Targeting the biology of aging to treat aging-related diseases
Corporate Presentation
February 2020
Forward-looking statements
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" 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 in combination with a rapalog, such as everolimus or sirolimus. All such forward-looking statements are based on management's current expectations of future events and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. The use of words such as, but not limited to, "may," "might," "will," "should," "expect," "plan," "anticipate," "believe," "estimate," "project," "intend," "future," "potential," or "continue," and other similar words or expressions are intended to identify forward-looking statements. Forward-looking statements are neither historical facts nor assurances of future performance. Instead, they are based on our current beliefs, expectations and assumptions regarding the future of our business, future plans and strategies, our clinical results and other future conditions. All statements other than statements of historical facts contained in this presentation, including statements regarding future results of operations and financial position, business strategy, current and prospective product candidates, ongoing and planned clinical trials and preclinical activities, including the initiation, timing, enrollment, progress and results of our preclinical and clinical studies and our research and development programs, product approvals, research and development costs, current and prospective collaborations, the timing and likelihood of success of our Phase 1b/2a clinical trial of RTB101, alone or in combination with sirolimus, in Parkinson's disease and the timing or likelihood of regulatory progress, results, filings and approvals, expectations regarding market acceptance and size, plans and objectives
of management for future operations, and future results of anticipated product candidates, are forward-looking statements. New risks and uncertainties may emerge from time to time, and it is not possible to predict all risks and uncertainties. No representations or warranties (expressed or implied) are made about the accuracy of any such forward-looking
statements.
These statements are also subject to a number of material risks and uncertainties that are discussed in the section entitled "Risk Factors" in resTORbio's annual report on Form 10-K for the fiscal year ended December 31, 2018, as well as discussions of potential risks, uncertainties, and other important factors in resTORbio's subsequent filings with the Securities and Exchange Commission. Any forward-looking statement speaks only as of the date on which it was made. Neither we, nor our affiliates, advisors or representatives, undertake any obligation to publicly update or revise any forward-looking statement, whether as a result of new information, future events or otherwise, except as required by law.
Certain information contained in this presentation relates to or is based on studies, publications, surveys and other data obtained from third-party sources and the Company's own internal estimates and research. While we believe these third-party sources to be reliable as of the date of this presentation, we have not independently verified, and we make no representation as to the adequacy, fairness, accuracy or completeness of any information obtained from third-party sources. In addition, all of the market data included in this presentation involves a number of assumptions and limitations, and there can be no guarantee as to the accuracy or reliability of such assumptions. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source.
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resTORbio highlights
Extensive preclinical data demonstrate that TORC1 inhibition may ameliorate multiple aging related diseases, including neurodegenerative diseases
TORC1 inhibition may be a promising approach for the treatment of Parkinson's disease (PD)
- Ameliorateslevodopa-induced dyskinesia in preclinical PD models
- Induces lysosomal biogenesis and autophagy, clearsalpha-synuclein aggregates and is neuroprotective in preclinical PD models
- Lead candidate, RTB101, is an oral, selective and potent TORC1 inhibitor that has been observed in preclinical models to cross the blood brain barrier and induce autophagy in neurons
Ongoing Phase 1b/2a clinical trial of RTB101 +/- sirolimus for PD
- Safety, tolerability and cerebrospinal fluid (CSF) exposure data are expected bymid-2020 in PD patients
- RTB101 has the potential to alleviatelevodopa-induced dyskinesia and may offer the first opportunity to slow disease progression by inducing autophagy in the brain of PD patients
- In interim data from three cohorts in the Phase 1b/2a study we observed that RTB101 is well tolerated, crosses the blood brain barrier, and reaches concentrations in cerebrospinal fluid observed to inhibit the activity of TORC1 and induce autophagy in neuronal cells
-Sirolimus at the dose of 2 mg, alone or in combination with RTB101, was not detected in the CSF
Cash, cash equivalents and marketable securities of $117.3 million as of September 30, 2019
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Pipeline
PROGRAM
CURRENT INDICATIONS* | RTB101 or |
RTB101 + | |
sirolimus | |
POTENTIAL INDICATIONS** | RTB101 or |
RTB101 + |
RTB101 + rapalog
RTB101 or rapalog
INDICATION | DISCOVERY | PRECLINICAL | PHASE 1 | PHASE 2 | PHASE 3 |
Parkinson's Disease | P H A S E 1 B / 2 A | ||||
O N G O I N G | |||||
Neurodegenerative
Diseases
Diseases associated with
TORC1 hyperactivation
- For Parkinson's disease, we may be required to file an investigational new drug application, or IND, with the U.S. Food and Drug Administration, prior to initiating Phase 2 clinical trials ** For neurodegenerative diseases and diseases associated with TORC1 hyperactivation, subject to review by the U.S. Food and Drug Administration, we believe we may
have the ability to initiate Phase 2 clinical trials without the need to conduct additional Phase 1 trials.
