#1CENTESSA PHARMACEUTICALS CORPORATE OVERVIEW#2Disclaimer This material has been made available to you with the consent of Centessa Pharmaceuticals plc ("we", "us", "our", or the "Company"). We have filed a registration statement (including a preliminary prospectus) on Form S-1 (File No. 333-255393) with the Securities and Exchange Commission ("SEC") for the offering to which this presentation relates. Such registration statement has not yet become effective. The securities proposed to be offered pursuant to such registration statement may not be sold, nor may offers to buy be accepted, prior to the time the registration statement becomes effective. You should read the preliminary prospectus in such registration statement and other documents we have filed with the SEC for more complete information about us and the offering. You may get these documents for free by visiting the SEC's website at www.sec.gov.Alternatively, copies of the prospectus may be obtained from Morgan Stanley & Co. LLC, 180 Varick Street, 2nd Floor, New York, New York 10014, Attn: Prospectus Department; Goldman Sachs & Co. LLC, 200 West Street, New York, New York 10282, Attn: Prospectus Department, Telephone: 866-471-2526, Email: prospectus- [email protected]; Jefferies LLC, Attention: Equity Syndicate Prospectus Department, 520 Madison Avenue, 2nd Floor, New York, NY 10012, by telephone at 877-821-7388 or by email at prospectus [email protected]; or Evercore Group L.L.C., Attention: Equity Capital Markets, 55 East 52nd Street, 36th Floor, New York, NY 10055, or by telephone at 888-474-0200, or by email at [email protected]. This presentation shall not constitute an offer to sell or the solicitation of an offer to buy securities, nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction. Statements in this presentation that are not statements of historical fact are forward-looking statements. Such forward-looking statements include, without limitation, statements regarding our asset- centric business model and the intended advantages and benefits thereof, research and clinical development plans, the scope, progress, results and costs of developing our product candidates or any other future product candidates, strategy, regulatory matters, including the timing and likelihood of success of obtaining approvals to initiate or continue clinical trials or market any products, market size and opportunity and our ability to complete certain milestones, our use of proceeds from the offering, our financial position and cash runway. 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Such statements reflect the current views of the Company with respect to future events and are subject to known and unknown risks, including business, regulatory, economic and competitive risks, uncertainties, contingencies and assumptions about the Company, including, without limitation, risks inherent in developing products and technologies, future results from the Company's ongoing and planned clinical trials, the Company's ability to obtain adequate financing to fund its planned clinical trials and other expenses, trends in the industry, the legal and regulatory framework for the industry and future expenditures, and the other risk factors contained in the preliminary prospectus to which this offering relates. In light of these risks and uncertainties, the events or circumstances referred to in the forward-looking statements may not occur. The actual results may vary from the anticipated results and the variations may be material. These forward-looking statements should not be taken as forecasts or promises nor should they be taken as implying any indication, assurance or guarantee that the assumptions on which such forward-looking statements have been made are correct or exhaustive or, in the case of the assumptions, fully stated in this presentation. