DNA FUNCTIONS TOMORROWS NEW HOPE AGAINST RESISTANT CANCER LISTED - - PowerPoint PPT Presentation

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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


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LISTED

EURONEXT │ Paris NASDAQ │ Copenhagen EPA: ONXEO

TODAY’S SCIENCE TARGETING TUMOR DNA FUNCTIONS TOMORROW’S NEW HOPE AGAINST RESISTANT CANCER

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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. The Information has not been subject to independent verification and is qualified in its entirety by the business, financial and other information that the Group is required to publish in accordance with the rules, regulations and practices applicable to companies listed on Euronext Paris, including in particular the risk factors in the Company’s Registration Document filed with the French Financial Markets Authority (Autorité des marchés financiers) under number D.17-0423 on April 24, 2017, in any other periodic report and in any other press release, which are available free of charge on the websites of the Group (www.onxeo.com) and/or the AMF (www.amf-france.org). This document contains information on the use of the Group's products and its competitive position. Some of the Information is from third parties. While this third party information has been obtained from sources believed to be reliable, there is no guarantee of the accuracy or completeness of such data. In addition, certain of the industry and market data comes from the Group's own internal research and estimates based on the knowledge and experience of the Group's management. While the Group believes that such research and estimates are reasonable and reliable, they, and their underlying methodology and assumptions, have not been verified by any independent source for accuracy or completeness and are subject to change without notice. Accordingly, undue reliance should not be placed on any of the industry, market or competitive position data contained in the Information. The Information is not directed to, or intended for distribution to or use by, any person or entity that is a citizen or resident of, or located in, any locality, state, country or other jurisdiction where such distribution or use would be contrary to law or regulation or which would require any registration or licensing within such jurisdiction. The Information does not constitute or form part of, and should not be construed as an offer or the solicitation of an offer to subscribe for or purchase of any securities. No public offering of securities may be conducted in France prior to the delivery by the French Financial Markets Authority of a visa on a prospectus that complies with the provisions of Directive 2003/71/CE as amended. This document is for information purposes only and does not constitute an offering document or an offer of securities to the public in the United Kingdom to which section 85 of the Financial Services and Markets Act 2000 of the United Kingdom applies. Securities may not be offered or sold in the United States absent registration under the US Securities Act of 1933, as amended, or an exemption from registration thereunder. This document contains certain forward-looking statements. All statements in this document other than statements of historical fact are or may be deemed to be forward looking statements. These statements are not guarantees of the Group's future performance. These forward-looking statements relate without limitation to the Group's future prospects, developments, marketing strategy regulatory calendar, clinical milestones, assumptions and hypothesis, clinical development approach and financial requirements and are based on analyses of earnings forecasts and estimates of amounts not yet determinable and other financial and non- financial information. Forward-looking statements are subject to a variety of risks and uncertainties as they relate to future events and are dependent on circumstances that may or may not materialize in the future. Forward-looking statements cannot, under any circumstance, be construed as a guarantee of the Group's future performance as to strategic, regulatory, financial or other matters, and the Group’s actual performance, including its financial position, results and cash flow, as well as the trends in the sector in which the Group operates, may differ materially from those proposed or reflected in the forward-looking statements contained in this document. Even if the Group’s performance, including its financial position, results, cash-flows and developments in the sector in which the Group operates were to conform to the forward-looking statements contained in this document, such results or developments cannot be construed as a reliable indication of the Group's future results or developments. The Group expressly declines any obligation to update or to confirm projections or estimates made by analysts or to make public any correction to any prospective information in order to reflect an event or circumstance that may occur after the date of this document.

Important Information

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April 2020

Developing disruptive therapies in the field of DNA Damage Response (DDR) to address unmet needs in oncology

3

NEXT KEY MILESTONES FUNDED

Financial visibility to Q3 2020 supports strategic plan to deliver key near-term clinical milestones

STRONG MANAGEMENT & OPERATIONAL TEAM

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

  • ligonucleotides, generating new compounds

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.

LISTED

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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SLIDE 4

April 2020

Cutting-edge R&D pipeline with unique mechanisms of action in DDR

4

Programs

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

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SLIDE 5

April 2020

Intense development efforts focused on AsiDNA™ and OX401

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

  • f 12 million warrants

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,

  • ptimal dose for

combo set at 600mg

May

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SLIDE 6

April 2020

April 6, 2020: a successful transaction to complete Onxeo’s strategic transition to a DDR focus company

6

Transaction grants full and worldwide rights to all territories ( ex. North America and India, already licensed to Acrotech), IP and know-how on all belinostat forms License with Pint Pharma for Latin America and contracts with Clinigen and iQone for the Named Patient Program in Europe assigned to Acrotech All future potential revenues from the belinostat franchise to revert to Acrotech Reflects Onxeo ability in terms of BD, alliance management and NPP around the world

