UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
Washington, D.C. 20549
FORM | ||
CURRENT REPORT
PURSUANT TO SECTION 13 OR 15(d) OF THE SECURITIES EXCHANGE ACT OF 1934
Date of Report (date of earliest event reported): August 14, 2023
(Exact name of Registrant, as specified in its charter)
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Registrant's telephone number, including area code: +44 7391 789784
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Check the appropriate box below if the Form 8-K filing is intended to simultaneously satisfy the filing obligation of the registrant under any of the following provisions (see General Instruction A.2. below):
Securities registered pursuant to Section 12(b) of the Act:
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*Not for trading, but only in connection with the listing of the American Depositary Shares on The Nasdaq Stock Market, LLC.
Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§240.12b-2 of this chapter).
Emerging growth company ☒
If an emerging growth company, indicate by check mark if the registrant has elected not to use the extended transition period for complying with any new or revised financial accounting standards provided pursuant to Section 13(a) of the Exchange Act. ☐
Item 2.02 Results of Operations and Financial Condition.
On August 14, 2023, Centessa Pharmaceuticals plc (the “Company”) announced its financial results for the quarter ended June 30, 2023. The full text of the press release issued in connection with the announcement is furnished as Exhibit 99.1 to this Current Report on Form 8-K.
Item 7.01 Regulation FD Disclosure.
The Company from time to time presents and/or distributes slide presentations to the investment community at various industry and other conferences to provide updates and summaries of its business. The Company is posting a copy of its current corporate slide presentation to the “Investors” portion of its website at www.centessa.com/events-presentations. These slides are attached to this Current Report on Form 8-K as Exhibit 99.2. The Company undertakes no obligation to update, supplement or amend the materials attached hereto as Exhibit 99.1.
The information in this Current Report on Form 8-K (including Exhibits 99.1 and 99.2) shall not be deemed “filed” for purposes of Section 18 of the Securities Exchange Act of 1934, as amended (the “Exchange Act”), or otherwise subject to the liabilities of that section, nor shall it be deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Exchange Act, except as expressly set forth by specific reference in such a filing.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
| Exhibit No. | |||||
| 99.1 | |||||
| 99.2 | |||||
| 104 | Cover Page Interactive Data (embedded within the Inline XBRL document) | ||||
SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the Registrant has duly caused this report to be signed on its behalf by the undersigned hereunto duly authorized.
Date: August 14, 2023
| By: | /s/ Saurabh Saha | |||||||
| Name: | Saurabh Saha, M.D., Ph.D. | |||||||
| Title: | Chief Executive Officer | |||||||
Exhibit 99.1
Centessa Pharmaceuticals Reports Financial Results and Business Highlights for the Second Quarter of 2023
•Enrollment and dosing ongoing in registrational study of SerpinPC for the treatment of hemophilia B
•Enrollment and dosing ongoing in Phase 1/2a Study of LB101, a PD-L1xCD47 LockBody® for the treatment of solid tumors
•IND-enabling activities advancing for ORX750, an oral selective orexin receptor 2 (OX2R) agonist for the treatment of narcolepsy and other sleep disorders; Announces ORX750 preclinical data to be presented at World Sleep Congress in October 2023
•Nominates second LockBody candidate, LB206, a conditionally bivalent PD-L1xCD3 bispecific monoclonal antibody
BOSTON and LONDON, August 14, 2023: Centessa Pharmaceuticals plc (Nasdaq: CNTA), a clinical-stage pharmaceutical company focused on discovering and developing medicines that are transformational for patients, today reported financial results and business highlights for the second quarter ended June 30, 2023.
“This is an exciting time for Centessa as we continue to execute across our portfolio with the goal of bringing transformative medicines to patients with unmet needs,” said Saurabh Saha MD PhD, Chief Executive Officer of Centessa. “We recently commenced dosing in our registrational PRESent-2 study of SerpinPC for the treatment of hemophilia B without inhibitors and are now enrolling subjects across multiple global sites. To date, clinical data support SerpinPC's potential to be a first-in-class subcutaneously administered therapy with a differentiated safety profile for persons with hemophilia B. In the months ahead, we plan to share new data from subjects with approximately 3 years of continuous treatment with SerpinPC from the ongoing Phase 2a study.”
