Adicet Bio, Inc. · NASDAQ:ACET
Adicet Bio — resTORbio — Investor Presentation (October 2018)
36 slides from Adicet Bio's investor presentation, Oct 16, 2018
Slide 1: October 2018
October 2018 Exhibit 99.1
Slide 2: Forward-looking statements
This presentation may contain “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995, including, but not limited to, statements regarding the safety, efficacy and regulatory and clinical progress of our product candidates, including RTB101 alone and i
Slide 3: The biology of aging is regulated by TORC1
The biology of aging is regulated by TORC1
Slide 4: TORC1 is an evolutionarily conserved pathway that regulates aging
TORC1 is an evolutionarily conserved pathway that regulates aging TORC1 inhibition extended lifespan and healthspan and improved the following aging-related conditions in preclinical studies: Mice Flies Worms Yeast Improved Immune Function Ameliorate Heart Failure Ameliorate Neurodegenerative Diseas
Slide 5: resTORbio highlights
resTORbio highlights Developing first in class and most advanced selective TORC1 program The lead indication for RTB101, our proprietary TORC1 inhibitor, is to decrease the incidence of respiratory tract infections (RTIs) in high-risk elderly by enhancing the function of the aging immune system RTIs
Slide 6: TORC1 Pathway
TORC]1 Pathway
Slide 7: Selective inhibition of TORC1 may have therapeutic benefit for aging-related diseases
mTOR Selective inhibition of TORC1 may have therapeutic benefit for the treatment of aging-related diseases Inhibition of TORC2 by genetic mutation decreases lifespan and causes hyperglycemia and hyperlipidemia in mice (Science, 2012; Aging Cell, 2014) S6K Ulk1 4EBP1 Atg Inhibition of TORC1 by genet
Slide 8: Spectrum of TORC1 inhibition with everolimus and RTB101
S6K Ulk1 TORC1 everolimus 4EBP1 S6K Ulk1 4EBP1 TORC1 RTB101 + everolimus 4EBP1 S6K Ulk1 4EBP1 TORC1 4EBP1 RTB101 Inhibiting the phosphorylation of 1 target of TORC1 Inhibiting the phosphorylation of 2 targets of TORC1 Inhibiting the phosphorylation of 3 targets of TORC1 Spectrum of TORC1 inhibition
Slide 9: RTB101 Program
RTB101 Program
Slide 10: Results of Phase 2a trial
Results of Phase 2a trial 264 mostly healthy elderly people randomized to the following TORC1 inhibitor treatment arms: Everolimus 0.1 mg + RTB101 10 mg RTB101 10 mg Everolimus 0.5 mg Everolimus 0.1 mg Placebo Both RTB101 10 mg QD and RTB101 10 mg + everolimus 0.1 mg QD significantly reduced the inc
Slide 11: RTB101 offers new approach to harnessing the immune system
IMMUNOTHERAPY: RTB101 alone or in combination with everolimus RTB101 offers new approach to harnessing the immune system to target multiple pathogens Sources: S. Jain et al., NEJM 2015 Indicates the annual number of pathogen-specific pneumonia hospitalizations per 10,000 adults ≥ 80 The majority of
Slide 12: Phase 2a to Phase 2b
Phase 2a to Phase 2b Phase 2a: 65 and older, 23% with comorbidities 4 ie BAN 65 and older w/ 65 and older w/ 65 and older, smokers diabetes OPD
Slide 13: Phase 2b design
Phase 2b design Primary Endpoint: Reduction in the percentage of patients with laboratory-confirmed RTIs through week 16 Population: Elderly subjects at increased risk of RTI-associated morbidity and mortality, defined as: ≥ 85 years of age 65-84 years of age with one or more comorbidities including
Slide 14: Dosing regimens in Phase 2b and TORC1 inhibition
