Imgatuzumab

~ Announced positive topline data from proof-of-concept study of SerpinPC in severe hemophilia A and B subjects not on prophylaxis, demonstrating 88% reduction in median Annualized Bleeding Rate (“ABR”) for all bleeds and 94% reduction in median ABR for spontaneous joint bleeds in highest dose tested ~ ~ Announced proof-of-mechanism data from first three PiMZ subjects dosed in Phase 1 Part B study evaluating ZF874 for the treatment of Alpha-1 Antitrypsin Deficiency (“AATD”) ~ ~ Announced collaboration between Orexia Therapeutics and Schrödinger to discover novel orexin receptor agonists ~ ~ Successful entry into a $300 million financing facility with Oberland Capital to enable further scale-up of development activities and pursuit of strategic business development opportunities ~ ~ Centessa leadership team strengthened through appointment of David Grainger, PhD, a leading biotech entrepreneur, as Chief Innovation Officer ~ ~ Programs across Centessa portfolio continue to progress, with multiple INDs/CTAs expected in 2022 ~ BOSTON and LONDON, Nov. 15, 2021 (GLOBE NEWSWIRE) -- Centessa Pharmaceuticals plc (Nasdaq: CNTA), a clinical-stage company (“Centessa” or “Company”) leveraging its innovative asset-centric business model to discover, develop and ultimately deliver impactful medicines to patients, today reported financial results for the quarter ended September 30, 2021, and provided a review of recent accomplishments and anticipated upcoming milestones. “This has been a very productive quarter, as we continued to build our team and shared the first two data updates since the formation of Centessa earlier this year. We announced positive topline data from our proof-of-concept study evaluating SerpinPC in severe hemophilia subjects and seek to move this program into registrational studies in 2022. More recently, in our Phase 1 Part B study evaluating ZF874 for the treatment of AATD, we reported encouraging proof-of-mechanism data from three initial PiMZ subjects and plan to provide an update in 2022 once we have data on PiZZ subjects at multiple doses. In addition to these exciting early results, we are continuing to progress programs across our entire portfolio,” said Saurabh Saha, MD, PhD, Chief Executive Officer of Centessa. Dr. Saha continued, “Our recent $300 million financing facility with Oberland Capital will provide additional financial flexibility to help further advance our portfolio and better enable the Company to pursue strategic business development opportunities.” Recent Business Highlights Announced Positive Topline Data from Proof-of-Concept Study of SerpinPC in Severe Hemophilia A and B Subjects Not on Prophylaxis: In September, the Company, together with subsidiary ApcinteX Limited (“ApcinteX”), announced positive topline results from the Phase 2a part of AP-0101, the six-month repeat dose portion of the ongoing first-in-human proof-of-concept study evaluating SerpinPC in severe hemophilia A and B subjects. In the highest dose cohort, SerpinPC reduced the self-reported all bleeds Annualized Bleeding Rate (“ABR”) by 88% during the last 12 weeks of treatment (pre-specified primary assessment period) as compared to the all bleeds ABR prospectively measured during the pre-exposure observation period. In this cohort, five out of eight subjects had zero or one bleed during the 12-week pre-specified primary assessment period and self-reported spontaneous joint bleeds ABR was reduced by 94%. SerpinPC was well-tolerated with no sustained elevations in D-dimer. Demonstrated Proof-of-Mechanism in First Three PiMZ Subjects Dosed in Part B of Phase 1 Study Evaluating ZF874: In November, the Company, together with subsidiary Z Factor Limited (“Z Factor”), announced proof-of-mechanism data from the first three PiMZ subjects dosed in the ongoing repeat dose Phase 1 Part B study of ZF874 in subjects carrying at least one Z-mutated alpha-1-antitrypsin allele (PiXZ). These are the first clinical data that suggest a pharmacological chaperone may be able to sufficiently increase functional Z-A1AT to levels greater than 11 micromolar in individuals with the PiZZ genotype, levels that have been the basis for approval of the existing A1AT augmentation therapies. Because one subject showed a delayed, reversible increase in ALT and AST, the Company will be exploring lower doses and different dosing regimens. The Company is taking steps to increase enrollment by adding sites in the United Kingdom and intends to expand the study to the European Union. Secured $300 Million Financing Facility with Oberland Capital Management LLC: In October, the Company entered into a $300 million financing facility (“Oberland Agreement”). Under the terms of the agreement, Oberland Capital Management LLC (“Oberland Capital”) will purchase up to $300 million of 6-year, interest-only, senior secured notes from the Company, including $75 million funded in October, a total of $125 million available within 24 months at the option of the Company, and $100 million available to fund M&A, in-licensing, or other strategic transactions, at the option of the Company and Oberland Capital. The Company’s pro forma cash position as of September 30, 2021, following receipt of the net proceeds from the first tranche of