Targeting New Pathways for Next Generation DME TherapiesDeveloping new Standard of Care Therapies for DME
Half Year Results Presentation Oxurion NV (Euronext : OXUR)
17 September 2020
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Patrik De Haes, M.D., CEO • +25 years of successful international management experience in the Life Science industry
• Led the global development and commercialization of the first biotech product at Sandoz (now Novartis)
• Former head of Roche’s Global Insulin Infusion division and CEO of Disetronic Medical Systems Inc (US)
Dominique Vanfleteren, CFO • +25 years of experience in senior finance, operational, control and reporting roles in pharma
• Former CFO of UCB’s Asia Pacific Operations and Finance Director of GSK’s Diversified Healthcare Services
Andy De Deene, M.D., MBA, CDO • +20 years of experience in drug development and regulatory approval in small and large pharma
• Former R&D at Innogenetics & Janssen Pharmaceuticals (Johnson & Johnson)
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Grace Chang, M.D., Ph.D., CMO • Practicing vitreoretinal surgeon, adjunct Clinical Associate Professor in the Department of Ophthalmology,
Vitreoretinal Service at the University of Southern California in Los Angeles, CA.
• Former CMO of Notal Vision, previous scientific and clinical development leadership at Alcon
Today’s Call Participants
Oxurion Developing the Industry Leading DME Franchise
Together THR-149 and THR-687 will allow us to potentially address all DME patient needs
• Diabetic macular edema is an area of high unmet medical need – target population 2.8 million (US, EU5 & Japan)
• $ 4.5 billion market p.a. – dominated by anti-VEGFs – scope to provide better treatment options for all patients
• Step change in patient outcomes needs access to new drugs with novel mode of actions
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• Existing patients (treatment-experienced)
Add-on to anti-VEGFs
• New patients (treatment-naïve)
• Existing patients (treatment-experienced)
Switch from anti-VEGFs
YTD 2020 Highlights
• THR-149 - Phase 2 DME study initiated/ Part A RECRUITING – Initial dose response data by mid 2021
• Follows on from positive Phase 1 data
• 7.5 letter improvement in BVCA at Day 14 from a single injection
• Rapid onset and extended duration of action - safe profile
• THR -687 Positive Phase 1 data read out announced
• Meaningful gain in BVCA – 12.5 letter improvement at Month 3 from a single injection – highest dose cohort
• Rapid onset and extended duration of action - safe profile
• Phase 2 DME Study planned /Part A start expected mid 2021 – Data H1 2022
• Strengthened management team
• Michaël Dillen as Chief Corporate Development Officer and Corporate Secretary.
• €37.9 million in cash as of June 30, 2020
5Abbreviation(s): DME, diabetic macular edema; HQ; R&D, research & development; VEGF, vascular endothelial growth factor; US, United States
Financial Review First half highlights
Reduced Half Year Loss
HY 2020 key figures
commercial support and Covid in Europe
• R&D expenses reduction mainly due halting of THR-317
program, reduced TB-403 and JETREA clinical support
but partly offset by increase in expenses for THR-149
and THR-687
commercial support in the US
• Reduced other operating income due to less costs re-
invoiced and JETREA settlement received in 2019
Research and development expenses -9.9 -12.0 2.1
General and administrative expenses -2.7 -3.3 0.6
Selling expenses -1.8 -3.4 1.6
In euro millions (for the period ended on June 30) 2020 2019 var
Income 1.3 1.8 -0.5
Other operating income 0.3 1.7 -1.5
Impairment losses 0.0 -16.9 16.9
Finance income and expense -0.1 0.1 -0.2
Operating result -13.3 -33.3 20.0
Profit & Loss comparison to HY 2019
Cash Resources of €37.9 million at end June 2020
Prudent cash management
Non-cash items (depreciation, rights of use, share based payments) 0.8
Acquisition of assets -0.3
Cash lease costs and interest -0.4
