AstraZeneca Investment (China) Co. Ltd.

• Preliminary results of NATHALI-01 and updated results of BALLI-01 Phase I clinical studies presented at the American Society of Hematology (ASH) 65th Annual Meeting • Execution of strategic collaboration and investment agreements with AstraZeneca • Cécile Chartier, Ph.D., appointed as a director of the Cellectis’ Board of Directors • Drawdown of the second tranche of €15 million under the credit facility agreement entered into with the European Investment Bank (EIB) • Cash position of $156 million as of December 31, 20231 NEW YORK, April 29, 2024 (GLOBE NEWSWIRE) -- Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene editing platform to develop life-saving cell and gene therapies, today provided business updates and reports preliminary financial results for the fourth quarter and full year 2023, ending December 31, 2023. “Cellectis remains deeply focused on advancing its ongoing Phase 1 clinical trials BALLI-01, NaThaLi-01 and AMELI-01. The clinical data presented at ASH last December, regarding our product candidates UCART22 and UCART20x22, both manufactured in-house, are very encouraging and show high expansion potency and a high preliminary response rate. UCART22 manufactured in-house, compared to UCART22 manufactured by an external CDMO, shows meaningful superiority at a lower dose. These results show the major advantage we have in the market: the control of our production from A to Z to deliver highly potent reproducible product candidates. Regarding UCART20x22, preliminary results presented at ASH showed one partial and two complete metabolic responses in patients who have failed prior autologous CD19 CAR T-cell therapies. These data support the continued study of UCART20x22 in r/r B-cell NHL,” said André Choulika, Ph.D., CEO of Cellectis. “In Q4 2023, Cellectis entered into strategic collaboration and investment agreements with AstraZeneca. We are very proud of our partnership to design and develop the next generation of cell and gene therapy medicines with one of the most respected pharmaceutical companies. This collaboration will allow Cellectis and AstraZeneca to join forces and advance potentially breakthrough innovations in the cell and gene therapy space. This year, Cellectis will continue to break new ground in the field of allogeneic cell therapy and we will provide regular updates in the advancements of our programs.” ________________________ 1 Cash position includes cash, cash equivalents, restricted cash and fixed-term deposits classified as current -financial assets. Restricted cash was $5 million as of December 31, 2023. Fixed-term deposits classified as current-financial assets was $15 million as of December 31, 2023. Pipeline Highlights UCART Clinical Programs BALLI-01 (evaluating UCART22) in relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) On April 11, 2023, Cellectis announced that a patient was dosed in France with its first in-house manufactured product candidate UCART22 and completed the 28-day dose limiting toxicity (DLT) period. On June 8, 2023, at the European Hematology Association (EHA) Cellectis presented updated clinical and translational data supporting the preliminary safety and efficacy pro UCART22 in a heavily pretreated r/r B-ALL population. On December 11, 2023, Cellectis presented a poster at the American Society of Hematology (ASH) Annual Meeting with updated results of the Phase I BALLI-01 trial. The poster presentation highlights the following data: In vitro comparability studies suggested that the new process used by Cellectis to manufacture in-house UCART22 (“UCART22 P2”) resulted in a more potent product than the process used by the external CDMO to manufacture UCART22 (“UCART22 P1”). As of July 1st, 2023, 3 patients were enrolled into the first UCART22 P2 cohort at dose level 2 (1 million cells/kg). UCART22 P2 was administered after fludarabine, cyclophosphamide, and alemtuzumab (FCA) lymphodepletion and was well tolerated. No DLTs or ICANS were observed, and the CRS observed was Grade 1 or 2. There was a higher preliminary response rate (67%) at dose level 2 for UCART22 P2 compared to a 50% response rate with a dose 5 times higher of UCART22 P1 (dose level 3). UCART22 expansion was observed in the responding patients and correlated with response and increases in serum cytokines and inflammatory markers. The study continues to enroll patients with UCART22 P2. NaThaLi-01 (evaluating UCART20x22) in relapsed or refractory B-cell non-Hodgkin lymphoma (r/r B-NHL) On December 9, 2023, Cellectis presented a poster at the ASH Annual Meeting with the initial first-in-human preliminary results from the NatHaLi-01 trial, a Phase 1/2a dose-finding and expansion study evaluating UCART20x22 in r/r B-cell NHL. The poster presentation highlights the following data: As of July 1st, 2023, 3 patients were enrolled and treated at dose level 1 (50 million cells flat dose). Cytokine release syndrome (CRS) Grade 1 or 2 occurred in all patients, and all CRS resolved with treatment. No immune effector cell associated neurotoxicity (ICANS) or graft versus host disease (GvHD) was observed. There were no UCART20x22 DLTs, and there was 1 DLT related to CLLS52 (alemtuzumab). All patients responded at Day 28, with 1 partial metabolic response and 2 complete metabolic responses in patients who had failed prior autologous CD19 CAR T-cell therapies. UCART20x22 expansion correlated with response and increases in serum cytokine and inflammatory marker levels as well as with CRS. These initial data support the continued study of UCART20x22 in r/r B-cell NHL and the study continues to enroll patients. AMELI-01 (evaluating UCART123) in relapsed or refractory acute myeloid leukemia (r/r AML) On May 17, 2023, Cellectis presented an oral presentation at the American Society of Gene and Cell Therapy (ASGCT) 2023 Annual Meeting that was an encore of the clinical data on the AMELI-01 clinical trial that were unveiled at an oral presentation at the ASH 2022 Annual Meeting. These preliminary data supported the continued administration of UCART123 after FCA lymphodepletion in patients with r/r AML. The study continues to enroll patients. MELANI-01 (evaluating UCARTCS1) in relapsed or refractory multiple myeloma (r/r MM) In April 2023, we announced our decision to stop enrollment and treatment of patients with UCARTCS1 under the MELANI-01 Study. Research Data & Preclinical Programs TALEN® Editing Process for Gene Correction and Gene Insertion in HSPCs On April 10, 2024, Cellectis published a scientific article in Molecular Therapy, demonstrating that TALEN-mediated intron editing of hematopoietic stem and progenitor cells (HSPCs) enables transgene expression restricted to the myeloid lineage. This approach could unlock new therapeutic avenues for the treatment of inborn metabolic diseases as well as neurological diseases that require delivery of therapeutics to the brain. On April 22, 2024, Cellectis revealed two posters' presentations on novel TALEN® editing process for gene correction and gene insertion in hematopoietic stem and progenitor cells (HSPCs), at the American Society of Gene and Cell Therapy (ASGCT) annual meeting that will be held in Baltimore, Maryland on May 7-11, 2024. Full abstracts and presentations will be available on Cellectis’ website following the event. TALEN®-edited MUC1 CAR T-cells On April 17, 2023, Cellectis released preclinical data on TALEN®-edited MUC1 CAR T-cells at the American Association for Cancer Research (AACR) Annual Meeting. The preclinical data presented in a poster showed the capability of armored allogeneic MUC1 CAR T-cells to excel in the immune suppressive tumor micro-environment suggesting that they could be an effective option in treating relapsed and refractory triple negative breast cancer (TNBC) patients with limited therapeutic options. On October 31, 2023, Cellectis presented preclinical data on MUC1-CAR T-cells to overcome key challenges of targeting solid tumors in a poster session at the Society for Immunotherapy of Cancer’s 38th Annual Meeting (SITC). The preclinical data presented highlight the capability of multi-armored allogeneic CAR T-cells to preserve their activity despite the immunosuppressive microenvironment, while mitigating potential safety concerns. Multiplex engineering for superior generation of efficient CAR T-cells On May 17, 2023, Cellectis presented preclinical data in a poster on multiplex engineering for superior generation of CAR T-cells, at the ASGCT Annual Meeting. In the presentation, Cellectis shows that we can use the state-of-the-art TALEN® technology to precisely edit up to four loci simultaneously while delivering several additional payloads to increase the efficacy and persistence of CAR T-cells. HBB gene correction of sickle cell mutation On June 5, 2023, preclinical data on gene editing process using Cellectis TALEN® technology to develop highly efficient HBB gene correction of sickle cell mutation, were presented in a poster at the International Society for Cell and Gene Therapy (ISCT) 2023 Annual Meeting. These results showed that non-viral DNA delivery associated with TALEN® gene editing reduces the toxicity usually observed with viral DNA delivery and allows high levels of HBB gene correction in long-term repopulating hematopoietic stem cells. TALE Base Editors (TALE-BE) On June 5, 2023, a comprehensive analysis to better design efficient TALE Base Editors (TALE-BE) using Cellectis’ TALEN® technology was presented in a poster at ISCT 2023 Annual Meeting. Cellectis developed a strategy that allowed to comprehensively characterize editing efficiencies in function of the TC position within the TALE-BE editing windows. This method is specifically taking advantage of the highly precise and efficient TALEN® mediated ssODN knock-in in primary T cells, allowing to focus on how target composition and spacer variations can affect TALE-BE activity/efficiency. On October 25, 2023, Cellectis presented a comprehensive analysis of TALE-BE editing determinants at the European Society of Gene and Cell Therapy (ESGCT) 30th annual congress. Cellectis believes that the knowledge presented will help ensure that genome editing-based strategies are skillfully designed to minimize the risk of potential genotoxic events, overall expanding the potential of TALE-BE for nuclear and mitochondrial therapeutic cell engineering. TALEN-mediated HBB gene correction strategy On October 24, 2023, Cellectis presented preclinical data on its program of gene therapy for HSPC at the European Society of Gene and Cell Therapy (ESGCT) 30th annual congress. Intronic editing enables lineage specific expression of therapeutics relevant for HSPC gene therapy. TALEN®-mediated intron editing of the CD11b locus results in the lineage-specific expression of a reporter transgene in myeloid cells, with negligible expression in HSPC or other cellular subsets in vitro and in vivo. Cellectis believes this intron editing approach could be disruptive in HSPC gene therapy and brain delivery of multiple therapeutics. Article published in Frontiers Bioengineering On May 12, 2023, Cellectis published an article in Frontiers Bioengineering demonstrating the efficacy of its TALEN® engineered FAP UCART-cells in cancer-associated fibroblast (CAF) depletion, reduction of desmoplasia and tumor infiltration. Over 90% of epithelial cancers including breast, colorectal, pancreatic and lung adenocarcinomas express the CAF-specific surface marker, fibroblast activation protein α (FAP), which makes it a promising CAR T-cell target. In this study, Cellectis