR mutations in NSCLC (≈20%
a critical population in lung cancer(1)
Potential to prevent resistance to anti-EGFR TKIs in 1st line Potential to increase PFS / efficacy of 1st line treatment
Current
Challenges
AsiDNA™ opportunity
Population
US 188,000 Japan 121,000 5 EU 184,000 China 427,000
(1) GlobalData (8MM = 5EU + US + JPN + Urban China).(2) Gao, J., Li, H., Jin, C. et al. Strategies to overcome acquired resistance
to EGFR TKI in the treatment of non-small cell lung cancer. Clin Transl Oncol 21, 1287–1301 (2019).
April 2020
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Patients selection: patients under 2nd line of maintenance with niraparib > 6 months Inclusion at CA 125 increase (CA 125 : well established predictive biomarker of resistance) n= up to 26 patients, platinum-sensitive relapsed ovarian cancer Primary objective: Safety run & CA125 decrease (GCIG criteria) Secondary objective: Efficacy: PFS (RECIST criteria) - OS
PI: Dr. Patricia Pautier (Arcagy Gineco Network)
Clinical collaboration
N = up to 26 pts (6 centers)
* Timelines may be affected by Covid-19 pandemic
April 2020
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AsiDNA™ 600 mg
Cohort 1
carboplatin AsiDNA™ 600 mg carboplatin + paclitaxel
Cohort 2
6 pts
+ +
Patients with ≥ 3 prior lines of treatment, progressing at inclusion Very good tolerance of the combination (no DLT) Disease stabilized (SD) in 2/3 patients for 5.5 mo. (TNBC 6th L) and 10 mo. (NSCLC 3rd L) Disease controlled with AsiDNA™ for significantly longer than with any of the prior treatment lines
3 pts
Preliminary data by end 2020 *
* Timelines may be affected by Covid-19 pandemic
April 2020
20
FPI
DRIIV-1b cohort 2 preliminary data
H2 2019 H1 2020 * H2 2020 *
DRIIV-1b cohort 1
* Timelines include first estimation of Covid-19 impacts, which may be further reviewed depending on
Covid-19 pandemic evolution DRIIV-1b cohort 2 preliminary data AsiDNA™ +TKI data to support clinical plan AsiDNA™ +TKI data to support clinical plan Preclinical validation
Tolerance in combination + first signals of efficacy
DRIIV–1b
AsiDNA™ + carboplatin +/- paclitaxel
REVOCAN phase 1b/2
AsiDNA™ + niraparib
Clinical Research agreement
Reversion of resistance Prevention of resistance
AsiDNA™ + TKI
Preclinical proof-of-concept
Next-gen PARPi + activation of immune response
OX401
Preclinical proof-of-mechanism
* *
REVOCAN First data set
April 2020
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