January 2024 Corporate Overview

This presentation has been prepared by Centessa Pharmaceuticals plc (the “Company”) for informational purposes only and not for any other purpose. This presentation does not contain all the information that is or may be material to investors or potential investors and should not be considered as advice or a recommendation to investors or potential investors in respect of the holding, purchasing or selling of securities or other financial instruments and does not take into account any investor’s particular objectives, financial situation or needs. The communication of this presentation may be restricted by law; it is not intended for distribution to, or use by any person in, any jurisdiction where such distribution or use would be contrary to local law or regulation. 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Our Mission: Discovering and developing medicines that are transformational for patients 3 Multiple potential blockbuster assets Strong momentum entering 2024 with clinical milestones anticipated across our most advanced programs Strong balance sheet

4 Our Most Advanced Potential First-in-Class/Best-in-Class Medicines for Patients ASSET DISEASE MECHANISM PRE- CLINICAL PHASE 1 PHASE 2 REGISTRATIONAL SerpinPC Hemophilia B Activated Protein C Inhibitor ORX750 Narcolepsy Type 1 (NT1) and other sleep disorders Orexin Receptor-2 (OX2R) Agonist LB101 Solid Tumors PD-L1xCD47 LockBody®

5 Executed and Delivered in 2023 ACHIEVED MILESTONES Entered and closed 2023 with strong balance sheet Cleared IND for LB101 (PD-L1xCD47 LockBody) Initiated Phase 1/2a LB101 clinical trial Named ORX750 orexin agonist dev candidate Presented ORX750 preclinical profile at World Sleep Initiated dosing in registrational studies for SerpinPC Granted Fast Track Designation for SerpinPC Shared SerpinPC Phase 2a data at ASH

6 2024 Driving Momentum ANTICIPATED MILESTONES LOCKBODY TECHNOLOGY PLATFORM LB101 Phase 1/2 study ongoing OREXIN AGONIST PROGRAM ORX750 Clinical POC data in healthy volunteers expected in 2024 HEMOPHILIA PROGRAM SerpinPC Registrational study interim analysis expected in 2024

7 Hemophilia Program LockBody Technology Platform Orexin Agonist Program

8 Hemophilia B: Large Growing Market with Unmet Need 1. Evaluate Pharma Analyst Consensus for 2023. 2. In Canada, a subcutaneous option is available for hemophilia B with inhibitors. A safe, subcutaneous and effective treatment has the potential to transform care for hemophilia B No subcutaneous treatment option currently available for hemophilia B in the US2 Limited options for hemophilia B with inhibitors2 ~$2.6B+ Hemophilia B Market1

9 SerpinPC has the potential to be a first-in-class subcutaneous therapy with a differentiated safety profile for people with hemophilia B1 Novel mechanism of action Achieved 96% reduction in median all- bleeds ABR1 Shown to have a favorable safety profile; No thrombosis observed1 SerpinPC is an investigational serine protease inhibitor (SERPIN) engineered to specifically inhibit activated protein C (APC), that has not been approved by the FDA or any other regulatory authority. ABR is annualized bleed rate. 1. Ongoing Phase 2a Study being conducted in Georgia and Moldova to evaluate safety, tolerability, pharmacokinetics and efficacy of SerpinPC in a population of severe hemophilia A and B subjects not on previous prophylaxis and with a history of frequent bleeding. Part 5: Blood (2023) 142 (Supplement 1): 2619. https://doi.org/10.1182/blood-2023-179969. Part 3-4: Blood (2022) 140 (Supplement 1): 460–461. https://doi.org/10.1182/blood-2022-159631. Additional information on the trial can be accessed at www.clinicaltrials.gov (NCT04073498).

SerpinPC Designed to reduce levels of circulating activated protein C (APC) SerpinPC: Novel Approach to Prevent and Reduce Bleeding 10 Pr ot hr om bi na se

96% Reduction in Median Annualized Bleeding Rate (ABR) Observed with SerpinPC in Phase 2a Study Efficacy Source: Phase 2a study data of SerpinPC from Part 5 (n=20). (Part 5: Blood (2023) 142 (Supplement 1): 2619. https://doi.org/10.1182/blood-2023-179969.) Part 5 dosing: 1.2 mpk of SerpinPC administered subcutaneously once every 2 weeks for 52 weeks.) 35.6 1.0 96% On SerpinPC treatmentBaseline 11

SerpinPC Potential for Differentiated Safety ProfileSafety No observed thrombotic events or treatment- related sustained elevations of D-dimer to-date Source: Phase 2a study data of SerpinPC. Part 5: Blood (2023) 142 (Supplement 1): 2619. https://doi.org/10.1182/blood-2023-179969. Part 3-4: Blood (2022) 140 (Supplement 1): 460– 461. https://doi.org/10.1182/blood-2022-159631. 12

SerpinPC Ongoing Global Registrational Studies for Hemophilia B Hemophilia B with inhibitors (n ≥ 12) Hemophilia B without inhibitors (n = 120) 77 SITES 20 COUNTRIESPrimary Endpoint: ABR at 24 weeks ABR is annualized bleeding rate. Primary endpoint is the rate of treated bleeds (expressed as ABR) in the observation period and during the first 24 weeks with SerpinPC. Interim Analysis for Part 1 of PRESent -2 Study expected in 2024. Additional information on the registrational program can be accessed at www.clinicaltrials.gov (NCT05605678, NCT05789524, NCT05789537). Primary Endpoint: ABR at 24 weeks 13

14 Potential Multi-Billion Dollar Market Opportunities Hemophilia A Rare Bleeding Disorders (RBD) SerpinPC Hemophilia B without inhibitors Hemophilia B with inhibitors Hemophilia A and RBD REPRESENT SIGNIFICANT EXPANSION OPPORTUNITIES Evaluate Pharma Analyst Consensus for 2023.