“We are also making great progress with our LockBody technology platform, enrolling and dosing subjects in the ongoing Phase 1/2a clinical trial of LB101, a PD-L1xCD47 LockBody molecule for the treatment of solid tumors. In addition, we are excited to announce LB206, a conditionally bivalent PD-L1xCD3 bispecific monoclonal antibody, as our second LockBody development candidate for the treatment of solid tumors, and share encouraging preclinical data for LB206 which demonstrated the potential of our LockBody technology to selectively drive potent CD3 activity within solid tumors in a difficult-to-treat mouse xenograft model with no apparent observed toxicity. We believe this progress marks an important milestone in advancing our novel LockBody technology platform,” said Dr. Saha.
“In parallel with progress on our two clinical programs, we are advancing ORX750, our first oral selective orexin receptor 2 (OX2R) agonist development candidate, through IND enabling studies for the treatment of narcolepsy, and are thrilled to present preclinical data for ORX750 at the World Sleep Congress in October 2023,” said Dr. Saha. “We are also excited to be exploring follow-up orexin agonists for potential expansion opportunities into a range of high value sleep disorders and broader neurological indications. With a team comprised of experienced and insightful scientists in the orexin field, we believe Centessa is well-positioned to play a leading role in orexin agonist development.”
Dr. Saha concluded, “We have line of sight to multiple potential clinical milestones expected over the next several quarters and with a cash runway into 2026, we believe we are well positioned to advance our pipeline of potentially transformative medicines and deliver value for our stakeholders.”
Recent Highlights
•Today, the Company shared new preclinical data for LB206, a PD-L1xCD3 LockBody development candidate, which demonstrated single agent regressions of large tumors in a difficult-to-treat mouse xenograft model. The preclinical data is shown in the Company’s corporate overview for August 2023 which is available at https://investors.centessa.com/events-presentations.
•In July, the Company announced the dosing of the first subject in its registrational PRESent-2 clinical study of SerpinPC for the treatment of hemophilia B without inhibitors. SerpinPC is an investigational subcutaneously administered novel inhibitor of activated protein C (APC).
•In May, the Company announced that the U.S. Food and Drug Administration (FDA) has granted Fast Track designation to SerpinPC for the treatment of hemophilia B, with or without inhibitors.
Anticipated Upcoming Program Milestones
•Hemophilia (SerpinPC) - The global registrational program for hemophilia B is ongoing. PRESent-5, an observational feeder study, continues enrolling subjects and the Company has commenced dosing in the registrational PRESent-2 clinical study of hemophilia B without inhibitors. Dosing in the registrational PRESent-3 clinical study of hemophilia B with inhibitors, is expected to begin this year. In addition, the Company expects to share data from Part 5 of the ongoing Phase 2a study of SerpinPC at a scientific meeting later this year.
•Solid Tumors
▪PD-L1xCD47 LockBody (LB101) - The Phase 1/2a first-in-human clinical study is ongoing.
▪PD-L1xCD3 LockBody (LB206) - LB206 has been named as a development candidate.
•Narcolepsy and Other Sleep Disorders (ORX750) - ORX750 is undergoing IND-enabling activities. The Company plans to share preclinical data on ORX750 at the World Sleep Congress taking place from October 20-25, 2023, in Rio de Janeiro, Brazil.
The Company has multiple earlier-stage preclinical assets including additional orexin agonists and discovery-stage programs. Where applicable, the Company plans to provide updates on preclinical programs as they advance toward clinical studies.
Second Quarter 2023 Financial Results
•Cash, Cash Equivalents and Short-term Investments: $303.6 million as of June 30, 2023. In addition, the Company received approximately $15.0 million in gross proceeds through ATM sales in August 2023. The Company expects its current cash, cash equivalents and short-term investments will fund operations into 2026, without drawing on the remaining available tranches under the Oberland credit facility.
•Research & Development Expenses: $33.7 million for the second quarter ended June 30, 2023, compared to $53.7 million for the second quarter ended June 30, 2022.
•General & Administrative Expenses: $13.3 million for the second quarter ended June 30, 2023, compared to $14.8 million the second quarter ended June 30, 2022.
•Net Loss Attributable to Ordinary Shareholders: $24.9 million for the second quarter ended June 30, 2023, compared to $64.7 million for the second quarter ended June 30, 2022. The net loss for the second quarter of 2023 included a tax benefit of $24.1 million, which primarily relates to a release of a valuation allowance on certain U.S. deferred tax assets in the quarter.