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date this presentation is given. This presentation discusses product candidates that are under clinical study and which have not yet been approved for marketing by the U.S. Food and Drug Administration. No representation is made as to the safety or effectiveness of these product candidates for the use for which such product candidates are being studied. The trademarks included herein are the property of the owners thereof and are used for reference purposes only. Such use should not be construed as an endorsement of such products. 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 make no representation as to the adequacy, fairness, accuracy or completeness of, any information obtained from third party sources. Finally, while we believe our own internal research is reliable, such research has not been verified by any independent source. CENTESSA#3Offering Summary Issuer Ticker / Exchange ADSs Issued Filing Range Estimated Gross Proceeds Over-Allotment Option Expected Pricing Use of Proceeds Lock-Up Period Bookrunners Centessa Pharmaceuticals plc CNTA / NASDAQ 15,000,000 $18 - $20 $285MM (at midpoint of price range) 15% (100% primary) Thursday, May 27th (post-close) To fund the continued development and pre-commercialization costs of our clinical-stage product candidates, to fund continued development of the other programs in our pipeline, including designing and conducting preclinical studies and clinical trials, as well as funding discovery, manufacturing, research and development; and the remainder for working capital and other general corporate purposes, as well as to fund the acquisition of, and drug development activities related to, new programs 180-day lock-up for directors, executive officers, affiliates and substantially all pre-IPO securityholders Morgan Stanley, Goldman Sachs, Jefferies, Evercore ISI XCENTESSA#4Team with Deep Experience Across VC, Biotech, and Pharma MANAGEMENT TEAM SAURABH SAHA MD PhD Chief Executive Officer Bristol Myers Squibb 6 ATLASVENTURE NOVARTIS O Delinia McKinsey&Company TIA BUSH Chief Quality Officer AMGEN ANTOINE YVER MD MSC Chief Medical Officer AstraZeneca of Schering Plough/ MERCK John John Fals - MARELLA THORELL Chief Accounting Officer realm PALLADIO Campbells EY ONF GREG WEINHOFF MD MBA Chief Financial Officer ARVELLE Amicus There AXOVANT Morgan Stanley C.CHE HEALTHCARE PARTNERS MEDIVATION THOMAS TEMPLEMAN PhD Chief Technology Officer Nuvation Blo "graybug axovant LIQUIDIA Hospira Johnwon-Johmien DAVID CHAO PhD Chief Administrative Officer BIOMED VALLEY X noctagon BIOKURO INSTITUTE NOVARTIS McKinsey&Company IQBAL HUSSAIN General Counsel Reed Smith Johnson Johnson ROPES&GRAY SLAUGHTER AND MAY CENTESSA#5The Inspiration Undiluted Program Focus Incentivization Alignment Lean & Agile Organization Clear Biological Rationale for Program Subject Matter Expertise GOAL: RE-INVENT R&D PRODUCTIVITY ASSET CENTRICITY One Program One Team XCENTESSA#6too big to parse...#7The Founding of Our Companies Janp¹H 2013 Apcintex CAPELLA BIOSCIENCE ZFactor 2014 PALLADIO BIOSCIENCES 10 00 MORPHOGEN-IX 2015 2016 LockBody 2017 Orexia Therapeutics 2018 PegaOne PearRiver 2019 2020 CENTESSA PHARMACEUTICALS 2021 CENTESSA#8IP ADDRESS. 51.89.224.65 TA and Modality Agnostic Programs with Clear Biological Rationale Palladio Biosciences ApcinteX Pega-One Z Factor Morphogen-IX ROADSHOW Capella BioScience IP ADDRESS 51.80.224.05 LockBody Orexia Therapeutics Janpix Pearl River Bio Therapeutic Area (TA) Nephrology Autosomal Dominant Polycystic Kidney Disease Hemophilia A, B Cutaneous Squamous Cell Carcinoma Alpha-1 Antitrypsin Deficiency Pulmonary Arterial Hypertension Idiopathic Pulmonary Fibrosis Systemic Sclerosis & Lupus Erythematosus Solid TumorsNTING, COPYING Narcolepsy Type 1 Acute Myeloid Leukemia NSCLC Hematology Oncology DISCOVERY Vasopressin V2 Receptor Inhibitor (Lixivaptan) Activated Protein C Inhibitor (Serpin PC) Anti-EGFR mAb (Imgatuzumab) Lead A1AT Folding Corrector (ZF874) A1AT Folding Corrector (ZF887) BMP9 Engineered Variant (MGX292) Anti-LIGHT mAb (CB5001) Anti-BDCA-2 mAb (CBS004) CD47 LockBody (LB1) CD3 LockBody (LB2) OX2R Agonist (Oral) OX2R Agonist (Intranasal) Dual-STAT3/5 Degrader EGFR-Ex20 Inhibitor EGFR-C7975 Inhibitor EGFR-Next Gen Hepatology LEAD OP/IND-ENABLING Pulmonology IS AND DISTRIBUTION OF Immunology/Inflammation CONF TIAL PHASE 1 IP ADDRESS 51.89.224.65 Neuroscience Reason to Believe in Target PHASE 2 PHASE 3 PRINTING, COPYING AND DISTRIBUTION OF ROADSHOW MATERIALS IS STRICTLY PROHIBIT Precedented Human Activity SHOW MATERIALS IS STRICTLY PROHIBIT Human Genetics 18 CENTESSA#9Programs Led by Dedicated Subject Matter Experts PALLADIO BIOSCIENCES Lorenzo Pellegrini Founder & COO Yale Capital Lock Body John Finlay Founder & CEO Pfizer Wyeth ZFactor Jim Huntington Founder & CEO UNIVERSITY OF CAMBRIDGE Takeda Orexia Therapeutics Deborah Hartman CSO Apcrex AstraZeneca Trevor Baglin Founder & CMO medic.xi Roche Jono Patrick Gunning CSO INTVERNTY OF TORONTO PegaOne Steffen Heeger CMO Selvita orphosis EMD SERONO Yale MORPHOGEN-IX Dana-Farber Cancer Instituts Nick Morrell Founder & CEO UNIVERSITY OF CAMBRIDGE Roman Thomas Co-Founder of Cologne PearRiver 100 CAPELLA BIOSCIENCE Steve Holmes Founder kymab Pro-Cure Johannes Hueckmann Co-Founder & CSO co oncology new CENTESSA#10ROADSHOW MATERIALS IS STRICTLY PROHIBITED IP ADDRESS. 51.89.224.65 Our Pipeline: Today's Focus PALLADIO BIOSCIENCIS ROADSHOW MATApcintexCTLY IP ADDRESS 51.89224.05 ZFactor OOO MORPHOGEN-IX PROGRAM Lixivaptan (Phase 3) SerpinPC (Phase 2) PROHIBITED MOA MGX292 (Lead Op/IND-Enabling) ROADSHOW MATE DEEP EXPERTISE Vasopressin V2 Receptor Antagonist PRINTING, COPYING, AND DISTR ZF874 (Phase 1) DDRESS: 51.80.224.65 MAIL [email protected] ZF887 (Lead Op/IND-enabling) Activated Protein C Inhibitor A1AT Folding Corrector BMP9 Engineered Variant Dr. Lorenzo Pellegrini Potentially more tolerable in autosomal Singly focused on lixivaptan 51. dominant polycystic kidney disease (ADPKD) EMAIL usen@ms with a differentiated profile from tolvaptan for past 6 years Dr. Trevor Baglin Lifelong hemophilia expert Dr. Jim Huntington 30 years studying the structure of Serpins PRINTING, COPY and A1AT KEY ATTRIBUTES CONF Potentially more tolerable rebalancing therapeutic that keeps clotting homeostasis intact and could be a one size fits all approach in hemophilia Potentially superior A1AT folding corrector based on structural understanding of the Z- pocket crystal structure Dr. Nick Morrell PRINTING, COPT Potentially disease modifying medicine Lifelong expert in the targeting a central causal pathway of PAH genetics of pulmonary MAIL@ms with human genetics support arterial hypertension CENTESSA 10#11Palladio Biosciences Developing lixivaptan, a Phase 3 stage vasopressin V2 receptor antagonist, as a potential best-in-class therapy for autosomal dominant polycystic kidney disease (ADPKD) Mission Develop a differentiated therapeutic for ADPKD that avoids liver safety issues requiring a REMS distribution program and with efficacy comparable to that of tolvaptan De-risking data 36 clinical studies and 1,600+ subjects dosed with lixivaptan in prior clinical program No evidence of liver toxicity during 14 months of dosing with lixivaptan in a patient with drug-induced liver toxicity while on tolvaptan PD effect of lixivaptan confirmed with dose-related suppression of urine osmolality in clinical pharmacology study of 31 ADPKD subjects PALLADIO BIOSCIENCES Market opportunity Prevalence of 140,000 patients currently diagnosed with ADPKD in US US sales of JYNARQUE (tolvaptan) of $620 million in second full-year (2020) after approval, reflecting ~5,000 patients on therapy, despite black box warning and REMS program for liver toxicity CENTESSA 11#12Lixivaptan: Potential for Best-in-Class Profile JYNARQUEⓇ (tolvaptan) REMS: Restricted distribution & prescription, frequent blood test monitoring for liver tox Initial data support thesis that lixivaptan avoids drug-induced liver injury (DILI) NON-CLINICAL EVIDENCE Tolvaptan causes DILI via 2 well-known hepatocyte injury mechanisms: disruption of bile acids homeostasis and mitochondrial dysfunction