proposed a novel and versatile approach of combination CAR T-cell therapy that can be extended to most stroma-rich cold tumors with relevant tumor-antigen targeting CAR T-cells which otherwise are recalcitrant to cell therapy. Article published in Molecular Therapy – Methods & Clinical Development On October 12, 2023, Cellectis announced the publication of a new research paper in Molecular Therapy – Methods & Clinical Development, demonstrating the efficacy of its TALEN-mediated gene correction of mutated PIK3CD gene in Activated phosphoinositide 3-kinase delta syndrome 1 (APDS1) T-cells. The study aims at exploring an alternative therapeutic strategy by correcting the mutated PIK3CD gene associated to APDS1 by gene editing. This article describes a TALEN®-mediated gene insertion strategy that allows targeted correction of the dominant gain-of-function mutation of the PIK3CD gene by insertion of a functional sequence in a precise manner. Results show efficient gene insertion in APDS1 patients’ T-cells, normalization of PI3K signaling and rescue of T-cell cytotoxic functions. Partnerships Collaboration and Investment Agreements with AstraZeneca In November 2023, Cellectis announced it has entered into (i) a joint research collaboration agreement (the “Collaboration Agreement”), (ii) an investment agreement relating to an initial equity investment of $80 million (the “Initial Investment Agreement”), and (iii) a subsequent investment agreement relating to an additional equity investment of $140 million, with AstraZeneca (the “Subsequent Investment Agreement”). Under the Collaboration Agreement, AstraZeneca Ireland (“AZ Ireland”) will leverage Cellectis’ proprietary gene editing technologies and manufacturing capabilities to design novel cell and gene therapy candidate products. As part of the Collaboration Agreement, 25 genetic targets have been exclusively reserved for AZ Ireland, from which up to 10 candidate products could be explored for development. AstraZeneca will have an option for a worldwide exclusive license on the candidate products, to be exercised before IND filing. Cellectis’ clinical-stage assets, UCART22, UCART123 and UCART20x22 will remain under Cellectis’ ownership and control. Under the Initial Investment Agreement, AstraZeneca Holdings (“AZ Holdings”) made an initial equity investment of $80 million in Cellectis by subscribing for 16,000,000 ordinary shares, at a price of $5.00 per share (the “Initial Investment”). Following settlement and delivery of the new shares, AZ Holdings owned approximately 22% of the share capital, and 21% of the voting rights of the Company. In addition to the Collaboration Agreement and the Initial Investment Agreement, on November 14, 2023, the Company and AZ Holdings entered into the Subsequent Investment Agreement. Under the Subsequent Investment Agreement, AZ Holdings will make a further equity investment in Cellectis of $140 million by subscribing for two newly created classes of convertible preferred shares of Cellectis: 10,000,000 “class A” convertible preferred shares and 18,000,000 “class B” convertible preferred shares, in each case at a price of $5.00 per share (the “Additional Investment”). Until they convert into ordinary shares, the “class A" convertible preferred shares would have single voting rights and would not carry any double voting rights, and the “class B” would carry no voting rights except on any distribution of dividends or reserves. Both classes of preferred shares would enjoy a liquidation preference (if any liquidation surplus remains after repayment of Cellectis’ creditors and of par value to all shareholders) and would be convertible into the same number of ordinary shares with the same rights as the outstanding ordinary shares. All the conditions precedents to the closing are met and the closing should occur on the earlier of (i) the third business day following the approval by the Cellectis' board of directors of the Company's annual and consolidated account for the financial year ended on December 31, 2023, and (ii) May 7, 2024 or such other date as may be agreed in writing by the parties. Immediately following the Additional Investment, it is anticipated that AZ Holdings would own approximately 44% of the share capital of the Company and 30% of the voting rights of the Company (based on the number of voting rights outstanding immediately after the completion of the Initial Investment) and as per the Company's shareholders decision dated December 22, 2023, Mr. Marc Dunoyer and Dr. Tyrell Rivers will serve on the Company's board of directors as members designated by AZ Holdings. Further, certain business decisions are subject to AZ Holdings’ approval, including, in particular, winding up any company of the Cellectis group, issuing securities senior to or pari passu with the convertible preferred shares or any shares without offering AstraZeneca the option to purchase its pro rata share of such securities (subject to customary exceptions, including issuances under employee equity incentive plans), declaring or paying dividends, prepaying indebtedness before due, and disposing of any material assets concerning gene editing tools or manufacturing facilities and selling, assigning, licensing, encumbering or otherwise disposing of certain material IP rights. Licensed Allogeneic CAR T-cell Development Programs Anti-CD19 programs Allogene’s AlloCAR T™ oncology programs utilize Cellectis technologies. ALLO-501 and cemacabtagene ansegedleucel are anti-CD19 products being developed under a collaboration agreement between Servier and Allogene based on an exclusive license granted by Cellectis to Servier. Servier grants to Allogene exclusive rights to ALLO-501 and cemacabtagene ansegedleucel in the U.S. Allogene announced it continues to focus on the development of its investigational product cemacabtagene ansegedleucel, or cema-cel (previously known as ALLO-501A) as part of the first line (1L) treatment plan for LBCL patients who are likely to relapse following 1L chemoimmunotherapy, in the ALPHA3 1L consolidation trial. Allogene announced start-up activities for the ALPHA3 trial are underway and the trial is expected to begin in mid-2024. In the first quarter, Allogene further announced it began enrollment in the ALPHA2 trial of the investigational product cema-cel in patients with relapsed/refractory (r/r) Chronic Lymphocytic Leukemia (CLL). Allogene: anti-CD70 program The anti-CD70 program is licensed exclusively from Cellectis by Allogene and Allogene holds global development and commercial rights to this program. Allogene announced it has developed and implemented a diagnostic and treatment algorithm that may mitigate the treatment-associated hyperinflammatory response without compromising the CAR T function needed to eradicate solid tumors in its solid tumor trial with ALLO-316 in renal cell carcinoma (RCC). Corporate Updates Financing On January 4, 2023, we entered into an amendment to the sales agreement, dated as of March 29, 2021, with Jefferies LLC with respect to an equity offering program under which we may offer and sell ADS having an aggregate offering price of up to $60.0 million from time-to-time following January 4, 2023, through Jefferies as our sales agent. As of the date of this Annual Report, we have not sold any ADS under the amended program subsequent to such date. We decided to discontinue the ATM. In February 2023, Cellectis announced (i) the completion of its offering by way of a capital increase, of 8,800,000 American Depository Shares (ADS), each representing one ordinary share with a par value of 0.05 euro each (the “Offering”), which had been launched on February 2, 2023 and (ii) the exercise by the underwriting banks, Jefferies LLC and Barclays Capital Inc., of their option (the “Option”) to purchase an additional 1,107,800 ordinary shares (the “Additional Ordinary Shares”) of the Company to be delivered in the form of 1,107,800 ADSs. Following the Offering and the Option exercise, the total number of ordinary shares issued in the form of ADSs amounts to 9,907,800, bringing the gross proceeds of the Offering and Option to approximately $24,769,500 (€22,695,162.18) and the aggregate net proceeds, after deducting underwriting commissions and estimated offering expenses, to approximately $22,783,330 (€20,875,325.27). Calyxt and Cibus Merger Agreement On May 31, 2023, Calyxt, Inc. (“Calyxt”) completed its all-stock, reverse merger business combination with Cibus Global, LLC (“Cibus”). Following the closing of this merger, effective on June 1, 2023, the combined company operates under the name of Cibus, Inc.. Cellectis’ equity interest in Calyxt was reduced to 2.9% after the closing of the Merger, which resulted in Cellectis losing control of Calyxt. Drawdown of 2 first tranches of the European Investment Bank financing On April 4, 2023, Cellectis announced it entered into the warrant agreement (the “Warrant Agreement”) and finalized the related ancillary documents required under the credit facility with the European Investment Bank (“EIB”) for up to €40 million previously announced on December 28, 2022. The Company also announced the drawdown of the first tranche of €20 million (“Tranche A”) under the Finance Contract, that has been disbursed by the EIB in early April 2023. Cellectis plans to use the proceeds of Tranche A towards the development of its pipeline of allogeneic CAR T-cell product candidates: UCART22, UCART20x22, UCART123. On January 16, 2024, Cellectis announced the drawdown of the second tranche of €15 million (“Tranche B”) under the credit facility agreement for up to €40 million entered into with the European Investment Bank (the “EIB”) on December 28, 2022 (the “Finance Contract”). The Company plans to use the proceeds of Tranche B towards the development of its pipeline of allogeneic CAR T-cell product candidates: UCART22, UCART20x22, and UCART123. Shareholders General Meeting During its meeting held on June 27, 2023, the shareholders of the Company appointed Mrs. Cécile Chartier as director of the Company’s board of directors. At the end of the meeting, the terms of office of Ms. Annick Schwebig and Mr. Hervé Hoppenot ended and Ms. Annick Schwebig and Mr. Hervé Hoppenot departed the board of directors as of such date. During its meeting held on December 22, 2023, the shareholders of the Company approved the Additional Investment of AstraZeneca. 