notes in October, was $653.4 million. Centessa Subsidiary, Orexia Therapeutics, Initiated Collaboration with Schrödinger to Discover Novel Orexin Receptor Agonists: In October, Orexia entered into an exclusive collaboration with Schrödinger focused on the discovery of novel therapeutics targeting the orexin-2 receptor (“OX2R”), which is known to play a role in a broad spectrum of sleep disorders including narcolepsy. The collaboration provides Orexia with substantial access to Schrödinger’s entire computational platform as well as Schrödinger’s extensive expertise in ultra-large-scale deployment of its technology. Leadership Team Strengthened by Appointment of Chief Innovation Officer: In October, the Company announced the appointment of David Grainger, PhD, as Chief Innovation Officer. Dr. Grainger will be a member of the Company’s executive leadership team and will be responsible for the overall management of the scientific and research activities. Upcoming Milestones ApcinteX’s SerpinPC, an activated protein C inhibitor for Hemophilia: During 2022, the Company expects to launch a global full development plan aimed at one or more registrations to maximize the broad potential for SerpinPC in the hemophilia space. The Company also expects to provide an update in 2022 on the ongoing Phase 2a open-label extension study. Palladio Biosciences’ lixivaptan, a vasopressin V2 receptor antagonist for Autosomal Dominant Polycystic Kidney Disease (“ADPKD”): By the end of 2021, the Company expects to report initial safety data from the ongoing open-label ALERT Study of subjects who previously discontinued JYNARQUE® (tolvaptan) due to liver toxicity. The Company expects to dose the first subject in the registrational Phase 3 ACTION Study by 1Q 2022. Z Factor’s ZF874, a Z-A1AT folding corrector for AATD: During 2022, the Company expects to report on additional PiMZ as well as PiZZ subjects from the expanded Phase 1 Part B. The Company anticipates starting a global Phase 2 study in 2Q 2022, with 6-month dosing to commence in 2H 2022 once a dose and regimen are established and chronic animal toxicology is completed. Pega-One’s imgatuzumab, a non-fucosylated anti-epidermal growth factor receptor (“EGFR”) monoclonal antibody (“mAb”) for Advanced Cutaneous Squamous Cell Carcinoma (“CSCC”): The Company expects to initiate an open-label, single arm, Phase 2 trial of imgatuzumab in advanced CSCC by the end of 2021 and dose the first subject in 1Q 2022. Capella Bioscience’s CBS001, an anti-LIGHT mAb for Idiopathic Pulmonary Fibrosis (“IPF”): In 1H 2022, the Company expects to submit a Clinical Trial Authorisation (“CTA”) application with the UK Medicines and Healthcare products Regulatory Agency (“MHRA”) for CBS001 and commence a Phase 1 study shortly thereafter. Capella Bioscience’s CBS004, an anti-BDCA2 mAb for Systemic & Cutaneous Lupus Erythematosus (“SLE/CLE”) and Systemic Sclerosis (“SSc”): In 2H 2022, the Company expects to submit an Investigational New Drug (“IND”) application with the U.S. Food and Drug Administration (“FDA”) for CBS004 and commence a Phase 1 study shortly thereafter. Orexia Therapeutics’ oral orexin receptor agonist for Narcolepsy Type 1 (“NT1”), and other neurological disorders characterized by excessive daytime sleepiness: The Company is on track to select a candidate for its oral program and commence IND enabling activities in 2022. Janpix Limited’s dual degrader of Signal Transducer and Activator of Transcription proteins 3 and 5 (“STAT3” and “STAT5”) for Acute Myeloid Leukemia: By the end of 2021, the Company expects to select a candidate for the STAT3/5 program. PearlRiver Bio’s small molecule kinase inhibitors for EGFR mutations in Non-Small Cell Lung Cancer (“NSCLC”): The Company is progressing an EGFR-C797S mutation inhibitor for the treatment of NSCLC and expects to report on ongoing candidate selection in 2022. The Company will not select a candidate for its exon20 mutation program in 2021 and is presently reviewing this program. Third Quarter 2021 Financial Results Cash Position: Cash and cash equivalents were $578.8 million as of September 30, 2021, compared to $613.8 million as of June 30, 2021, a reduction of $35 million. On a pro forma basis as of September 30, 2021, cash and cash equivalents were $653.4 million, inclusive of the net proceeds of $74.6 million from the first tranche received under the Oberland Agreement on October 4, 2021. Based on the current, non-risk-adjusted operating plan, the Company expects the cash and cash equivalents as of September 30, 2021, plus the net proceeds of the first tranche, supplemented by the additional funds available under the Oberland Agreement, if drawn, to fund its operations into mid-2024. Research & Development (“R&D”) Expenses: R&D expenses for the Company for the three months ended September 30, 2021, were $25.9 million, compared to $1.9 million for the Centessa Predecessor Group (comprised of Z Factor Limited, LockBody Therapeutics Ltd, and Morphogen-IX Limited, three of the Centessa Subsidiaries acquired in January 2021) for the three months ended September 30, 2020. The $23.9 million increase is primarily attributable to the growth in the portfolio of product candidates under development following the acquisition of the