hepatocyte mitochondrion MRP4 bile salts DM-4103 tolvaptan BSEP • Long-lived metabolite of tolvaptan contributes to toxicity • Lixivaptan does not share metabolites with tolvaptan IN SILICO EVIDENCE DILISym (highly predictive quantitative systems toxicology tool) • Correctly predicted DILI potential of numerous drug pairs • Accurately reproduced liver toxicity of tolvaptan • Predicted lixivaptan not likely to cause DILI and may be better tolerated than tolvaptan with respect to liver tox Tolvaptan Lixivaptan ALT > 3x ULN DILIsym Simulated 7.9% 0.0% PALLADIO BIOSCIENCES Actual Clinical 4.4% to 5.6% Hy's Law Cases DILISym Simulated Yes No Actual Clinical Yes CENTESSA 12#13Lixivaptan: No Liver Tox Observed in Single Patient Who Experienced Liver Tox On Tolvaptan Initial experience with tolvaptan Young patient with ADPKD developed drug-induced liver toxicity (DILI) on each of three unsuccessful attempts to initiate therapy with tolvaptan Patient's response to tolvaptan shows classic signs of idiosyncratic DILI Subsequent experience with lixivaptan Same patient enrolled in compassionate use study under Palladio's IND for treatment of ADPKD Lixivaptan did not cause any signs of liver toxicity in this highly susceptible patient during 14 months of therapy Dose (mg/day) 100 80 60 40 20 0 500 400 300 200 100 0 Tolvaptan Dose 0 4 8 12 048 12 16 20 24 28 32 36 40 weeks 16 Ny N 20 Lixivaptan Dose 24 Tolvaptan Discontinued ALT 28 32 36 weeks 40 44 44 48 48 PALLADIO BIOSCIENCES 52 56 60 52 56 60 100 80 60 40 20 0 100 80 60 40 20 0 ALT (U/L) ALT (U/L) CENTESSA 13#14Lixivaptan: Phase 2 Results Support Potential in ADPKD DATA SUPPORTS POTENTIAL EFFICACY OF LIXIVAPTAN IN ADPKD • Lixivaptan treatment associated with potent, prolonged suppression of urine osmolality (Uosm), a pharmacodynamic marker of vasopressin V2 receptor inhibition, in ADPKD patients • Data from two 200 mg BID dose cohorts confirm choice of 200 mg BID as highest dose in Phase 3 Uosm (mOsm/kg) 600 AM dose 500 400 300 200 100 0 0 Time Course of Mean Spot Urine Osmolality PM dose Target: Maintain Uasm under 300 mOSM/kg 10 12 14 16 18 Time (hr) 20 22 24 Baseline Day 1 Day 7 URINE OSMOLALITY EFFECT OBSERVED TO BE SIMILAR TO TOLVAPTAN % ADPKD Subjects Meeting Target Trough Uosm <300 mOSM/kg (cross-study comparison to published results for tolvaptan) Tolvaptan (TEMPO Study) Lixivaptan (Study PA-102) 200 mg BID 50 mg BID 50% 60% 70% PALLADIO BIOSCIENCES 80% 90% CONCLUSIONS Phase 2 study achieved intended goals for lixivaptan . Demonstrated potent vasopressin V2 receptor inhibition in CKD patients • Defined highest dose for Phase 3: 200 mg BID • Defined "no effect" dose: 50 mg BID • Demonstrated similar PK profile to that in normal healthy volunteers • Observed tolerability profile consistent with previous studies 100% CENTESSA 14#15Lixivaptan: Phase 3 Pivotal Trial Design Part 1 Screening Placebo Baseline measurements x 2:1 Randomization of 1200 subjects Lixivaptan Placebo H Double-blind treatment period Primary endpoint • Annualized change in eGFR from baseline to follow-up in Part 1 No drug 52-week measurements Endpoint comparisons Part 2 Lixivaptan Lixivaptan All patients participating in Part 1 will continue to Part 2 of study Open label maintenance period (52 weeks) No drug PALLADIO BIOSCIENCES Final measurements Key secondary endpoints • Incidence of serum ALT levels 3 x ULN in participants randomized to lixivaptan compared to those randomized to placebo in Part 1 Annualized change in eGFR from baseline to follow-up in Part 2 • Annualized rate of change (slope) in eGFR, based on all eGFR determinations during the double-blind, randomized treatment period in Part 1 X CENTESSA 15#16Lixivaptan: Status and Competition STATUS & UPCOMING MILESTONES The ALERT Study The ACTION Study Mid-to-late 2021 Early-to-mid 2022 Ongoing clinical study in up to 50 ADPKD patients who previously discontinued tolvaptan due to liver toxicity • Aims to assess lixivaptan's safety profile in patient population enriched for DILI • Patient