Infant Bacterial Therapeutics Ab Class B · OMXSTO:IBT_B
Infant Bacterial Therapeutics Ab Class B — Shareholder Meeting (May 2019)
58 slides from Infant Bacterial Therapeutics Ab Class B's shareholder meeting presentation, May 6, 2019
Slide 1: Infant Bacterial Therapeutics
Infant Bacterial Therapeutics May 6, 2019 Staffan Strömberg
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: Corporate overview
Infant Bacterial Therapeutics AB Corporate overview ❏ Founded in 2013 in Stockholm, Sweden as a subsidiary of BioGaia ❏ IPO in 2016, currently listed on Nasdaq Stockholm Mid-Cap ❏ Cash end of Q1 2019 MSEK 540, sufficient to fund development to market ❏ Planned Phase III start during H1 2019 ❏ Market
Slide 4: Corporate development since 2018 AGM
Corporate development since 2018 AGM ❏ List change to regulated market Nasdaq Stockholm Mid-Cap in September 2018 ❏ Analyst coverage: SEB (Sweden) and Chardan (US) (not commissioned research) 4
Slide 5: First distribution deal for IBP-9414 in place
First distribution deal for IBP-9414 in place With Megapharm for IBP-9414 for the Israeli market and the Palestinian Authority’s territories. ❏ Megapharm responsible for local registration, price negotiation and marketing ❏ IBT will receive 70% of revenue after an initial period ❏ Potential to inclu
Slide 6: The IBT concept
The IBT concept Altering the human microbiome to treat diseases related to poor gut function Newborn infant microbiome is dynamic Human bacterial strains derived from human breast milk Published proof-of-concept clinical signal 6
Slide 7: High unmet medical need
High unmet medical need
Slide 8: Our patients
Prenatal development Week 1 2 3 4 5 6 7 8 91011 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 Classification Preterm | Term A A 50% survival Childbirth on average
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Slide 10: Mortality
GI tract left untreated in preterm infants Incubator use Parenteral Mortality nutrition Surfactant prophylaxis Focus on GUT breastfeeding FUNCTION CDC/NCHS, National Vital Statistics System 10
Slide 11: Causes of death
Causes of death 100- Proportion of All Deaths in Each Age Group (%) Unknown Other Congenital anomalies © CNS injury © Infection @ Bronchopulmonary dysplasia @ Necrotizing enterocolitis i Respiratory distress syndrome @ Immaturity Birth to 12 hr >12 to 72 hr >72 hr to 7 days 8 to 14 days 15 to 28 day
Slide 12: Necrotizing enterocolitis (NEC)
Necrotizing enterocolitis (NEC) ❏ NEC is severe inflammation of the bowel in preterm infant where 20-40% need complicated and costly surgery ❏ Survivors have long-term consequences such as short-bowel syndrome, abnormal growth, cognitive, visual and hearing impairments ❏ There is no therapy availabl
Slide 13: Economic burden of NEC
Economic burden of NEC Costs continue after NICU discharge Accumulated cost USD between 6-36 months NEC Economic Burden is estimated to be 20% of the total cost of initial care and USD 5 Billion spent annually on NEC in the US. Long term costs associated with sequelae such as impaired growth, short
Slide 14: Causes of death
Causes of death 100- Proportion of All Deaths in Each Age Group (%) Unknown Other Congenital anomalies © CNS injury © Infection @ Bronchopulmonary dysplasia @ Necrotizing enterocolitis i Respiratory distress syndrome @ Immaturity Birth to 12 hr >12 to 72 hr >72 hr to 7 days 8 to 14 days 15 to 28 day
Slide 15: Feeding the preterm infant
Feeding the preterm infant ❏ Establishing enteral (mouth) feeding in preterm infants to establish “catch up growth” that is important for e.g. cognitive development. ❏ Prolonged parenteral (needle feeding) nutrition increases cost and causes complications: cholestasis, increased risk of BPD, pulmona
Slide 16: Causes of death
Causes of death 100- Proportion of All Deaths in Each Age Group (%) Unknown Other Congenital anomalies © CNS injury © Infection @ Bronchopulmonary dysplasia @ Necrotizing enterocolitis i Respiratory distress syndrome @ Immaturity Birth to 12 hr >12 to 72 hr >72 hr to 7 days 8 to 14 days 15 to 28 day
Slide 17: Feeding the preterm infant
Feeding the preterm infant ❏ Prolonged parenteral (needle feeding) nutrition increases cost and causes complications: cholestasis, increased risk of BPD, pulmonary vascular resistance, infections and sepsis. ❏ Establishing enteral (mouth) feeding is one important goal in preterm infants for “catch u
Slide 18: Feeding the preterm infant
Feeding the preterm infant ❏ Prolonged hospital stay of the preterm infant is associated with a high direct cost burden - $3,200 per day ❏ Long Term: Improved growth velocity improves neurodevelopmental outcomes in extremely low birth weight infants Ganapathy, 2011 and Ehrenkranz et al 2006 18