$6.6m paid by US partner Acrotech Biopharma LLC for exclusive WW rights to belinostat Financial visibility extended into Q2 2021, beyond key clinical milestones* for AsiDNA™

* Timelines may be affected by Covid-19 pandemic

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April 2020

Consolidated P&L account

7

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

  • of which deferred taxes

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

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SLIDE 8

April 2020

Consolidated balance sheet - Assets

8

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

  • Investments in equity-accounted companies

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

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SLIDE 9

April 2020

Consolidated balance sheet - Liabilities

9

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

  • f bond financing -€1.1m

Impact of SpeBio/SpePharm €2.8m penalty paid early 2019

(netted with the €1.5m current account)

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April 2020

Consolidated cash outlook

10

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

Financial visibility extended into Q2 2021

Post Q1 2020 information

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SLIDE 11

April 2020

AsiDNA™ is a first-in-class therapy for combination designed to address the #1 challenge in oncology: resistance to treatment

11

Decoy Agonist mechanism of action does not induce resistance Differentiated Decoy Agonist mechanism

  • f action in the clinically-validated field
  • f DNA Damage Response

Long IP (up to 2040) Clinical-stage asset

Favorable safety profile incl. in combination Proof of mechanism / signals of efficacy

Strategic focus on the abrogation of resistance to targeted therapies

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

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SLIDE 12

April 2020

Our strategic priority: raise AsiDNA™ as the new treatment paradigm to abrogate resistance

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Preventing resistance – a major challenge for targeted therapies such as PARPis & TKIs - would lead to prolonged efficacy

❶ ❷

“Resistance is the biggest challenge in cancer biology” (Paul Workman – ICR)

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)

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SLIDE 13

April 2020

New preclinical results: AsiDNA™ abrogates acquired resistance to PARP inhibitors (class effect)

13

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

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April 2020

Results confirmed in in vivo experiments in a triple negative breast cancer model

AsiDNA™ abrogates acquired resistance to PARP inhibitors

14

MDAMB-436 (TNBC HR deficient - PARPi sensitive)

Source: Onxeo, data on file

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SLIDE 15

April 2020

Non Small Cell Lung Cancer model – anti-EGFR sensitive

AsiDNA™ eradicates cells resistant to anti-EGFR and anti-ALK

New preclinical results: AsiDNA™ prevents resistance to TKI

15

3 5 6 7 10 12 13 14 17 21 24 27 34 38 41 46 49 52

  • 20

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

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SLIDE 16

April 2020

Relapsed ovarian cancer: a high unmet medical need

16

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%

  • f pts)(1) treated with niraparib in 2nd line maintenance

( 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

  • f therapeutic options

> 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

  • ptions

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

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SLIDE 17

April 2020

EGFR-mutant NSCLC : a large worldwide market

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%

  • f Caucasians and ≈50% of Asians) makes this subset

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

  • ptions

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).

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SLIDE 18

April 2020

Ready to start REVocan Phase Ib/II study: obtain proof-of-concept of the abrogation of resistance to PARP inhibitors by late 2020/early 2021

18

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

REVocan REVersion of resistance in Ovarian Cancer with AsiDNA™ and Niraparib FPI expected from H1 2020 => Preliminary data by end 2020/Early 2021 *

PI: Dr. Patricia Pautier (Arcagy Gineco Network)

Clinical collaboration

N = up to 26 pts (6 centers)

* Timelines may be affected by Covid-19 pandemic

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SLIDE 19

April 2020

Ongoing DRIIV-1b Phase 1b study : Confirm safety and efficacy signals in reference combo by year end

19

AsiDNA™ 600 mg

Cohort 1

carboplatin AsiDNA™ 600 mg carboplatin + paclitaxel

Cohort 2

6 pts

  • ngoing

+ +

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

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SLIDE 20

April 2020

Short term key catalysts in 2020/early 2021 with moderate impact of Covid-19 on milestones to date

20

FPI

DRIIV-1b cohort 2 preliminary data

H2 2019 H1 2020 * H2 2020 *

DRIIV-1b cohort 1

  • prelim. data

* 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

  • f OX401 profile

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

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SLIDE 21

April 2020

Onxeo: A fruitful year 2019 and ready for the 2020 challenges

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AsiDNA™: positioned to address resistance, the biggest challenge in oncology

The only decoy agonist in clinical development in the field of DDR Confirmed activity in man and very favorable safety profile in IV, including in combo Key readouts from Phase 1b/2 REVOCAN study to validate the ability to abrogate resistance to targeted therapies expected in late 2020/early 21

OX 401: Compelling next candidate designed by capitalizing on company expertise Cash visibility extended to Q2 2021, bridging our key catalysts Operations maintained with minimal impact to date from Covid-19 on planned

  • perations and key milestones
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Thank you for your attention!