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Broad TORC1 inhibition with RTB101 has the potential to ameliorate levodopa- induced dyskinesia and to be neuroprotective in Parkinson's disease patients
Decreased phosphorylation of S6K and 4EBP1 decrease protein synthesis and are
RTB101
TORC1
S6K
4EBP1
ULK1
TFEB
Activation of ULK1 and TFEB have been shown to promote autophagy and lysosomal
associated with amelioration of levodopa- induced
Decreased
Protein
Synthesis
SREBP
Increased Autophagy
biogenesis which are associated with neuroprotection in
Decreased
Increased
dyskinesia in preclinical PD models
Protein
Synthesis
Decreased
Lipid
Synthesis
Lysosomal Biogenesis
preclinical PD models
Nyfeler et al. Molecular and Cellular Biology, 2011; Nyfeler et al. PLoS ONE,2012; Eid et al. PNAS, 2017; Roczniak-Ferguson et al. Sci Signal, 2012; Santini et al. Sci Signaling, 2009 | 5 |
Neurodegenerative Diseases
Parkinson's Disease: Disease modification
Protein aggregation is a common pathogenic mechanism in aging- related neurodegenerative diseases
Alzheimer's | Parkinson's | Huntington's |
Disease | Disease | Disease |
Amyloid β | Phosphorylated | α-synuclein | Mutated |
protein | tau | huntingtin | |
Amyloid | Neurofibrillary | Lewy | Aggregated |
plaques | tangles | bodies | huntingtin |
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Parkinson's Disease
Prevalence
- Second most common neurodegenerative disease
- Affects 1% of population over 55 years of age in the U.S.
Pathology
- Accumulation of Lewy body protein aggregates containing a- synuclein and death of the neurons that produce the neurotransmitter dopamine in the substantia nigra
Clinical manifestations
- Four cardinal motor symptoms:
- Resting tremor
- Bradykinesia (slowed movement)
- Muscle rigidity
- Postural instability
Current therapies treat symptoms of PD but do not alter disease progression
- Levodopa is used to treat PD; however, its effect tends to wear off over time and can lead to disablinglevodopa-induced dyskinesia
Image from Wikiwand
Parkinson's
Disease
α-synuclein
Lewy bodies
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Defective autophagy may contribute to the accumulation of aggregated proteins in PD and other neurodegenerative diseases
Autophagy is a mechanism by which aggregated misfolded proteins and dysfunctional organelles are broken down and recycled in cells
Toxic protein | Phagophore | Autophagosome | Autophagolysosome |
Aggregate |
Lysosome
Neuroprotection
Menzies et al. Neuron, 2017 | 9 |
Mutations in autophagy-related proteins are found in PD and other neurodegenerative diseases suggesting that deficient autophagy contributes to neurodegenerative disease pathogenesis
Menzies et al. Neuron, 2017 | 10 |
TORC1 inhibitors have the potential to be disease modifying in neurodegenerative diseases by upregulating autophagy and lysosomal biogenesis
Toxic protein | Phagophore | Autophagosome | Autophagolysosome |
Aggregate |
TORC1
inhibition
P
Increased
ULK1phagophoreLysosomeformation
P | TFEB | Increased |
TFEB | Lysosomal | |
Nucleus | Biogenesis |
Neuroprotection
Menzies et al. Neuron, 2017; Roczniak-Ferguson et al. Sci Signal, 2012; Nyfeler et al. Molecular and Cellular Biology, 2011 | 11 |
TORC1 inhibition is neuroprotective in PD pre-clinical models
Increased TFEB | Clearance of toxic | Improved | Improved | ||||
nuclear | Neuronal | Motor | |||||
a-syn aggregates | |||||||
translocation | Survival | Performance | |||||
C. | D. | ||||||
A. | B. | ||||||
*p < 0.05 compared with the 3-wkα-syn group #p < 0.05 compared with α-syn+vehicle group
In a rat PD model that overexpresses a-syn in the substantia nigra, the TORC1 inhibitor CCI-779 started 3 weeks after adenoviral delivery of a-syn (3w) and given every other day for 5 weeks was shown (A)to correct impaired TFEB function (as reflected by increased TFEB nuclear translocation), (B)decreased striatal a-syn levels (both monomeric and high molecular weight (HMW) aggregates), (C)increased dopaminergic neuron survival and (D)improved motor function.