Slide 19: Mechanism of Action – Lactobacillus reuteri
MECHANISM OF ACTION –Lactobacillus reuteri
Slide 20: Lactobacillus reuteri
Lactobacillus reuteri Active substance of IBP-9414 Lactobacillus reuteri present Lactobacillus reuteri (orange) on women’s breasts adhering to intestinal mucus Picture with the permission Versalovic 20
Slide 21: L. reuteri mechanisms of action
L. reuteri mechanisms of action Combats dysbiosis Reduces inflammation Improves gut motility Improved GUT function! Short term: reduction of NEC and Sepsis Long term: catch up growth for preterm leading to e.g. better cognitive function 21
Slide 22: Clinical Efficacy Signal – L. reuteri
CLINICAL EFFICACY SIGNAL – L. reuteri
Slide 23: 9 studies show clinically significant reduction of NEC
9 studies show clinically significant reduction of NEC Study Number of patients Reduction in NEC incidence ■ 40% in the total study population Rojas et al. (2012) ■ 750 patients ■ 37% in infants ≤1,500g ■ 20% in the total study population Oncel et al. (2014) ■ 400 patients ■ 38% in infants ≤1,000g S
Slide 24: Clear clinical signal (1/4)
Clear clinical signal (1/4) Randomised double-blind placebo-controlled clinical studies indicate reduction of NEC 1 2 3 Rojas et al. (2012) Oncel et al. (2014) Spreckels et al. (2018) ■ Determine whether prophylactic administration ■ Evaluate the effect of administration of L. ■ Measure the coloniza
Slide 25: Clear clinical signal (2/4)
Clear clinical signal (2/4) Retrospective cohort clinical studies indicate reduction of NEC 4 5 Hunter et al. (2012) & Dimaguila et al. (2013) Jerkovic Raguz et al. (2016) ■ Examine the potential benefit of administering L. ■ Analyse the treatment, course and outcome of premature Aim of the study re
Slide 26: Clear clinical signal (3/4)
Clear clinical signal (3/4) Retrospective cohort clinical studies indicate reduction of NEC 6 7 Sanchez Alvarado (2017) Rolnitsky et al. (2017) ■ Demonstrate that the use of Lactobacillus reuteri ■ Quality improvement study to reduce NEC rates in infants Aim of the study prevents NEC in premature in
Slide 27: Clear clinical signal (4/4)
Clear clinical signal (4/4) Other studies indicating reduction of NEC 8 9 Shadkam et al. (2015) Hernandez-Enriquez et al. (2016) ■ Evaluate the effects of Lactobacillus reuteri on the ■ Evaluate the effectiveness of the use of Aim of the study gastrointestinal complications and feeding Lactobacillus
Slide 28: NEC clinical signals
NEC clinical signals Incidence of NEC Meta-analysis: NEC <1500g all randomized controlled trials gives an Odds Ratio of 0.51 28
Slide 29: L. reuteri demonstrates clear signal on improved feeding tolerance
L. reuteri demonstrates clear signal on improved feeding tolerance Study Number of patients Results Rojas et al. (2012) ■ 750 patients ■ 34% reduction in episodes of feeding intolerance (p=0.08) Oncel, et al. (2014) ■ 400 patients ■ 29% reduction in episodes of feeding intolerance (p=0.015) Oncel et
Slide 30: Clear clinical signal (1/2)
Clear clinical signal (1/2) Randomised double-blind placebo-controlled clinical studies indicate improved feeding tolerance 1 2 Rojas et al. (2012) Oncel et al. (2014) ■ Determine whether prophylactic administration ■ Evaluate the effect of administration of L. of L. reuteri to pre-term infants redu
Slide 31: Feeding tolerance – clinical signals
Feeding tolerance – clinical signals Reported feeding intolerance events Time to full enteral feeding 31
Slide 32: Hospital stay – clinical signal
Hospital stay – clinical signal Days in hospital 32
Slide 33: Plan endorsed by stakeholders – Regulatory agencies and KOLs
PLAN ENDORSED BY STAKEHOLDERS – Regulatory agencies and KOLs
Slide 34: Network of KOLs
Network of KOLs IBT has developed the IBP-9414 program with deep considerations of KOLs experience and clinical practice Some of the external medical experts Aideen Moore, The Hospital for Sick Children, Toronto, Canada. Alexandre Lapillonne, Necker Hospital for Sick Children, Paris, France Andreas
Slide 35: FDA meeting - November
FDA meeting - November 20 Two Primary Endpoint “NEC and/or Feeding tolerance” Additional Endpoints Additional Endpoints NEC Feeding Medical NEC Surgical Time to full feed NEC Hospital days etc etc 35
Slide 36: Strong interest from the market
STRONG INTEREST FROM THE MARKET
Slide 37: IBP-9414 Target Product Profile
IBP-9414 Target Product Profile For the prevention of necrotizing enterocolitis For the prevention ■ Oralof necrotizing enterocolitis suspension Product description ■ Supplied as a freeze-dried powder in a prefilled, clear, glass vial ■ To be reconstituted in sterile water and delivered in enteral s
Slide 38: A valuable pharmaceutical
A valuable pharmaceutical 38
