Bicycle Therapeutics Plc · NASDAQ:BCYC
Bicycle Therapeutics — Corporate Update (October 2021)
30 slides from Bicycle Therapeutics's corporate update, Oct 7, 2021
Slide 1: Interim Phase I Update on BT5528 and Preliminary Findings from BT8009 Program
Interim Phase I Update on BT5528 and Preliminary Findings from BT8009 Program October 7, 2021
Slide 2: Forward-looking statements
This presentation may contain forward - looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 . These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts”, “goal,
Slide 3: Agenda
Agenda October - 21 3 Introduction Kevin Lee Chief Executive Officer Review monotherapy trials to date: BT5528 BT8009 Dominic Smethurst Chief Medical Officer Beyond BT5528 and BT8009 Nick Keen Chief Scientific Officer Closing remarks Lee Kalowski President and Chief Financial Officer Q&A Executive M
Slide 4: Robust proprietary and partnered pipeline
Robust proprietary and partnered pipeline 4 Target / Product Partner / Sponsor Indication Modality Pre - clinical IND - enabling Phase I Phase II Internal programs BT5528 (EphA2) Oncology Bicycle ® Toxin Conjugate BT8009 (Nectin - 4) Oncology Bicycle ® Toxin Conjugate BT7480 (Nectin - 4/CD137) Immun
Slide 5: BT5528 Monotherapy
BT5528 Monotherapy
Slide 6: Background to BT5528 and ADC target: EphA2
Background to BT5528 and ADC target : EphA2 October - 21 6 • Erythropoietin - producing hepatocellular A2 receptor: member of Eph subfamily of receptor tyrosine kinases • Regulates cell migration, adhesion, proliferation and differentiation • Overexpressed in human cancers and correlates with tumor
Slide 7: BT5528: trial design
BT5528 phase I dose escalation: trial design 7 Inclusion/Exclusion criteria: • Standard first - in - human criteria • Prior neuropathy must have returned to ≤Grade 1 • IHC based enrichment for EphA2(+) tumors introduced mid - trial Objectives: • Primary – Safety and tolerability • Secondary – PK, PD
Slide 8: Overview of key demographics for patients enrolled in BT5528 trial
Overview of key demographics for patients enrolled in BT5528 phase I dose escalation trial October - 21 8 Demographics Total 24 (100%) Age, years, median (range) 65.5 (49 - 76) Sex, n (%) Male 7 (29%) Female 17 (71%) ECOG, n (%) 0 (Good performance status) 11 (46%) 1 13 (54%) 2+ 0 (0%) Prior therapi
Slide 9: Overview of key adverse events observed in BT5528 trial
Overview of key adverse events observed in BT5528 phase I dose escalation trial October - 21 9 • Total number of adverse events: 235 1 • Adverse events related to BT5528: 101 1 • Other toxicities (<Gr 3) were predominantly hematological and GI 1 • Two Gr 5 events observed, one following data cut - o
Slide 10: BT5528 – establishment of RP2D range
BT5528 phase I dose escalation – establishment of RP2D range 10 October - 21 BT5528 2.2mg/m 2 QW 4.4mg/ m 2 QW 8.5mg/ m 2 QW 10mg/m 2 Q2W 6.5mg/m 2 QW 8.5mg/m 2 Q2W 2 out of 2 DLTs: Grade 3 fatigue, pneumonitis 1 Recommended phase 2 dose range: 6.5 - 8.5mg/ m 2 Q2W Transient Grade 3/4 neutropenia no
Slide 11: BT5528: Preliminary responses observed during trial
Responses observed: • Ovarian • 1 PR 1 of 8 ovarian cancer patients, PR observed by month 4 • 4 of 5 with EphA2 staining showed some shrinkage • Urothelial • 2 of 2 PRs 1 , both at 2 months • Both responses by first scan October - 21 11 Change in target lesion size relative to baseline 0 2 4 6 8 10
Slide 12: Emerging observed relationship between EphA2 staining and responses
Emerging observed relationship between EphA2 staining and responses October - 21 12 • More EphA2 staining = more tumor shrinkage • Early relationship with low numbers BT5528 Data as of 14Jul21, not fully QCed
Slide 13: BT5528 expansion: overall trial design
BT5528 expansion: overall trial design 13 October - 21 BT5528
Slide 14: BT5528 – Phase I dose escalation preliminary conclusions and next steps
BT5528 – Phase I dose escalation preliminary conclusions and next steps • BT5528 is a first - in - class Bicycle ® toxin conjugate • No evidence of BT5528 clotting abnormalities vs multiple disseminated intravascular coagulation events for MEDI - 547 ADC • Doses tolerated within expected therapeutic
Slide 15: BT8009 Monotherapy
BT8009 Monotherapy
Slide 16: Background to BT8009 and ADC target: Nectin-4
Background to BT8009 and ADC target : Nectin - 4 October - 21 16 • A cell adhesion molecule and one of four members of the nectin family • All nectins s hare the same overall structure defined by three extracellular immunoglobulin domains, a single transmembrane helix and an intracellular domain • O
