Infant Bacterial Therapeutics Ab Class B · OMXSTO:IBT_B
Infant Bacterial Therapeutics Ab Class B — Investor Presentation (January 2018)
59 slides from Infant Bacterial Therapeutics Ab Class B's investor presentation, January 2018
Slide 1: Infant Bacterial Therapeutics Corporate Presentation January 2018
Infant Bacterial Therapeutics Corporate Presentation January 2018 1
Slide 2: Disclaimer
Disclaimer You must read the following before continuing. The following applies to this document and the information provided in this presentation by Infant Bacterial Therapeutics AB (publ) (the “Company”) or any person on behalf of the Company and any other material distributed or statements made i
Slide 3: Periods
Periods Week nr. Month nv. Birth classification Antepartum or 3f4[s[el7[a[9 Tro] 11] 12] 13]14]15]16[17]18]19| 20] 21]22] 23] 24] 25] 26 [27] 28] 29] 30] 31] 32] 33[ 34] 35 50% survival,
Slide 4: Lead drug candidate IBP-9414 to prevent necrotizing enterocolitis
Lead drug candidate IBP-9414, to prophylactically prevent necrotizing enterocolitis (“NEC”), a fatal, rare disease that afflicts premature infants Label Patient Population 56,000 children in US estimated up to USD 350m per year in US market for IBP-9414 Market Approval for IBP-9414 target 2020 / 202
Slide 5: The IBT concept
The IBT concept n IBT focuses on concepts of altering the human microbiome to prevent or treat diseases n Microbiome of the newborn infant is more dynamic than that of the mature human n Utilize co-evolved human bacterial strains derived from human breast milk n Clinical proof-of-concept signal publ
Slide 6: Capital Raise
Capital Raise n Directed share issue of approximately SEK 105 million to 8 new institutional investors n Rights issue of approximately SEK 440 million • Covered by subscription undertakings, guarantee commitments and declarations of intent to subscribe to 89% of rights issue without any separate com
Slide 7: IBP-9414 for the prevention of necrotizing enterocolitis
IBP-9414 for the prevention of necrotizing enterocolitis 1 NEC HIGH UNMET MEDICAL NEED 2 5 MECHANISM OF SAFETY PROFILE ACTION Safe and well L. reuteri for the tolerated prevention of NEC 6 9 ESTABLISHED PRIORITY CONTROLLED REVIEW DRUG VOUCHER PRODUCTION IBT has the 3 4 eligibility at MA EFFICACY IBP
Slide 8: 1. Necrotizing enterocolitis, a high unmet medical need
1. Necrotizing enterocolitis, a high unmet medical need 8
Slide 9: Necrotizing Enterocolitis
Necrotizing Enterocolitis NEC is a severe inflammation and necrosis of the preterm infant bowel True unmet medical need • There is no therapy available today • 20-40% need complicated and costly surgery • One of the leading causes of death in NICU • Up to 40% death rate, 1500 US and 3700 EU infants
Slide 10: Who gets NEC?
Who gets NEC? Infants birth NEC incidence NEC mortality Mortality (% of weight rate (%) rate (%) weight cohort) 501-750g 12.0% 42.0% 5.0% High incidence 751-1,000g 9.2% 29.4% 2.7% and mortality 1,001-1250g 5.7% 21.3% 1.2% 1,251-1,500g 3.3% 15.9% 0.5% 1,501-2,500g 0.4% 8.2-17% 0.03-0.06% >2,500g 0.1%
Slide 11: Target population
Target population A preventive therapy for all preterm infants at risk of NEC Current clinical NEC progression Target label population 100 premature infants (751-1,000g) Based on the expected IBP-9414 drug label, the targeted annual label population is: 9 NEC cases n US: 56,000 premature infants (≤1
Slide 12: 2. Mechanism of Action – Lactobacillus reuteri for the prevention of NEC
2. MECHANISM OF ACTION –Lactobacillus reuteri for the prevention of NEC 12
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Slide 14: Lactobacillus reuteri
Lactobacillus reuteri Active substance of IBP-9414 Lactobacillus reuteri (orange) Lactobacillus reuteri present adhering to intestinal mucus on women’s breasts Picture with the permission Versalovic 14
Slide 15: Evolutionary adaptation of L. reuteri to the human gut
Evolutionary adaptation of L. reuteri to the human gut Figure 1 AFLP analysis of a global collection of Lactobacillus reuteri strains from humans, Host Poultry Human Porcine Rodents Genetic relatedness of global L. reuteri genomes 0.02 Evolution of the gut symbiont L. reuteri PL Oh et al C ii B D E
Slide 16: L. reuteri an ideal candidate for NEC