Slide 39: A global need
A global need 15 Million Pre-term births annually ® EU5 56000 label 108 000 label 408 000 label population = 360 population population MUSD annual sales for NEC prevention =
Slide 40: Plan for 2019 and beyond
Plan for 2019 and beyond ● Commence Phase III - “The Connection Study” that IBT needs to register the IBP-9414 drug to allow sales of product (CTA/IND filed in US, UK, FR, SP, HU and hopefully this week in Israel) ● Finding good partners, e.g. like Megapharm in Israel, for distribution of the IBP-94
Slide 41: IBP-9414 our lead Phase III program
IBP-9414 our lead Phase III program Ticks all relevant pillars for the development of a successful drug Medical need ✔ Mechanism of action ✔ Clinical data ✔ Safe ✔ Aligned regulatory agencies ✔ GMP manufacture ✔ Market exclusivity ✔ Aligned payers ✔ 41
Slide 42: Thank you
Thank you Infant Bacterial Therapeutics AB +46 (0) 8 410 145 55 www.ibtherapeutics.com 42
Slide 43: Continuous interactions with regulators
Continuous interactions with regulators 2017 Financing PIII Safety and Tolerability Phase II Results EMA PIP Submission EMA PIP Approval FDA Mtg Request 43
Slide 44: Continuous interactions with regulators
Continuous interactions with regulators 2018 Meeting granted Nov 20 Meeting Meeting cancelled by FDA 44
Slide 45: Continuous interactions with regulators
Continuous interactions with regulators 2019 FDA Interactions and Submissions UK, FR, ES, HU IL Planned study start 45
Slide 46: NEC – a devastating disease
NEC – a devastating disease The smaller the premature infant is at birth, the more likely he/she will die NEC incidence rate NEC mortality rate 501-750g 42.0% 751-1,000g 29.4% 1,001-1250g 21.3% 1,251-1,500g 15.9% 1,501-2,500g 12,7% Shelley 2012, Bolisetty 2000, Llanos 2002, Fitzgibbons 2009, Abdulla
Slide 47: Infant Bacterial Therapeutics Overview
Infant Bacterial Therapeutics Overview ❏Pharmaceutical microbiome ❏Orphan Drug Designation from ❏Financial resources sufficient company focused on areas of FDA and EMA finance development to unmet medical need ❏Rare Pediatric Disease application for market ❏Lead drug candidate IBP-9414, Designation
Slide 48: Feeding the preterm infant
Feeding the preterm infant ❏ Prolonged parenteral (needle feeding) nutrition increases cost and causes complications: cholestasis, increased risk of BPD, pulmonary vascular resistance, infections and sepsis. ❏ Establishing enteral (mouth) feeding is one important goal in preterm infants for “catch u
Slide 49: Causes of death
Causes of death 100- Proportion of All Deaths in Each Age Group (%) Unknown Other Congenital anomalies © CNS injury © Infection @ Bronchopulmonary dysplasia @ Necrotizing enterocolitis i Respiratory distress syndrome @ Immaturity Birth to 12 hr >12 to 72 hr >72 hr to 7 days 8 to 14 days 15 to 28 day
Slide 50: Dysbiosis in NEC
Dysbiosis in NEC Dysbiosis with pathogen blooms in the microbiota can contribute to necrotizing enterocolitis in preterm infants NEC Controls Days after birth Bloom of pathogen-rich gamma Microbiome optimization may provide proteobacteria prior to onset of NEC a novel strategy for preventing NEC War
Slide 51: 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 52: Anti-pathogen effects in infants
Anti-pathogen effects in infants Infant fecal pathogens after 1 month L. reuteri treatment * Number of positive feces samples for identified pathogens from 30 infants * P≤0.05 * L. reuteri decreased gut pathogen colonization in infants Savino 2015 52
Slide 53: Inflammation
Inflammation 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 53
Slide 54: Strain specific anti-inflammation in rodents
Strain specific anti-inflammation in rodents Treg Teff FoxP3 Treg cell modulation Teff cell modulation L. reuteri L. L. reuteri L. acidophilus A acidophilus B L. reuteri has strain specific anti-inflammatory activity through recruitment of Treg cells and down regulation of Teff cells Liu 2014 54
Slide 55: Anti-inflammatory in infants
Anti-inflammatory in infants Treg cells increase in infant blood after L. reuteri administration Treg * P≤0.05 FoxP3 * FOXP3 mRNA levels Placebo L. reuteri L. reuteri recruitment of Treg cells now shown in infants Savino 2017 55
Slide 56: L. reuteri improves gut motility ex vivo
L. reuteri improves gut motility ex vivo Spatiotemporal mapping of mouse gut motility Krebs alone Krebs + L. reuteri Colon motility increased within Effect is strain specific and minutes of L. reuteri addition gut region specific Wu 2013 56
Slide 57: 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 58: 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 Liu, 2012 & Liu 2013 (rat), Liu 2014 (mouse) 58
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