Dosing regimens in Phase 2b result in different estimated duration and spectrum of TORC1 inhibition S6K Ulk1 4EBP1 TORC1 4EBP1 RTB101 5 mg QD Transient inhibition of two TORC1 targets RTB101 10 mg QD 0 12 24 Estimated duration of TORC1 inhibition (hrs) RTB101 10 mg BID Persistent inhibition of two T
Slide 15: Phase 2b data supports RTB101 potential efficacy
Phase 2b data supports RTB101 potential efficacy for enhancing immune function and reducing the incidence of infections Statistically significant reduction in percent of patients with laboratory-confirmed RTIs (announced Jul 2018) 30.6% reduction in the percentage of patients with laboratory-confirm
Slide 16: RTI Data
RT| Data resTORbIO 16
Slide 17: Significant reduction in laboratory-confirmed RTIs in RTB101 10 mg QD cohort
A significant reduction in the percentage of patients with laboratory-confirmed RTIs was observed in the RTB101 10 mg QD cohort p-value1 0.109 0.025 0.560 0.700 Odds ratio2 (CI3) 0.618 (0.325; 1.176) 0.601 (0.391; 0.922) 1.050 (0.618; 1.782) 1.187 (0.694; 2.030) Active N 61 176 120 115 NRTI4 21 34 2
Slide 18: Odds ratio supports dose selection of RTB101 10 mg QD
Odds ratio further supports dose selection and potential efficacy of RTB101 10 mg QD 21/61 26/60 0.618 0.109 34/176 50/180 0.601 0.025* 25/120 24/120 1.050 0.560 25/115 24/120 1.187 0.700 Active rate1 Placebo rate1 Odds ratio2 p-value3 1No. of patients in cohort with one or more laboratory-confirmed
Slide 19: RTB101 10 mg QD showed consistent benefit in pre-specified analyses
RTB101 10 mg QD showed consistent benefit in multiple pre-specified analyses of lab-confirmed RTIs Odds ratio of experiencing lab-confirmed RTIs through Week 16 – primary endpoint Odds ratio of experiencing severe lab-confirmed RTI symptoms through Week 16 Odds ratio of experiencing lab-confirmed RT
Slide 20: Greatest effect in 85+ and 65+ with asthma subpopulations
RTB101 10 mg QD showed the greatest effect in the 85+ and 65+ with asthma subpopulations (pre-specified analyses) 85+: % subjects with 1 or more laboratory-confirmed RTIs Asthma T2DM COPD Smokers 65+: % subjects with 1 or more laboratory-confirmed RTIs Southern Hemisphere Northern Hemisphere Souther
Slide 21: Odds ratio supports effect in 85+ and 65+ with asthma
Odds ratio further supports effect seen in the 85+ and 65+ with asthma subpopulations Southern Hemisphere Northern Hemisphere Both Hemispheres Southern Hemisphere Northern Hemisphere Both Hemispheres Southern Hemisphere Northern Hemisphere Both Hemispheres Southern Hemisphere Northern Hemisphere Bot
Slide 22: Preclinical data: mTOR inhibition in asthma and smoking
Preclinical data: mTOR inhibition decreased airway inflammation in asthma and increased airway inflammation due to smoking Asthma Smoking mTOR inhibition with rapamycin (Rapa) significantly decreased airway inflammation in a preclinical asthma model in which mice were exposed to intranasal house dus
Slide 23: High responder population: non-smoking 85+ and 65+ with asthma
High responder population identified as non-smoking subjects who are 85+ and 65+ with asthma RTB101 5 mg QD RTB101 10 mg BID RTB101 10 mg + everolimus 0.1 mg RTB101 10 mg QD p-value1 0.019 0.0002 0.153 0.361 Odds ratio2 (CI3) 0.292 (0.109; 0.777) 0.208 (0.099; 0.435) 0.582 (0.244; 1.389) 0.833 (0.35
Slide 24: Odds ratio in non-smoking subjects 85+ and 65+ with asthma
Odds ratio further supports effect of RTB101 10 mg QD in non-smoking subjects who are 85+ and 65+ with asthma 11/30 16/26 0.292 0.019* 10/69 28/68 0.208 0.0002** 8/42 12/42 0.582 0.153 10/40 12/42 0.833 0.361 Active rate1 Placebo rate1 Odds ratio2 p-value3 Odds ratio (90% confidence interval) Odds r
