Vivoryon Therapeutics N.V. · EURONEXT:VVY
Vivoryon Therapeutics — Probiodrug — FY2017 Earnings Presentation
44 slides from Vivoryon Therapeutics's earnings presentation, Apr 3, 2018
Slide 1: The 2017 financial year – Full year results
The 2017 financial year Full year results Halle (Saale), 03 April 2018 Konrad Glund Hendrik Liebers Inge Lues Frank Weber CEO CFO CDO CMO
Slide 2: Important notice and disclaimer
Important no*ce and disclaimer This Presenta*on has been prepared and issued by Probiodrug AG (the “Company”) and has not been independently verified by any third party. No representa*on or warranty is given as to the achievement or reasonableness of, and no reliance should be placed on, any projec*o
Slide 3: Content
Content 1. Corporate overview 2. Results 2017 3. Outlook 4. Q & A 5. Appendix 3
Slide 4: Longstanding track-record and renowned investor base
Longstanding track-record and renowned investor base Brief history Major investors ¡ 1997: Founda*on, pioneered a new class of an*-diabe*cs (glip*ns) – partnerships with Merck & Co, Ferring and Novar*s ¡ 2004: Sold diabetes franchise to OSI Pharmaceu*cals – proceeds par*ally returned to shareholders
Slide 5: Experienced management team
Experienced management team Management team Biography Konrad Glund, PhD ¡ Co-founder of Probiodrug, CEO since 2006 CEO ¡ Led development of DPP 4 inhibitors, transac*ons with Merck, Novar*s, OSI and Ferring Co-founder ¡ COO & VP business development OSI (Prosidion) in 2004-2006 Chairman of the manag
Slide 6: The AD Paradigm
The AD Paradigm Neurofibrillary Tangles Abeta plaques NeuroinflammaLon ¡ There are three pathological hallmarks of AD in the brain: } Plaques formed from Amyloid beta (“Abeta”), a small protein fragment, originated from the precursor protein APP } Tangles are misfolded forms of a protein called Tau }
Slide 7: A different approach
A different approach TargeLng post-translaLonally modified Abeta – pGlu Abeta Oligomers Plaques sAPPβ APP Aβ(x-40/42 ) Outside cell β-secretase γ-secretase Inside cell QC Abeta pGlu-Abeta ¡ pGlu-Abeta is crucial in the forma*on of synapto-/neurotoxic toxic oligomers ¡ Oligomers act directly on synap*c
Slide 8: pGlu-Abeta - N-terminal modified, toxic Abeta
pGlu-Abeta - N-terminal modified, toxic Abeta Jawhar, S., Wirths, O., Bayer, T.A. JBC 286, 45, 2011 8
Slide 9: Target pGlu-Abeta: small molecule approach (QC inhibitor)
Target pGlu-Abeta: small molecule approach (QC inhibitor) Probiodrug was first to discover the role of QC and has full ownership of broad target IP Jawhar, S., Wirths, O., Bayer, T.A. JBC 286, 45, 2011; modified 9
Slide 10: Target pGlu-Abeta: antibody approach
Target pGlu-Abeta: an*body approach Probiodrug’s complementary approach with a pGlu-Abeta specific anLbody Jawhar, S., Wirths, O., Bayer, T.A. JBC 286, 45, 2011; modified 10
Slide 11: Emerging landscape of disease modifyers in AD
Emerging landscape of disease modifyers in AD Immunotherapy ModulaLng Abeta producLon ¡ AZD3293: Phase 2/3 Passive } Beta secretase inhibitor, mild AD ¡ Aducanumab (BIIB037): Phase 3 ¡ E2609: Phase 2 } Beta secretase inhibitor, prodromal or mild to moderate AD } early AD ¡ JNJ54861911: Phase 2a ¡ Cr
Slide 12: Focused proprietary pipeline