screening and recruitment underway Preparing to initiate global, pivotal Phase 3 clinical study in ADPKD patients Preliminary data from the ALERT study Start of Phase 3 pivotal clinical trial COMPETITIVE LANDSCAPE Tolvaptan, vasopressin V2 inhibitor: Marketed (Otsuka,~Sep 2026 patent expiry) Venglustat, glucosylceramide synthase inhibitor: Phase 3 (Sanofi) Bardoxolone, oral Nrf2 activator: Phase 3 (Reata Pharmaceuticals) PALLADIO BIOSCIENCES CENTESSA 16#17ApcinteX Developing SerpinPC, a Phase 2 stage specific inhibitor of activated protein C (APC) for treatment of hemophilia A & B (HA, HB) Mission Develop a monthly subcutaneous therapeutic for hemophilia A & B patients that significantly reduces bleeding rates and avoids excessive blood coagulation via inhibition of activated protein C De-risking data Coinheritance of Factor V Leiden mutation (reduced APC) with hemophilia associated with mild bleeding phenotype Single injection of SerpinPC in 12 subjects with severe hemophilia resulted in marked reduction in all bleeds, including in joint and muscle, over 8-week period Apcintex Lack of D-dimer elevation in animal species, HVs, and hemophilia patients Market opportunity Estimated global prevalence of HA and HB ~400,000 individuals ~$11 billion global hemophilia market CENTESSA 17#18SerpinPC: Potential First-in-Class Rebalancing Agent with Unique MoA MOA OVERVIEW • Supported by human genetics: coinheritance of Factor V Leiden mutation (which mimics effect of reduced APC) with severe hemophilia produces mild bleeding phenotype • Innovative pharmacology built on alpha-1- antitrypsin scaffold to produce desired PK and low immunogenicity • Designed to 'mop-up' pre-existing APC by Ecovalent mechanism thereby prolonging activity of prothrombinase formed during initiation stage of hemostasis • Designed to directly increase amount of thrombin generated at site of tissue damage . Modest rate of inhibition intended to allow newly formed APC to attenuate thrombin generation • No interaction with protein C, thereby leaving cytoprotective signaling through Endothelial Protein C receptor intact SERPINPC'S MODE OF ACTION SerpinPC- Prothrombin Intrinsic Tenase APC Prothrombinase Extrinsic Tenase Protein C Feedback Loop Thrombin Apcintex CENTESSA 18#19SerpinPC: Complete Correction of Mouse Hemophilia Phenotype Target Protease SerpinPC is the Serpin: alpha-1-antitrypsin COMPLETE RESCUE OF HA MICE BY PROLONGED EXPOSURE SerpinPC administered subcutaneously every other day prevented death of HA mice from spontaneous internal bleeding Pre-treatment with SerpinPC 12 hours before tail Mice Alive transection reduced blood loss in HA mice in a dose- dependent manner 10- 8- Bleeding Volume (ul) 6- 2- 800- €700+ 600 500+ 400- 300- 200 100- Survival SINGLE DOSE RESTORED NORMAL BLEEDING IN HEMOPHILIA MICE Vehicle 0+ 0 0.01 mg/kg 0- 0 5 10 15 20 25 30 35 40 45 50 55 60 Day Untreated HA Blood Loss 1 mg/kg 0.1 mg/kg Wild-type Blood Loss 5 SerpinPC dose (mg/kg) 10 Apcintex CENTESSA 19#20SerpinPC: Emerging Safety Data and Ability to Reduce Bleeding PHASE 1 SAD COMPLETED Healthy Volunteers SerpinPC conc. (ng/ml) 1500- n-3, SerpinPC 0.03 mg/kg SC* SPAVALANK THE n=3, SerpinPC 0.003 mg/kg IV inf 1000- n=3, SerpinPC 0.01 mg/kg IV inf FAVORABLE PK OBSERVED 500- n-3, SerpinPC 0.003 mg/kg IV inf n=3, SerpinPC 0.001 mg/kg IV inf 200 0.6mg/kg 400 Time (hours) n=3, SerpinPC 1.2 mg/kg 5C 600 n-3, Serpin PC 0.6mg/kg SC n-3, SerpinPC 0.3 mg/kg SC* Tmax 50 hours Terminal t₁/24 -5 days n-3, Serpin PC 0.1 mg/kg SC* 800 Patients with severe hemophilia EMERGING SAFETY DATA IN PHASE 1 STUDY • No SerpinPC related adverse events • No injection site reactions • No thrombosis Apcintex • No Serpin PC-related increase in cytokines • No increase in D-dimer - including following treatment of breakthrough bleeds with factor concentrate • No ADAs REDUCED BLEEDING AFTER SINGLE INJECTION During 8 weeks following single injection of SerpinPC in 12 subjects with severe hemophilia • 55% reduction in all bleeds 72% reduction in joint & muscle bleeds . 