About Centessa Pharmaceuticals
Centessa Pharmaceuticals plc is a clinical-stage pharmaceutical company that aims to discover and develop medicines that are transformational for patients. Our programs span discovery-stage to late-stage development and cover a range of high-value indications. We operate with the conviction that each one of our programs has the potential to change the current treatment paradigm and establish a new standard of care. For more information, visit http://www.centessa.com/, which does not form part of this release.
About SerpinPC
SerpinPC is a subcutaneously administered novel inhibitor of APC being developed as a potential treatment for hemophilia, regardless of severity or inhibitor status, and which may also be developed to prevent bleeding associated with other bleeding disorders. The ongoing registrational program for
SerpinPC in hemophilia B includes a set of clinical studies with multiple components. PRESent-5 is an observational feeder study to collect prospective observational data for minimum defined periods before switching to dosing subjects in the interventional studies. The interventional studies include PRESent-2 (moderately severe to severe hemophilia B without inhibitors, and severe hemophilia A with or without inhibitors) and PRESent-3 (hemophilia B with inhibitors). Additional information on the trials can be accessed at www.clinicaltrials.gov (NCT05605678, NCT05789524, NCT05789537). The U.S. Food and Drug Administration (FDA) has granted Fast Track designation to SerpinPC for the treatment of hemophilia B, with or without inhibitors. SerpinPC is an investigational agent that has not been approved by the FDA or any other regulatory authority.
About the LockBody Technology Platform and LB101
Centessa’s proprietary LockBody technology platform aims to redefine immuno-oncology treatment for patients with cancer. LockBody drug candidates are designed to selectively drive potent effector function activity, such as CD47 or CD3, to the tumor micro-environment (TME) while avoiding systemic toxicity. The first LockBody candidate is LB101, a conditionally tetravalent PD-L1xCD47 bispecific monoclonal antibody which has two anti-CD47 domains blocked by two anti-PD-L1 domains, with proprietary human IgG-derived hinges linking the anti-CD47 and anti-PD-L1 domains. The cell-killing mechanism of action, CD47, is designed to be blocked by the PD-L1 tumor targeting domain until the IgG-derived hinges are naturally degraded in the TME, thus unlocking and activating the CD47 effector function activity in the tumor. LB101 is in a Phase 1/2a clinical trial. Additional information on the trial can be accessed at www.clinicaltrials.gov (NCT05821777). LB101 is an investigational agent that has not been approved by the FDA or any other regulatory authority.
Forward Looking Statements
This press release contains forward-looking statements. These statements may be identified by words such as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “ongoing,” “aim,” “seek,” 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 discover and develop transformational medicines for patients; its expectations for executing on the Company's pipeline;
its expectations on its cash runway into 2026; the timing of commencement of new studies or clinical trials or clinical and preclinical data related to SerpinPC, LB101, LB206, other LockBody candidates, the LockBody technology platform, ORX750 and other orexin agonist molecules; its ability to identify, screen and recruit a sufficient number of or any subjects in its existing and anticipated studies or clinical trials including PRESent-5, the observational feeder study, PRESent-2 and PRESent-3 and studies or trials of LB101, LB206, and any other LockBody candidates, ORX750 and other orexin agonist molecules and its expectations on executing its research and clinical development plans and the timing thereof; the Company’s ability to differentiate SerpinPC, LB101, LB206, ORX750, other orexin agonist molecules, and other LockBody candidates from other treatment options; the development and therapeutic potential of SerpinPC, LB101, LB206, other LockBody candidates, the LockBody technology platform, ORX750 and other orexin agonist molecules; and regulatory matters, including the timing and likelihood of success of obtaining authorizations to initiate or continue clinical trials. Any forward-looking statements in this press release are based on our current expectations, estimates, assumptions 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 the safety and tolerability profile of our product candidates; our ability to identify, screen and recruit a sufficient number of or any subjects in our anticipated new studies or clinical trials including PRESent-2, PRESent-3, PRESent-5, and studies or trials of LB101 or within anticipated timelines; our ability to execute IND-enabling activities in a timely manner or at all, including with respect to ORX750 and LB206; our ability to protect and maintain our intellectual property position; business (including commercial viability), regulatory, economic and competitive risks, uncertainties, contingencies and assumptions about the Company; risks inherent in developing product candidates 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/or commercialized; the risk that the historical results of preclinical studies or clinical studies will not be predictive of future results in ongoing or future studies; economic risks to the United States and United Kingdom banking systems; and geo-political risks such as the Russia-Ukraine war.
