Bridgebio Oncology Therapeutics, Inc. · NASDAQ:BBOT

Bridgebio Oncology Therapeutics — SPAC Merger (February 2025)

50 slides from Bridgebio Oncology Therapeutics's SPAC merger presentation, Feb 28, 2025

  1. Slide 1: BridgeBio Oncology Therapeutics Confidential overview

    Q1 2025 BridgeBio Oncology Therapeutics Confidential overview

  2. Slide 2: Disclaimer (1 of 3)

    Disclaimer (1 of 3) 2 Confidential and proprietary. Do not duplicate without permission from BridgeBio Oncology Therapeutics. This presentation (together with oral statements made in connection herewith, this “Presentation”) is for informational purposes only . This Presentation has been prepared to

  3. Slide 3: Disclaimer (2 of 3)

    Disclaimer (2 of 3) 3 Confidential and proprietary. Do not duplicate without permission from BridgeBio Oncology Therapeutics. Participants in the Solicitation In connection with the Proposed Business Combination, the parties intend to prepare and file with the SEC a registration statement containing

  4. Slide 4: Disclaimer (3 of 3)

    Disclaimer (3 of 3) 4 Confidential and proprietary. Do not duplicate without permission from BridgeBio Oncology Therapeutics. Forward Looking Statements (continued) If any of these risks materialize or HLXB’s or Theras ’ assumptions prove incorrect, actual results could differ materially from the re

  5. Slide 5: Advancing next generation RAS-pathway targeted small molecules

    Advancing next generation RAS - pathway targeted small molecules 5 Financing Multiple clinical assets with anticipated value inflection points over the next 9 - 18 months , and a proven drug discovery engine Total cash of $500M * at closing (exp. mid - 2025) provides runway into mid - 2027 to execut

  6. Slide 6: Distinguished management team, experienced board and investor syndicate

    Led by a highly distinguished management team and complemented by an experienced BOD and sophisticated investor syndicate Led teams responsible for the discovery of multiple approved drugs including Welireg , Mektovi , Tukysa , and Koselugo 6 Eli Wallace, PhD Global Discovery Research leader for mul

  7. Slide 7: Great need to improve standard of care for RAS- and PI3Kα mutant cancers

    There is great need to improve the Standard of Care for patients with RAS - and PI3K  mutant cancers 7 BBOT is working to fully unlock the potential of RAS - focused therapies by optimizing target coverage ▪ Portfolio designed to enable direct dual inhibition of KRAS ON and OFF states and panRAS in

  8. Slide 8: BBOT's pipeline poised to close key activity gaps in RAS-focused space

    BBOT’s pipeline is poised to close key activity gaps in the RAS - focused therapeutic space 8 Opportunity Status Mechanism of Action Program / Target KRAS G12C NSCLC Phase 1 monotherapy and PD - 1 combination dose escalation enrolling ▪ First direct inhibitor of KRAS G12C (ON) ▪ Inhibits both KRAS G

  9. Slide 9: Assets designed to be synergistic across several indications

    Assets are designed to be synergistic across several indications to achieve the most benefit for broad patient populations 9 BBO - 8520 Direct KRAS G12C (ON/ OFF ) BBO - 11818 Pan - KRAS (ON/OFF) BBO - 10203 RAS:PI3K  Breaker BBO - 10203 is uniquely positioned to combine with mutant - specific RAS

  10. Slide 10: BBO-8520 Dual KRAS G12C ON and OFF inhibitor

    BBO - 8520 10 Dual KRAS G12C ON and OFF inhibitor

  11. Slide 11: Inhibition of KRAS G12C ON may be necessary for optimal target coverage

    Inhibition of KRAS G12C ON may be necessary for optimal target coverage and prevention of adaptive mechanisms of resistance 11 Always On Mutations amplify ON state of KRAS G12C First Wave of Inhibitors Falls Short Current direct approaches only target OFF states of KRAS G12C A different approach BBO

  12. Slide 12: BBO-8520 differentiated MoA binding ON and OFF states of KRAS G12C

    BBO - 8520 is designed with a differentiated MoA , binding directly to the ON and OFF states of KRAS G12C with a high degree of potency and selectivity 12 Confidential and proprietary. Do not duplicate without permission from BridgeBio Oncology Therapeutics. Note: MoA : Mechanism of Action Source: D

  13. Slide 13: BBO-8520 preclinical results compared to divarasib

    BBO - 8520 showed promising results compared to divarasib in preclinical models at a fraction of the plasma exposure 13 Notes: * BBO - 8520 preclinical data collected in NCI - H358 G12C NSCLC mouse model Source: Slide contains aggregated data from: ( divarasib data): Tran et al., Anal Chem 2023; AAC