Decressac et al. PNAS, 2013 | 12 |
TORC1 inhibitors under evaluation in a Phase 1b/2a trial in Parkinson's disease
sirolimus (rapamycin):
- Allosteric inhibitor of TORC1
- Partial TORC1 inhibitor: only consistently inhibits S6K downstream of TORC1
- Approved for use in humans
RTB101:
- ATP competitive catalytic site inhibitor of mTOR protein kinase
- Consistently inhibits phosphorylation of all targets downstream of TORC1
- Crosses the blood brain barrier in animal models
- Tested in >1,000 humans
- Human maximum tolerated dose: 1,200 mg/day
sirolimus
(rapamycin)
RTB101
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Potential spectrum of TORC1 inhibition with RTB101 and sirolimus
High Concentration of RTB101 or Low Concentrations of RTB101+ sirolimus
sirolimus
TORC1
S6K | ULK1 |
4EBP1TFEB
TORC1 | |
S6K | ULK1 |
4EBP1 | TFEB |
SREBP |
Targets for neuroprotection
Decreased
Protein
Synthesis
SREBP
Decreased | Increased |
Protein | |
Synthesis | Autophagy |
DecreasedIncreased
ProteinLysosomal
SynthesisBiogenesis
Decreased
Lipid
Synthesis
in PD
Indicates consistent inhibition of target phosphorylation
Nyfeler et al. Molecular and Cellular Biology, 2011; Nyfeler et al. PLoS ONE,2012; Eid et al. PNAS, 2017; Roczniak-Ferguson et al. Sci Signal, 2012
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The combination of RTB101 and sirolimus synergize to inhibit TORC1 and may lower the RTB101 brain exposure required to induce autophagy
SK-N-SH neuroblastoma cells were exposed to increasing concentrations of RTB101 (y axis) and/or increasing concentrations of sirolimus (x axis). Orange shaded areas indicate concentrations of RTB101 and/or sirolimus that induce >50% maximal autophagy activation. Autophagocytic flux was measured using an mCherry- GFP-LC3 cell- based assay
Total Free (5%)
87.50 | 4.38 | 130.58 | 114.37 | 156.80 | 170.61 | 173.28 | 181.56 | 196.15 | 174.61 | 158.67 | 216.07 | ||
43.75 | 2.19 | 91.48 | 71.47 | 123.06 | 118.25 | 166.88 | 154.73 | 189.63 | 194.12 | 190.70 | 214.89 | ||
21.88 | 1.09 | 31.89 | 25.16 | 81.50 | 100.98 | 125.12 | 137.82 | 212.58 | 197.37 | 166.87 | 218.33 | ||
10.94 | 0.55 | 0.02 | 4.25 | 29.25 | 41.45 | 88.97 | 138.95 | 155.32 | 184.65 | 146.93 | 179.15 | ||
% maximal | (nM) | 5.47 | 0.27 | -12.14 | -14.12 | -1.11 | 8.36 | 44.22 | 81.09 | 103.23 | 143.72 | 120.56 | 123.57 |
activation of | |||||||||||||
autophagy | RTB101 | 2. | 0.14 | -12.10 | -6.71 | -0.19 | -1.19 | 25.53 | 43.99 | 75.14 | 96.76 | 73.48 | 100.10 |
1 | 0.07 | -7.40 | -17.37 | 0.03 | 0.09 | 13.03 | 29.69 | 41.98 | 54.65 | 60.23 | 68.35 | ||
68 | 0.03 | -23.25 | -25.36 | 3.41 | -2.42 | 5.87 | 16.31 | 26.84 | 52.55 | 33.51 | 31.80 | ||
0.34 | 0.02 | -16.81 | -28.70 | -7.67 | -5.83 | 5.18 | 14.95 | 9.42 | 33.10 | 21.35 | 43.68 | ||
0 | 0 | -11.63 | -20.72 | -6.80 | -6.46 | -1.54 | 9.74 | 2.82 | 13.34 | 10.25 | -4.02 | ||
Free (2.5%) | 0 | 0.000053 0.000214 0.000854 0.003418 0.013672 0.054688 0.218750 0.875000 | 3.5 | ||||||||||
Total | 0 | 0.002136 0.008545 0.034180 0.136719 0.546875 2.187500 | 8.75 | 35.00 | 140.00 | ||||||||
sirolimus (nM) |
RTB101 300 mg monotherapy cerebrospinal fluid concentration
observed in PD patients
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Neurodegenerative Diseases