These and other risks concerning our programs and operations are described in additional detail in our Annual Report on Form 10-K, Quarterly Reports on Form 10-Q, and our other reports, which are on file with the U.S. Securities and Exchange Commission (SEC). We explicitly disclaim any obligation to update any forward-looking statements except to the extent required by law.
Contact:
Kristen K. Sheppard, Esq.
SVP of Investor Relations
investors@centessa.com
Centessa Pharmaceuticals plc
Consolidated Statements of Operations and Comprehensive Loss
(unaudited)
(amounts in thousands except share and per share data)
| Three Months Ended June 30, 2023 | Three Months Ended June 30, 2022 | Six Months Ended June 30, 2023 | Six Months Ended June 30, 2022 | |||||||||||||||||||||||
| Operating expenses: | ||||||||||||||||||||||||||
| Research and development | $ | 33,673 | $ | 53,651 | $ | 66,499 | $ | 90,504 | ||||||||||||||||||
| General and administrative | 13,346 | 14,763 | 29,397 | 29,148 | ||||||||||||||||||||||
| Change in fair value of contingent value rights | — | — | — | 1,980 | ||||||||||||||||||||||
| Loss from operations | (47,019) | (68,414) | (95,896) | (121,632) | ||||||||||||||||||||||
| Interest income | 2,059 | 25 | 4,590 | 129 | ||||||||||||||||||||||
| Interest expense | (2,450) | (1,653) | (4,795) | (3,153) | ||||||||||||||||||||||
| Other (expense) income, net | (1,527) | 5,359 | (2,873) | 5,555 | ||||||||||||||||||||||
| Loss before income taxes | (48,937) | (64,683) | (98,974) | (119,101) | ||||||||||||||||||||||
| Income tax (benefit) expense | (24,051) | (22) | (23,374) | 58 | ||||||||||||||||||||||
| Net loss | (24,886) | (64,661) | (75,600) | (119,159) | ||||||||||||||||||||||
| Other comprehensive income (loss): | ||||||||||||||||||||||||||
| Foreign currency translation adjustment | 762 | (1,124) | 1,660 | (1,830) | ||||||||||||||||||||||
| Unrealized gain on available for sale securities, net of tax | 783 | — | 783 | — | ||||||||||||||||||||||
| Other comprehensive income (loss) | 1,545 | (1,124) | 2,443 | (1,830) | ||||||||||||||||||||||
| Total comprehensive loss | $ | (23,341) | $ | (65,785) | $ | (73,157) | $ | (120,989) | ||||||||||||||||||
| Net loss per ordinary share - basic and diluted | $ | (0.26) | $ | (0.69) | $ | (0.80) | $ | (1.29) | ||||||||||||||||||
| Weighted average ordinary shares outstanding - basic and diluted | 95,162,734 | 94,109,089 | 95,050,940 | 92,317,172 | ||||||||||||||||||||||
Centessa Pharmaceuticals plc
Condensed Consolidated Balance Sheets
(unaudited)
(amounts in thousands)
| June 30, 2023 | December 31, 2022 | ||||||||||
| Total assets: | |||||||||||
| Cash and cash equivalents | $ | 145,220 | $ | 393,644 | |||||||
| Short-term investments | 158,367 | — | |||||||||
| Other assets | 89,334 | 50,663 | |||||||||
Total assets | $ | 392,921 | $ | 444,307 | |||||||
| Total liabilities | |||||||||||
| Other liabilities | $ | 43,015 | $ | 38,338 | |||||||
| Long term debt | 73,300 | 69,800 | |||||||||
Total liabilities | $ | 116,315 | $ | 108,138 | |||||||
Total shareholders’ equity | $ | 276,606 | $ | 336,169 | |||||||
Total liabilities and shareholders' equity | $ | 392,921 | $ | 444,307 | |||||||
Corporate Overview AUGUST 2023 Asset-Centric. Patient-Centric.
