On May 4, 2023 Cellectis, a clinical-stage biotechnology company using its pioneering gene-editing platform to develop life-saving cell and gene therapies, today provided a business update and announced its results for the three-month period ending March 31, 2023 (Press release, Cellectis, MAY 4, 2023, View Source [SID1234632946]).
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"Cellectis took a notable step forward this quarter with the first patient being dosed in France with our in-house manufactured product candidate UCART22 in the BALLI-01 clinical study. UCART22 is currently the most advanced allogeneic CAR T-cell product in development for relapsed or refractory B-cell acute lymphoblastic leukemia. We believe that our off-the-shelf treatment approach, coupled with our ability to manufacture UCART product candidates entirely in-house, gives us a main advantage on the market: it potentially maximizes the chances for eligible patients to be treated without delay", said André Choulika, Ph.D., CEO of Cellectis.
"Cellectis also announced last month that it implemented the use of Sanofi’s alemtuzumab as a Cellectis Investigational Medicinal Product, coded as CLLS52, as part of the lymphodepletion regimen for UCART22 in the BALLI-01 clinical trial, for UCART123 in the AMELI-01 clinical trial, and for UCART20x22 in the NATHALI-01 clinical trial. This follows the partnership and supply agreements we entered with Sanofi regarding alemtuzumab.
This quarter, Cellectis announced the closing of the global offering of 25 million dollars of its Depository Shares, launched in February – the net proceeds of the global offering and option of the Company is 22.8 million dollars – and in April, the drawdown of the 20 million euros under the Finance Contract for up to 40 million euros credit facility made with the European Investment Bank in December 2022. Cellectis plans to use the net proceeds of the funds to focus on the development of its pipeline of allogeneic CAR T-cell product candidates UCART22, UCART20x22 and UCART123, the Company decided to stop enrollment and treatment of patients with UCARTCS1. Indeed, to accelerate the speed of enrollment of patients in the MELANI-01 study, evaluating UCARTCS1, the Company would have had to invest meaningful amount of resources. To optimize its resources, Cellectis decided to focus its development efforts on the BALLI-01, AMELI-01 and NATHALI-01 studies.
We are excited about the drive in our clinical trials, building on the momentum of our lead product candidates in our pipeline, and the upcoming milestones for 2023."
Pipeline Highlights
UCART Clinical Developments Programs
BALLI-01 (evaluating UCART22) in relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL)
UCART22 is an allogeneic CAR T-cell product candidate targeting CD22 and is being evaluated in patients with r/r B-ALL in the BALLI-01 Phase 1/2a clinical study.
On April 11, Cellectis announced that the first patient in Europe was dosed in France with its in-house manufactured product candidate UCART22 and completed the 28-day Dose Limiting Toxicity period.
UCART22 is currently the most advanced allogeneic CAR T-cell product in development for relapsed or refractory B-cell acute lymphoblastic leukemia. Last December, Cellectis presented updated clinical data on its BALLI-01 clinical trial at a Live Webcast.
The BALLI-01 study is now enrolling patients after FCA (fludarabine, cyclophosphamide and alemtuzumab) lymphodepletion.
NATHALI-01 (evaluating UCART20x22) in relapsed or refractory B-cell non-Hodgkin lymphoma (r/r NHL)
UCART20x22 is Cellectis’ first allogeneic dual CAR T-cell product candidate targeting both CD20 and CD22 and is being evaluated in patients with r/r NHL in the NATHALI-01 Phase 1/2a clinical study.
The NATHALI-01 study is now enrolling patients.
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.
On May 17, Cellectis will present clinical data on the AMELI-01 clinical trial in an oral presentation at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 2023 Annual Meeting. These data were presented in an oral presentation at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting last December. Details from the presentation will be available following the event on the Cellectis website at: View Source
The AMELI-01 study is now enrolling patients after FCA (fludarabine, cyclophosphamide and alemtuzumab) lymphodepletion in a two-dose regimen arm.
MELANI-01 (evaluating UCARTCS1) in relapsed or refractory multiple myeloma (r/r MM)
UCARTCS1 is an allogeneic CAR T-cell product candidate targeting CS1 and is being evaluated in patients with r/r MM in the MELANI-01 Phase 1 dose-escalation clinical study.
To accelerate the speed of enrollment of patients in the MELANI-01 study, the Company would have had to invest meaningful amount of resources. To optimize its resources, the Company decided to focus its development efforts on the BALLI-01, AMELI-01 and NATHALI-01 studies and therefore to stop enrollment and treatment of patients in the MELANI-01 study.
Research Data & Preclinical Programs
TALEN-edited MUC1 CAR T-cells
On April 17, Cellectis released preclinical data on TALEN-edited MUC1 CAR T-cells at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2023.
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.
Poster of the presentation is available on Cellectis’ website: View Source
Multiplex engineering for superior generation of efficient CAR T-cells
On May 17, 2023, Cellectis will present preclinical data on multiplex engineering for superior generation of CAR T-cells, at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 2023 Annual Meeting. Details from the presentation will be available following the event on the Cellectis website at: View Source
Licensed Allogeneic CAR T-cell Development Programs
Servier and Allogene: anti-CD19 programs
Allogene continues to enroll patients in the industry’s first potentially pivotal Phase 2 allogeneic CAR T clinical trial with ALLO-501A. Allogene announced that the single-arm ALPHA2 trial will enroll approximately 100 r/r large B cell lymphoma (LBCL) patients who have received at least two prior lines of therapy and have not received prior anti-CD19 therapy. Allogene expects to complete enrollment in H1 2024.After the close of the quarter, Allogene announced that pooled data from the Phase 1 ALPHA/ALPHA2 trials of ALLO-501/501A, in r/r LBCL would be presented at the American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting June 2 – 6, 2023 in Chicago, Illinois.
