Adicet Bio, Inc. · NASDAQ:ACET
Adicet Bio — resTORbio — Technical Presentation (October 2019)
24 slides from Adicet Bio's technical presentation, Oct 3, 2019
Slide 1: TORC1 inhibition with RTB101 as a potential pan-antiviral immunotherapy
Joan Mannick MD Amelia Tomlinson PhD, Grace Teo PhD, Sarb Shergill PhD, Lloyd Klickstein MD PhD TORC1 inhibition with RTB101 as a potential pan-antiviral immunotherapy to decrease the incidence of respiratory tract infections due to multiple respiratory viruses in older adults Exhibit 99.1
Slide 2: Forward-looking statements disclaimer
This presentation has been prepared by resTORbio, Inc. (“we,” ”us,” “our,” “resTORbio,” or the “Company”) and is made for informational purposes only and does not constitute an offer to sell or a solicitation of an offer to buy securities. This presentation may contain “forward-looking statements” w
Slide 3: Majority of RTIs are caused by viruses with no approved therapies
The majority of RTIs are caused by viruses for which there are no approved therapies3 RTIs are the 4th most common cause for hospitalization in people 65+1 (2nd in 85+1)… 1Pfunter, HCUP Statistical Brief #162, 2013; 2National Vital Statistics Report (2019), Deaths, Final Data for 2017; 3Jain, S., et
Slide 4: Community-acquired pneumonia hospitalizations by pathogen
Adapted from Jain S, et al. NEJM 2015 COMMUNITY-ACQUIRED PNEUMONIA HOSPITALIZATIONS 1/10,000 hospitalizations in adults ≥80 years = S. pneumoniae S. aureus M. pneumoniae L. pneumophila Human Rhinovirus Influenza A or B Parainfluenza Virus Coronavirus Respiratory Syncytial Virus Human Metapneumovirus
Slide 5: TORC1 inhibition may increase innate antiviral immunity
TORC1 inhibition may increase innate antiviral immunity TORC1 Inhibition of SREBP2 decreases viral titers in lungs of mice infected with murine gammaherpesvirus MHV-68 Inhibition of SREBP2 with shRNA upregulates antiviral gene expression TORC1 inhibition decreases SREBP2 activation York et al. Cell,
Slide 6: Phase 2b study design
Phase 2b study to determine if TORC1 inhibition upregulates innate antiviral immunity and decreases RTI incidence in high-risk elderly patients % of subjects with ≥ 1 laboratory-confirmed RTIs 16 weeks during winter cold and flu season POPULATION: DOSING DURATION: Phase 2b Study Design RTB101, an or
Slide 7: Phase 2b evaluation of range of TORC1 inhibitory regimens
Intermittent inhibition of the phosphorylation of most TORC1 targets Persistent inhibition of the phosphorylation of most TORC1 targets RTB101 5 mg QD RTB101 10 mg QD RTB101 10 mg BID RTB101 10 mg + everolimus 0.1 mg QD Persistent inhibition of the phosphorylation of all TORC1 targets QD = once dail
Slide 8: Why might intermittent TORC1 inhibition improve immune function?