L. reuteri an ideal candidate for NEC L. reuteri has strain-specific attributes which affect the NEC pathogenesis Major processes involved in NEC L. reuteri strain-specific benefits Dysbiosis Anti-pathogen effects Improvement of gut Impaired gut motility motility Unregulated Anti-inflammatory Inflam
Slide 17: Dysbiosis in NEC
Dysbiosis in NEC Dysbiosis with pathogen blooms in the microbiota can contribute to necrotizing enterocolitis in preterm infants A NEC Cases Controls Controls 100 Gammaproteobacteria Bacilli Clostridia 90 Negativicutes 80 70 Proportion of reads (%) 60 50 40 30 20 10 0 1–15 16–30 31–45* 46–60† 1–15 1
Slide 18: Anti-pathogen effects in vitro
Anti-pathogen effects in vitro L. reuteri produces species-specific antimicrobial substance called reuterin Bacteria § Bacillus subtilis § Escherichia coli (patogena) § Listeria monocytogenes § Salmonella typhimurium § Campylobacter jejuni § Enterobacter sakazakii § Porphyromonas gingivalis § Shigel
Slide 19: Anti-pathogen effects in infants
Anti-pathogen effects in infants Infant fecal pathogens after 1 month L. reuteri treatment 18 * Number of positive feces samples for identified pathogens from 30 infants 16 L. reuteri group n= 30 Control group n=30 14 * P≤0.05 12 10 * 8 6 4 2 0 Diarrheagenic Salmonella Cronobacter Hafinia alvei Kleb
Slide 20: Impaired gut motility in NEC
Impaired gut motility in NEC Poor gastrointestinal motility is associated with NEC Term infant healthy gut motility Movement Movement Premature infant impaired gut motility Standstill Increased risk of accumulation of noxious substances which can cause intestinal damage Source Lin et al, 2008 20
Slide 21: L. reuteri improves gut motility ex vivo
A 80 ** B 4 ** C 10 15 ns A 100 (mm s–1(mm PPr (hPa 60 (mHz) ( (mHz) ( L. reuteri improves gut motility ex vivo Frequency Frequency 40 2 ) 80 60 3 40 VelocityVelocity 5 10 PPr (hPa) 20 1 60 20 Frequency Frequency Spatiotemporal mapping of mouse gut motility 40 2 40 0 0 0 5 0 20 1 20 Kr s SM s SM s S
Slide 22: Modulation of gut motility in preterm infants
Modulation of gut motility in preterm infants Fasting antral area Regurgitation * * P≤0.05 * No. of episodes of regurgitation Formula Formula Gastric emptying Stooling + L. reuteri + placebo * * No. of episodes of evacuations Formula Formula + L. reuteri + placebo Preterm infants given L. reuteri sh
Slide 23: Excessive inflammation in NEC
Excessive inflammation in NEC Toll-like receptors (TLR4) IEC ⚡ ⚡ ⚡ ⚡ Teff Teff cells Treg Treg DC cells FoxP 3 Mphage Inflammatory cytokines Teff Teff Treg FoxP3 Teff Teff Anti- Teff inflammatory cytokines 23
Slide 24: Anti-inflammation in NEC
Anti-inflammation in NEC L. reuteri reduces inflammation Toll-like Receptors (TLR4) ⚡ IEC Teff Teff cells Treg Treg DC cells FoxP 3 Mphage Inflammatory Treg cytokines Teff FoxP3 Treg Treg FoxP3 Anti- FoxP3 inflammatory cytokines Source Liu 2010, Liu 2012, Liu 2014 24
Slide 25: Anti-inflammation in NEC animal model
We examined the effects of human-derived probiotic L. reuteri strains DSM 17938 and ATCC PTA 4659 on experimental NEC. Anti-inflammation in NEC animal model Our hypothesis was that different strains would differ in their anti-inflammatory effects in this disease. Previous studies from our laboratory
Slide 26: Strain specific anti-inflammation in NEC animal model
Strain specific anti-inflammation in NEC animal model L. reuteri DSM 17938 AFFECTS EFFECTOR/MEMORY T AND Tr Treg Teff FoxP3 Treg cell modulation Teff cell modulation L. reuteri L. acidophilus L. reuteri L. acidophilus A B Fig. 4. LR17938 reversed frequency of CD4!Foxp3! regulatory Fig. 6. LR17938 T
Slide 27: Anti-inflammatory in infants
Anti-inflammatory in infants Treg cells increase in infant blood after L. reuteri administration Treg 60 * P≤0.05 * FoxP3 50 FOXP3 mRNA levels 40 30 20 10 Placebo 0 L. reuteri -10 -20 L. reuteri recruitment of Treg cells now shown in infants Source Savino 2017 27
Slide 28: Protection against NEC in animal models
Protection against NEC in animal models L. reuteri increases survival reproducibly in NEC model L. reuteri reduces NEC in rodent models Source Liu, 2012 & Liu 2013 (rat), Liu 2014 (mouse) 28
Slide 29: 3. Efficacy Signal – L. reuteri clinical signal in prevention of NEC
3. EFFICACY SIGNAL – L. reuteri has shown strong clinical signal in the prevention of NEC 29
Slide 30: Clear clinical signal (1/4)