Centessa Subsidiaries in January 2021, as well as increased spending in the Centessa Predecessor Group. General & Administrative (“G&A”) Expenses: G&A expenses for the Company for the three months ended September 30, 2021, were $12.5 million, compared to $0.2 million for the Centessa Predecessor Group during the three months ended September 30, 2020. The $12.2 million increase is primarily attributable to public company costs, the operating costs of Centessa Pharmaceuticals plc and Centessa Pharmaceutical Inc., including professional fees and personnel costs, and the increase in operating costs resulting from the acquired Centessa subsidiaries. In addition, the increase in personnel related expenses includes an increase in headcount and an increase in share-based compensation expense of $2.6 million which is primarily attributable to the equity awards issued at the time of the acquisition and the subsequent issuances of awards through September 30, 2021. Net Loss: Net Loss attributable to common stockholders for the quarter ended September 30, 2021, was $40.2 million, or $0.45 per share, compared to a net loss of $2.1 million for the Centessa Predecessor Group for the quarter ended September 30, 2020. About Centessa Pharmaceuticals Centessa Pharmaceuticals plc aims to bring impactful new medicines to patients by combining the strengths of an asset-centric model with the benefits of scale and diversification typical of larger R&D organizations. The asset-centric model refers to a highly specialized, singular-focused company that is led by a team of well-recognized subject matter experts. Centessa’s asset-centric companies’ programs range from discovery-stage to late-stage development and include diverse therapeutic areas such as oncology, hematology, immunology/inflammation, neuroscience, hepatology, pulmonology and nephrology. For more information, visit . Forward Looking Statements This press release contains forward-looking statements. These statements may be identified by words such as “aims,” “anticipates,” “believes,” “could,” “estimates,” “expects,” “forecasts,” “goal,” “intends,” “may,” “plans,” “possible,” “potential,” “seeks,” “will,” and variations of these words or similar expressions that are intended to identify forward-looking statements. Any such statements in this press release that are not statements of historical fact may be deemed to be forward-looking statements including statements related to the Company’s ability to deliver impactful medicines to patients; the ability of our key executives to drive execution of the Company’s portfolio of programs; 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; our collaborations and the intended benefits thereof; 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; our ability to complete certain milestones; the availability of funding to operate our business and pursue our objectives; and our cash position and runway. Any forward-looking statements in this press release are based on our current expectations, estimates and projections only as of the date of this release and are subject to a number of risks and uncertainties that could cause actual results to differ materially and adversely from those set forth in or implied by such forward-looking statements. These risks and uncertainties include, but are not limited to, risks related to our ability to protect and maintain our intellectual property position; business, regulatory, economic and competitive risks, uncertainties, contingencies and assumptions about the Company; risks inherent in developing products and technologies; future results from our ongoing and planned clinical trials; our ability to obtain adequate financing, including through our financing facility with Oberland, to fund our planned clinical trials and other expenses; trends in the industry; the legal and regulatory framework for the industry, including the receipt and maintenance of clearances to conduct or continue clinical testing; future expenditures risks related to our asset-centric corporate model; the risk that any one or more of our product candidates will not be successfully developed and commercialized; the risk that the results of preclinical studies or clinical studies will not be predictive of future results in connection with future studies; and risks related to the COVID-19 pandemic including the effects of the Delta and any other variants. These and other risks concerning our programs and operations are described in additional detail in our reports that we the SEC. We explicitly disclaim any obligation to update any forward-looking statements except to the extent required by law. Contacts: Investors: Jennifer Porcelli, Head of Investor Relations Centessa Pharmaceuticals Jennifer.Porcelli@centessa.com Media: Dan Budwick, 1AB dan@1abmedia.com Centessa Pharmaceuticals plc (Successor) and Centessa Predecessor Group (Predecessor) Consolidated and Combined Statements of Operations and Comprehensive Loss (unaudited) (amounts in thousands except share and per share data) Successor Predecessor Three months ended September 30, 2021 Period from January 30, 2021 through September 30, 2021 Period from January 1, 2021 through January 29, 2021 Three months ended September 30, 2020 Nine months ended September 