Parkinson's Disease: Levodopa-induced dyskinesia
Advantage of PD as a clinical indication for TORC1 inhibitors: levodopa- induced dyskinesia (LID) is a potential clinical endpoint that can be assessed in a shorter time frame than disease progression
- LID is a disabling side effect of chronic levodopa treatment associated with significantly impaired quality of life and increased health care costs1
- Most common dyskinesias:
- chorea (jerky involuntary movements, especially around the face, shoulders, and hips)
- dystonia (involuntary muscle contraction leading to twisting, repetitive movements, or abnormal posture in affected muscle or muscle group)
- Average time to onset of dyskinesia estimated at 6.5 years1
- > 90% of PD patients will have LID after 15 years of levodopa therapy3
1and figure Calabresi et al., 2010; 2Tran et al., 2018; 3Ahlskog and Muenter 2001 and Hely et al2005 | 17 |
Multiple pathways implicated in levodopa-induced dyskinesia (LID) pathogenesis converge on ERK and downstream TORC1 hyperactivation
TSC
Medium Spiny Neuron | ||
TORC1 | 4EBP1 | Dyskinesia |
S6K |
Adapted from Calabrisi P et al., Lancet Neurol, 2010 Santini et al. Sci Signaling, 2009 | 18 |
TORC1 is hyperactivated in medium spiny neurons in preclinical PD models of LID and TORC1 inhibition alleviates LID
A | B | |
TORC1 Activation (pS6 levels) |
Control mice treated with L-DOPA
PD Mice treated with L-DOPA
PD Mice treated with L-DOPA+rapamycin 2mg/kg
A: Administration of levodopa in a mouse model of PD (unilateral 6- OHDA lesion) led to hyperactivation of TORC1(as assessed by pS6 levels) in medium spiny neurons and development of dyskinesia.
B: Rapamycin inhibited TORC1 activation and ameliorates dyskinesia, as assessed by an abnormal involuntary movement score (AIMs), determined by an observer blind to treatment assignment. ooo,*** P<0.001 versus untreated control.
PD Mice treated with L-DOPA+rapamycin 5 mg/kg
Santini et al. Sci Signaling, 2009 | 19 |
resTORbio Phase 1b/2a Parkinson's disease trial
Randomized, Placebo-Controlled
Phase 1b/2a Study (4-week dosing)
Design | • | Mild-moderate PD patients (mH&Y I-III) |
•On standard of care PD drugs | ||
• | Once weekly dosing |
Study SizeN=45 (2:1 randomization)
Primary endpoint:
- Safety and tolerability
Secondary endpoint:
Key Endpoints•Exposure in blood, plasma and CSF
Exploratory endpoints:
- Biomarkers in plasma and CSF
- Clinical assessments, wearables
Cohort | RTB 101 | sirolimus | ||
dose | dose | |||
(mg) | (mg) | |||
1 | 300 | 0 | ||
2 | 0 | 2 | or | |
3 | 300 | 2 | ||
matching | ||||
placebo | ||||
4 | 300 | 4 | ||
5 | 300 | 6 | ||
- Study initiated in 1Q19
- Data expected bymid-2020
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RTB101 CSF Concentrations in 6 PD patients dosed with RTB101 300 mg once weekly
CSF RTB101 (nM) | |||||
4h post Dose 4 | |||||
4.50 | |||||
4.00 | |||||
3.50 | |||||
3.00 | |||||
2.50 | |||||
2.00 | |||||
1.50 | |||||
1.00 | |||||
0.50 | |||||
0.00 | |||||
101-004 | 101-901 | 102-001 | 103-001 | 103-003 | 103-006 |
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The combination of RTB101 and sirolimus synergize to inhibit TORC1 and may | |||||||||||||||
lower the RTB101 brain exposure predicted to be required for clinical benefit | |||||||||||||||