5/12 subjects had zero spontaneous bleeds All subjects requested enrollment in Phase 2a multiple dose study CENTESSA 20#21SerpinPC: Status and Competition STATUS & UPCOMING MILESTONES Phase 2a multiple repeat dose study ongoing Early-to-mid 2021 Mid-to-late 2021 Mid-to-late 2022 • 6mo study of monthly subq dosing of SerpinPC at 3 dose levels in severe HA & HB +/-inhibitors patients • 23 subjects enrolled • Primary Objective: Safety and tolerability of SerpinPC • Secondary Objective: Assess pharmacokinetics of SerpinPC • Exploratory Objective: Explore effect of SerpinPC on annualized bleeding rate (ABR) and factor usage Start of 48-week open label extension study Data from 24-week Phase 2a multiple repeat dose study Data from 12-month open label extension study COMPETITIVE LANDSCAPE Emicizumab, recombinant, bispecific mAb treatment ~HA: Marketed (Roche) Concizumab, anti-TFPI mAb ~HB: Phase 3 (Novo Nordisk) Fitusiran, siRNA therapy "HB: Phase 3 (Sanofi) Valoctocogene roxaparvovec, AAV-FVIII gene therapy ~HA: Phase 3 (BioMarin) Fidanacogene elaparvovec, AAV-FIX gene therapy ~HB: Phase 3 (Pfizer / Spark) Apcintex CENTESSA 21#22Z Factor Developing Phase 1 and preclinical stage folding correctors for Z-variant of alpha-1-antitrypsin (A1AT), to treat both liver and lung disease manifestations of A1AT deficiency Mission Develop a potent and specific catalytic folding corrector of Z-A1AT to increase serum levels and reduce liver burden to treat liver and lung disease manifestations of A1AT deficiency De-risking data ZF874 increased levels of active Z-A1AT in the blood and improved markers of liver pathology in Piz mice Seven cohorts of healthy volunteers successfully dosed up to 50mg/kg of ZF874 with excellent oral bioavailability and all doses well tolerated except for transient apparent Cmax effect at 50mg/kg in fasted state ZFactor Market opportunity Estimated prevalence of 200,000 Pizz individuals worldwide PiMZ prevalence of 42.4 million individuals and observed in large subset of COPD and NASH populations CENTESSA 22#23ZF874: Increased Plasma Levels of Z-A1AT, Reduced Liver Accumulation and Pathology in PiZ Mice DOSED IN DRINKING WATER FOR 28 DAYS Z-A1AT levels were increasing at end of treatment day 28 8mg/ml %change from baseline 200- % change from baseline 12 16 20 Day Fold change relative to vehicle on day 28 7.6x 600- 500- 400- 300- 200- 100- 0- Vehicle 4.9x 2 mg/ml 6.4x 4 mg/ml 2 mg Vehicle 8 mg/ml DOSED IN CHOW FOR 12 WEEKS Z-A1AT Polymer Accumulation in Piz mice PAS-D (% Area Staining) 25 19 13 6 D Marker of Liver Damage ALT Activity (U/L) 30 15 8 D Vehicle Observed 7.6x increase falls in range of predicted 7 to 10x required for full correction ZF874 Vehicle ZFR74 Vehicle 2F874 WT Mice PIZ Mice Z-A1AT Polymer Accumulation (PAS-D Staining of Liver Sections) vehicle ZF874 Marker of Liver Fibrosis in Piz mice Sirius Red (% Fibrosis) 2 20 Marker of Liver Inflammation Normalised TIMP-1 Levels 40 30 10 Vehicle D ZFactor ZF874 ZF874 reduced formation of new Z-A1AT polymers and associated with natural liver clearance mechanisms to remove existing polymers Vehicle 2F874 Vehicle 2F874 WT Mice PIZ Mice CENTESSA 23#24ZF874: Status and Competition STATUS & UPCOMING MILESTONES Phase 1 study ongoing • Single ascending dose study in 7 cohorts of healthy volunteers (Part A) • 28 days of BID dosing in subjects with at least one Z allele (PiXZ) subjects (Part B) • Seven cohorts of healthy volunteers successfully dosed up to 50mg/kg fasted • All doses well-tolerated, except for a transient apparent Cmax effect at 50mg/kg in the fasted state, similar to what was observed in the dog at doses above 100mg/kg • 50mg/kg was well-tolerated when given as 25mg/kg bid (12-hour interval) • PK is consistent with expectations, with excellent oral availability and a ~4- hour half-life • Food effect decreases rate of absorption, but not AUC • Exposure in humans is 7-times greater than in mice, so a dose ~7mg/kg/day Mid-to-late 2021 Mid-to-late 2021 in humans