In euro millions (for the period ended on June 30) 2020
Opening Cash & investments 52.9
Finance income/expense 0.1
Decrease in current assets and receivables -1.8
Closing cash and investments 37.9
Simplified statement of cash flows
Creating Our DME Franchise Based on THR-149 and THR-687
DME results from diabetic retinopathy - a serious chronic complication of diabetes DR is a chronic sight-threatening, and life-altering disease - major public health concern globally
Retina of the eye
Retinal venules Retinal
Patient vision
Blurring & scotomata
10 Abbreviation(s): DR, diabetic retinopathy
Diabetic macular edema is an accumulation of fluid in the macula* due to leaking blood vessels – can occur at any stage of DR
Courtesy of Heidelberg Engineering Courtesy of Heidelberg Engineering
Diabetic macular edemaNormal eye
Retina Macula
Macular edema
11 *The macula is the part of the retina that controls detailed vision
Abbreviation(s): DR, diabetic retinopathy
DME Management has multiple unresolved challenges
anti-VEGF therapy the mainstay of treatment, but fails to meet the needs of a significant number of patients with DME
Abbreviation(s): BCVA, best-corrected visual acuity; DME, diabetic macular edema; VEGF, vascular endothelial growth factor
Patient needs
of onset
Better therapeutic effect in terms of visual function (BCVA) and response rate (proportion of patients)
Extent
Decrease treatment burden
Increase duration of response for longer treatment intervals
Duration
Significant opportunity to improve treatment outcomes
13Source : Gonzalez, VH et al., 2016. Am. J. Ophthalmology
Sub optimal responders to
anti-VEGFs
Oxurion aims to be a GAME CHANGER in the treatment of DME
14Abbreviation(s): DME, diabetic macular edema; SOC, standard of care; VEGF, vascular endothelial growth factor
• Potential to become SOC for DME patients, sub- optimally responders to anti-VEGF therapy
• Targeting a VEGF-independent pathway
• Positive Phase 1 data after a single IVT administration
THR-149 Phase 2 study – Multiple injections - Part A recruiting, data mid 2021
THR-687 Phase 2 study – Part A expected to start recruiting by mid 2021
Targeting a market opportunity worth $4.5 billion p.a.
• Potential to become SOC for all DME patients
• Broader biological effect – potential to replace anti-VEGF therapy
• Positive Phase 1 after a single IVT administration
Pan-RGD integrin antagonist
Designed to Improve on anti-VEGF therapy
New generation of DME treatments, beyond VEGF targeting, to answer substantial unmet medical needs
THR-149 – Improving on anti-VEGF therapy Multiple injections could deliver even better patient outcomes
• Highly potent plasma kallikrein inhibitor targeting a VEGF-independent pathway
• THR-149 discovered by Bicycle Therapeutics
• IP protection 2034-2039
• Key hallmarks of DME
• Data from pre-clinical models has shown that multiple injections of THR-149 could potentially be even more effective both in terms of BVCA and CST
• Potential to become the standard of care for the ~ 40% of DME patients who respond sub-optimally to anti- VEGF therapy
Screening Primary Endpoint
THR-149 Clinical evidence Phase 1 study design in DME patients
Open-label, multicenter, 3+3 dose-escalation study to evaluate safety and preliminary efficacy (NCT03511898)
Study treatment
BCVA ≤ 62 and ≥ 23 letters
History of response to prior anti-VEGF / corticosteroid treatment
17 Abbreviation(s): BCVA, best-corrected visual acuity; CST, central subfield thickness; D, day; DLT, dose-limiting toxicity; DME, diabetic macular edema; IVT, intravitreal; OCT, optical coherence tomography; VEGF, vascular endothelial growth factor
DLT criteria
BCVA: 10 ETDRS letter score decrease in BCVA from baseline
D56
THR-149 Phase 1 evidence Mean change in BCVA from baselinea
BCVA increased rapidly and was maintained for 3 months after a single injection
0
3.9
• A gain in mean BCVA was seen at every visit
• Mean change in BCVA from baseline was the highest at D14 and was maintained at M3