in PD | Total | Free (5%) | |||||||||||||
87.50 | 4.38 | 100 | 99 | 104 | 99 | 101 | 104 | 102 | 101 | 105 | 99 | ||||
43.75 | 2.19 | 97 | 101 | 100 | 102 | 95 | 102 | 104 | 104 | 102 | 103 | ||||
21.88 | 09 | 84 | 86 | 99 | 98 | 100 | 101 | 104 | 102 | 99 | 104 | ||||
% maximal | 10.94 | .55 | 51 | 62 | 79 | 99 | 102 | 104 | 103 | 104 | 105 | 104 | |||
SK-N-SH | Inhibition of | 5.47 | 0.27 | 26 | 38 | 54 | 91 | 98 | 104 | 103 | 103 | 105 | 104 | ||
2.73 | 0.14 | 12 | 30 | 39 | 74 | 97 | 102 | 103 | 104 | 104 | 104 | ||||
neuroblastoma cells | pS6K | 1.37 | 0.07 | 8 | 18 | 27 | 56 | 89 | 101 | 103 | 103 | 104 | 102 | ||
were exposed to | 0.68 | 0.03 | 14 | 12 | 30 | 49 | 85 | 101 | 103 | 105 | 103 | 104 | |||
increasing | 0.34 | 0.02 | 6 | 7 | 21 | 49 | 79 | 100 | 104 | 104 | 105 | 103 | Target inhibition for | ||
0 | 0 | 6 | 12 | 16 | 45 | 73 | 98 | 103 | 103 | 104 | 103 | ||||
concentrations of | |||||||||||||||
RTB101 (y axis) | Free (5%) | levodopa-induced | |||||||||||||
and/or increasing | 87 | 4.38 | 55 | 57 | 65 | 73 | 79 | 87 | 93 | 97 | 99 | 96 | dyskinesia | ||
concentrations of | 75 | 2.19 | 25 | 33 | 39 | 54 | 65 | 72 | 83 | 71 | 77 | 89 | |||
.88 | 1.09 | 5 | 16 | 13 | 28 | 38 | 62 | 62 | 68 | 62 | 76 | ||||
sirolimus (x axis). | % maximal | ||||||||||||||
(nM) | .94 | 0.55 | -6 | -7 | -7 | 0 | 13 | 28 | 36 | 40 | 45 | 51 | |||
Orange shaded areas | Inhibition of | .47 | 0.27 | -7 | -12 | -21 | -44 | -8 | 6 | 13 | 12 | 25 | 30 | ||
indicate | p4EBP1 | 2.73 | 0.14 | -12 | -10 | -8 | -10 | -12 | -2 | -6 | 1 | 9 | 18 | ||
RTB101 | 1. | 0.07 | -9 | -10 | -10 | -22 | -25 | -9 | -4 | -3 | 6 | 5 | |||
concentrations of | 0. | 0.03 | -7 | -6 | -4 | -16 | -33 | -10 | -6 | -3 | 5 | 4 | |||
RTB101 and/or | |||||||||||||||
0.02 | -17 | -15 | -11 | -21 | -31 | -17 | -9 | -10 | 9 | 0 | |||||
sirolimus that induce | 0 | 0 | -16 | -15 | -8 | -13 | -25 | -11 | -9 | -10 | 1 | -3 | |||
>50% maximal S6K or | |||||||||||||||
4EBP1 | 87.50 | Free (5%) | 130.58 | 114.37 | 156.80 | 170.61 | 173.28 | 181.56 | 196.15 | 174.61 | 158.67 | 216.07 | |||
phosphorylation | 4.38 | ||||||||||||||
% maximal | 43.75 | 2.19 | 91.48 | 71.47 | 123.06 | 118.25 | 166.88 | 154.73 | 189.63 | 194.12 | 190.70 | 214.89 | |||
inhibition or >50% | |||||||||||||||
21.88 | 1.09 | 31.89 | 25.16 | 81.50 | 100.98 | 125.12 | 137.82 | 212.58 | 197.37 | 166.87 | 218.33 | ||||
maximal autophagy | activation of | 10. | 0.55 | 0.02 | 4.25 | 29.25 | 41.45 | 88.97 | 138.95 | 155.32 | 184.65 | 146.93 | 179.15 | Target inhibition for | |
activation | 2.73 | 0.27 | -12.14 | -14.12 | -1.11 | 8.36 | 44.22 | 81.09 | 103.23 | 143.72 | 120.56 | 123.57 | |||
0.14 | -12.10 | -6.71 | -0.19 | -1.19 | 25.53 | 43.99 | 75.14 | 96.76 | 73.48 | 100.10 | neuroprotection and | ||||
1.37 | 0.07 | -7.40 | -17.37 | 0.03 | 0.09 | 13.03 | 29.69 | 41.98 | 54.65 | 60.23 | 68.35 | ||||
0.68 | 0.03 | -23.25 | -25.36 | 3.41 | -2.42 | 5.87 | 16.31 | 26.84 | 52.55 | 33.51 | 31.80 | disease modification | |||
0.34 | 0.02 | -16.81 | -28.70 | -7.67 | -5.83 | 5.18 | 14.95 | 9.42 | 33.10 | 21.35 | 43.68 | ||||
0 | 0 | -11.63 | -20.72 | -6.80 | -6.46 | -1.54 | 9.74 | 2.82 | 13.34 | 10.25 | -4.02 | ||||
RTB101 300 mg | Free | ||||||||||||||