2023 Financial Results The annual consolidated financial statements of Cellectis have been prepared in accordance with International Financial Reporting Standards, as issued by the International Accounting Standards Board (“IFRS”). On January 13, 2023, Calyxt, Cibus, and certain other parties named therein, entered into an Agreement and Plan of Merger (the “Merger Agreement”), pursuant to which, subject to the terms and conditions thereof, Calyxt and Cibus will merge in an all-stock transaction (the “Calyxt Merger”). As a consequence of the foregoing, Calyxt met the “held-for-sale” criteria specified in IFRS 5 and was classified as a discontinued operation until May 31, 2023. On June 1, 2023, Calyxt and Cibus closed the merger transaction and now operate under the name Cibus, Inc. Consequently, Calyxt was deconsolidated and Calyxt's cash, cash equivalent and restricted cash are no longer included in the Group's cash, cash equivalent and restricted cash since June 1, 2023. As from June 1, 2023 and the deconsolidation of Calyxt, which corresponded to the Plants operating segment, we view our operations and manage our business in a single operating and reportable segment corresponding to the Therapeutics segment. For this reason, we are no longer presenting financial measures broken down between our two reportable segments - Therapeutics and Plants. The results of Calyxt until the date of deconsolidation are isolated under “Income (loss) from discontinued operations” in the appendices of this Q4 and full year 2023 financial results press release. Cash: As of December 31, 2023, Cellectis had $156 million in consolidated cash, cash equivalents, restricted cash and fixed-term deposits classified as current-financial assets. This compares to $95 million in consolidated cash, cash equivalents and restricted cash as of December 31, 2022. This $61 million increase is driven by cash inflows including the $80 million proceeds related to the AstraZeneca Initial Investment, a $23 million net cash inflow from the capital raise closed in February, the $25 million upfront payment related to AstraZeneca Collaboration Agreement, a $2 million net cash inflow from licenses, a $21 million net cash inflow from the EIB loan, $6 million received from research tax credit prefinancing, a $3 million cash inflow related to the grant and refundable advance from BPI, $4 million of financial investments’ capital gain and interests and $1 million reimbursement of social charges paid on stock options. Our cash position is also impacted by a $2 million favorable impact of foreign exchange. These cash inflows are partially offset by $105 million of cash outflows, which include $32 million for R&D suppliers, $16 million for SG&A suppliers, $40 million for staff costs, $11 million for lease payments and $5 millions of reimbursement of the “PGE” loan. With cash and cash equivalents of $137 million and a $15 million term deposit maturing in May 2024 classified as a current financial asset as of December 31, 2023, and taking into account the €15 million under Tranche B of the €40 million Finance Contract with EIB received in January 2024, the Company believes its cash runway is extended into the third quarter of 2025 and therefore will be able to operate for at least twelve months following the consolidated financial statements’ publication. Pursuant to the Subsequent Investment Agreement with AstraZeneca, and the shareholders' approval on December 22, 2023, Cellectis is eligible to receive a payment of $140 million in the form of an equity transaction. All the conditions precedents to the closing are met and the closing of the Subsequent Investment should occur on the earlier of (i) the third business day following the approval by the Cellectis' board of directors of the Company's annual and consolidated account for the financial year ended on December 31, 2023, and (ii) May 7, 2024 or such other date as may be agreed in writing by the parties. Assuming the receipt of the additional $140 million, the Company expects that its cash and cash equivalents will be sufficient to fund its operation into 2026. Revenues and Other Income: Consolidated revenues and other income were $9.2 million for the twelve months ended December 31, 2023 compared to $25.7 million for the twelve months ended December 31, 2022. This $16.5 million decrease between the twelve months ended December 31, 2023 and 2022 was mainly attributable to (i) the recognition of a $15.8 million milestone from a licensee in 2022, (ii) the recognition of two milestones under Cellectis’ agreement with Cytovia for an aggregate of $1.5 million in 2022 and (iii) the recognition of $1.0 million related to the change of control of a licensee pursuant to the terms of its license agreement with Cellectis and the amendment to such license agreement in 2022, while revenues recognized for the year ended December 31, 2023 are mainly related to Iovance research collaboration and exclusive license agreement. R&D Expenses: Consolidated R&D expenses were $87.6 million for the twelve months ended December 31, 2023, compared to $97.5 million for the twelve months ended December 31, 2022. The $9.9 million decrease between the twelve months of 2023 and 2022 was primarily attributable to (i) a decrease of purchases, external expenses and other by $4.4 million (from $54.9 million in 2022 to $50.5 million in 2023) mainly relating to lower consumables purchases and subcontracting expenses due to continuing internalization of our manufacturing and quality activities to support our R&D pipeline, (ii) personnel expenses decreased by $5.5 million (from $42.6 million in 2022 to $37.2 million in 2023) primarily due to headcounts decrease in 2022 and 2023. SG&A Expenses: Consolidated SG&A expenses were $16.8 million for the twelve months ended December 31, 2023 compared to $17.5 million for the twelve months ended December 31, 2022. The $0.7 million decrease primarily reflects (i) a $0.4 million decrease in purchases, external expenses and other (from $9.8 million in 2022 to $9.4 million in 2023) (ii) a $0.3 million decrease in personal expenses. Other operating income and expenses: Other operating income and expenses were a $1.3 million net expense for the twelve months ended December 31, 2023 compared to a $1.4 million net income for the twelve months ended December 31, 2022. The $2.7 million increase in net expenses primarily reflects (i) the recognition of costs related to a commercial litigation for $0.5 million, (ii) the unfavorable outcome of the litigation with the French administration which led to the reimbursement of $0.7 million of research tax credit and the provision for risk of $0.5 million related to 2015 and 2016 research tax credit and (iii) the favorable outcome of a claim with the French social tax authorities regarding tax on stock options for $1.0 million that was a one-time item recognized in 2022. Net financial gain (loss): Consolidated net financial loss was a $19.2 million for the twelve months ended December 31, 2023, compared to a $8.9 million loss for the twelve months ended December 31, 2022. The $10.2 million difference reflects mainly (i) an increase in gain from our financial investments of $2.5 million and (ii) a $4.3 million difference in the loss on change in fair value of Cytovia’s note receivable (from a $12.1 million loss in 2022 to a $7.8 million loss in 2023), partially offset by (i) the loss on change in fair value on our retained investment in Calyxt since deconsolidation for $5.9 million, (ii) a $5.7 million loss on change in fair value of the derivative instrument recognized on the Subsequent Investment Agreement with AstraZeneca, (iii) a $2.4 million loss on change in fair value of the EIB warrants, (iv) a $1.9 million increase of interest expense on our borrowings and (v) a $1.7 million decrease in net foreign exchange gain. Net income (loss) from discontinued operations: Net income (loss) from discontinued operations includes Calyxt loss until deconsolidation and profit from deconsolidation. All tables referring to the year-end period ended December 31, 2023 present Calyxt’s results over a five-month period from January 1, 2023 to May 31, 2023. Net income from discontinued operations was $8.4 million for the twelve months ended December 31, 2023, compared to a net loss of $15,3 million for the twelve months ended December 31, 2022.The $23.7 million difference is primarily driven by (i) a $22.6 million profit from Calyxt’s deconsolidation recognized in 2023 and (ii) Calyxt's $8.5 million net loss in the third and fourth quarter of 2022 compared with $0 in the third and fourth quarter of 2023 as Calyxt was deconsolidated, partially offset by a $7.3 million increase in the net loss over the first two quarters between 2022 and 2023. This $7.3 million increase breaks down as follows: (i) an increase of $9.2 million of net financial loss and (ii) a $1.9 million decrease of operating loss, the decrease of operating expenses being partially offset by restructuring and merger transaction costs. Net Income (loss) Attributable to Shareholders of Cellectis: The consolidated net loss attributable to shareholders of Cellectis was $101.1 million (or $1.77 per share) for the twelve months ended December 31, 2023, of which $116.8 million was attributed to Cellectis continuing operations, compared to $106.1 million (or $2.33 per share) for the twelve months ended December 31, 2022, of which $98.7 million was attributed to Cellectis continuing operations. This $5.1 million decrease in net loss attributable to shareholders of Cellectis between the twelve months of 2023 and 2022 was primarily driven by (i) a $9.9 million decrease of research and development , (ii) a $0.7 million decrease of SG&A expenses and (iii) a $23.2 million increase in profit from discontinued operations attributable to shareholders of Cellectis (from a $7.5 million loss in 2022 to $15.8 million profit in 2023), partially offset by (i) a decrease of $16.5 million of revenues and other income, (ii) an increase in other operating expenses of $2.7 million and (iii) an increase in net financial loss of $10.2 million. Adjusted Net Income (Loss) Attributable to Shareholders of Cellectis: The consolidated adjusted net loss attributable to shareholders of Cellectis was $94.0 million (or $1.65 per share) for the twelve months ended December 31, 2023, compared to a net loss of $98.1 million (or $2.15 per share) for the twelve months ended December 31, 2022. Please see "Note Regarding Use of Non-IFRS Financial Measures" for reconciliation of GAAP net income (loss) attributable to shareholders of Cellectis to adjusted net income (loss) attributable to shareholders of Cellectis. We currently foresee focusing our cash spending at Cellectis for 2023 in the following areas: Supporting the development of our pipeline of product candidates, including the manufacturing and clinical trial expenses of UCART123, UCART22, UCART20x22 and potential new product candidates, and Operating our state-of-the-art manufacturing capabilities in Paris (France), and Raleigh (North Carolina, USA); and Continuing strengthening our manufacturing and clinical departments. CELLECTIS S.A. CONDENSED CONSOLIDATED STATEMENTS OF FINANCIAL POSITION ($ in thousands, except per share data) As of December 31, 2022 December 31, 2023 ASSETS Non-current assets Intangible assets 718 671 Property, plant, and equipment 63,621 54,681 Right-of-use assets 44,275 38,060 Non-current financial assets 8,791 7,853 Total non-current assets 117,406 101,265 Current assets Trade receivables 772 569 Subsidies receivables 14,496 20,900 Other current assets 9,078 7,722 Cash and cash equivalent and Current financial assets 97,697 203,815 Total current assets 122,043 233,005 Total assets held for sale 21,768 0 TOTAL ASSETS 261,216 334,270 LIABILITIES Shareholders’ equity Share capital 2,955 4,365 Premiums related to the share capital 583,122 522,785 Currency translation adjustment (28,605 ) (36,690 ) Retained earnings (333,365 ) (304,707 ) Net income (loss) (106,139 ) (101,059 ) Total shareholders’ equity - Group Share 117,968 84,695 Non-controlling interests 7,973 0 Total shareholders’ equity 125,941 84,695 Non-current liabilities Non-current financial liabilities 20,531 49,125 Non-current lease debts 49,358 42,948 Non-current provisions 2,390 2,200 Deferred tax liabilities 0 158 Total non-current liabilities 72,279 94,431 Current liabilities Current financial liabilities 5,088 5,289 Current lease debts 7,872 8,502 Trade payables 21,456 19,069 Deferred revenues and deferred income 59 110,325 Current provisions 477 1,740 Other current liabilities 13,179 10,219 Total current liabilities 48,131 155,144 Total liabilities related to asset held for sale 14,864 0 TOTAL LIABILITIES AND SHAREHOLDERS’ EQUITY 261,216 334,270 Cellectis S.A. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS For the three-month period ended December 31, 2023 (unaudited) $ in thousands, except per share amounts For the three-month period ended December 31, 2022 (unaudited) 2023 (unaudited) Revenues and other income Revenues 16,024 283 Other income 1,298 1,707 Total revenues and other income 17,322 1,990 Operating expenses Cost of revenue (690 ) (167 ) Research and development expenses (21,433 ) (25,526 ) Selling, general and administrative expenses (1,698 ) (4,671 ) Other operating income (expenses) 728 (1,204 ) Total operating expenses (23,094 ) (31,568 ) Operating income (loss) (5,772 ) (29,578 ) Financial gain (loss) (19,955 ) (12,210 ) Income tax (87 ) (6 ) Income (loss) from continuing operations (25,813 ) (41,795 ) Income (loss) from discontinued operations (2,744 ) (0 ) Net income (loss) (28,558 ) (41,795 ) Attributable to shareholders of Cellectis (26,814 ) (41,795 ) Attributable to non-controlling interests (1,744 ) (0 ) Basic and diluted net income (loss) attributable to shareholders of Cellectis, per share ($/share) (0.59 ) (0.64 ) Basic and diluted net income (loss) attributable to shareholders of Cellectis from discontinued operations, per share ($ /share) (0.02 ) (0.00 ) Cellectis S.A. CONDENSED CONSOLIDATED STATEMENTS OF OPERATIONS For the year ended December 31, 2023 $ in thousands, except per share amounts For the year ended December 31, 2022 2023 Revenues and other income Revenues 19,171 755 Other income 6,553 8,438 Total revenues and other income 25,725 9,193 Operating expenses Cost of revenue (1,772 ) (737 ) Research and development expenses (97,501 ) (87,646 ) Selling, general and administrative expenses (17,494 ) (16,812 ) Other operating income (expenses) 1,377 (1,300 ) Total operating expenses (115,390 ) (106,495 ) Operating income (loss) (89,666 ) (97,302 ) Financial gain (loss) (8,935 ) (19,163 ) Income tax (87 ) (371 ) Income (loss) from continuing operations (98,688 ) (116,835 ) Income (loss) from discontinued operations (15,345 ) 8,392 Net income (loss) (114,034 ) (108,443 ) Attributable to shareholders of Cellectis (106,139 ) (101,059 ) Attributable to non-controlling interests (7,894 ) (7,384 ) Basic and diluted net income (loss) attributable to shareholders of Cellectis, per share ($/share) (2.33 ) (1.77 ) Basic and diluted net income (loss) attributable to shareholders of Cellectis from discontinued operations, per share ($ /share) (0.16 ) 0.28 Note Regarding Use of Non-IFRS Financial Measures Cellectis S.A. presents adjusted net income (loss) attributable to shareholders of Cellectis in this press release. Adjusted net income (loss) attributable to shareholders of Cellectis is not a measure calculated in accordance with IFRS. We have included in this press release a reconciliation of this figure to net income (loss) attributable to shareholders of Cellectis, which is the most directly comparable financial measure calculated in accordance with IFRS. Because adjusted net income (loss) attributable to shareholders of Cellectis excludes Non-cash stock-based compensation expense—a non-cash expense, we believe that this financial measure, when considered together with our IFRS financial statements, can enhance an overall understanding of Cellectis’ financial performance. Moreover, our management views the Company’s operations, and manages its business, based, in part, on this financial measure. In particular, we believe that the elimination of Non-cash stock-based expenses from Net income (loss) attributable to shareholders of Cellectis can provide a useful measure for period-to-period comparisons of our core businesses. Our use of adjusted net income (loss) attributable to shareholders of Cellectis has limitations as an analytical tool, and you should not consider it in isolation or as a substitute for analysis of our financial results as reported under IFRS. Some of these limitations are: (a) other companies, including companies in our industry which use similar stock-based compensation, may address the impact of Non-cash stock- based compensation expense differently; and (b) other companies may report adjusted net income (loss) attributable to shareholders or similarly titled measures but calculate them differently, which reduces their usefulness as a comparative measure. Because of these and other limitations, you should consider adjusted net income (loss) attributable to shareholders of Cellectis alongside our IFRS financial results, including Net income (loss) attributable to shareholders of Cellectis. RECONCILIATION OF IFRS TO NON-IFRS NET INCOME – Fourth Quarter (unaudited) ($ in thousands, except per share data) For the three-month period ended December 31, 2022 2023 Net income (loss) attributable to shareholders of Cellectis (26,814 ) (41,795 ) Adjustment: Non-cash stock-based compensation expense attributable to shareholders of Cellectis 2,739 4,621 Adjusted net income (loss) attributable to shareholders of Cellectis (24,074 ) (37,174 ) Basic adjusted net income (loss) attributable to shareholders of Cellectis ($/share) (0.53 ) (0.57 ) Basic adjusted net income (loss) attributable to shareholders of Cellectis from discontinued operations ($ /share) (0.05 ) 0.00 Weighted average number of outstanding shares, basic (units) (1) 45,653,279 65,234,522 Diluted adjusted net income (loss) attributable to shareholders of Cellectis ($/share) (1) (0.53 ) (0.57 ) Diluted adjusted net income (loss) attributable to shareholders of Cellectis from discontinued operations ($/share) (0.05 ) 0.00 Weighted average number of outstanding shares, diluted (units) (1) 45,653,279 65,234,522 RECONCILIATION OF IFRS TO NON-IFRS NET INCOME – Full Year (unaudited) ($ in thousands, except per share data) For the year ended December 31, 2022 2023 Net income (loss) attributable to shareholders of Cellectis (106,139 ) (101,059 ) Adjustment: Non-cash stock-based compensation expense attributable to shareholders of Cellectis 8,071 7,086 Adjusted net income (loss) attributable to shareholders of Cellectis (98,069 ) (93,973 ) Basic adjusted net income (loss) attributable to shareholders of Cellectis ($/share) (2.15 ) (1.65 ) Basic adjusted net income (loss) attributable to shareholders of Cellectis from discontinued operations ($ /share) (0.11 ) 0.31 Weighted average number of outstanding shares, basic (units) (1) 45,547,359 57,012,815 Diluted adjusted net income (loss) attributable to shareholders of Cellectis ($/share) (1) (2.15 ) (1.65 ) Diluted adjusted net income (loss) attributable to shareholders of Cellectis from discontinued operations ($/share) (0.11 ) 0.31 Weighted average number of outstanding shares, diluted (units) (1) 45,547,359 57,012,815 About Cellectis Cellectis is a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies. Cellectis utilizes an allogeneic approach for CAR-T immunotherapies in oncology, pioneering the concept of off-the-shelf and ready-to-use gene-edited CAR T-cells to treat cancer patients, and a platform to make therapeutic gene editing in hemopoietic stem cells for various diseases. As a clinical-stage biopharmaceutical company with over 24 years of experience and expertise in gene editing, Cellectis is developing life-changing product candidates utilizing TALEN®, its gene editing technology, and PulseAgile, its pioneering electroporation system to harness the power of the immune system in order to treat diseases with unmet medical needs. Cellectis’ headquarters are in Paris, France, with locations in New York, New York and Raleigh, North Carolina. Cellectis is listed on the Nasdaq Global Market (ticker: CLLS) and on Euronext Growth (ticker: ALCLS). Cautionary Statement This press release contains “forward-looking” statements within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by words such as “anticipate,” “believe,” “intend”, “expect,” “plan,” “potentially,” “scheduled,” “could,” “may” and “will,” or the negative of these and similar expressions. These forward-looking statements, which are based on our management’s current expectations and assumptions and on information currently available to management, including information provided or otherwise publicly reported by our licensed partners. Forward-looking statements include statements about future financings, and strategic transactions, including the closing of the Additional Investment, advancement, timing and progress of clinical trials (including with respect to patient enrollment and follow-up), the timing of our presentation of data, the sufficiency of cash to fund operation. These forward-looking statements are made in light of information currently available to us and are subject to numerous risks and uncertainties, including with respect to the numerous risks associated with market conditions, and with biopharmaceutical product candidates development. With respect to our cash runway, our operating plans, including product development plans, may change as a result of various factors, including factors currently unknown to us. Furthermore, many other important factors, including those described in our Annual Report on Form 20-F and in our annual financial report (including the management report) for the year ended December 31, 2023 and subsequent filings Cellectis makes with the Securities Exchange Commission from time to time, which are available on the SEC’s website at , as well as other known and unknown risks and uncertainties may adversely affect such forward-looking statements and cause our actual results, performance or achievements to be materially different from those expressed or implied by the forward-looking statements. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. Media contact: Pascalyne Wilson, Director, Communication +33 (0)7 76 99 14 33, media@cellectis.com Patricia Sosa Navarro, Chief of Staff to the CEO, +33 (0)7 76 77 46 93 Investor Relations contacts: Arthur Stril, Chief Business Officer, +1 (347) 809 5980, investors@cellectis.com Ashley R. Robinson, LifeSci Advisors, +1 (617) 430 7577 Bing C. Wang, Chief Financial Officer, +1 (408) 515 8229

