Bicycle Therapeutics Plc · NASDAQ:BCYC
Bicycle Therapeutics — Technical Presentation (April 2022)
23 slides from Bicycle Therapeutics's technical presentation, Apr 12, 2022
Slide 1: BT8009 clinical trial update
BT8009 clinical trial update NASDAQ: BCYC April 2022 Exhibit 992 SP1
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 3 Introduction Kevin Lee Chief Executive Officer Technology overview Nick Keen Chief Scientific Officer BT8009 clinical experience to date Dominic Smethurst Chief Medical Officer Q&A Executive Management Team
Slide 4: Deeply experienced team and clinical stage company overview
Deeply experienced team Located Cambridge UK and Lexington, MA ~119 Employees * NASDAQ: BCYC Cash balance $438.7M * (expected cash runway into 2024) Clinical stage biopharma company pioneering Bicycles – a new differentiated class of innovative medicines 4 Focused on oncology and immuno - oncology w
Slide 5: Robust proprietary and partnered pipeline
Robust proprietary and partnered pipeline 5 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 6: Bicycles combine the advantages of small molecules and antibodies
Bicycles are designed to combine the advantages of both small molecules and antibodies 6 Bicycle ® Small molecule Antibody Small size Yes – 1.5 - 2kDa Yes – <0.8kDa No – >150kDa Specificity High Low Multiple Chemical synthesis (NCEs) Yes Yes No Rapid tissue penetration Yes Yes No Complex protein tar
Slide 7: Bicycle Toxin Conjugates: higher potency and specificity than ADCs
MWt of 1.5 - 2kDa 50 - 100x smaller than antibodies High selectivity Allows more potent toxin to be delivered directly to tumor BTCs – preclinical data indicates higher potency and specificity with fewer side effects than ADCs 7 Antibody Bicycle ® 0.001 0.010 0.100 1.000 0 12 24 36 48 60 72 [Tissue]
Slide 8: BT8009 Monotherapy
BT8009 Monotherapy
Slide 9: Key takeaways from trial to date
Key takeaways from phase I dose escalation trial to date * 9 Promising clinical activity seen at 5mg/m 2 weekly; dose tolerated, with potential for differentiated and industry - leading product profile • 50% ORR and 75% disease control, including 1 (13%) complete response • Durable responses, with t
Slide 10: Dose escalation progress and strategy
Dose escalation progress and strategy 10 Dose finding 2.5mg/m 2 QW (68%) 5mg/m 2 QW (135%) 7.5mg/m 2 Q2W (100%) 7.5mg/m 2 QW (200%) Further exploration of dosing and frequency MMAE equivalents of 1.25mg/kg Padcev/cycle Clinical activity seen at all weekly doses Soft DLTs Well tolerated Dose and regi
Slide 11: Demographics
Demographics Total N=37 Age, years, median (range) 66 (44 - 83) Sex, n (%) Male 22 (59%) Female 15 (41%) ECOG, n (%) 0 (Good performance status) 15 (41%) 1 22 (59%) Prior therapies, median 3 11 Overview of key demographics for all patients enrolled in BT8009 phase I dose escalation trial
Slide 12: Demographics: tumor type
Demographics Total N=37 Tumor type Breast 4 (11%) Esophageal 1 (3%) Head/Neck 2 (5%) Lung 5 (14%) Ovarian 1 (3%) Pancreatic 6 (16%) Urothelial 18 (49%) 12 Overview of disease history for all patients enrolled in BT8009 phase I dose escalation trial
Slide 13: Responses observed in urothelial cancer patients
Responses * observed in 2.5, 5 and 7.5mg/m 2 phase I dose escalation in response evaluable urothelial cancer patients 13 2.5mg/m 2 QW (N=4) • 1 of 4 responses (25% ORR) • 59% tumor reduction • Deepened from 37% at 30Sept21 • Remains on therapy; approaching 11 months • 2 of 4 stable disease • 75% dis