Focused proprietary pipeline Pre- Product Phase 1 Phase 2a POC Phase 2b clinical PQ-912 ¡ Small molecule QC inhibitor Top line data reported PBD-C06 ¡ pGlu-Abeta specific monoclonal an*body PQ-1565 ¡ Small molecule QC inhibitor 12
Slide 13: The Probiodrug Share
The Probiodrug Share KEY INFORMATION Major Shareholder* § ISIN: DE0007921835 § WKN: 792183 § Ticker Symbol: PBD § Type of shares: Bearer shares § Number of shares: 8,208,009 § Stock exchange: Euronext Amsterdam § Liquidity Provider: Kempen & Co. § Lis*ng Agent: Kempen & Co. * Calculated on the basis
Slide 14: Content
Content 1. Corporate overview 2. Results 2017 3. Outlook 4. Q & A 5. Appendix 14
Slide 15: Highlights 2017 (1)
Highlights 2017 (1) ¡ PQ912 delivers posi*ve pharmacodynamic and efficacy results in a Phase 2a study, the SAPHIR study, in early stage AD pa*ents ¡ Phase 2a SAPHIR study results presented in November 2017 at Clinical Trials on Alzheimer’s Disease (CTAD), Boston, USA ¡ Ini*a*on of PQ912 Phase 2b core
Slide 16: Highlights 2017 (2)
Highlights 2017 (2) ¡ Successful seulement of pending tax liability ¡ Annual Shareholders’ Mee*ng held on 13 June 2017 ¡ Expenditures and corresponding cash posi*on in line with management expecta*ons ¡ Cash and cash equivalents of EUR 10.3 million as of 31 December 2017, providing according to pres
Slide 17: Key financial figures (according to IFRS)
Key financial figures (according to IFRS) In EUR k 2017 2016 Earnings, Financial and Net Assets Posi4on Opera*ng loss -9,961 -13,777 Finance income/loss 850 -114 Income tax gain 1,102 0 Net loss for the period -8,009 -13,891 Equity (end of the year) 8,923 16,376 Equity ra*o (end of the year) (in %) 82
Slide 18: Details of the Financial Results (according to IFRS)
Details of the Financial Results (according to IFRS) Net loss Opera*ng loss § Expenditures in line with company`s projec*ons kEUR 9,961 § Net loss without income tax gain in line with expecta*ons Finance income/ § Opera*ng loss primarily driven by R&D expenses Income tax gain kEUR 1,964 § Finance in
Slide 19: PQ912 Clinical Development Strategy AD
PQ912 Clinical Development Strategy AD ¡ Phase 1: Comprehensive single and mul*ple dose studies Focus on mechanism based biomarker, PK / PD model, safety Delivered target occupancy model, good safety margins, drug formula*on strategy, drug metabolism ¡ Phase 2a: Pilot double blind study in target AD
Slide 20: SAPHIR – first in patient Phase 2a study
SAPHIR – first in pa*ent Phase 2a study INTENTION § Using a high dose of PQ912 resul*ng in a high QC-occupancy – to find both Ø early-on safety and tolerability signs and Ø any signal on the various sensi*ve secondary exploratory outcome measures – in a rela*vely short *me frame of 12 weeks § To guide
Slide 21: SAPHIR Phase 2a trial in early AD patients
SAPHIR Phase 2a trial in early AD pa*ents Objec*ve: safety and early pharmacodynamic effects SAPHIR Phase 2a trial design ObjecLves and read-outs ¡ Seven EU countries, 21 Sites, PI P. Scheltens ¡ Primary objecLve: To assess safety and Amsterdam tolerability of PQ912 compared with placebo ¡ Total numb
Slide 22: SAPHIR Phase 2a trial in early AD patients – Safety Results
SAPHIR Phase 2a trial in early AD pa*ents Safety Results ¡ No significant differences in the number AE or SAE between ac*ve and control arm ¡ Significantly higher number of pa*ents discon*nuing within first weeks of treatment with PQ912 800mg q12h compared to placebo ¡ Clinically relevant differences in