• Strategic Collaboration and Investment Agreements signed with AstraZeneca Updated results of the Phase I BALLI-01 Trial evaluating UCART22 in r/r B-cell ALL and preliminary results of the Phase I NATHALI-01 Trial evaluating UCART20x22 in r/r B-cell NHL to be presented at ASH 65th Annual meeting.Clinical trials ongoing: BALLI-01 (evaluating UCART22), NATHALI-01 (evaluating UCART20x22) and AMELI-01 (evaluating UCART123) studies for patients with r/r B-cell ALL, r/r B-cell NHL and r/r AML, respectively.Preclinical data on HSPC gene therapy and a comprehensive analysis of TALE-BE editing determinants presented at ESGCT 2023 30th annual congress.Preclinical data on Multi-armored Allogeneic MUC1-CAR T-cells targeting Triple-Negative Breast at SITC 2023 annual event.Cash position of $721 million as of September 30, 2023. Cash runway into 2026 including Initial AstraZeneca Investment and Potential Additional AstraZeneca Investment.Conference call scheduled for 8.00am ET / 2.00 pm CET on November 7, 2023 NEW YORK, Nov. 06, 2023 (GLOBE NEWSWIRE) -- Cellectis (the “Company”) (Euronext Growth: ALCLS - NASDAQ: CLLS), a clinical-stage biotechnology company using its pioneering gene editing platform to develop life-saving cell and gene therapies, today provided business updates and financial results for the nine-month period ending September 30, 2023. On November 1st 2023, Cellectis and AstraZeneca Holdings B.V. (“AstraZeneca”) entered into a joint research collaboration agreement (the “Collaboration Agreement”), pursuant to which AstraZeneca makes an upfront payment of $25 million, an investment agreement relating to an initial equity investment of $80 million (the “Initial Investment Agreement”) and a non-binding memorandum of understanding relating to an additional equity investment subject to conditions set forth in the MOU of $140 millions (the “MOU”). This research collaboration will leverage Cellectis’ gene editing technologies and manufacturing capabilities to accelerate the development of next-generation therapeutics in areas of high unmet need, including oncology, immunology and rare diseases. Cellectis has exclusively reserved 25 genetic targets for AstraZeneca, from which up to 10 novel candidate products could be explored for development. Cellectis’ clinical-stage assets, UCART22, UCART123 and UCART20x22 will remain under Cellectis’ ownership and control. Pipeline Highlights UCART Clinical Development Programs BALLI-01 (evaluating UCART22) in relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL) Cellectis will present a poster at the ASH Annual Meeting with updated results of the Phase I BALLI-01 Trial of UCART22 (P2), an anti-CD22 allogeneic CAR T- cell product manufactured in-house, in patients with relapsed or refractory (r/r) CD22+ B-Cell acute lymphoblastic leukemia (B-ALL). The poster presentation highlights the following data: In vitro comparability studies suggested that UCART22 process 2 (P2) (manufactured in-house) is more potent than UCART22 process 1 (P1) (manufactured by an external CDMO), and as of July 1st, 2023, 3 patients were enrolled into the first UCART22 P2 cohort at dose level 2 (1 million cells/kg).UCART22 P2 was administered after fludarabine, cyclophosphamide, and alemtuzumab (FCA) lymphodepletion and was well tolerated. No DLTs or ICANS was observed, and the CRS observed was Grade 1 or 2.There was a higher preliminary response rate (67%) at dose level 2 with one million cells/kg with UCART22 P2 compared to 50% response rate with a dose 5 times higher at dose level 3 of UCART22 P1 that was manufactured by an external CDMO.UCART22 expansion was observed in the responding patients and correlated with increases in serum cytokines and inflammatory markers.The study continues to enroll patients at dose level 2i (2.5 million cells/kg) with UCART22 P2. NATHALI-01 (evaluating UCART20x22) in relapsed or refractory B-cell non-Hodgkin lymphoma (r/r B-NHL) Cellectis will present a poster at the ASH Annual Meeting with the initial preliminary results from the NATHALI-01 trial (NCT05607420), a Phase 1/2a dose-finding and expansion study evaluating UCART20x22 in r/r B-cell NHL. The poster presentation highlights the following data: As of July 1st, 2023, 3 patients were enrolled and treated at dose level 1 (50 million cells). Cytokine release syndrome (CRS) Grade 1 or 2 occurred in all patients, and all CRS resolved with treatment. No immune effector cell associated neurotoxicity (ICANS) or graft versus host disease (GvHD) was observed. There were no UCART20x22 dose limiting toxicities (DLTs), and there was 1 DLT in connection with CLLS52 (alemtuzumab).All patients responded at Day 28, with 1 partial metabolic response and 2 complete metabolic responses in patients who had failed prior autologous CD19 CAR T-cell therapies.UCART20x22 expansion correlated with increases in serum cytokine and inflammatory marker levels as well as with CRS.These initial data support the continued study of UCART20x22 in r/r B-cell NHL. AMELI-01 (evaluating UCART123) in relapsed or refractory acute myeloid leukemia (r/r AML) UCART123 is an allogeneic CAR T-cell product candidate targeting CD123 and is being evaluated in patients with r/r AML in the AMELI-01 Phase 1 dose-escalation clinical study.The AMELI-01 study is currently enrolling patients after FCA lymphodepletion in a two-dose regimen arm. Research Data & Preclinical Programs Cellectis announced the publication of a new research paper in Molecular Therapy – Methods & Clinical Development, demonstrating the efficacy of its TALEN-mediated gene correction of mutated PIK3CD gene in Activated phosphoinositide 3-kinase delta syndrome 1 (APDS1) T-cells.Cellectis presented encouraging data on gene editing process using TALEN®-based gene editing platform, to overcome the challenges of the “cold” tumor microenvironment in a poster at the CICON 2023 (CRI-ENCI-AACR 7th International Cancer Immunotherapy Conference).Cellectis presented preclinical data on MUC1-CAR T-cells to overcome key challenges of targeting solid tumors in a poster session at the Society for Immunotherapy of Cancer’s 38th Annual Meeting (SITC 2023).Cellectis presented preclinical data on its program of gene therapy for HSPC at the European Society of Gene and Cell Therapy (ESGCT) 30th annual congress.Cellectis presented a comprehensive analysis of TALE-BE editing determinants at the European Society of gene and Cell Therapy (ESGST) 30th annual congress. Licensed Allogeneic CAR T-cell Development Programs Allogene Therapeutics, Inc.’s CAR T programs utilize Cellectis technologies. ALLO-501 and ALLO-501A are anti-CD19 products that were jointly developed under a collaboration agreement between Les Laboratoires Servier (“Servier”) and Allogene Therapeutics, Inc. (“Allogene”) until 15 December 2022 based on an exclusive license granted by Cellectis to Servier2. Servier grants to Allogene exclusive rights to ALLO-501 and ALLO-501A in the U.S., Allogene continues the development for this territory while Servier retains exclusive rights for all other countries. Allogene’s anti-CD70 and anti-Claudin18.2 programs are licensed exclusively from Cellectis to Allogene and Allogene holds global development and commercial rights to these programs. Servier and Allogene: anti-CD19 programs Allogene announced that its ALPHA2 study will enroll approximately 100 patients who have received at least two prior lines of therapy and have not received prior anti-CD19 therapy.Allogene announced it will have two poster presentations from the ALPHA/ALPHA2 trials focused on lymphodepletion in allogeneic cell therapy at ASH 2023. The first poster is a comprehensive safety review of all 85 patients treated in the Phase 1 ALPHA/ALPHA2 studies in relapsed/refractory (r/r) Large B Cell Lymphoma (LBCL) and follicular lymphoma (FL) to characterize the overall safety profile when ALLO-647 is added to standard lymphodepletion. The second poster showcases translational results from ALPHA2 generated through a collaboration with MD Anderson Cancer Center. This study compared expansion kinetics among 11 allogeneic CAR T recipients treated with the ALLO-501A product candidate in the ALPHA2 trial. According to Allogene, this study revealed the impact of recipient alloreactive CD8+ T cells in allogeneic CAR T rejection and the results of this study could help define strategies to improve allogeneic CAR T expansion, persistence and efficacy. Allogene: anti-CD70 and anti-Claudin18.2 programs Allogene announced that the Phase 1 dose escalation TRAVERSE trial in patients with advanced or metastatic renal cell carcinoma (RCC) who have progressed on standard therapies including an immune checkpoint inhibitor and a VEGF-targeting therapy is ongoing.Allogene announced that SITC 2023 will include a review of research which provided early validation of ALLO-182, an AlloCAR T candidate currently in the IND-enabling phase of development targeting Claudin18.2 for the treatment of patients with gastric and pancreatic cancers. Corporate Updates Strategic Collaboration and Investment Agreements with AstraZeneca Under the terms of the Collaboration Agreement, AstraZeneca will leverage Cellectis’ proprietary gene editing technologies and manufacturing capabilities to design novel cell and gene therapy candidate products. As part of the Collaboration Agreement, 25 genetic targets have been exclusively reserved for AstraZeneca, from which up to 10 candidate products could be explored for development. AstraZeneca will have an option for a worldwide exclusive license on the candidate products, to be exercised before IND filing. Cellectis’ clinical-stage assets, UCART22, UCART123 and UCART20x22 will remain under Cellectis’ ownership and control. Pursuant to the Collaboration Agreement, Cellectis’ research costs under the collaboration will be funded by AstraZeneca and Cellectis will receive an upfront payment of $25 million. Under the terms of the Collaboration Agreement, Cellectis is also eligible to receive an investigational new drug (IND) option fee and development, regulatory and sales-related milestone payments, ranging from $70 million up to $220 million, per each of the 10 candidate products, plus tiered royalties. As a condition to the signing of the Collaboration Agreement, AstraZeneca has agreed to make an initial equity investment of $80 million in Cellectis by subscribing for 16,000,000 ordinary shares, at a price of $5.00 per share (the “Initial Investment”). The new shares are issued to AstraZeneca by the board of directors of Cellectis pursuant to the 17th resolution of Cellectis’ shareholders meeting held on June 27, 2023. Following settlement and delivery of the new shares (expected to be on November 6, 2023), AstraZeneca will own approximately 22% of the share capital, and 21% of the voting rights of the Company, will have the right to nominate a non-voting observer on the board of directors of Cellectis, and will have the right to participate pro rata in Cellectis’s future share offerings. Additionally, the MOU contemplates that AstraZeneca will make a potential further equity investment in Cellectis of $140 million by subscribing for two newly created classes of convertible preferred shares of Cellectis: 10,000,000 “class A” convertible preferred shares and 18,000,000 “class B” convertible preferred shares, in each case at a price of $5.00 per share (the “Additional Investment”). Until they convert into ordinary shares, the “class A" convertible preferred shares would have single voting rights and would not carry any double voting right at any moment, and the “class B” would carry no voting rights except on any distribution of dividends or reserves. Both class of preferred shares would enjoy a liquidation preference (if any liquidation surplus remains after repayment of Cellectis’ creditors and of par value to all shareholders) and would be convertible into the same number of ordinary shares with the same rights as the outstanding ordinary shares. The MOU is non-binding and the Additional Investment remains to be confirmed by both parties following a consultation process with Cellectis’ works council. If confirmed, the closing of the Additional Investment will remain subject to (i) Cellectis’ shareholders’ approval at a two-thirds majority of the votes cast by voting shareholders, (ii) clearance of such investment from the French Ministry of Economy according to the foreign direct investment French regulations, and (iii) other customary closing conditions. Immediately following the Additional Investment, it is anticipated that AstraZeneca would own approximately 44% of the share capital of the Company and 30% of the voting rights of the Company (based on the number of voting rights outstanding immediately after the completion of the Initial Investment) and would have the right to nominate two directors to the board of directors of Cellectis. Further, certain business decisions are subject to AstraZeneca’s approval, including, in particular, winding up any company of the Cellectis group, issuing securities senior to or pari passu with the convertible preferred