All treated subjects, overall
Abbreviation(s): BCVA, best-corrected visual acuity; BL, baseline; CST, central subfield thickness; D, day; DME, diabetic macular edema; ETDRS, early treatment diabetic retinopathy study; M, month
Positive data
THR-149 Phase 2 study Design Trial Now Recruiting Multiple injections - Primary Endpoint: BCVA – Secondary Endpoints: CST, AE’s
Screening Dose-level selection for Part B
D1 M1 M2 M3 M4 M5 M6
Part A : Dose level selection THR-149 N=18, rando 1:1:1 Results by mid 2021
Part B: Topline data N=104, rando 1:1 Results by H1 2023
0.01 mg 0.04 mg 0.13 mg
Screening Primary Endpoint Secondary endpoints
D1 M1 M2 M3 M4 M5 M6
Selected dose THR-149 Part A Aflibercept 2 mg
Anti-VEGF suboptimal responders:
BCVA ≤ 73 and ≥ 39 letters
≥ 5 anti-VEGF injections
Abbreviations: AE, adverse event; BCVA, best-corrected visual acuity; CST, central subfield thickness; D, day; DME, diabetic macular edema; M, month; N, number; OCT, optical coherence tomography; Rando, randomization; VEGF, vascular endothelial growth factor
N
N
Part A results expected by mid 2021
• Targeting a better than the 7.5 letter improvement in BCVA at Day 14 seen with a single injection in the Phase 1
• Confirm work in animal models that multiple injections could have a significant positive effect on CST
• Part A focused on dose-selection
• also expected to provide initial efficacy data and to confirm fast onset of action and durability of response seen in Phase 1 study – data by mid 2021
• Part B will assess the difference in BCVA at Month 3 of THR-149 vs control and is statistically powered
• Data generated will be used to design planned Phase 3 study
THR-687 Potential to replace anti-VEGF therapy
New generation of DME treatments, beyond VEGF targeting, to answer substantial unmet medical needs
Abbreviation: DME, diabetic macular edema; VEGF, vascular endothelial growth factor
THR-687 – Potential to replace anti-VEGF therapy
Initially targeting a significant opportunity as first line standard of care in DME
• THR-687 is a pan-RGD integrin antagonist
• in-licensed from Galapagos
• IP protection 2039-2044
• Neovascularization
• Potential to become SOC for all DME patients, replacing anti-VEGFs
• Significant longer-term potential across multiple diabetic eye diseases
22
0
5
10
15 THR-687 0.4mg (N=3) THR-687 1.0mg (N=3) THR-687 2.5mg (N=6)
6.7
1.7
THR-687 Phase 1 evidence Mean change BCVA from Day 0
Largest BCVA improvement in the high dose group, with a mean BCVA gain of 12.5 letters at M3
12.5
All treated subjects, by dose
D14 M1D0 D7D1 M2 M3
Study visit
M ea
n c
h an
ge in
B C
V A
f ro
m D
0 (E
TD R
S le
tt er
Preparing for Phase 2 DME study; Significant potential beyond DME
Clinical development plans
• Phase 2 DME Study planned /Part A start expected mid 2021 – Data H1 2022
• Part B expected to start 2022 – Data 2023
Pre-clinical activities
- Diabetic retinopathy
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Oxurion aims to be a GAME CHANGER in the treatment of DME
• Building the industry leading DME franchise
• THR-149 - Phase 2 DME study initiated/ Part A RECRUITING – Initial dose response data by mid 2021
• Phase 2 study evaluating the potential of multiple injections to deliver better outcomes – BCVA and CST
• Follows on from positive Phase 1 data
• Clinically meaningful gain in BCVA – 7.5 letter improvement at Day 14 from a single injection
• Rapid onset and extended duration of action - safe profile
• THR -687 Positive Phase 1 data read out announced
• Clinically meaningful gain in BVCA – 12.5 letter improvement at Month 3 from a single injection – highest dose cohort
• Rapid onset and extended duration of action - safe profile
• Phase 2 DME Study planned /Part A start expected mid 2021 – Data H1 2022
• Significant potential beyond DME
• Strengthened management team
• Committed to delivering new standard of care therapies for all DME patients, a $ 4.5 billion market opportunity
25Abbreviation(s): DME, diabetic macular edema
Q&A