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. This presentation is not directed to or intended for distribution, or transfer, either directly or indirectly to, or use by, any person or entity that is a citizen or resident or located in any locality, state, country or other jurisdiction where such distribution, transfer, publication, availability or use would be contrary to law or regulation or which would require any registration or licensing within such jurisdiction. This presentation may contain forward-looking statements made pursuant to the safe harbor provisions of the Private Securities Litigation Reform Act of 1995. Statements in this presentation that are not statements of historical fact are forward-looking statements, including, without limitation, 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; the development and therapeutic potential of our product candidates, including SerpinPC, LB101, LB206, other LockBody candidates, our LockBody technology platform, ORX750 and other orexin agonist molecules; strategy; regulatory matters, including the timing and likelihood of success of obtaining approvals to initiate or continue clinical trials or market any products; enroll subjects in clinical trials; market size and opportunity for our product candidates; and our anticipated cash runway. Words such as “may,” “might,” “will,” “could,” “would,” “should,” “expect,” “intend,” “plan,” “objective,” “anticipate,” “believe,” “estimate,” “predict,” “potential,” “continue,” “ongoing,” “aim,” “seek,” and variations of these words or similar expressions are intended to identify forward-looking statements, though not all forward-looking statements necessarily contain these identifying words. These forward- looking statements are based on the beliefs of the Company's management as well as assumptions made by and information currently available to the Company. Such statements reflect the current views of the Company with respect to future events and are subject to known and unknown risks, including, without limitation, 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, Omicron and any other variants, geo-political risks such as the Russia-Ukraine conflict and other risk factors contained in our filings with the U.S. Securities and Exchange Commission. 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. All projections, valuations and statistical analyses are provided for information purposes only. We expressly disclaim any obligation or undertaking to release publicly any updates or revisions to any forward looking statements contained herein to reflect any change in our expectations or any changes in events, conditions or circumstances on which any such statement is based, except as may be required by law. They may be based on subjective assessments and assumptions and may use one among alternative methodologies that produce different results and to the extent they are based on historical information, they should not be relied upon as an accurate prediction of future performance. 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 or any other regulatory agency. No representation or warranty, express or implied, 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 or warranty, express or implied, 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. Disclaimer 2
Discovering and developing medicines that are transformational for patients Multiple potential blockbuster assets Cash runway into 2026 enables multiple clinical readouts World-class R&D team 3 Note: The Company reported $303.6 million in cash, cash equivalents and short-term investments as of June 30, 2023. In addition, the Company received approximately $15.0 million in gross proceeds through ATM sales in August 2023.
DIFFERENTIATION We are a transformational pharmaceutical company fueling an innovative pipeline 4 Lead Assets Disease Estimated Market Size* SerpinPC Hemophilia B $2B+1 PD-L1xCD47 LockBody® (LB101) Solid Tumors $10B1 PD-L1xCD3 LockBody® (LB206) Solid Tumors $10B1 ORX750 Narcolepsy (NT1) and other sleep disorders $2B+1 MULTIPLE PATHWAYS TO SIGNIFICANT VALUE CREATION *Source: 1Evaluate Pharma 2021 and internal estimates Focused development teams Minimal infrastructure Data-driven ‘go / no-go’ decisions Innovative and uncorrelated assets Asset-Centric. Patient-Centric. Centessa has multiple early-stage programs including additional orexin agonists and discovery-stage programs not reflected on this slide. Where applicable, Centessa plans to provide updates on preclinical programs as they advance toward clinical studies.