Slide 23: Summary results - efficacy
Summary results - efficacy Summary of exploratory Exploratory results inreadouts SAPHIR trial CSF: Ø Strong QC-inhibi*on, target occupancy about 90% Clear proof of Ø Strong trends to reduce the synap*c marker neurogranin, Mechanism of AcLon and the inflammatory marker YKL40, which are both enhanced in
Slide 24: Results and Conclusions
Results and Conclusions Ø Results: § Primary endpoints: Safety signal in skin and GI events in the first weeks of treatment period § Secondary endpoints: Very strong target engagement, significant effects on One back Test and on qEEG theta power and encouraging results in the right direc*on on synap*c
Slide 25: Outlook: Overarching Phase 2b Development Strategy
Outlook: Overarching Phase 2b Development Strategy SAPHIR gave highly valuable results regarding dosing and efficacy endpoints / biomarker ¡ EU Phase 2b study design - inbuilt newest FDA and EMA guidance for early AD } Seamless design: Stage 1: tolerability dose-LtraLon (150-600 mg bid): Inves*gate
Slide 26: Dosing option POC study
Dosing op*on POC study D o s e -R e s p o n s e Phase 2 a: high dose, 90% Target Occupancy (TO); 800 mg bid 100 3 months (T a rg e t o c c u p a n c y ) 80 Under discussion % Q C in h ib it io n 60 Phase 2 POC- Dosing opLons v Doses between 600 mg bid (*trated) and 100 mg bid 40 v TO between 40 and
Slide 27: EU Phase 2b Study SAPHIR 2
EU Phase 2b Study SAPHIR 2 Objec*ve: Clinical Proof of Concept in Cogni*on – changes possible Trial metrix and design ObjecLves and read-outs ¡ 10 EU countries, PI P. Scheltens, Amsterdam ¡ Primary objecLve: To assess the efficacy of ¡ Total projected: 250 pa*ents PQ912 on cogni*ve func*on in early AD
Slide 28: SAPHIR 2 – Patient dosing and time schedule
SAPHIR 2 – Pa*ent dosing and *me schedule Safety decision * Study end aser 90 pa*ents 600 mg (bid)** 600 mg (bid)** 24 weeks 300 mg (bid)** 8 weeks Up and down –*tra*on op*on 150 mg (bid) 4 weeks Up-*tra*on Randomisa*on 0 4 12 36 48 60 72 84 Weeks on treatment * All pa*ents will have a study dura*on
Slide 29: Corporate Review (1)
Corporate Review (1) General MeeLng of Shareholders on June 13, 2017 All resolu*ons proposed by the Company’s Management and Supervisory Board were approved at the mee*ng with a large majority: ¡ Adop*on of a resolu*on on the approval of the ac*ons of the management board members for the financial ye
Slide 30: Corporate Review (2)
Corporate Review (2) Supervisory Board ¡ Shareholder mee*ng on 13 June 2017, re-elected Dr Erich Platzer, Dr Dinnies von der Osten and Dr Jörg Neermann as Supervisory Board Members. ¡ The Supervisory Board then re-elected Dr Erich Platzer as chairman and Dr Dinnies von der Osten as vice chairman. ¡
Slide 31: Content
Content 1. Corporate overview 2. Results 2017 3. Outlook 4. Q & A 5. Appendix 31
Slide 32: Outlook
Outlook Mid-term focus of Probiodrug’s business acLviLes are summarised as follows: ¡ Execu*on of the Phase 2b clinical study program for PQ912, ¡ Con*nuing the development of PBD-C06, ¡ Conclusion of one or more industrial partnerships, ¡ Further scien*fic analysis of poten*al second indica*ons for
Slide 33: News flow (selection)