shares or any shares without offering AstraZeneca the option to purchase its pro rata share of such securities (subject to customary exceptions, including issuances under employee equity incentive plans), declaring or paying dividends, prepaying indebtedness before due, and disposing of any material assets concerning gene editing tools or manufacturing facilities and selling, assigning, licensing, encumbering or otherwise disposing of certain material IP rights. Financial Results The interim condensed consolidated financial statements of Cellectis, have been prepared in accordance with International Financial Reporting Standards, as issued by the International Accounting Standards Board (“IFRS”). On January 13, 2023, Calyxt, Cibus Global LLC (Cibus) and certain other parties named therein, entered into an Agreement and Plan of Merger (the “Merger Agreement”), pursuant to which, subject to the terms and conditions thereof, Calyxt and Cibus will merge in an all-stock transaction (the “Calyxt Merger”). As a consequence of the foregoing, Calyxt met the “held-for-sale” criteria specified in IFRS 5 and was classified as a discontinued operation until May 31, 2023. On June 1, 2023, Calyxt and Cibus closed the merger transaction and now operate under the name Cibus, Inc. Consequently, Calyxt was deconsolidated and Calyxt's cash, cash equivalent and restricted cash are no longer included in the Group's cash, cash equivalent and restricted cash since June 1, 2023. As from June 1, 2023 and the deconsolidation of Calyxt, which corresponded to the Plants operating segment, we view our operations and manage our business in a single operating and reportable segment corresponding to the Therapeutics segment. For this reason, we are no longer presenting financial measures broken down between our two reportable segments - Therapeutics and Plants. The results of Calyxt until the date of deconsolidation are isolated under “Income (loss) from discontinued operations” in the appendices of this Q3 2023 financial results press release. Cash: As of September 30, 2023, Cellectis, had $72 million in consolidated cash, cash equivalents, and restricted cash. This compares to $95 million in consolidated cash, cash equivalents and restricted cash as of December 31, 2022. This $23 million difference mainly reflects $79 million of cash out, which include $23 million for R&D suppliers, $12 million for SG&A suppliers, $32 million for staff costs, $8 million for rents and taxes, $4 millions of reimbursement of the “PGE” loan, and a $2 million unfavorable impact on Forex partially offset by a $23 million net cash inflow from the capital raise closed in February, a $21 million net cash inflow from EIB loan, a $6 million of net cash received from research tax credit prefinancing, a $1 million cash inflow related to the grant and refundable advance from BPI, $3 millions of financial investments’ capital gain and interests, a $1 million reimbursement of social charges paid on stock options, and a $2 million net cash inflow from licenses and other cash receipts. With cash and cash equivalents of $67.4 million as of September 30, 2023, our anticipated borrowing of €15.0 million under Tranche B of the €40.0 million Finance Contract with EIB and the $105 million from AstraZeneca's agreements, the Company believes it has sufficient resources to continue operating for at least twelve months following the consolidated financial statements’ publication. Additionally, the MOU contemplates that AstraZeneca will make a potential further equity investment in Cellectis of $140M by subscribing for two newly created classes of convertible preferred shares of Cellectis (the “Additional Investment”). The MOU is non-binding and the Additional Investment remains to be confirmed by both parties following a consultation process with Cellectis’ works council. If confirmed, the closing of the Additional Investment will remain subject to (i) Cellectis’ shareholders’ approval at a two-thirds majority of the votes cast by voting shareholders, (ii) clearance of such investment from the French Ministry of Economy according to the foreign direct investment French regulations, and (iii) other customary closing conditions. With cash and cash equivalents of $67.4 million as of September 30, 2023, our anticipated borrowing of €15.0 million under Tranche B of the €40.0 million Finance Contract with EIB and the $105 million from AstraZeneca's payments under the Collaboration Agreement and the Initial Investment Agreement, the Company believes it has sufficient resources to continue operating until Q2 2025. Concurrent with the potential additional $140 million, we expect that the Company would extend its cash runway into 2026. Revenues and Other Income: Consolidated revenues and other income were $7.2 million for the nine months ended September 30, 2023 compared to $8.4 million for the nine months ended September 30, 2022. The decrease of $1.0 million reflects the recognition of two milestones related to Cellectis’ agreement with Cytovia for $1.5 million in 2022 and a milestone of $1.0 million with another partner while recognition of revenues in 2023 is not material, and partially offset by the increase of the research tax credit for $0.6 million and the partial recognition of a grant signed with “BPI” of $0.8 million. R&D Expenses: Consolidated R&D expenses were $62.1 million for the nine months ended September 30, 2023, compared to $76.1 million for the nine months ended September 30, 2022. The $13.9 million decrease was primarily attributable to (i) a $8.9 million decrease in personal expenses due to departures not replaced and decrease in stock-based compensation expenses consecutive to the non-achievement of certain performance obligations of October 2020 free shares plan (ii) a $5.0 million decrease in purchases, external expenses and other (from $41.4 million in 2022 to $36.4 million in 2023) mainly due to continuing internalization of our manufacturing and quality activities to support our R&D pipeline. SG&A Expenses: Consolidated SG&A expenses were $12.1 million for the nine months ended September 30, 2023, compared to $15.8 million for the nine months ended September 30, 2022. The $3.7 million decrease primarily reflects (i) a $2.4 million decrease in purchases, external expenses and (from $9.5 million in 2022 to $7.1 million in 2023) mainly explained by the implementation of our ERP in 2022 (ii) a $1.3 million decrease in personal expenses and non-cash stock-based compensation expenses. Net financial gain (loss): Consolidated net financial gain was $14.9 million for the nine months ended September 30, 2023, compared to 11.0 million for the nine months ended September 30, 2022. The $3.9 million increase primarily reflects (i) a $22.8 million increase of financial income, mainly attributable to the profit from Calyxt’s deconsolidation, partially offset by (ii) the loss in fair value on our retained investment in Calyxt since deconsolidation for $6.2 million, (iii) a $7.9 million decrease in the net value of Cytovia’s note receivable. Net income (loss) from discontinued operations: Pursuant to Calyxt deconsolidation income from discontinued operation for the nine-month period ended September 30, 2023, 2023 only include five months of activity. The $2.2 million decrease in net loss from discontinued operations between the nine-month periods ended September 30, 2022 and 2023 is primarily driven by Calyxt's $5.7M net loss in the third quarter of 2022 compared with $0 in the third quarter of 2023 as Calyxt was deconsolidated, partially offset by a 3.5M$ increase in the net loss over the first two quarters between 2022 and 2023. This $3.5M increase breaks down as follows: (i) an increase of $9.2 million of net financial loss and (ii) an increase of $1.5 million of other operating expenses, partially offset by (i) a decrease of $2.8 million of R&D expenses (from $6.3 million in 2022 to $3.5 million in 2023) and (ii) a decrease of $4.5 million of SG&A expenses (from $6.8 million in 2022 to $2.3 million in 2023). Net Income (loss) Attributable to Shareholders of Cellectis: The consolidated net loss attributable to shareholders of Cellectis was $58.2 million (or $1.07 per share) for the nine months ended September 30, 2023, of which $53.2 million was attributed to Cellectis continuing operations, compared to $79.3 million (or $1.74 per share) for the nine months ended September 30, 2022, of which $72.9 million was attributed to Cellectis continuing operations. This $21.1 million decrease in net loss between the first nine months of 2023 and 2022 was primarily driven by (i) a $13.9 million decrease of R&D expenses, (ii) a $3.7 million decrease of SG&A expense, (iii) an increase of $3.9 million of the financial gain due to the deconsolidation of Calyxt compensated in part by the decrease of fair value of Cytovia’s note receivable and, (iv) a decrease of $2.2 million of loss from discontinued operations attributable to Shareholders of Cellectis. These downward impacts on the net loss were partially offset by (i) a decrease of $1.2 million of revenues and other income. Adjusted Net Income (Loss) Attributable to Shareholders of Cellectis: The consolidated adjusted net loss attributable to shareholders of Cellectis was $56.8 million (or $1.05 per share) for the nine months ended September 30, 2023, compared to a net loss of $72.1 million (or $1.58 per share) for the nine months ended September 30, 2022. Please see "Note Regarding Use of Non-IFRS Financial Measures" for reconciliation of GAAP net income (loss) attributable to shareholders of Cellectis to adjusted net income (loss) attributable to shareholders of Cellectis. We currently foresee focusing our cash spending at Cellectis for 2023 in the following areas: Supporting the development of our pipeline of product candidates, including the manufacturing and clinical trial expenses of UCART123, UCART22, UCART 20x22 and potential new product candidates;Operating our state-of-the-art manufacturing capabilities in Paris (France), and Raleigh (North Carolina, USA); andContinuing to strengthen our manufacturing and clinical departments. CELLECTIS S.A. STATEMENT OF CONSOLIDATED FINANCIAL POSITION (unaudited) ($ in thousands) As of December 31, 2022 September 30, 2023 ASSETS Non-current assets Intangible assets 718 662 Property, plant, and equipment 63,621 56,774 Right-of-use assets 44,275 39,146 Non-current financial assets 8,791 16,624 Total non-current assets 117,406 113,205 Current assets Trade receivables 772 393 Subsidies receivables 14,496 20,255 Other current assets 9,078 8,488 Cash and cash equivalent and Current financial assets 97,697 67,358 Total current assets 122,043 96,494 Total assets held for sale 21,768 0 TOTAL ASSETS 261,216 209,700 LIABILITIES Shareholders’ equity Share capital 2,955 3,492 Premiums related to the share capital 583,122 473,325 Currency translation adjustment (28,605) (37,505)Retained earnings (333,365) (304,994)Net income (loss) (106,139) (58,197)Total shareholders’ equity - Group Share 117,968 76,123 Non-controlling interests 7,973 0 Total shareholders’ equity 125,941 76,123 Non-current liabilities Non-current financial liabilities 20,531 43,248 Non-current lease debts 49,358 43,816 Non-current provisions 2,390 2,560 Total non-current liabilities 72,279 89,625 Current liabilities Current financial liabilities 5,088 5,058 Current lease debts 7,872 8,203 Trade payables 21,456 20,476 Deferred revenues and deferred income 59 117 Current provisions 477 946 Other current liabilities 13,179 9,153 Total current liabilities 48,131 43,953 