5 CASH RUNWAY INTO 2026 ENABLES MULTIPLE CLINICAL READOUTS Centessa has multiple early-stage programs including additional orexin agonists and discovery-stage programs not reflected on this slide. INNOVATIVE PIPELINE 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 LB101 Solid Tumors PD-L1xCD47 LockBody LB206 Solid Tumors PD-L1xCD3 LockBody ORX750 Narcolepsy Type 1 (NT1) and other sleep disorders Orexin Receptor-2 (OX2R) Agonist
LEADERSHIP Team with deep R&D experience and focused on execution 6 DAVID CHAO PhD Chief Administrative Officer TIA BUSH Chief Technology & Quality Officer SAURABH SAHA MD PhD Chief Executive Officer ANTOINE YVER MD MSc EVP & Chairman of Development DAVID GRAINGER PhD Chief Innovation Officer IQBAL HUSSAIN General Counsel GREG WEINHOFF MD MBA Chief Financial Officer KAREN ANDERSON Chief People Officer KRISTEN SHEPPARD ESQ SVP, Investor Relations & Corp. Comm. HARRIS ROTMAN PhD SVP, Regulatory Affairs PATRICK YUE MD SVP, Clinical Development
SerpinPC in Hemophilia 7
SerpinPC: Novel, subcutaneously administered biologic inhibitor of APC 8 Novel MoA; Showed significant reduction in bleeding2 Shown to have a favorable safety and well tolerated profile2; No thrombosis observed2 In registrational studies for the treatment of hemophilia B HEMOPHILIA B UNMET NEED Inconvenient, frequent and invasive IV dosing required with standard of care factor prophylaxis Data for potentially competitive agents has shown potential risk of thrombosis High proportion of patients outside U.S. and Europe are not treated ~ 500,000 Estimated global prevalence ~ $9B+ Hem A market1 ~$2B+ Hem B market1 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. MoA is mechanism of action. Source: 1. Evaluate Pharma 2021. 2. Ongoing Phase 2a Study (AP-0101) 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. Designed as convenient subcutaneous injection
SerpinPC: Designed to exploit novel pharmacology to prevent and reduce bleeding 9 Primary APC is the target of SerpinPC All beds Spontaneous joint bleeds • Human genetic target validation • Engineered to specifically inhibit APC • Inhibition of APC increases thrombin • Feedback loop designed to prevent excess thrombin generation SerpinPC 3D-model of SerpinPC Modified a1 anti-trypsin with 3 substitution mutations to confer selective inhibition of activated protein C (APC)
10 SerpinPC Phase 2a Study Robust and highly differentiating clinical data With total exposure of over 40 patient-years across multiple dosing regimens, Phase 2a data showed: The top graph shows the D-dimer results in the 17 subjects who had results < 500 and the 5 subjects who had non-consecutive results > 500. The bottom graph shows the results in the 2 subjects who had two or more consecutive results > 500. The blue line represents a subject who suffered a large traumatic hematoma (hip bleed), and the orange line represents a subject diagnosed with cancer, neither of which were determined to be treatment-related elevations. 1. Phase 2a study data from Part 3 and Part 4 were presented in oral presentations at ASH and EAHAD in December 2022 and February 2023, respectively. 2. There were no thromboembolic events and no treatment-related sustained elevations of D-dimer observed across the Phase 2a study, to date. D-dimer is a sensitive measure of excessive thrombin generation. No observations of thrombosis or treatment-related, non-transient elevations in D-dimer1,2 Favorable Safety Profile1,2
11 SerpinPC Phase 2a Study Robust and highly differentiating clinical data With total exposure of over 40 patient-years across multiple dosing regimens, Phase 2a data showed: 1. Phase 2a study data from Part 3 and Part 4 were presented in oral presentations at ASH and EAHAD in December 2022 and February 2023, respectively. SerpinPC administered subcutaneously at 60 mg flat Q4W (Part 3) and 1.2 mpk Q2W (Part 4). Favorable Tolerability Profile1 No observations of treatment- related, adverse events1
12 SerpinPC Phase 2a Study Robust and highly differentiating clinical data With total exposure of over 40 patient-years across multiple dosing regimens, Phase 2a data showed: SerpinPC reduced median all-bleeds ABR by 93% at highest dose tested ABR is annualized bleeding rate. 1. Phase 2a study data from Part 4 presented at ASH and EAHAD in December 2022 and February 2023, respectively. Part 4 Dosing: 1.2 mpk of SerpinPC administered subcutaneously once every 2 weeks for 24 weeks Reduction in Bleeding1