  14. Slide 14: BBO-8520 preclinical activity with anti-PD-1 therapy

    BBO - 8520 has demonstrated positive preclinical activity in combination with anti - PD - 1 therapy 14 CT26 - KRAS G12C - luc Syngeneic Liver Model CT26 - KRAS G12C Syngeneic Subcutaneous Model 0 7 14 21 28 35 42 49 56 63 0 500 1000 1500 2000 Days on Treatment T u m o r v o l u m e ( m m 3 ) Termina

  15. Slide 15: ONKORAS-101 Phase 1a dose escalation enrolling

    ONKORAS - 101 is currently enrolling Phase 1a dose escalation in monotherapy and PD - 1 combination; expansion studies are planned for 2H 2025 15 ONKORAS - 101 Phase 1a Dose Escalation Monotherapy & combination with pembrolizumab Confidential and proprietary. Do not duplicate without permission from

  16. Slide 16: BBO-8520 responses across all dose levels with favorable safety

    BBO - 8520 has shown responses across all dose levels of monotherapy escalation while supporting a favorable safety profile 16 -60 -50 -40 -30 -20 -10 0 10 Best % change from baseline in target lesions E 30 N 24 E 12 E 12 N 18 N 24 N 18 N 12 E 12 N 18 SD** → SD** SD → SD^ PR → PR → PR → PR → PR → PR

  17. Slide 17: Preliminary safety signals generally tolerable and manageable

    Preliminary safety signals have been generally tolerable and manageable with only grade 1/2 treatment - related adverse events and no AST / ALT elevation of any grade 17 Number of Patients (N=16) TRAEs occurring in ≥10% of patients, n (%) TRAEs All Grade G3 or higher G2 G1 7 (44%) 0 (0%) 2 (12.5%) 5

  18. Slide 18: BBO-10203 Breaker of the RAS:PI3Kα interaction

    BBO - 10203 18 Breaker of the RAS:PI3K  interaction

  19. Slide 19: RAS and PI3Kα interaction in malignant cells but not normal physiology

    The interaction between RAS and PI3K  plays a critical role in malignant cells but not in normal human physiology Note: GF: Growth Factor, RTK: Receptor Tyrosine Kinase, AKT: Protein Kinase B, RAS: Rat Sarcoma Virus, PI3K α : Phosphoinositide 3 - kinase alpha 19 Normal Context Malignant Context Cel

  20. Slide 20: Genetic disruption of RAS:PI3Kα interaction inhibits KRAS G12D tumor growth

    Genetic disruption of the RAS:PI3K α interaction has been shown to inhibit KRAS G12D - driven tumor growth with no observed hyperglycemia Note: RBD: RAS Binding domain; GF: Growth Factor, RTK: Receptor Tyrosine Kinase, AKT: Protein Kinase B, RAS: Rat Sarcoma Viru s, PI3K α : Phosphoinositide 3 - kin

  21. Slide 21: BBO-10203 novel MOA inhibiting RAS and PI3Kα interaction

    BBO - 10203 utilizes a novel MOA that is designed to inhibit the physical interaction between RAS and PI3K   disrupting RAS - driven PI3K  /AKT signaling Notes: TE: Target engagement (PI3K α RBD); BBOT cell and in vivo data: KYSE - 410 (HER2/KRAS G12C ); MOA – mechanism of action Source: Internal

  22. Slide 22: BBO-10203 activity while avoiding hyperglycemic effects

    BBO - 10203 showed strong activity while avoiding the hyperglycemic effects associated with approved kinase inhibitors in preclinical models 22 KYSE - 410 CDX HER2 amp / KRAS G12C ED 90 (mg/kg) [95% CI] ED 50 (mg/kg) [95% CI] 3.9 [3.4 – 4.5] 2.5 [1.5 - 4.2] Pharmacodynamic Assay Blood Glucose Levels

  23. Slide 23: BBO-10203 activity with SoC in breast cancer models

    BBO - 10203 showed strong activity with SoC in HER2+ and ER+ PIK3CA mut breast cancer preclinical models across both helical and kinase mutants 23 MDA - MB - 453 CDX w/ Trastuzumab HER2+ / PIK3CA H1047R EFM - 19 CDX w/ Fulvestrant ER+ / PIK3CA H1047L MCF - 7 CDX w/ Palbociclib ER+ / PIK3CA E545K 0 7

  24. Slide 24: Portfolio enables concurrent inhibition of pAKT and pERK

    We believe BBOT’s portfolio will enable concurrent inhibition of pAKT and pERK in a tumor selective manner as BBO - 10203 can optimize target coverage for KRASi ▪ Mutant KRAS strongly drives both the MAPK and AKT pathways in most mutant KRAS tumor cells ▪ In response to MAPK pathway inhibition, WT R