Slide 25: Other Infection Data
Other Infection Data
Slide 26: RTB101 may reduce incidence of total infections of any kind
RTB101 may also reduce the incidence of total infections of any kind Odds ratio of experiencing any infection (lab-confirmed RTI and all other infections) through Week 16 Odds ratio of experiencing urinary tract infections through Week 16 OR = Odds ratio represents the odds of experiencing one or mo
Slide 27: RTB101 was well-tolerated in high-risk elderly patients
RTB101 was well-tolerated in high-risk elderly patients through Week 24 Adverse events (AEs) were balanced between the RTB101 10 mg QD and placebo cohorts 1 unrelated death occurred in the RTB101 10 mg QD cohort (patient was hit by car while riding a bicycle), 1 unrelated death occurred in the RTB10
Slide 28: Summary of Phase 2b RTI data
Summary of Phase 2b RTI data The study successfully identified the dose and patient population for pivotal trials: Dose: RTB101 10 mg QD: 30.6% reduction in the percentage of patients with laboratory-confirmed RTIs (p=0.025) 52.1% reduction in percentage of patients with severe laboratory-confirmed
Slide 29: Medical Need & Market Opportunity
Medical Need & Market Opportunity
Slide 30: RTIs represent a significant healthcare burden
RTIs are the 4th most common cause for hospitalization in 65+ (2nd in 85+)1 RTIs are the 7th leading cause of death in 65+ (5th in 85+)2 Mortality from RTIs is higher than mortality from colorectal, pancreatic, breast or prostate cancer3 RTIs cause the majority of asthma exacerbations in the elderly
Slide 31: Estimated number of people 85+ and 65+ with asthma in key geographies
US EU5 JP CN Elderly (65-84 years old) with asthma: 3.2M 3.3M1 2.1M2 2.5M3 Very elderly (85+ years old): 6.5M 9.3M 5.5M 8.9M # Elderly People 10M 13M 8M 11M Estimated number of people 85+ and 65+ with asthma in key geographies 1Based on estimated percentage of asthmatics in older adults in high-inco
Slide 32: Physician survey: expected use in target populations
% Reduction in RTI Estimated % prescribed in patients (patient-weighted means) ≥85 65-84 with asthma 65-84 with comorbidities 25% 33% 36% 36% 33% 41% 44% 47% 40% 46% 48% 51% Survey of 100 physicians to determine potential usage in the target patient populations Medical Specialty Geriatrics 25 Primar
Slide 33: Most advanced pipeline targeting aging-related diseases
RTB101 Respiratory Tract Infections Parkinson’s Disease Program Indication Phase 1 Phase 2 Phase 3 Anticipated Milestones Discovery Heart Failure with Preserved Ejection Fraction Preclinical Other Infections* * Other infections include those that the elderly are at increased risk of contracting, suc
Slide 34: Near term planned clinical milestones and path forward
Q1 Q2 Q3 Q4 H1 H2 Near term planned clinical milestones and path forward Ph 2b topline data Initiation of POC clinical study in Parkinson’s Disease Initiation of POC clinical study in 3rd indication Pivotal trial initiation 2018 2019 Science Translational Medicine publication Additional data from Ph
Slide 35: resTORbio highlights
resTORbio highlights Developing first in class and most advanced selective TORC1 program The lead indication for RTB101, our proprietary TORC1 inhibitor, is to decrease the incidence of RTIs in high-risk elderly by enhancing the function of the aging immune system RTIs are the 4th leading cause for
Slide 36: October 2018
October 2018