13 SerpinPC In registrational studies for hemophilia B, with or without inhibitors SerpinPC has not been approved by the FDA or any other regulatory authority. Granted Fast Track designation by the FDA in May 2023 Granted Orphan Drug Designation by the FDA in Sept. 2022
LB101 and LB206 in Solid Tumors 14
LockBody® “It’s all about the hinge” LockBody Technology Platform: Aims to redefine immuno-oncology treatment 15 Novel pharmacology focused on human IgG-derived hinges susceptible to natural intra-tumoral hinge cleavage Designed as single agent systemic treatment to selectively drive potent effector function activity, such as CD47 or CD3, in a solid tumor while avoiding systemic toxicity Robust non-clinical activity demonstrating potential wide therapeutic index LB101 (PD-L1xCD47) in Phase 1/2a study Phase 1/2a trial of first LockBody candidate (LB101) is ongoing LB101 and LB206 are investigational agents that have not been approved by the FDA or any other regulatory authority. Company initiated Phase 1/2a clinical trial of LB101 and dosed first subject in March 2023. LB206 was announced a PD-L1xCD3 development candidate in Aug. 2023. TME is tumor micro-environment. LB206 (PD-L1xCD3) development candidate
LB101: A novel, conditionally tetravalent PD-L1xCD47 bispecific monoclonal antibody 16 Tumor Unlocking: IgG1 hinges susceptible to cleavage in diseased tissue by various natural processes Peripheral Stability: IgG1 hinges naturally resistant to cleavage in serum Constitutive Fabs: PD-L1 Domains Fully human Contingent Fabs: Locked CD47 Domains IgG1 Fc LOCKED UNLOCKED Exposed CDRs TME is tumor micro-environment 1. Constitutive Fabs drive tumor enrichment 2. Natural cleavage of IgG-derived hinges in tumors Designed to optimally deliver PD-L1 targeted anti-CD47 activity to the TME
LB101 showed improved efficacy and durability over atezolizumab in a difficult-to-treat mouse model while being well tolerated 17 In vivo study showed systemically delivered LB101 exhibited significant tumor regression In vivo study showed LB101 was well tolerated with no weight loss Note: MC38 hPD-L1+ syngeneic model in mouse; Arrows indicate dosing every 3 days (Q3d x 6) at Days 0, 3, 6, 9, 12, and 15. 5 mg/kg of atezolizumab is equivalent to 8.5 mg/kg of LB101.
LB101 shown to have favorable safety and tolerability profile in non- human primates up to 50 mg/kg weekly x 4 weeks 18 In-vivo: LB101 delivered IV at 5, 20, 50mg/kg (q7d x 4) in non-human primates • Human IgG1-like PK • No adverse observations - No anemia or thrombocytopenia - No changes in pathology, clinical chemistry or coagulation parameters Pharmacokinetics Bodyweight RBC Platelets Hemoglobin Neutrophils
19 LB101 LockBody in Phase 1/2a Clinical Trial Phase 1/2a Clinical Trial • Open-label, multicenter, dose escalation with expansion cohorts • Part 1: LB101 monotherapy in subjects with selected, advanced solid tumors; determine recommended dose(s) for expansion (Part 2) • Part 2: Design depends on Part 1 results; will further evaluate the safety, efficacy, tolerability, pharmacokinetics, and immune response of LB101 • Study to provide insights on LockBody technology platform in clinical setting Dosing subjects in ongoing Phase 1/2a first-in-human clinical trial of LB101
LB206: A novel, conditionally bivalent PD-L1xCD3 bispecific monoclonal antibody 20 Tumor Unlocking: IgG1 hinges susceptible to cleavage in diseased tissue by various natural processes Peripheral Stability: IgG1 hinges naturally resistant to cleavage in serum Constitutive Fabs: PD-L1 Domain Fully human Contingent Fabs: Locked CD3 Domain IgG1 Fc LOCKED UNLOCKED Exposed CDRs1. Constitutive Fabs drive tumor enrichment 2. Natural cleavage of IgG-derived hinges in tumors PD-L1 Domain CD3 Domain (unlocked) LB206 is a development candidate. IgG1 Fc PD-L1 Domain CD3 Domain (Deactivated) IgG1 Fc DEACTIVATED Deactivation: Second cleaving event terminates CD3 activity
Tumor Unlocking IgG1 hinges susceptible to cleavage in diseased tissue by various natural processes Peripheral Stability IgG1 hinges naturally resistant to cleavage in serum Deactivation Second cleaving event terminates CD3 activity LB206: Designed to concentrate and drive potent CD3 activity in solid tumors with a wide therapeutic index DEACTIVATIONACTIVATION PD-L1LB206 is a development candidate.