News flow (selec&on) 2016 2017 2018 PQ912 results of long term tox ✔ NIH grant applica*on ✔ ✔ PQ912 Phase 2a SAPHIR results studies submiued PQ912 POP* combina*on therapy Secure non-dilu*ve Promising an*-inflammatory with BACE inhibitor funding components effect by ac*va*ng the ✔ resolu*on process in a
Slide 34: Financial Calendar
Financial Calendar ¡ 15 May 2018 Interim Management Statement Q1 2018 ¡ 21 June 2018 Annual General Mee*ng of Shareholders ¡ 30 August 2018 Interim Report, half year results 2018 ¡ 29 November 2018 Interim Management Statement Q3 2018 34
Slide 35: Content
Content 1. Corporate overview 2. Results 2017 3. Outlook 4. Q & A 5. Appendix 35
Slide 36: Content
Content 1. Corporate overview 2. Results 2017 3. Outlook 4. Q & A 5. Appendix 36
Slide 37: Operational Review (1)
Opera*onal Review (1) PQ912 ¡ January 2017: CompleLon of recruitment for the SAPHIR Phase 2a study of Glutaminyl Cyclase Inhibitor PQ912 in early Alzheimer’s disease pa*ents. A total of 120 pa*ents have been randomised, surpassing the 110 pa*ents planned in the study protocol. ¡ April 2017: Probiodr
Slide 38: Operational Review (2)
Opera*onal Review (2) PQ912 ¡ October 2017: Probiodrug announced the iniLaLon of the Phase 2b core program for PQ912 and detailed the strategy. The Phase 2b core program is planned to comprise of two complementary clinical Proof of Concept studies in Europe and the USA. The development strategy has
Slide 39: Operational Review (3)
Opera*onal Review (3) PQ912 - CombinaLon therapies § March 2017: Probiodrug presented at the 13th InternaLonal Conference on Alzheimer's and Parkinson's Diseases (AD/PDTM 2017) § an oral presenta*on en*tled: “Selec*ve targe*ng of pGlu-Abeta with an IgG2a in tg mice is effec*ve in lowering plaque path
Slide 40: Operational Review (4)
Opera*onal Review (4) PQ912 – HunLngton’s disease § April 2017: Probiodrug is exploring poten*al second indica*ons for its QC inhibitors. PQ912 demonstrated beneficial effects in a preclinical Hun*ngton´s disease (HD) model; the data of this study have been presented at the 12th Annual HD TherapeuLcs
Slide 41: Operational Review (5)
Opera*onal Review (5) PBD-C06 ¡ Monoclonal an*body targe*ng pGlu-Abeta, while leaving non-toxic forms of Abeta untouched ¡ Currently in preclinical stage ¡ Successfully humanized and de-immunized ¡ Unique profile - IgG1 isotype – no complement ac*va*on to prevent complement triggered inflamma*on ¡ For
Slide 42: Operational Review (6)
Opera*onal Review (6) PublicaLons ¡ 13th Interna4onal Conference on Alzheimer's and Parkinson's Diseases (AD/PDTM 2017), Vienna, Austria: In March 2017 Probiodrug presented an oral presenta*on en*tled: “Selec&ve targe&ng of pGlu- Abeta with an IgG2a in tg mice is effec&ve in lowering plaque pathology
Slide 43: Operational Review (7)
Opera*onal Review (7) PublicaLons ¡ Journal of Biological Chemistry: In August 2017 the unique binding mode of PBD-C06 to pGlu-Abeta pep*des was published (“Structural and func&onal analyses of pyroglutamate-amyloid-β-specific an&bodies as a basis for Alzheimer immunotherapy”; Piechoua et al. J. Biol
Slide 44: Operational Review (8)
Opera*onal Review (8) Partnerships ¡ In December 2017 Probiodrug and dutch company Crossbeta Biosciences B.V. extended their strategic partnership in the field of Alzheimer’s disease biomarkers in order to u*lize Crossbeta’s proprietary technology to support of Probiodrug’s biomarker development ac*v