is expected to have a similar effect to the dose of 50mg/kg/day in the PIZ mouse on plasma levels of Z-A1AT and liver burden Up to 14 subjects with at least one Z allele (PiXZ) are being recruited for Part B (2 placebos) Data from 28-day repeat dosing study in PiXZ subjects (Phase 1, Part B) US IND Filing COMPETITIVE LANDSCAPE VX-864, Z-A1AT folding corrector: Phase 2 (Vertex Pharmaceuticals) ~ exp readout Q2 2021 ~ ARO-AAT, RNAi therapy for knockdown of Z-A1AT: Phase 2 (Arrowhead/Takeda) Belcesiran, RNAi therapy for knockdown of Z-A1AT: Early clinical trials (Dicerna) ALN-AATO2, RNAi therapy for knockdown of Z-A1AT: Early clinical trials (Alnylam) ZFactor CENTESSA 24#25Morphogen-IX Developing MGX292, a preclinical stage disease-modifying, protein-engineered variant of human bone morphogenetic protein 9 (BMP9), targeting the central causal pathway of pulmonary arterial hypertension (PAH) Mission Develop a disease-modifying, protein- engineered variant of human BMP9 that is designed to overcome deficiency in BMP9 signaling, reverse disease pathology, and avoid undesired bone formation for patients with PAH De-risking data 75% of patients with a family history of PAH have heterozygous loss-of-function mutations in the bone morphogenetic protein type 2 receptor (BMPR2) 000 MORPHOGEN-IX Mutations in BMPR2 are found in 15% to 40% of patients with idiopathic PAH Market opportunity ~70,000 patients in North America, Europe and Japan affected by PAH The total global market for PAH is ~$6.0 billion per annum based on sales of approved drugs CENTESSA 25#26MGX292: Key Data Lacks Osteogenic Activity In Vivo Ectopic bone BMP2 Mouse hind limb X-rays BMP9 Ectopic bone Vs. 000 MORPHOGEN-IX MGX292 Intramuscular cardiotoxin and BMP (10µg) in matrigel; assessment at 2 weeks BMP2 is positive control XCENTESSA 26#27MGX292: Key Data 200 MORPHOGEN-IX MGX292 reverses vascular lesions in rat Sugen-hypoxia model of Pulmonary Arterial Hypertension (PAH) Normal rat lung Sugen-hypoxia (7 weeks) Vascular lesions typical of PAH MGX292 Treatment 30 µg/kg (4 weeks) Disease reversal CENTESSA 27#28MGX292: Status and Competition STATUS & UPCOMING MILESTONES MGX292 is currently in preclinical development Mid-to-late 2022 US IND Filing COMPETITIVE LANDSCAPE 000 MORPHOGEN-IX Sotatercept, a ligand trap with high selectivity for multiple proteins within the TGF-B superfamily: Phase 3 (Acceleron Pharma) KER-012, a protein therapeutic designed to bind to and inhibit the signaling of TGF-B ligands: Preclinical development (Keros Therapeutics) CENTESSA 28#29Our Pipeline: Other Programs PegaOne Janp¹H CAPELLA BION Orexia Therapeutics LockBody PearRiver PROGRAM Imgatuzumab STAT3/5 Degrader CB5001 CBS004 OX2R Agonists.com Oral/Intranasal CD47 LB1 CD3 LB2 Exon20 C7975 NextGen MoA Anti-EGFR mAb Dual-STAT3/5 Degrader Anti-LIGHT mAb Anti-BDCA-2 mAb WODOX2R Agonist CD47 Bi-specific CD3 Bi-specific EGFR-EX20 Inhibitor EGFR-C797S Inhibitor EGFR Inhibitor DEEP EXPERTISE Dr. Steffen Heeger Physician deeply involved in the development of Imclone's anti- EGFR mAb cetuximab Dr. Patrick Gunning 15+ years experience in STAT structural understanding, deep biochemistry knowledge Dr. Steve Holmes 30+ years experience in development of mAb therapeutics (Domantis, GSK) Dr. Deborah Hartman Deep experience in orexin drug development (Takeda) Dr. John Finlay 20+ years experience in biopharmaceutical discovery and development (Pfizer, Wyeth) Dr. Roman Thomas Has worked on the genetics and biology of lung cancer for more than 15 years KEY ATTRIBUTES Next generation anti-EGFR mAb treatment for CSCC with enhanced Fc-receptor based immune effector activity with potential synergy with immunotherapies Covalent binding non-PROTAC small molecule degrader of STAT3 and STAT5 for hematological malignancies High potency mAbs designed to treat chronic progressive inflammatory disease Deep structure resolution-based design of orexin receptor agonists for oral or intranasal delivery Efficient targeting and local-only release of highly active immune modulating anti-CD47 and anti-CD3 therapeutics Structural insights into Ex20 mutations Novel mode of action to potentially address Osimertinib resistance mutations (C7975) CENTESSA 29#30ROADSHOW MATERIALS IS STRICTLY PROHIBITED IP ADDRESS. 