cerebrospinal fluid concentration | (2.5%) | 0 | 0.000053 | 0.000214 | 0.000854 0.003418 0.013672 0.054688 0.218750 0.875000 | 3.5 | |||||||||
observed in PD patients | Total | 0 | 0.002136 | 0.008545 | 0.034180 | 0.136719 | 0.546875 | 2.187500 | 8.75 | 35.00 | 140.00 | ||||
22 | |||||||||||||||
sirolimus (nM) | |||||||||||||||
Neurodegenerative Diseases
Huntington's disease
Induction of autophagy with TORC1 inhibitors may have potential benefit in multiple neurodegenerative diseases in which protein aggregation contributes to disease pathogenesis
Alzheimer's | Parkinson's | Huntington's |
Disease | Disease | Disease |
Amyloid β | Phosphorylated | α-synuclein | Mutated |
protein | tau | huntingtin | |
Amyloid | Neurofibrillary | Lewy | Aggregated |
plaques | tangles | bodies | huntingtin |
24
In a preclinical model of Huntington's disease, the combination of RTB101 and everolimus (an analog of sirolimus) cleared protein aggregates and
was neuroprotective
Aggregated mHtt protein levels in cultured cortico- striatal slices from R6/2 Huntington's disease mouse.
250nM 50nMevero RTB101evero RTB101
RTB101
Drug concentrations in the figures are total concentrations
250 nM everolimus | 50 nM RTB101 | 300 nM RTB101 |
250 nM everolimus | 250 nM everolimus | 250 nM everolimus | |
+ 10 nM RTB101 | + 30 nM RTB101 | + 50 nM RTB101 | |
Neurofilament is a | DARPP-32 is a marker |
marker of axons | of cell soma |
Source: Novartis Data on file | 25 |
resTORbio highlights
Extensive preclinical data demonstrate that TORC1 inhibition may ameliorate multiple aging related diseases, including neurodegenerative diseases
TORC1 inhibition may be a promising approach for the treatment of Parkinson's disease (PD)
- Ameliorateslevodopa-induced dyskinesia in preclinical PD models
- Induces lysosomal biogenesis and autophagy, clearsalpha-synuclein aggregates and is neuroprotective in preclinical PD models
- Lead candidate, RTB101, is an oral, selective and potent TORC1 inhibitor that has been observed in preclinical models to cross the blood brain barrier and induce autophagy in neurons
Ongoing Phase 1b/2a clinical trial of RTB101 +/- sirolimus for PD
- Safety, tolerability and cerebrospinal fluid (CSF) exposure data are expected bymid-2020 in PD patients
- RTB101 has the potential to alleviatelevodopa-induced dyskinesia and may offer the first opportunity to slow disease progression by inducing autophagy in the brain of PD patients
- In interim data from three cohorts in the Phase 1b/2a study we observed that RTB101 is well tolerated, crosses the blood brain barrier, and reaches concentrations in cerebrospinal fluid observed to inhibit the activity of TORC1 and induce autophagy in neuronal cells
-Sirolimus at the dose of 2 mg, alone or in combination with RTB101, was not detected in the CSF
Cash, cash equivalents and marketable securities of $117.3 million as of September 30, 2019
26
Targeting the biology of aging to treat aging-related diseases
Corporate Presentation
February 2020
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resTORbio Inc. published this content on 24 February 2020 and is solely responsible for the information contained therein. Distributed by Public, unedited and unaltered, on 24 February 2020 22:53:08 UTC