30, 2020 Operating expenses: Research and development 25,850 54,126 600 1,923 6,604 General and administrative 12,464 29,900 121 193 831 Change in fair value of contingent value rights — 11,312 — — — Acquired in-process research and development — 220,454 — — — Loss from operations (38,314 ) (315,792 ) (721 ) (2,116 ) (7,435 ) Interest income (expense), net 65 100 (9 ) (22 ) (56 ) Amortization of debt discount — — (37 ) (78 ) (220 ) Other income (expense), net (1,906 ) (4,605 ) — 6 (5 ) Gain on extinguishment of debt — — — 72 339 Net loss (40,155 ) (320,297 ) (767 ) (2,138 ) (7,377 ) Other comprehensive loss: Foreign currency translation adjustment (487 ) 2,828 45 372 (359 ) Total comprehensive loss $ (40,642 ) $ (317,469 ) $ (722 ) $ (1,766 ) $ (7,736 ) Net loss per ordinary share - basic and diluted $ (0.45 ) $ (4.60 ) Weighted average ordinary shares outstanding - basic and diluted 89,899,454 69,597,648 Centessa Pharmaceuticals plc (Successor) and Centessa Predecessor Group (Predecessor) Condensed Consolidated and Combined Balance Sheets (unaudited) (amounts in thousands except share and per share data) Successor Predecessor September 30, 2021 December 31, 2020 Total Assets Cash and cash equivalents $ 578,815 $ 7,227 Other assets 33,392 4,490 Total assets $ 612,207 $ 11,717 Total Liabilities Liabilities $ 29,144 $ 8,619 Contingent value rights 33,930 — Total liabilities 63,074 8,619 Total combined deficit and shareholders' equity 549,133 3,098 Total liabilities, combined deficit and shareholders' equity $ 612,207 $ 11,717

Two months after Centessa Pharmaceuticals launched following the merger of 10 private biotech companies, the company is already eyeing a $100 million splash on the Nasdaq stock exchange. Founded by Medicxi, Centessa burst onto the scene in February with a $250 million Series A. The company hit the ground running following the merger of 10 private companies that will continue to operate under the Centessa umbrella as “asset-focused” companies. When Centessa launched in February, it said each subsidiary team is focused on a single program or biological pathway, which will enable Centessa to develop multiple impactful medicines for patients. “The vision of Centessa is to build a pharmaceutical company with a unique operational framework that aims to reduce some of the key R&D efficiencies that classical pharmaceutical companies face because of structural constraints,” Francesco De Rubertis, co-founder and partner at Medicxi and chairman of the board of Centessa said at the time of the company’s launch. Centessa is comprised of ApcinteX, Capella BioScience, Janpix, LockBody, Morphogen-IX, Orexia Therapeutics, Palladio Biosciences, PearlRiver Bio, Pega-One and Z Factor. The Centessa portfolio consists of four clinical stage programs, including two in late-stage clinical development, and more than ten additional programs that span diseases with high unmet need across oncology, hematology, immunology, inflammation, neuroscience, and rare diseases. Each of the companies is primarily based in the United Kingdom and is between two and five years old. Centessa’s most advanced candidate is lixivaptan, which has been under development from Palladio Biosciences. Lixivaptan is an oral non-peptide, a new chemical agent that works by selectively suppressing the activity of the hormone vasopressin at the V2 receptor being developed for autosomal dominant polycystic kidney disease. The company has two Phase II candidates in its pipeline. ApcinteX is developing SerpinPC for hemophilia A and B. SerpinPC is a specific inhibitor of the anticoagulant protease-activated protein C (APC). PegaOne is developing imgatuzumab, a humanized, non-fucosylated, anti-EGFR monoclonal antibody to treat cutaneous squamous cell carcinoma other solid tumor indications. Another Centessa subsidiary, Orexia Therapeutics, is developing oral and intranasal orexin receptor agonists to treat narcolepsy type 1. The agonists have the potential to directly address the underlying pathology of orexin neuron loss, as well as other neurological disorders characterized by excessive daytime sleepiness. When Centessa burst onto the scene, it did so with former GlaxoSmithKline Vaccines and Operation Warp Speed head Moncef Slaoui in chief scientific officer and company advisor. However, after allegations of sexual harassment and inappropriate conduct that occurred during his tenure at GSK surfaced, Slaoui stepped down from his role at Centessa. Slaoui was also forced to leave his role as chairman of Galvani Bioelectronics, a position he held since the company's formation. Centessa filed to sell American Deposit Shares on the Nasdaq under the ticker symbol “CNTA.” In its filing with the U.S. Securities and Exchange Commission, the company did not disclose the share price range for its stocks. While the company is seeking to raise $100 million in the IPO, that number is likely just a placeholder. Given the fact that its Series A was a quarter of a billion dollars, it is likely Centessa will garner a much higher raise in its IPO. Centessa joins numerous other companies in a rush to go public. Earlier this week, Talaris Therapeutics, Gyroscope Therapeutics and Sagimet Biosciences announced their intentions to trade on the Nasdaq.