51.89.224.65 2021 Expected Milestones Data Readouts ApcinteX Phase 2a repeat dose study OF ROADSHOW MATERIALS IS STRICTLY PROHIBITED P ADDRESS 51,80Z Factor Phase 1 study Palladio Biosciences.com Alert study (Rolling) Study Initiations ApcinteX 48-week OLE study PRINTING, COPYING, AND DISTRIBUTION OF ROADSHOW MATERIALS IS STRICTLY PROHIBITED IP ADDRESS: 51.89.224.65 Pega-One Phase 2 study Z Factor US IND COPYING, AND DISTRIBUTION OF 51.89.224.65 CONF IP ADDRESS: 51.69.224.65 IP ADDRESS 51.89.224.65 Pre-clinical Progress PRINTING, COPYING AND DISTRIBUTION OF ROADSHOW MATERIALS IS STRICTLY PROHIBIT Janpix Candidate Selection.com Pearl River Bio Candidate Selection CENTESSA 3:0#31IPO Use of Proceeds: $285m offering Gross Proceeds of $285m, together with existing cash and cash equivalents², expected to fund Centessa's programs and working capital needs through mid-2023 assuming no attrition, no partnering proceeds and no new acquisitions 1. 2. Clinical Stage Subsidiaries Preclinical Stage Subsidiaries Working Capital & General Corporate Purposes Spend is net of expected UK R&D tax credits reimbursed in cash March 31" Cash and Cash Equivalents balance is $298.6m 3. Non-exhaustive Spend ¹ $110m $60m $45m $50m $200m Remainder . Use of Proceeds³ Continuation of Phase 3 safety study (ALERT) for lixivaptan, initiation of a Phase 3 pivotal trial (ACTION) Initiation of Phase 2 clinical trials for imgatuzumab Completion of ongoing Phase 1 for ZF874 and initiation of future clinical studies for ZF874; IND enabling studies and initiation of Phase 1 for ZF877 Completion of ongoing Phase 2a clinical trial, initiation of future clinical trials for SerpinPC Fund continued development of the other programs in our pipeline, including designing and conducting preclinical studies and clinical trials, as well as funding discovery, manufacturing, research and development; Working capital, and other general corporate purposes Build out and ongoing staffing and systems expenses related to our centralized operational and R&D support functions and the integration of operations at the Centessa Subsidiaries into our larger organization CENTESSA 31#32Committed Investors & Board Support Backed by a broad array of healthcare-dedicated investors and fundamentally-driven mutual funds medicxi U.S.-based, healthcare-focused fund venrock FRANKLIN TEMPLETON INVESTMENTS BOARD OF DIRECTORS Francesco De Rubertis Board Chairman; Partner, Medicxi Saurabh Saha Chief Executive Officer, Centessa Samarth Kulkarni CEO, CRISPR Therapeutics GENERAL ATLANTIC BOXER CAPITAL TAVISTOCK GROUP WELLINGTON MANAGEMENT® LOGOS CAPITAL Mary Lynne Hedley Former President & COO, Tesaro Brett Zbar Managing Director, General Atlantic VIDA ventures T.Rowe Price BVF PARTNERS LP SAMSARA BIOCAPITAL Arjun Goyal Partner, Vida Ventures Robert Califf Janus Henderson Former Commissioner, U.S. Food & Drug Admin. INVESTORS CORMORANT ASSET MANAGEMENT EcoR1 CAPITAL LIFESCI VENTURE PARTNERS Carol Stuckley Former CFO, Galderma North America Aaron Kantoff Venture Partner, Medicxi CENTESSA 32#33Key Investment Highlights Team: Management team with deep experience developing breakthrough medicines who partner with entrepreneurs offering subject matter expertise 33 Assets: Diversified portfolio of 16 high-conviction uncorrelated programs with potential for biotech-like upside and pharma-like risk profile R&D Model: Combines asset centricity with benefits of scale designed to enable agile and fit-for-purpose research and development Strong Investor Support: Backed by a broad and high-quality group of investors who believe in the vision for our reimagined R&D model Optionality: Evergreen pipeline potentially offers multiple paths to long-term value creation and enhanced shareholder returns CENTESSA 33