Clear clinical signal (1/4) Randomised double-blind placebo-controlled clinical studies indicate reduction of NEC 1 Rojas et al. (2012) 2 Oncel et. al (2014) n Determine whether prophylactic administration of n Evaluate the effect of administration of L. reuteri L. reuteri to pre-term infants reduce
Slide 31: Clear clinical signal (2/4)
Clear clinical signal (2/4) Retrospective cohort clinical studies indicate reduction of NEC 3 4 Hunter et al. (2012) & Dimaguila et al. (2013) Jerkovic Raguz et al. (2016) n Examine the potential benefit of administering L. n Analyse the treatment, course and outcome of Aim of the study reuteri on t
Slide 32: Clear clinical signal (3/4)
Clear clinical signal (3/4) Retrospective cohort clinical studies indicate reduction of NEC 5 6 Sanchez Alvarado (2017) Rolnitsky et al. (2018) n Demonstrate that the use of Lactobacillus reuteri n Quality improvement study to reduce NEC rates in Aim of the study prevents NEC in premature infants <1
Slide 33: Clear clinical signal (4/4)
Clear clinical signal (4/4) Other studies indicating reduction of NEC 7 8 Shadkam et al. (2015) Hernandez-Enriquez et al. (2016) n Evaluate the effects of Lactobacillus reuteri on n Evaluate the effectiveness of the use of Aim of the study the gastrointestinal complications and feeding Lactobacillus
Slide 34: Clear efficacy signal from L. reuteri
Clear efficacy signal from L. reuteri All studies show clinically significant reduction of NEC Study Number of patients Reduction in NEC incidence n 40% in the total study population Rojas et al. (2012) n 750 patients n 37% in infants ≤1,500g n 20% in the total study population Oncel et al. (2014) n
Slide 35: Benefits to all premature infants
Benefits to all premature infants Premature infants are extremely difficult to feed Infants require intravenous fluids solution for brain and body Intravenous nutrition is inadequate IV nutrition (TPN) can also be toxic to the liver L. Reuteri demonstrates Clear signal on improved feeding tolerance
Slide 36: 4. Plan endorsed by stakeholders – Regulatory agencies and KOLs
4. PLAN ENDORSED BY STAKEHOLDERS – Regulatory agencies and KOLs 36
Slide 37: Network of KOLs
Network of KOLs IBT has developed IBP-9414 program with deep considerations of KOLs experience and clinical practice Some of the external participants Aideen Moore, The Hospital for Sick Children, Toronto, Canada. Key Opinion Leader Meetings Alexandre Lapillonne, Necker Hospital for Sick Children, P
Slide 38: Regulatory achievements
Regulatory achievements IBT has had close interaction with regulatory agencies on the IBP-9414 development program FDA ✅ Sep-13: pre-IND type B FDA meeting ✅ Aug-13: FDA approval of Orphan Drug Designation ✅ Dec-15: IND becomes effective ✅ Mar-16: FDA grants Rare Pediatric Disease product status EMA
Slide 39: IBP-9414 – development plan
IBP-9414 – development plan A development program consisting of two clinical trials developed according to advice from regulators and KOLs Drug development plan 2016 2017 2018 2019 Safety and tolerability trial n A randomized, double blind, parallel-group, dose escalation placebo-controlled multicen
Slide 40: 5. Safety Profile – IBP-9414 safe and well-tolerated in preterm infants
5. SAFETY PROFILE – IBP-9414 a safe and well-tolerated in preterm infants 40
Slide 41: IBP-9414 Safety and Tolerability study
IBP-9414 Safety and Tolerability study A randomized double blind, parallel-group, dose escalation placebo-controlled multicenter study to investigate the safety and tolerability of IBP-9414 administered in preterm infants 120 patients 2 weight cohorts 2 doses 15 US sites Neu, Gainesville FL, PI Del
Slide 42: IBP-9414 Safety and Tolerability study
IBP-9414 Safety and Tolerability study Conclusions § Recruitment rate was higher than estimated without a difference between big and small babies § Demographics of the study was representative of the target population § Similar Adverse Event and Serious Adverse Event profile between active and place
Slide 43: IBP-9414 Safety and Tolerability study
IBP-9414 Safety and Tolerability study Conclusions cont. § No evidence of cross-contamination with IBP-9414 in placebo treated infants § Treatment with IBP-9414 leads to presence of bacterium in the feces on day of last dose § Smaller infants needed the higher dose to display IBP-9414 in the feces §
Slide 44: 6. Established Controlled Pharmaceutical Production
6. ESTABLISHED CONTROLLED PHARMACEUTICAL PRODUCTION 44
Slide 45: Why product quality is important?