Total liabilities related to asset held for sale 14,864 0 TOTAL LIABILITIES AND SHAREHOLDERS’ EQUITY 261,216 209,700 Cellectis S.A.UNAUDITED STATEMENTS OF CONSOLIDATED OPERATIONS For the three-month period ended September 30, 2023$ in thousands, except per share amounts For the three-month period endedSeptember 30, 2022 * 2023 Revenues and other income Revenues 175 155 Other income 1,704 1,489 Total revenues and other income 1,879 1,644 Operating expenses Cost of revenue (367) (181)Research and development expenses (23,837) (18,894)Selling, general and administrative expenses (4,903) (3,227)Other operating income (expenses) (125) (12)Total operating expenses (29,233) (22,314) Operating income (loss) (27,353) (20,671) Financial gain (loss) 1,807 3,295 Income tax 0 (106)Income (loss) from continuing operations (25,548) (17,482)Income (loss) from discontinued operations (5,718) 0 Net income (loss) (31,265) (17,482)Attributable to shareholders of Cellectis (28,467) (17,482)Attributable to non-controlling interests (2,798) (0)Basic net income (loss) attributable to shareholders of Cellectis, per share ($/share) (0.63) (0.31) Diluted net income (loss) attributable to shareholders of Cellectis, per share ($/share) (0.63) (0.31) Basic net income (loss) attributable to shareholders of Cellectis from discontinued operations, per share ($ /share) (0.06) 0.00 Diluted net income (loss) attributable to shareholders of Cellectis from discontinued operations, per share ($ /share) (0.06) 0.00 * These amounts reflect adjustments made in connection with the presentation of the discontinued operation Cellectis S.A.UNAUDITED STATEMENTS OF CONSOLIDATED OPERATIONS For the nine-month period ended September, 2023$ in thousands, except per share amounts For the nine-month period endedSeptember 30, 2022 * 2023 Revenues and other income Revenues 3,147 472 Other income 5,255 6,731 Total revenues and other income 8,402 7,.203 Operating expenses Cost of revenue (1,081) (570)Research and development expenses (76,067) (62,119)Selling, general and administrative expenses (15,797) (12,141)Other operating income (expenses) 649 (96)Total operating expenses (92,297) (74,926) Operating income (loss) (83,894) (67,723) Financial gain (loss) 11,019 14,875 Income tax 0 (365)Income (loss) from continuing operations (72,875) (53,213)Income (loss) from discontinued operations (12,601) (10,377)Net income (loss) (85,476) (63,590)Attributable to shareholders of Cellectis (79,326) (58,197)Attributable to non-controlling interests (6,150) (5,393)Basic net income (loss) attributable to shareholders of Cellectis, per share ($/share) (1.74) (1.07) Diluted net income (loss) attributable to shareholders of Cellectis, per share ($/share) (1.74) (1.07) Basic net income (loss) attributable to shareholders of Cellectis from discontinued operations, per share ($ /share) (0.14) (0.09) Diluted net income (loss) attributable to shareholders of Cellectis from discontinued operations, per share ($ /share) (0.14) (0.09) * These amounts reflect adjustments made in connection with the presentation of the discontinued operation Note Regarding Use of Non-IFRS Financial Measures Cellectis S.A. presents adjusted net income (loss) attributable to shareholders of Cellectis in this press release. Adjusted net income (loss) attributable to shareholders of Cellectis is not a measure calculated in accordance with IFRS. We have included in this press release a reconciliation of this figure to net income (loss) attributable to shareholders of Cellectis, which is the most directly comparable financial measure calculated in accordance with IFRS. Because adjusted net income (loss) attributable to shareholders of Cellectis excludes Non-cash stock-based compensation expense—a non-cash expense, we believe that this financial measure, when considered together with our IFRS financial statements, can enhance an overall understanding of Cellectis’ financial performance. Moreover, our management views the Company’s operations, and manages its business, based, in part, on this financial measure. In particular, we believe that the elimination of Non-cash stock-based expenses from Net income (loss) attributable to shareholders of Cellectis can provide a useful measure for period-to-period comparisons of our core businesses. Our use of adjusted net income (loss) attributable to shareholders of Cellectis has limitations as an analytical tool, and you should not consider it in isolation or as a substitute for analysis of our financial results as reported under IFRS. Some of these limitations are: (a) other companies, including companies in our industry which use similar stock-based compensation, may address the impact of Non-cash stock- based compensation expense differently; and (b) other companies may report adjusted net income (loss) attributable to shareholders or similarly titled measures but calculate them differently, which reduces their usefulness as a comparative measure. Because of these and other limitations, you should consider adjusted net income (loss) attributable to shareholders of Cellectis alongside our IFRS financial results, including Net income (loss) attributable to shareholders of Cellectis RECONCILIATION OF IFRS TO NON-IFRS NET INCOMEFor the three-month period ended September 30, 2023(unaudited) - ($ in thousands except per share data) For the three-month period endedSeptember 30, 2022 * 2023 Net income (loss) attributable to shareholders of Cellectis (28,467) (17,482)Adjustment: Non-cash stock-based compensation expense attributable to shareholders of Cellectis 1,880 (2,653)Adjusted net income (loss) attributable to shareholders of Cellectis (26,587) (20,135) Basic adjusted net income (loss) attributable to shareholders of Cellectis ($/share) (0.58) (0.37)Basic adjusted net income (loss) attributable to shareholders of Cellectis from discontinued operations ($ /share) (0.05) 0.00 Weighted average number of outstanding shares, basic (units) 45,540,315 55.583.768 Diluted adjusted net income (loss) attributable to shareholders of Cellectis ($/share) (0.58) (0.36)Diluted adjusted net income (loss) attributable to shareholders of Cellectis from discontinued operations ($/share) (0.05) 0.00 Weighted average number of outstanding shares, diluted (units) 45,540,315 55.583.768 *These amounts reflect adjustments made in connection with the presentation of the discontinued operation RECONCILIATION OF IFRS TO NON-IFRS NET INCOME (unaudited) For the nine-month period ended September 30, 2023 ($ in thousands, except per share data) For the nine-month period endedSeptember 30, 2022 * 2023 Net income (loss) attributable to shareholders of Cellectis (79,326) (58,197)Adjustment: Non-cash stock-based compensation expense attributable to shareholders of Cellectis 7,211 1,400 Adjusted net income (loss) attributable to shareholders of Cellectis (72,115) (56,797) Basic adjusted net income (loss) attributable to shareholders of Cellectis ($/share) (1.58) (1.05)Basic adjusted net income (loss) attributable to shareholders of Cellectis from discontinued operations ($ /share) (0.11) (0.08) Weighted average number of outstanding shares, basic (units) 45,511,626 54,231,943 Diluted adjusted net income (loss) attributable to shareholders of Cellectis ($/share) (1.58) (1.05)Diluted adjusted net income (loss) attributable to shareholders of Cellectis from discontinued operations ($/share) (0.11) (0.08) Weighted average number of outstanding shares, diluted (units) 45,511,626 54,231,943 *These amounts reflect adjustments made in connection with the presentation of the discontinued operation About Cellectis Cellectis is a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies. Cellectis utilizes an allogeneic approach for CAR-T immunotherapies in oncology, pioneering the concept of off-the-shelf and ready-to-use gene-edited CAR T-cells to treat cancer patients, and a platform to make therapeutic gene editing in hemopoietic stem cells for various diseases. As a clinical-stage biopharmaceutical company with over 23 years of experience and expertise in gene editing, Cellectis is developing life-changing product candidates utilizing TALEN®, its gene editing technology, and PulseAgile, its pioneering electroporation system to harness the power of the immune system in order to treat diseases with unmet medical needs. Cellectis’ headquarters are in Paris, France, with locations in New York, New York and Raleigh, North Carolina. Cellectis is listed on the Nasdaq Global Market (ticker: CLLS) and on Euronext Growth (ticker: ALCLS). Forward-looking StatementsThis press release contains “forward-looking” statements within the meaning of applicable securities laws, including the Private Securities Litigation Reform Act of 1995. Forward-looking statements may be identified by words such as “anticipate”, “expect”, “plan”, “could”, “will,” “accelerate,” “suggest,” “eligible,” “encouraging”, “believe”, subject to,” “potential,” “up to,” and “may” or the negative of these and similar expressions. These forward-looking statements, which are based on our management’s current expectations and assumptions and on information currently available to management, including information provided or otherwise publicly reported by our licensed partners. Forward-looking statements include statements about the potential payments for which Cellectis is eligible under the Collaboration Agreement; the possible size of the proposed equity investment by AstraZeneca, the preliminary results for the NATHALI-01 and BALLI-01 clinical trials and the objectives of such trials, which remain ongoing; the ability to progress our clinical trials and to present any additional data from these trials; clinical outcomes from our clinical trials, which may materially change as more patient data becomes available, potential benefits of our UCART product candidates, the operational capabilities at our manufacturing facilities, and the sufficiency of cash to fund our operations. These forward-looking statements are made in light of information currently available to us and are subject to numerous risks and uncertainties, including (i) the numerous risks associated with biopharmaceutical product candidate development, (ii) with respect to the AstraZeneca agreements, the risk that conditions to closing, including necessary regulatory approvals, are not satisfied in a timely manner or at all; the risks arising from Cellectis’s reliance on AstraZeneca to conduct certain development and commercialization activities, including the potential for disagreements or disputes under the Collaboration Agreement; the risk that AstraZeneca may exercise its discretion in a manner that limits the resources contributed toward the development of certain projects under the Collaboration Agreement or may exercise its faculty to terminate without cause the Agreement; the risk that subsequent studies and ongoing or future clinical trials may not generate favorable data; and the risk that the Company may not be able to secure additional capital on attractive terms, if at all, and (iii) our cash runway, our operating plans, including product development plans, may change as a result of various factors, including factors currently unknown to us. Furthermore, many other important factors, including those described in our Annual Report on Form 20-F and the financial report (including the management report) for the year ended December 31, 2022 and subsequent filings Cellectis makes with the Securities Exchange Commission from time to time, as well as other known and unknown risks and uncertainties may adversely affect such forward-looking statements and cause our actual results, performance or achievements to be materially different from those expressed or implied by the forward-looking statements. Except as required by law, we assume no obligation to update these forward-looking statements publicly, or to update the reasons why actual results could differ materially from those anticipated in the forward-looking statements, even if new information becomes available in the future. For further information on Cellectis, please contact:     Media contact:       Patricia Sosa Navarro, Chief of Staff to the CEO, +33 (0)7 76 77 46 93, media@cellectis.com  Investor Relations contacts:       Arthur Stril, Chief Business Officer, +1 (347) 809 5980, investors@cellectis.com       Ashley R. Robinson, LifeSci Advisors, +1 617 430 7577  1 Cash position includes cash, cash equivalents and restricted cash. Restricted cash was $5 million as of September 30, 2023.2 Servier is a global independent pharmaceutical group. Attachment Press release earnings Q3 2023_ENGLISH

