Adicet Bio, Inc. · NASDAQ:ACET
Adicet Bio — resTORbio — Investor Presentation (July 2018)
33 slides from Adicet Bio's investor presentation, Jul 30, 2018
Slide 1: July 2018
July 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 Improved Immune Function Ameliorate Heart Failure Ameliorate Neurodegenerative Diseases TORC1 inhibition extended lifespan and healthspan and improved the following aging-related conditions in preclinical studies: Mice Flies Worms Yea
Slide 5: resTORbio highlights
resTORbio highlights Developing first in class and most advanced selective TORC1 program TORC1 inhibition improves immune, cardiac and neurologic function in aging preclinical species Proprietary TORC1 inhibitor, RTB101, in clinical development Positive topline results in Phase 2b study of RTRB101 t
Slide 6: TORC1 Pathway
TORC]1 Pathway
Slide 7: Selective and more complete inhibition of TORC1 may have therapeutic benefit
mTOR Selective and more complete 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
Slide 8: RTB101 and RTB101+everolimus target multiple nodes downstream of TORC1
RTB101 and RTB101+everolimus target multiple nodes downstream of TORC1 RTB101 Catalytic mTOR>PI3K inhibitor Over 1,000 patients exposed S6K Ulk1 Atg Knock out of S6K extends lifespan and healthspan (Science,2009) Overexpression extends lifespan (Cell, 2009) TORC1 RTB101 4EBP1 Transgenic overexpressi
Slide 9: 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 once daily and RTB101 10 mg + everolimus 0.1 mg once daily significantly
Slide 10: 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 11: RTB101 Phase 2b Topline Data
RTB101 Phase 2b Topline Data
Slide 12: Goal of Phase 2b dose-finding study
Goal of Phase 2b dose-finding study: To determine dose and patient population for pivotal trials The study successfully identified dose and patient population for pivotal trials: Dose: RTB101 10 mg once daily: Led to a statistically significant and clinically meaningful 30.6% reduction in the percen
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 including: ≥ 85 years of age 65-84 years of age with one or more of the following comorbid
Slide 14: Demographics
Demographics Part 1 Part 2 Parameter Statistics RTB101 5mg (N=61) RTB101 10mg QD1 (N=58) Placebo (N=60) Total (N=179) RTB101 10mg QD (N=118) RTB101 10mg BID2 (N=120) RTB101 + everolimus (N=115) Placebo (N=120) Total (N=473) Age at Randomization (Year) n 61 58 60 179 118 120 115 120 473 Mean (SD) 74.
Slide 15: Significant reduction in RTIs in the RTB101 10 mg once daily cohort
A significant reduction in the percentage of patients with laboratory-confirmed RTIs was observed in the RTB101 10 mg once daily cohort -20.6% 8.5% 8.5% -30.6% RTB101 5mg QD RTB101 10mg QD RTB101 10mg BID RTB101 10mg + everolimus 0.1mg 1One-sided p-value; 2Odds ratio represents the odds of experienc
Slide 16: RTB101 10mg once daily, all parts
RTB101 10mg once daily, all parts RTB101 10mg QD (n=58) RTB101 10mg QD (n=118) RTB101 10mg QD (n=176) Part 1 Part 2 Part 1 & 2 p-value1 0.013 0.272 0.026 Odds ratio2 (CI3) 0.394 (0.197; 0.787) 0.815 (0.468; 1.419) 0.604 (0.394; 0.927) -15.5% -44.3% -30.6% * * 1One-sided p-value; 2Odds ratio represen
Slide 17: Efficacy in subpopulations 85+ and 65+ with asthma
RTB101 10mg once daily monotherapy showed unprecedented efficacy in subpopulations 85+ and 65+ with asthma 85+: % subjects with 1 or more LC-RTI Asthma T2DM COPD Smokers 65+: % subjects with 1 or more LC-RTI Part 1 Part 2 Part 1 & 2 (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) (%) -66.7%
Slide 18: RTB101 10mg once daily, all subgroups, all parts
RTB101 10mg once daily, all subgroups, all parts RTB101 10mg QD n 12 15 27 16 30 46 21 65 86 45 86 131 50 98 148 nRTI4 2 2 4 4 2 6 5 10 15 9 12 21 12 14 26 Placebo n 12 15 27 19 32 51 18 66 84 47 87 134 49 104 153 nRTI4 6 6 12 14 7 21 8 12 20 21 16 37 25 23 48 85+ Asthma T2DM Non-COPD Non-Smokers 85
Slide 19: 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 20: Greater proportion of high responders in Part 1