  25. Slide 25: BBO-10203 plus BBO-8520 superior to monotherapy

    BBO - 10203 combined with BBO - 8520 showed superior activity relative to monotherapy in RAS - driven cancers in multiple preclinical models 25 Note: BBOT cell derived xenograft models shown with tumor volume as measurement of activity; * RMANOVA Source: Internal BBOT data 0 7 14 21 28 0 200 400 600

  26. Slide 26: H2122 combination reduced proliferation and increased apoptosis

    Safety Data Body Weight % Change In the H2122 model, the combination of BBO - 8520 and BBO - 10203 reduced proliferation and increased apoptosis with generally favorable tolerability Note: BBOT cell derived xenograft models shown with tumor volume as measurement of activity; Tumor Volume: Two - way

  27. Slide 27: BREAKER-101 Phase 1a dose escalation enrolling

    BREAKER - 101 is currently enrolling Phase 1a dose escalation in monotherapy; combination studies are planned for 2H 2025 27 BREAKER - 101 Phase 1a Dose Escalation Monotherapy & combination Confidential and proprietary. Do not duplicate without permission from BridgeBio Oncology Therapeutics. Mono C

  28. Slide 28: BBO-11818 Dual panKRAS ON and OFF inhibitor

    BBO - 11818 28 Dual panKRAS ON and OFF inhibitor

  29. Slide 29: BBO-11818 panKRAS ON/OFF inhibitor with potency against G12D and G12V

    BBO - 11818 is a panKRAS ON/OFF inhibitor designed with strong potency against G12D and G12V mutants 29 Crystal structure of BBO - 11818 bound to KRAS G12D BBO - 11818 Assay 17 / 0.00013 G12D SPR: KRAS - GppNHp / GDP KD ( nM ) 14 / 0.037 G12V 26 / 0.14 WT 39 G12D PPI: KRAS/RAF1 effector - GTP IC 50

  30. Slide 30: BBO-11818 inhibition of MAPK signaling and viability in KRAS mutant cells

    BBO - 11818 has shown potent inhibition of MAPK signaling and viability in KRAS mut cells… 30 BBO - 11818 EC 50 (nM) Histotype Cell Line Genotype 3D Viability pERK 0.244 0.352 CRC GP2D G12D 0.878 1.14 Panc SW1990 1.48 4.07 Panc AsPC - 1 4.19 3.43 Panc HPAC 0.778 0.916 Panc KP4 2.88 6.41 Panc Capan -

  31. Slide 31: Anti-tumor activity across KRAS G12D/V CDX models

    … and has shown anti - tumor activity across multiple KRAS G12D/V CDX preclinical models 31 0 7 14 21 28 0 200 400 600 800 1000 1200 1400 Days on Treatment T u m o r v o l u m e ( m m 3 ) Vehicle (BID, po) BBO-11818 (10 mg/kg, BID, po) BBO-11818 (30 mg/kg, BID, po) BBO-11818 (100 mg/kg, BID, po) * *

  32. Slide 32: BBO-11818 with BBO-10203 showed tumor regression

    Safety Data Body Weight % Change BBO - 11818 in combination with BBO - 10203 showed tumor regression driven by decreased proliferation and increased apoptosis in preclinical models 32 Increased apoptosis Capan - 2 (G12V) Efficacy​ Tumor volume Mechanism BrdU and Caspase - 3 assays 0 7 14 21 28 0 200

  33. Slide 33: Opportunity: Large market and multiple upcoming catalysts

    Opportunity 33 Large market and multiple upcoming catalysts

  34. Slide 34: Large opportunity with ~250K annual incident patients in the US

    BBOT has a large opportunity with ~250K annual incident patients in the US across the core indications of breast, lung, colorectal, and pancreatic cancer KRAS G12X opportunities ▪ The ability to combine multiple BBOT agents in KRAS G12X cancers creates opportunities for synergistic efficacy, lifecyc

  35. Slide 35: Expected upcoming clinical catalysts

    BBOT expected upcoming clinical catalysts 35 2H 2025 1H 2026 2H 2026 onwards BBO - 8520 (KRAS G12C ON / OFF) Phase 1 monotherapy data and safety in combination with pembrolizumab BBO - 10203 (RAS:PI3K α Breaker) Phase 1 data BBO - 11818 (Pan - KRAS ON / OFF) Phase 1* data and broader expansion datas

  36. Slide 36: Transaction Overview: Pro forma valuation and ownership

    Transaction Overview Pro forma valuation and ownership 36 Confidential and proprietary. Do not duplicate without permission from BridgeBio Oncology Therapeutics. • Helix Acquisition Corp. II to combine with BBOT at an implied $446 mm pre - money equity value (1) • $196 mm in Trust (2) • $261 mm PIPE