SUZHOU, China, and ROCKVILLE, Md., Oct. 15, 2023 /PRNewswire/ -- Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancer, chronic hepatitis B (CHB), and age-related diseases, announced today that it has entered into a clinical collaboration with AstraZeneca Investment (China) Co., Ltd. (or "AstraZeneca"). The two companies will jointly conduct a registrational Phase III study of the Bcl-2 inhibitor, APG-2575 (lisaftoclax), in combination with AstraZeneca's Bruton's tyrosine kinase (BTK) inhibitor, CALQUENCE® (acalabrutinib), in treatment-naive patients with first-line chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL). This global multi-center, randomized-controlled, open-label, pivotal Phase III confirmatory trial is designed evaluate the efficacy and safety of lisaftoclax combined with acalabrutinib versus immunochemotherapy in patients with treatment-naïve CLL/SLL. This collaboration marks another step-forward in the joint clinical development of the lisaftoclax plus acalabrutinib combination by Ascentage Pharma and AstraZeneca. In June 2020, Ascentage Pharma entered into a clinical collaboration with Acerta Pharma, a research and development center of the AstraZeneca Group, to jointly conduct a global Phase II study designed to assess the safety, tolerability, and efficacy of lisaftoclax, Ascentage Pharma's investigational Bcl-2 selective inhibitor, in combination with acalabrutinib, Acerta Pharma's BTK inhibitor. In the study, lisaftoclax combined with acalabrutinib showed strong therapeutic potential, with an objective response rate (ORR) of 98% in patients with relapsed/refractory (R/R) CLL/SLL, an ORR of 100% in treatment-naïve patients with CLL/SLL, and an excellent safety profile that is on par with that of lisaftoclax monotherapy[1]. Those results were released as an Oral Presentation at the 2022 American Society of Hematology (ASH) Annual Meeting. CLL/SLL is a hematologic malignancy caused by mature B-cell neoplasms. Primarily affecting older populations, CLL/SLL is among the most common leukemia subtypes in adults and accounts for a quarter of all leukemia cases in the Western World, with over 100,000 new diagnoses reported globally each year[2]. In China, CLL/SLL is occurring at a rapidly rising incidence rate, with a younger age of onset and higher aggressiveness[3], thus posing a serious threat to public health in the country. Advancements in basic research and targeted therapies have brought meaningful survival benefit to patients with CLL/SLL. However, CLL/SLL still presents major clinical challenges and urgent medical needs for new treatment options that can offer both efficacy and safety. Lisaftoclax is a novel, orally administered small-molecule Bcl-2 selective inhibitor being developed by Ascentage Pharma to treat malignancies by selectively blocking the antiapoptotic protein Bcl-2 and hence restoring the normal apoptosis process in cancer cells. With strong global best-in-class potential, lisaftoclax is the first Bcl-2 inhibitor in China and the second anywhere globally that has demonstrated compelling clinical activity and entered a pivotal registrational study. At present, lisaftoclax is being evaluated in multiple clinical studies across the world and more than 300 patients with CLL/SLL have already been treated with the drug. Interim results suggest that lisaftoclax, both as a monotherapy and in combination regimens, offers potent efficacy in patients with CLL/SLL and has the potential as a safer, more efficacious and more patient-friendly treatment option. It is also worth noting that in August 2023, lisaftoclax was cleared by the US Food and Drug Administration (FDA) to enter a global registrational Phase III study designed to assess the efficacy and safety of lisaftoclax combined with a BTK inhibitor in patients with CLL/SLL who have received prior therapies. Acalabrutinib, a new generation highly selective BTK inhibitor that can specifically inhibit the BTK pathway, is a globally-adopted standard of care treatment for patients with CLL. In 2017, acalabrutinib was approved through the Priority Review process by the US Food and Drug Administration (FDA) for the second-line treatment of patients with mantle cell lymphoma (MCL), and subsequently in 2019, the drug was approved for the additional indication of adult patients with CLL/SLL. Meanwhile, acalabrutinib has been approved in more than 50 countries/regions, such as European Union and Japan until now. In China this year, acalabrutinib was sequentially approved for two indications that include patients with MCL who have received at least one prior therapy; and adult patients with CLL/SLL who have received at least one prior therapy. Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, said, "Combining Bcl-2 inhibitors and BTK inhibitors as a therapeutic approach has long attracted interest from both the research community and the industry. The Bcl-2 inhibitor lisaftoclax is a key drug candidate in Ascentage Pharma's apoptosis-targeted pipeline. Results from the global Phase II study of lisaftoclax combined with acalabrutinib show that the combination regimen holds the promise as a patient-centric treatment strategy with enormous therapeutic potential. The clinical management of CLL/SLL overseas has already entered an era that is free of chemotherapies, and patients in China also desperately need a safer and more effective Bcl-2 inhibitor that can be combined with BTK inhibitors. Fulfilling our mission of addressing unmet clinical needs in China and around the world, we will work closely with AstraZeneca to actively advance this clinical development program of lisaftoclax and try to bring the drug to market as soon as possible for the benefit of more patients." Ms. Haiying Yang, Vice President and Head of Medical Affairs at AstraZeneca China, commented, "Phase III results from the ASCENT, ELEVATE-TN, and ELEVATE-RR trials have solidified AstraZeneca's position in the hematology field, while acalabrutinib-based combination regimens have been widely adopted as standard of care treatments. BTK inhibitors offer survival benefits to patients with lymphoma. However, there remains substantial clinical challenges in this therapeutic area and patients are in desperate need for new therapies that are both safe and efficacious, particularly fixed duration therapies. We are confident that acalabrutinib-based combinations can bring more effective and precision-targeting therapies to patients with hematologic malignancies in China as we take further steps in rendering hematologic malignancies into manageable chronic conditions. Through these innovative partnerships with local Chinese companies, we aspire to expand to more therapeutic areas and bring clinical benefit to a broader population of cancer patients in China." References About Ascentage Pharma Ascentage Pharma (6855.HK) is a globally focused biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B, and age-related diseases. On October 28, 2019, Ascentage Pharma was listed on the Main Board of the Stock Exchange of Hong Kong Limited with the stock code 6855.HK. Ascentage Pharma focuses on developing therapeutics that inhibit protein-protein interactions to restore apoptosis, or programmed cell death. The company has built a pipeline of 9 clinical drug candidates, including novel, highly potent Bcl-2, and dual Bcl-2/Bcl-xL inhibitors, as well as candidates aimed at IAP and MDM2-p53 pathways, and next-generation tyrosine kinase inhibitors (TKIs). Ascentage Pharma is also the only company in the world with active clinical programs targeting all three known classes of key apoptosis regulators. The company is conducting more than 40 clinical trials in the US, Australia, Europe, and China. Ascentage Pharma has been designated for multiple Major National R&D Projects, including five Major New Drug Projects, one New Drug Incubator status, four Innovative Drug Programs, and one Major Project for the Prevention and Treatment of Infectious Diseases. Olverembatinib, the company's core drug candidate developed for the treatment of drug-resistant chronic myeloid leukemia (CML) and the company's first approved product, has been granted Priority Review Designations and Breakthrough Therapy Designations by the Center for Drug Evaluation (CDE) of China National Medical Products Administration (NMPA). To date, the drug had been included into the China 2022 National Reimbursement Drug List (NRDL). Furthermore, olverembatinib has been granted an Orphan Drug Designation (ODD) and a Fast Track Designation (FTD) by the US FDA, and an Orphan Designation by the EMA of the EU. To date, Ascentage Pharma has obtained a total of 16 ODDs, 2 FTDs, and 2 Rare Pediatric Disease (RPD) Designations from the US FDA and 1 Orphan Designation from the EMA of the EU for 4 of the company's investigational drug candidates. Leveraging its robust R&D capabilities, Ascentage Pharma has built a portfolio of global intellectual property rights and entered into global partnerships with numerous renowned biotechnology and pharmaceutical companies and research institutes such as UNITY Biotechnology, MD Anderson Cancer Center, Mayo Clinic, Dana-Farber Cancer Institute, MSD, and AstraZeneca. The company has built a talented team with global experience in the discovery and development of innovative drugs and is setting up its world-class commercial manufacturing and Sales & Marketing teams. One pivotal aim of Ascentage Pharma is to continuously strengthen its R&D capabilities and accelerate its clinical development programs, in order to fulfil its mission of addressing unmet clinical needs in China and around the world for the benefit of more patients. Forward-Looking Statements The forward-looking statements made in this article relate only to the events or information as of the date on which the statements are made in this article. Except as required by law, Ascentage Pharma undertakes no obligation to update or revise publicly any forward-looking statements, whether as a result of new information, future events, or otherwise, after the date on which the statements are made or to reflect the occurrence of unanticipated events. You should read this article completely and with the understanding that our actual future results or performance may be materially different from what we expect. In this article, statements of, or references to, our intentions or those of any of our Directors or our Company are made as of the date of this article. Any of these intentions may alter in light of future development. SOURCE Ascentage Pharma