Slide 14: Responses in 5mg/m2 QW cohort in urothelial patients
Responses * observed in 5mg/m 2 QW cohort phase I dose escalation in response - evaluable urothelial patients 14 * Responses under response evaluation criteria in solid tumors (RECIST) version 1.1 Urothelial Responses • 4 responses in 8 patients • 1 Complete Response • 3 Partial Responses • 71% tumo
Slide 15: Complete responder tumor images before and after treatment
Comparison of complete responder pre - dose tumor images with tumor images after six months treatment (5mg/m 2 QW) 15 Lung lower lobe left Lung lower lobe right Baseline Follow - up 1 Follow - up 2 Follow - up 3 Target lesions were reduced by 100% after four months of BT8009 treatment Disappeared Di
Slide 16: Phase I interim results from enfortumab vedotin (Padcev)
Phase I interim results from enfortumab vedotin (Padcev ® ) 16 100% patients pre - screened 60% patients ≥2 prior therapies ≥≥ Median PFS and DoR both 16 weeks ORR 10/33 or 30%
Slide 17: BT8009 interim data in response-evaluable urothelial patients
Data from BT8009 interim phase I dose escalation trial to date in response - evaluable urothelial cancer patients 17 2.5mg/m 2 5mg/m 2 No of patients 4 8 Median age 75 67 ≥2 prior lines (%) 4 (100%) 8 (100%) IHC pre - screen (%) 0 0 Partial or Complete Response (ORR %) 1 (25%) 4 (50%) Stable Disease
Slide 18: Adverse events observed in BT8009 trial across all patients
Overview of adverse events observed in BT8009 phase I dose escalation trial across all patients 18 Preferred Term Incidence ( ≥ 15%) Fatigue 40.5% Nausea 37.8% Diarrhea 32.4% Pyrexia 32.4% Anemia 32.4% Decreased appetite 32.4% Constipation 29.7% Urinary tract infection 27.0% Neutrophil count decreas
Slide 19: Adverse event information from Padcev FDA label
Summary of adverse event information from Padcev ® FDA label 19 Adverse Event Median time to onset (months) * Padcev incidence * Padcev severity ( Gr≥3) * Which trial(s) N subjects Skin tox 0.6 55% 13% All 680 Neuropathy 4.6 52% 4% All 680 Ocular disorders 1.6 40% N/A EV - 201, EV - 101, EV - 102 38
Slide 20: Key adverse events observed across all cohorts
Overview of key adverse events observed in BT8009 phase I dose escalation trial across all cohorts 20 Adverse Event Incidence Severity ( Gr≥3) Related Skin tox 19% 0% 14% Neuropathy 24% 3% 19% Ocular disorders 3% 0% 3% Hyperglycemia 8% 0% 5% Febrile neutropenia 0% 0% 0% Pneumonitis 0% 0% 0%
Slide 21: Other adverse events of interest across all cohorts
Other adverse events of interest in BT8009 phase I dose escalation trial across all cohorts 21 Adverse Events Incidence Severity (Gr≥3) Related Neutropenia 30% 14% 30% Gastrointestinal Disorders: Nausea Diarrhea Vomiting 38% 32% 11% 3% 5% 3% 36% 24% 11%
Slide 22: Potential efficacy in other tumor types in Phase II expansion
Potential efficacy in other tumor types will be explored more thoroughly in Phase II expansion trial 22 Demographics Total N=37 Tumor type Breast 4 (11%) Esophageal 1 (3%) Head/Neck 2 (5%) Lung 5 (14%) Ovarian 1 (3%) Pancreatic 6 (16%) Urothelial 18 (49%) • 1 SD at 7.5mg Q2W. Disappearance of non -
Slide 23: Key takeaways from trial to date
Key takeaways from phase I dose escalation trial to date 23 Promising clinical activity seen at 5mg/m 2 weekly; dose tolerated, with potential for differentiated and industry - leading product profile • 50% ORR and 75% disease control, including 1 (13%) complete response • Durable responses, with tu
Bicycle Therapeutics — Technical Presentation (April 2022) on 6ix