  37. Slide 37: Appendix

    Appendix 37

  38. Slide 38: Patient characteristics for ONKORAS-101 efficacy evaluable patients

    Patient characteristics for ONKORAS - 101 efficacy evaluable patients 38 n=10 Efficacy evaluable* ONKORAS - 101 patient characteristics 68 (43 - 90) Age median (range) 5 (50%) Female n (%) Race n (%) 6 (60%) White 1 (10%) Asian 1 (10%) Black or African American 2 (20%) Unknown ECOG n (%) 3 (30%) 0 7

  39. Slide 39: Tumor response over time and weeks on treatment for ONKORAS-101

    Preliminary data: Tumor response over time and weeks on treatment for ONKORAS - 101 efficacy evaluable patients 39 Confidential and proprietary. Do not duplicate without permission from BridgeBio Oncology Therapeutics. Note: Data extract date January 19, 2025; * Efficacy evaluable defined as at leas

  40. Slide 40: BBO-11818 plus anti-PD-1 combination activity in CRC model

    BBO - 11818 + anti - PD - 1 showed combination activity in the CRC KRAS G12D CT26 syngeneic mouse model 40 Median Overall Survival (day) Day 67 Group (n=10) Complete Regression Survival p value vs combo p value vs vehicle 19 0/10 0% - - Vehicle (BID) 25 0/10 0% <0.0001 0.0054 BBO - 11818 (100 mg/kg,

  41. Slide 41: Combination benefit for BBO-11818 with cetuximab

    Combination benefit for BBO - 11818 with cetuximab was observed in vitro and in vivo 41 LS513 CDX (KRAS G12D ) Tumor Volume Confidential and proprietary. Do not duplicate without permission from BridgeBio Oncology Therapeutics. Note: Cell derived xenograft models shown with tumor volume as measureme

  42. Slide 42: Risk Factors

    Risk Factors 42

  43. Slide 43: Risk factors (1 of 8)

    Risk factors (1 of 8) 43 Confidential and proprietary. Do not duplicate without permission from BridgeBio Oncology Therapeutics. Certain factors may have a material adverse effect on our business, financial condition and results of operations . The risks and uncertainties described below are not the

  44. Slide 44: Risk factors (2 of 8)

    Risk factors (2 of 8) 44 Confidential and proprietary. Do not duplicate without permission from BridgeBio Oncology Therapeutics. Risks Related to BBOT’s Product Development, Regulatory Approval and Commercialization (cont . ) ▪ We may not be able to submit investigational new drug applications (“IND

  45. Slide 45: Risk factors (3 of 8)

    Risk factors (3 of 8) 45 Confidential and proprietary. Do not duplicate without permission from BridgeBio Oncology Therapeutics. Risks Related to Regulatory Approval and other Legal Compliance Matters ▪ We may be unable to obtain U . S . or foreign regulatory approval and, as a result, may be unable

  46. Slide 46: Risk factors (4 of 8)

    Risk factors (4 of 8) 46 Confidential and proprietary. Do not duplicate without permission from BridgeBio Oncology Therapeutics. Risks Related to Regulatory Approval and other Legal Compliance Matters (cont . ) ▪ Our business activities may be subject to the U . S . Foreign Corrupt Practices Act (“F

  47. Slide 47: Risk factors (5 of 8)

    Risk factors (5 of 8) 47 Confidential and proprietary. Do not duplicate without permission from BridgeBio Oncology Therapeutics. Risks Related to BBOT’s Intellectual Property ▪ Derivation proceedings may be necessary to determine priority of inventions, and an unfavorable outcome may require us to c

  48. Slide 48: Risk factors (6 of 8)

    Risk factors (6 of 8) 48 Confidential and proprietary. Do not duplicate without permission from BridgeBio Oncology Therapeutics. Risks Related to BBOT’s Dependence on Third Parties ▪ We rely on third parties to conduct our preclinical studies and clinical trials, and those third parties may not perf

  49. Slide 49: Risk factors (7 of 8)

    Risk factors (7 of 8) 49 Confidential and proprietary. Do not duplicate without permission from BridgeBio Oncology Therapeutics. Risks Related to Operating as a Public Company Following the Business Combination (cont . ) ▪ Incorrect estimates, including those related to the size of our addressable p

  50. Slide 50: Risk factors (8 of 8)

    Risk factors (8 of 8) 50 Confidential and proprietary. Do not duplicate without permission from BridgeBio Oncology Therapeutics. Risks Related to the Business Combination and Redemptions ▪ The consummation of the business combination is subject to a number of conditions, including regulatory approva

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