Why might intermittent TORC1 inhibition lead to improvement in immune function? TORC1 becomes dysregulated and overactive with aging Feeding Fasting Feeding Fasting TORC1 Activity TORC1 is activated by feeding, stimulating cell growth TORC1 is inhibited by fasting, leading to upregulation of protect
Slide 9: RTB101 10mg QD reduced incidence of laboratory-confirmed RTIs through Week 16
RTB101 10mg QD was observed to reduce the incidence of laboratory-confirmed RTIs through Week 16 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 incidence1 Placebo incidence1 Odds ratio2 p-value3 1No. of subjects in cohort with one or mor
Slide 10: RTI reduction by subgroup and hemisphere
= placebo cohort; = RTB101 10mg once daily cohort; one-sided p-value 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 Southern & Northern Hemispheres (%) (%) (%) (%) (%)
Slide 11: RTB101 increased expression of interferon-stimulated antiviral genes
RTB101 10mg QD was observed to increase expression of interferon-stimulated antiviral genes Placebo n (%) RTB101 10mg QD n (%) p-value ISGs upregulated(mean ddCT ≤0) 5 (25%) 19 (95%) 0.00001 ISGs not upregulated (mean ddCT >0) 15 (75%) 1 (5%) -
Slide 12: RTB101 10mg QD reduced RTIs due to multiple viruses
RTB101 10mg QD was observed to reduce RTIs due to multiple viruses
Slide 13: Post-hoc analysis: reduced time to alleviation of symptoms
Post-hoc analysis: RTB101 10 mg QD was observed to reduce time to alleviation of moderate or severe symptoms Patients Without Alleviation of Moderate or Severe Symptoms (%) Days from Start of Moderate or Severe Symptoms Full Analysis Set RTB101 10 mg QD (n=28) Placebo (n=40) Treatment Median time to
Slide 14: Post-hoc analysis: reduced all-cause hospitalization at Week 16
Post-hoc analysis: RTB101 10mg QD was observed to reduce all-cause hospitalization at Week 16 Number of events in treatment group RTB101 10 mg QD Placebo Rate Ratio (90% CI) p-value* All-cause hospitalization 6 14 0.439 (0.196-0.983) 0.047 *One-sided p-value
Slide 15: Safety: adverse events balanced between RTB101 and placebo
10mg QD is 1/120th of the RTB101 maximum tolerated dose in humans Adverse events (AEs) were balanced between the RTB101 10 mg QD and placebo cohorts 3 unrelated deaths: 1 patient in RTB101 10 mg QD cohort hit by car while riding a bicycle 1 unrelated death occurred in the RTB101 10 mg BID cohort fro
Slide 16: Summary
Summary In a Phase 2b study, RTB101 10mg once daily was well tolerated and observed to upregulate innate antiviral gene expression and reduce the incidence of RTIs caused by multiple different viruses A Phase 3 program is underway to confirm these findings
Slide 17: Many thanks to the resTORbio team
Many thanks to the resTORbio team
Slide 18: Backup Slides
Backup Slides
Slide 19: TORC1 inhibition may improve function of multiple aging organ systems
Inhibition of TORC1 has potential to improve the function of multiple aging organ systems Improvement in physical activity Selman et al., Science, 2011 Harrison et al., Nature, 2009 Wilkinson et al., Aging Cell, 2014 Flynn et al., Aging Cell, 2013 Reversal of aging-related immune dysregulation Chen
Slide 20: RTB101 is an oral, potent inhibitor of TORC1
RTB101 is an oral, potent inhibitor of TORC1 RTB101 offers a potential new approach: harnessing the innate immune system to defend against illnesses associated with viral RTIs Half-life = 4-6 hours Therapeutic dose is 1/120th of the maximum tolerated dose in humans Dosed in >1,000 subjects Potential
Slide 21: Intermittent TORC1 inhibition may restore normal circadian rhythm of TORC1
Intermittent TORC1 inhibition may restore the normal circadian rhythm of TORC1 TORC1 activity (pS6 in liver) Fed Fasted Young Mice Old Mice Feeding activates TORC1 and increases protein and lipid synthesis TORC1 activity remained aberrantly elevated during fasting, which may prevent upregulation of
Slide 22: Adapted from Schneider et al. Annu Rev Immunol, 2014
Adapted from Schneider et al. Annu Rev Immunol, 2014
Slide 23: Treatment-emergent adverse events through week 16
Treatment-emergent AEs observed in ≥2% of subjects in RTB101 10 mg QD or placebo cohorts through week 16 n (%) of patients in treatment group RTB101 10mg QD Placebo (N = 176) (N = 180) Headache 10 (5.7) 13 (7.2) Constipation 3 (1.7) 10 (5.6) Diarrhea 8 (4.5) 6 (3.3) Fatigue 6 (3.4) 6 (3.3) Fall 6 (3
Slide 24: Future directions: Phase 3 program
Patient population: ≥65 years, excluding smokers/COPD patients 1:1 randomization n = 1,024 1:1 randomization n = 1,600 RTB101 10 mg QD Matching placebo RTB101 10 mg QD Matching placebo Duration of treatment: 16 weeks during winter cold and flu season Duration of treatment: 16 weeks during winter col