Slide 17: BT8009 trial design – currently escalating to 7.5mg/m2
BT8009 phase I dose escalation trial design – currently escalating to 7.5mg/m 2 QW and Q2W 17 Inclusion/Exclusion criteria: • Standard first - in - human criteria • Any prior Nectin - 4 target therapy excluded • Urothelial patients were not IHC screened for Nectin - 4 Objectives: • Primary – Safety
Slide 18: Overview of key demographics for evaluable patients enrolled in BT8009 trial
Overview of key demographics for evaluable patients enrolled in BT8009 phase I dose escalation trial Demographics Total 26 (100%) Age, years, median (range) 66 (44 - 81) Sex, n (%) Male 15 (58%) Female 11 (42%) ECOG, n (%) 0 (Good performance status) 11 (42%) 1 15 (58%) 2+ 0 Prior therapies, median
Slide 19: BT8009 trial: evaluable patients enrolled by tumor type
BT8009 phase I dose escalation trial: evaluable patients enrolled by tumor type October - 21 19 Demographics Total 26 (100%) By tumor type: Urothelial 11 (42%) Pancreatic 6 (23%) NSCLC 4 (15%) TNBC 3 (12%) Head & Neck 1 (4%) Ovarian 1 (4%) Data as of 30Sept21, not fully QCed BT8009
Slide 20: Key demographics of evaluable urothelial cancer patients in BT8009 trial
Key demographics of evaluable urothelial cancer patients participating in BT8009 phase I dose escalation trial Demographics Total 11 (100%) Age, years, median (range) 69 (54 - 81) Sex, n (%) Male 9 (82%) Female 2 (18%) ECOG, n (%) 0 (Good performance status) 7 (64%) 1 4 (36%) 2+ 0 Prior therapies, m
Slide 21: Overview of key adverse events observed in BT8009 trial
Overview of key adverse event s observed in BT8009 phase I dose escalation trial across all patients (N=27) Data as of 30Sept21, not fully QCed 21 October - 21 Adverse Events Related Gr ≥3 AE N=10 events Anemia N=4 Neutropenia N=3 Hypertension N=1 Hypokalemia N=1 Asthenia N=1 BT8009
Slide 22: BT8009: preliminary responses by dose in urothelial cancer patients
BT8009: preliminary responses observed in phase I dose escalation by dose in response evaluable urothelial cancer patients October - 21 22 0 2 4 Cycle +20% -30% -60% 2.5mg/m 2 0 2 4 Cycle +20% -30% -60% 5mg/m 2 Change in target lesion size relative to baseline 1. P artial responses under response ev
Slide 23: Comparison of BT8009 to enfortumab vedotin (Padcev) – urothelial cancer
Comparison of BT8009 to enfortumab vedotin ( Padcev © ) phase I dose escalation – urothelial cancer October - 21 23 Comparison * BT8009 2.5mg/m 2 BT8009 5mg/m 2 BT8009 both cohorts Enfortumab (1mg/ kg and below) ** Enfortumab (All cohorts) ** No of patients 4 7 11 26 33 Median age 75 68 69 67 67 ≥2
Slide 24: More information on preliminary responses in urothelial cancer patients
October - 21 24 Patient A Patient B Patient C Patient D Dose (mg/m 2 ) 2.5 5.0 5.0 5.0 Age 81 68 66 62 Sex M M M M Prior lines of therapy 2 2 2 2 Partial response - 37% - 89% - 44% - 52% Data as of 30Sept21, not fully QCed BT8009 More informati on on preliminary responses observed for urothelial can
Slide 25: Comparison of Patient B pre-dose tumor images with images after 2 months
Comparison of Patient B pre - dose tumor images with tumor images after 2 months treatment (5mg/m 2 Q2W) October - 21 25 Pre - treatment Post - cycle 2 on BT8009 Lung lower lobe left Lung lower lobe right Non - target lung lesion was reduced by - 89% after two cycles of BT8009 treatment BT8009
Slide 26: BT8009 Phase I dose escalation summary as of Sept
BT8009 phase 1 dose escalation summary as of Sept 30 • No DLTs observed and escalation remains ongoing, with patients currently being enrolled in 7.5 mg/m 2 weekly and every - other - week cohorts • BT8009 anti - tumor activity observed in pre - treated, urothelial cancer patients in both cohorts •
Slide 27: Beyond BT5528 and BT8009
Beyond BT5528 and BT8009
Slide 28: Well positioned to be the next generation of targeted oncology therapeutics
D E P T H We believe we are well positioned to be the next generation of targeted oncology therapeutics 28 Bicycle Toxin Conjugates ® Bicycle ® TICAs Tumor targeting Bicycles • Clinical signal observed • Generalizable to other payloads • Intend to build on current clinical trial observations with “w
Slide 29: Looking forward
Looking forward • Plan to initiate BT5528 expansion cohorts in 2022 • BT8009 dose escalation to 7.5 mg/m 2 will continue during Q4. Expect to present additional Phase I data in 2022 • BT7480 - a Nectin - 4 - CD137 Bicycle TICA ® - anticipate dosing first patient by year end 2021 • Third generation B
Slide 30: Question and Answer
Question and Answer
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