15 Hemophilia Program LockBody Technology Platform Orexin Agonist Program

Orexin agonists have the potential to transform standard of care for individuals with sleep-wake disorders 16

ORX750 Highly potent, selective orexin receptor type 2 agonist Designed to restore orexinergic neurotransmission MOA 17

18 ORX750 a Potential Best-in-Class Oral OX2R Agonist for the Treatment of Narcolepsy and Other Sleep-Wake Disorders Preclinical data support potential expansion into broader sleep-wake disorders, including narcolepsy type 2 and idiopathic hypersomnia1 1. ORX750 preclinical data presentation at World Sleep Congress, Oct. 25, 2023. https://investors.centessa.com/static-files/7377defd-f7b4-49fe-8806-e86c31e8e5de Highly potent, selective, novel OX2R agonist that closely mimics function of endogenous peptide1 Achieved maximal wake times and cataplexy suppression in highly predictive, translational narcolepsy type 1 mouse models1

Wakefulness Latency to Cataplexy Maximal effect Maximal effect ORX750 (mg/kg, p.o.) ORX750 Increased Wakefulness and Suppressed Cataplexy in NT1 Mice NT1 is Narcolepsy Type 1. % of Time Awake refers to time spent awake in the first 3 hours after oral dosing. ORX750 preclinical data presentation at World Sleep Congress, Oct. 25, 2023. NT1 model shown is orexin/tTA;tetO diphtheria toxin fragment A (DTA) mice. Age at first dose 23-27 wks (7 wks after removal of doxycycline chow); 16 males used; EEG, EMG recorded using intraperitonially implanted telemeters with video and manually scored in 10-sec epochs; dosing at start of dark period (active phase). *For all doses p < 0.05 vs. 0 mg/kg, Holm-Sidak multiple comparisons test following repeated-measures analysis of variance in counterbalanced design. ORX750 (mg/kg, p.o.) Efficacy 19

20 Potential Multi-Billion Dollar Market Opportunities Narcolepsy Type 1 Narcolepsy Type 2 Idiopathic hypersomnia Excessive daytime sleepiness (EDS) in common disorders ORX750 & Follow Up Orexin Agonists Evaluate Pharma Analyst Consensus for 2023.

ORX750 Clinical POC data in healthy volunteers expected in 2024 21

22 Hemophilia Program LockBody Technology Platform Orexin Agonist Program

23 LockBody Technology Platform aims to redefine immuno-oncology treatment Novel pharmacology combining tumor enrichment with activation of effector function Designed as single agent systemic treatment Potential wide therapeutic index1 LB101 is an investigational agent that has not been approved by the FDA or any other regulatory authority. Information on the Phase 1/2a trial of LB101 can be accessed at www.clinicaltrials.gov (NCT05821777). 1. LB101 in-vivo preclinical data: MC38 hPD-L1+ syngeneic model in mouse, and in non-human primates where LB101 was delivered IV at 5, 20, 50mg/kg (q7d x 4).

Locked Configuration MOA LockBody LB101 Conditionally tetravalent PD-L1xCD47 bispecific monoclonal antibody 24

Unlocked Configuration LockBody LB101 Conditionally tetravalent PD-L1xCD47 bispecific monoclonal antibody MOA 25

Significant Tumor Regression Observed In-Vivo with LB101Efficacy Source: In vivo- 5 mg/kg of atezolizumab is equivalent to 8.5 mg/kg of LB101. Data presented at ASCO in June 2022. https://investors.centessa.com/static-files/2f9bffb4-97a6-4320-8885- 70f12aa4d036. MC38 hPD-L1+ syngeneic model in mouse. Triangles indicate dosing schedule. 26

Observed to be Well Tolerated in Non-Human Primates (NHPs) with LB101 Doses up to 50mg/kg Safety Source: In-vivo- LB101 delivered IV at 5, 20, 50mg/kg (q7d x 4) in non-human primates. No anemia/ thrombocytopenia No weight loss No change in red blood cell or hemoglobin 27

Dosing subjects in ongoing Phase 1/2a first-in-human clinical trial of LB101 28

2024 Driving Momentum ANTICIPATED MILESTONES LOCKBODY TECHNOLOGY PLATFORM LB101 Phase 1/2 study ongoing OREXIN AGONIST PROGRAM ORX750 Clinical POC data in healthy volunteers expected in 2024 HEMOPHILIA PROGRAM SerpinPC Registrational study interim analysis expected in 2024 29

Our Mission: Discovering and developing medicines that are transformational for patients Multiple potential blockbuster assets Strong momentum entering 2024 with clinical milestones anticipated across our most advanced programs Strong balance sheet 30