22 0 50 100 150 200 250 300 350 0 3 6 9 12 15 18 21 M e a n t u m o r v o l. ( m m 3 ) Time on treatment (days) IgG1 Control LB206 8.5 mg/kg (n=8) 4.5 mg/kg (n=8) 8.5 mg/kg (n=8) Dose administered 1 Mean body weight values for Day 0 and Day 20 within +/- 6% range for each of the four groups. Potent CD3-driven anti-tumor activity observed in MDA-MB-231 mouse xenograft model LB206 is a development candidate. Atezolizumab 8.5 mg/kg (n=8) LB206: In vivo data demonstrated significant tumor regressions with LB206 in a difficult-to-treat mouse model In vivo mouse xenograft1 LB206 is a development candidate.LB206 is a PD-L1xCD3 development candidate.
23 LB206: In vivo data from follow-up experiment demonstrated regression of large tumors in a difficult-to-treat mouse model 0 100 200 300 400 500 600 0 3 6 9 12 15 18 21 0 100 200 300 400 500 600 0 3 6 9 12 15 18 21 Time on treatment (days) Time on treatment (days) LB206 8.5 mg/kg (n=5) LB206 1.5 mg/kg (n=5) 1 5 2 3 4 1 5 2 3 4 1 2 3 4 5 1 2 3 4 5 In d iv . t u m o r v o l. ( m m 3 ) In d iv . t u m o r v o l. ( m m 3 ) 1 MDA-MB231 mouse xenograft model. For 10 mg/kg IgG1 effector null control, mean tumor volume increased from 426 mm3 on Day 0 to 784 mm3 on Day 13 (n=4, 1 control mouse with morbidity sacrificed after Day 4 and excluded from calculation of mean). In vivo follow-up mouse xenograft1 LB206 is a PD-L1xCD3 development candidate.
ORX750 in Narcolepsy 24
Highly validated human target with clinical proof of concept in NT1 Exploring follow-up orexin agonists for potential expansion opportunities into sleep disorders and broader neurological indications 25 ORX750: Orally administered, selective orexin receptor-2 (OX2R) agonist High unmet need EDS is excessive daytime sleepiness. In March 2023, ORX750 was announced as the Company’s product candidate for the treatment of NT1 with potential expansion into other sleep disorders. 1. Evaluate Pharma 2021. 2. Maski K, et al. J Clin Sleep Med 2017;13;419–25. Narcolepsy Type 1 (NT1) A rare neurological condition that affects the brain’s ability to regulate the normal sleep-wake cycle Caused by a profound loss of orexin neurons in the brain ~ 3M Estimated global prevalence of narcolepsy Approx. ~ 50% of narcolepsy patients have NT1 ~$2B+ narcolepsy market1 ORX750 designed to reactivate orexin signaling in the brain Current treatments do not restore normal function; symptoms persist despite polypharmacy In preclinical development for treatment of NT1; IND-enabling activities underway 50% patients still have 1-2 cataplexy episodes per day2 75% patients experience EDS1
Structure-based drug design has enabled the discovery of ORX750 as potential orexin signaling ‘replacement therapy’ for NT1, with potential indication expansion beyond NT1 Illustration of OX2R structure bound to prototype small molecule orexin agonist (shown in purple) 26
ORX750 increased wakefulness in NT1 model and wild type mice 27 NT1 model mice *P < 0.05 vs. 0 mg/kg • ORX750 increased time awake in an NT1 mouse model, showing maximal wake promotion (ceiling effect) at doses shown • Wake % time in wild type mice showed a dose- related response which supports potential indication expansion beyond NT1 • Additional ORX750 preclinical data to be presented at World Sleep in Oct. 2023 0 0.3 1 3 0 20 40 60 80 100 mg/kg W a k e % t im e ✱ ✱✱ 0 1 3 10 0 20 40 60 80 100 mg/kg W a k e % t im e ✱ ✱ ✱ Wild type mice ORX750 was dosed orally during the rest phase in the PiezoSleep assay; percent time spent awake in the first 2 h after dosing is quantified. NT1 model shown here is orexin/ataxin-3 (Atax) mice, which recapitulates the degeneration of orexin neurons associated with NT1.
Centessa is fueling multiple pathways to value creation 28 Multiple potential blockbuster assets Cash runway into 2026 enables multiple clinical readouts World-class R&D team Note: The Company reported $303.6 million in cash, cash equivalents and short-term investments as of June 30, 2023. In addition, the Company received approximately $15.0 million in gross proceeds through ATM sales in August 2023.
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