Greater proportion of high responders in Part 1 Patients aged 85+ or with asthma (no COPD or smokers) All other patients Greater proportion of high responder group in Part 1 may account in part for the larger reduction in RTIs in Part 1 compared to Part 2
Slide 21: Reduction in RTIs in all monotherapy doses (non-smokers)
A significant reduction in the percentage of patients with laboratory-confirmed RTIs was observed in all monotherapy doses [non-smokers] RTB101 5mg QD RTB101 10mg BID RTB101 10mg + Everolimus 0.1mg RTB101 10mg QD p-value1 0.043 0.001 0.041 0.140 Odds ratio2 (CI3) 0.413 (0.177; 0.962) 0.309 (0.165; 0
Slide 22: 65+ with Asthma or 85+ Years of Age (Non-Smokers)
65+ with Asthma or 85+ Years of Age (Non-Smokers) RTB101 5mg QD RTB101 10mg BID RTB101 10mg + Everolimus 0.1mg RTB101 10mg QD p-value1 0.0195 0.0003 0.134 0.352 Odds ratio2 (CI3) 0.292 (0.110; 0.779) 0.213 (0.102; 0.447) 0.557 (0.234; 1.326) 0.824 (0.356; 1.908) * *** 1One-sided p-value; 2Odds ratio
Slide 23: Consistent efficacy of RTB101 once daily in Phase 2 trials
Consistent efficacy of RTB101 10 mg once daily observed in Phase 2 clinical trials Phase 2a (n=264) 23% with comorbidities Phase 2b Part 1 (n=179) 100% with comorbidities Phase 2b Part 2 (n=473) 100% with comorbidities 42%** RTIs 47% RTIs in asthma pts 44%* RTIs 66%** RTIs in asthma pts 67% RTIs in
Slide 24: RTB101 was well-tolerated in high-risk elderly patients
RTB101 was well-tolerated in high-risk elderly patients Adverse events (AEs) were balanced between the RTB101 10 mg once daily and placebo cohorts 1 unrelated death occurred in the RTB101 10 mg once daily cohort (patient was hit by car while riding a bicycle), 1 unrelated death occurred in the place
Slide 25: Summary of 16-week analysis of Phase 2b
Summary of 16-week analysis of Phase 2b Study successfully defined the dose and patient populations to include in our pivotal trials: RTB101 10 mg once daily Consistent efficacy seen in two phase 2 trials enrolling more than 900 elderly people 65 years or older with asthma, or 85 years and older, no
Slide 26: Medical Need & Market Opportunity
Medical Need & Market Opportunity
Slide 27: RTIs are the 4th most common cause for hospitalization in 65+
RTIs are the 4th most common cause for hospitalization in 65+1 (2nd in 85+1) RTIs are the 7th leading cause of death in 65+2 (5th in 85+2) RTIs are the leading cause of asthma exacerbations3 RTIs represent a significant healthcare burden 1Pfunter, A (2013) HCUP Statistical Brief #162; 2Kochanek KD,
Slide 28: Elderly population at increased risk of RTIs in US, EU5 and Japan
US EU5 JP Elderly people (65-74 years old): With comorbidities (COPD, asthma, T2DM, CHF) 11M 13M 7M Elderly people (75-84 years old): With comorbidities (COPD, asthma, T2DM, CHF) 7M 11M 6M Elderly people (85+ years old): 6M 9M 5M # Elderly People (2016) 24M 33M 18M Average Annual Growth Rate 3% 2% 1
Slide 29: 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 30: TORC1 inhibition may ameliorate multiple aging related diseases
TORC1 inhibition may ameliorate multiple aging related disease 1st Phase 2a Reduction In RTI Incidence Preclinical Validation 2nd Phase 2a Phase 2b Phase 3 Heart Failure Preclinical Validation Clinical Signal Phase 2 UTIs + RTI Tx Preclinical Validation Clinical Signal in Phase 2a Phase 2 Neurodegen
Slide 31: 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 POC clinical study 2nd indication Initiation of POC clinical study 3rd indication Pivotal Trial Initiation 2018 2019 Second Ph 2a Publication Ph 2b 24 week data Completed dosing all patients in Ph
Slide 32: resTORbio Highlights
resTORbio Highlights Developing first in class and most advanced selective TORC1 program TORC1 inhibition improves immune, cardiac and neurologic function in aging preclinical species Proprietary TORC1 inhibitor, RTB101, in clinical development Positive topline results in Phase 2b study of RTRB101 t
Slide 33: July 2018
July 2018