Cellectis Reports Financial Results for the Fourth Quarter and Full Year 2023

• 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, 2023[1]

 

 

New York, NY – April 29, 2024 - 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.”

 

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 profile of 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 1^st, 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 1^st, 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 38^th 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) 30^th 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.