Allogene: anti-BCMA and anti-CD70 programs
Allogene presented interim data from its Phase 1 TRAVERSE trial of ALLO-316, its first investigational product candidate for solid tumors, during an oral presentation at the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting in April. The ongoing dose escalation study is enrolling patients with advanced or metastatic renal cell carcinoma (RCC) who have progressed on standard therapies that included an immune checkpoint inhibitor and a VEGF-targeting therapy. The data reported to date is primarily from the DL1 and DL2 cohorts.
Anti-tumor activity was primarily observed in patients with tumors confirmed to express CD70 (N=10). Among 18 patients evaluable for efficacy, the disease control rate (DCR) was 89%. In the 10 patients whose tumors were known to express CD70, the disease control rate was 100%, which included three patients who achieved partial remission (two confirmed, one unconfirmed). The longest response lasted until month eight. There was a trend toward greater tumor shrinkage in patients with higher levels of CD70 expression. In patients evaluable for safety (N=19), ALLO-316 demonstrated an adverse event profile generally consistent with autologous CAR T therapies.
Dose escalation in the TRAVERSE trial is expected to be completed in 2023.
During the quarter, data from the Phase 1 UNIVERSAL trial with ALLO-715 for the treatment of r/r multiple myeloma (MM) was published in Nature Medicine. UNIVERSAL is the first allogeneic anti-BCMA CAR T to demonstrate proof-of-concept in MM with response rates that are similar to an approved autologous CAR T therapy. Allogene is evaluating manufacturing processes improvements across its BCMA candidates to achieve optimal performance.
Partnerships
Cytovia Therapeutics, Inc. ("Cytovia")
On January 20, Cellectis announced that it has amended certain financial terms of the $20 million convertible note issued by its partner, Cytovia Therapeutics, in payment of the upfront collaboration consideration provided for pursuant to the research collaboration and non-exclusive license agreement between Cellectis and Cytovia.
The amended and restated note provides for automatic conversion into common stock of Cytovia in the case of certain fundamental transactions pursuant to which Cytovia becomes a public reporting company and for conversion at Cellectis’ option in connection with certain financing transactions, upon a company sale and at final maturity. In each case such conversion is subject to a 9.9% ownership cap, with the balance issuable in the form of pre-funded warrants. Among other changes, the amended and restated note increases the applicable interest rate of the note to 10% per annum, subject to a 10% step up upon the occurrence and continuation of an event of default, provides for the repayment of 50% of the outstanding amount on April 30, 2023 and extends the final maturity date for the repayment of the remaining outstanding amount to June 30, 2023.
Corporate Updates
Global offering and American Depositary Shares (ADS)
On January 4, 2023, Cellectis established an At-The-Market (ATM) Program on Nasdaq. Cellectis has filed a prospectus supplement with the Securities and Exchange Commission ("SEC"), pursuant to which it may offer and sell to eligible investors a maximum gross amount of up to $60.0 million of American Depositary Shares ("ADS"), each representing one ordinary share of Cellectis, nominal value €0.05 per share, from time to time in sales deemed to be an "at the market offering" pursuant to the terms of a sales agreement with Jefferies LLC ("Jefferies"), acting as sales agent. The timing of any sales will depend on a variety of factors.
On February 2, 2023 Cellectis announced the launch of the Cellectis Follow-on Offering in which it offered $22 million of its ADS. Jefferies LLC and Barclays Capital Inc. (the "Underwriters") acted as joint book-running managers for the Global Offering. Pricing occurred on February 2, 2023, at $2.50 per ADS for 8,800,800 ADSs. On February 7, 2023, Cellectis has announced the exercise by the Underwriters 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 an aggregate of 1,107,800 ADSs (the "Additional ADSs"). As a consequence, the total number of ordinary shares issued in the form of ADSs amounted to 9,907,800 for the base offering plus the Option exercise bringing the gross proceed to $24.8 million. The aggregate net proceeds to the Company, after deducting underwriting commissions and estimated offering expenses, amounted to approximately $22.8 million.
The Company plans to use approximately $17.0 million (€15.6 million) of the net proceeds of the Global Offering to fund the continued clinical development of UCART 123, UCART22 and UCART20x22 and any remainder for working capital and other general corporate purposes.
Calyxt and Cibus Merger Agreement
On January 13, 2023, Calyxt and Cibus, and the other parties thereto entered into the definitive Merger Agreement under which Calyxt and Cibus will merge in an all-stock transaction. Under the terms of the Merger Agreement, Calyxt will issue shares of its common stock to Cibus shareholders in an exchange ratio such that upon completion of the merger, Calyxt shareholders are expected to own approximately 5% of the combined company, subject to adjustments permitted by the Merger Agreement. The Boards of Directors of both companies unanimously approved the Calyxt Merger. Concurrent with the execution of the merger agreement, certain officers of Calyxt, all of Calyxt’s directors, and Cellectis executed support agreements in favor of the Calyxt Merger. On March 1, 2023, as stated in the Merger Agreement, Calyxy’s Board authorized the grant of 3,487,503 RSUs to all employees. These awards will vest upon completion of the Transactions, and accordingly, the expense associated with these awards will be recognized over the period from the date of grant to the estimated closing date of the Transactions. Consequently, after the completion of the Transaction, and subject to the issuance of some or all of such RSUs, Cellectis will own approximately 2.4% of Calyxt.
Cellectis currently holds a 48.2 % equity interest in Calyxt. Following the closing of the merger, Cellectis is expected to own approximately 2.4% of the equity interests of the combined company.
Warrant agreement with the European Investment Bank
On April 4, 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.