Why product quality is important? The Solgar incident October 2014 November 2014 December 2014 Consequences n A premature infant n Solgar issued a n FDA/CDC warning n Pressure to conform given a Solgar voluntary recall of letter issued to FDA’s rigorous product (ABC the product standards due to risk
Slide 46: Manufacturing Process of IBP-9414
Manufacturing Process of IBP-9414 Stringent control of manufacturing environment Cell Bank Filling Pre-culture Freeze-drying Fermentation Packaging & Labelling Filtration IBP-9414 powder for oral suspension Mixing Formulated Cell Suspension 46
Slide 47: 7. Multi-layer Protection on the market
7. MULTI-LAYER PROTECTION on the market 47
Slide 48: IBP-9414 Market Exclusivity
IBP-9414 Market Exclusivity Three layers of protection MA* 2013 2016 2020 2030 2035 EU Granted Patent Patent Protection SPC 5y + .5y pedia US Granted Patent PTE 3y + 0,5y pedia Bill A2041 Patent Application Pending Orphan Drug EU Orphan Drug Designation Orphan Drug Exclusivity 10y + 2y pedia US Orph
Slide 49: 8. Strong Interest from the Market
8. STRONG INTEREST FROM THE MARKET 49
Slide 50: IBP-9414 Target Product Profile
IBP-9414 Target Product Profile For the prevention of necrotizing enterocolitis n Pharmaceutical therapy approved as Orphan Drug in EU and US to prevent NEC Product description n The first FDA and EMA-approved drug product to prevent NEC Route of n Oral / enteral Administration n Demonstrates 33% re
Slide 51: Neonatologists show high willingness to prescribe IBP-9414
Neonatologists show high willingness to prescribe IBP-9414 Clearview US market research indicates an overall 78% physician preference share reflecting a high unmet medical need <1,000 g Infants 1,000 – 1,500 g Infants Physician Preference Share Physician Preference Share ~40% ~90% ~70% (%) ~60% (%)
Slide 52: Treatment up to 34 weeks
Treatment up to 34 weeks 1000 – 1,500 g ~3.4 Infants Weeks <1,000 g ~7.8 Infants Weeks 22 23 24 25 26 27 28 29 30 31 32 33 34 35 Gestational Age (Weeks) Physicians expected to halt IBP-9414 treatment once infants had reached 32 to 34 weeks postmenstrual age 52
Slide 53: Expected Formulary Inclusion by Institution Type
Expected Formulary Inclusion by Institution Type In the United States, high adoption in hospitals is anticipated in institutions which have the biggest share of premature infants Small Community Institution Type Major Medical Centers Medium Hospitals Hospitals Share of Premature ~60% ~30% ~10% Infan
Slide 54: Market potential for IBP-9414 assessment
Market potential for IBP-9414 assessment IBT has mandated consultants to assess the market opportunity… n Including 60 Neonatology Key Opinion Leaders interviews …who have interviewed the relevant key stakeholders n 15 Pharmacy and Therapeutics neonatologists and pharmacists (P&T members) across US
Slide 55: Global preterm births
Global preterm births 15 Million preterm births annually USA 3,5% Rest of the World 96,5% Source H. Blencowe et al. 2012 55
Slide 56: 9. Priority Review Voucher
9. PRIORITY REVIEW VOUCHER 56
Slide 57: IBP-9414's eligibility for a Priority Review Voucher
IBP-9414’s eligibility for a Priority Review Voucher § FDA granted Rare Pediatric Disease product status to IBT for IBP-9414, this means that IBT should be awarded a priority review voucher at the time of approval § This voucher is transferrable and cannot expire. 16 vouchers were awarded by year en
Slide 58: IBP-9414 for the prevention of necrotizing enterocolitis
IBP-9414 for the prevention of necrotizing enterocolitis IBP-9414 is based on all relevant pillars 2. MECHANISM OF for the development of a successful drug ACTION L. reuteri for the prevention of NEC 1. NEC: HIGH UNMET MEDICAL NEED 3. EFFICACY SIGNAL n Medical need ✔ 8 independent clinical No curren
Slide 59: Thank you!
Thank you! Visit us in Stockholm, Sweden Infant Bacterial Therapeutics AB Bryggargatan 10 www.ibtherapeutics.com ☏: +46 (0) 8 410 145 55 info@ibtherapeutics.com 59
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