On March 3, 2022 Cellectis (Euronext Growth: ALCLS – Nasdaq: CLLS), a clinical-stage biotechnology company using its pioneering gene-editing platform to develop potentially life-saving cell and gene therapies, reported its results for the fourth quarter of 2021, and full year ending December 31, 2021 (Press release, Cellectis, MAR 3, 2022, View Source [SID1234609461]).
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"In 2021, Cellectis presented encouraging preliminary data from patients who received fludarabine, cyclophosphamide and alemtuzumab preconditioning in the BALLI-01 study at the American Society of Hematology (ASH) (Free ASH Whitepaper) 2021 annual meeting. BALLI-01 supports our mission to develop products for patients who remain in dire need of effective treatment options. These results showed that our preconditioning regimen, that included alemtuzumab, was well tolerated and promoted the expansion and clinical activity of UCART22 in patients with advanced B-cell Acute Lymphoblastic Leukemia. Both our Raleigh and Paris manufacturing facilities are now fully operational, with Paris producing plasmids, mRNA and viral vectors, and Raleigh manufacturing UCART22 and UCART20x22." said Dr. André Choulika, CEO of Cellectis.
"In 2022, we are focusing on patient recruitment into our three ongoing Phase 1 clinical trials BALLI-01, AMELI-01, MELANI-01, (evaluating UCART22, UCART123, and UCARTCS1 respectively) and plan to file an investigational new drug application (IND) in the U.S. for our first allogeneic dual CAR T-cell therapy, UCART20x22. To further support our clinical trials, and with both manufacturing sites now fully operational, we will start dosing patients with investigational medicinal products made in-house."
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1 Cash position includes cash, cash equivalent, current financial assets and restricted cash. Restricted cash was $5million as of December 31, 2021.
Pipeline highlights
UCART Clinical Development Programs
BALLI-01 (evaluating UCART22) in relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL)
In December 2021, the Company reported preliminary results from the FCA arm of the BALLI-01 study of UCART22, for patients with r/r B-ALL at the 63rd Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) (ASH 2021).
Overall, UCART22 after FCA lymphodepletion regimen demonstrated promising signs of anti-leukemic activity at Dose Level 2 (DL2) and Dose Level 2 Intermediate (DL2i), without unexpected or significant treatment-related toxicity. The preliminary data shows that adding alemtuzumab to the fludarabine and cyclophosphamide (FC) lymphodepletion regimen did not adversely affect the overall safety profile and sustained host lymphocyte suppression and promoted expansion of UCART22.
BALLI-01 is currently enrolling patients at Dose Level 3 (DL3) with FCA preconditioning regimen and Cellectis plans to initiate dosing with a UCART22 product candidate manufactured in-house in H2 2022.
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 being evaluated in patients with r/r AML in the AMELI-01, multi-center dose-escalation clinical study.
AMELI-01 is currently enrolling patients at DL2 with FCA preconditioning regimen.
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, multi-center dose-escalation clinical study.
In May 2021, early preliminary data from the first patients enrolled in the MELANI-01 trial were presented at the American Society of Gene and Cell Therapy (ASGCT) (Free ASGCT Whitepaper) 24th annual meeting. The data validated CS1 as a target for allogeneic CAR T-cells in r/r MM. Moreover, UCARTCS1 expansion and persistence was observed and correlated with changes in relevant serum cytokines and with anti-myeloma activity.
Cellectis is currently enrolling patients at Dose Level 1 (DL1) with FC preconditioning regimen.
UCART Preclinical Programs
UCART20x22 in relapsed or refractory non hodgkin’s lymphoma (r/r NHL)
UCART20x22 is our first allogeneic dual CAR T-cell product candidate being developed for patients with r/r NHL. The dual targeting of CD20 and CD22, both validated targets in B-cell malignancies, is designed both for better tumor cell killing and to prevent antigen escape. Further, UCART20x22 is designed to be active against malignant B-cells that express one or both of the target antigens and to offer an alternative to CD19-directed therapies.
UCART20x22 will also be Cellectis’ first product candidate fully designed, developed and manufactured in-house, showcasing the Company’s transformation into an end-to-end cell and gene therapy platform from discovery, product development, GMP manufacturing, to clinical development.
An Investigational New Drug application (IND) for UCART20x22 is expected to be filed in 2022.
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 being jointly 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 ALLO-501A in the U.S. while Servier retains exclusive rights for all other countries. Allogene’s anti-BCMA and anti-CD70 programs are licensed exclusively from Cellectis by Allogene and Allogene holds global development and commercial rights to these programs.
On January 10, 2022, Allogene announced that the U.S. Food and Drug Administration (FDA) had removed the clinical hold on all of Allogene’s clinical trials which had been announced on October 7, 2021. After extensive investigation by Allogene, it was determined that the chromosomal abnormality detected in a single patient treated with ALLO-501A was unrelated to TALEN gene editing or Allogene’s manufacturing process and had no clinical significance.
Servier and Allogene: anti-CD19 programs
Allogene presented Phase 1 data from the ALPHA trial with ALLO-501 and ALPHA2 trial with ALLO-501A for the treatment of r/r NHL at the 2021 ASH (Free ASH Whitepaper) Annual Meeting. According to Allogene, data from these trials continue to support the promise of its platform to provide a safe and durable alternative to approved autologous CAR T therapies in CAR T naïve patients.
Enrollment in the Phase 1 ALLO-501 ALPHA trial in r/r NHL has completed accrual. Allogene disclosed that its focus remains on preparing for the pivotal Phase 2 ALPHA2 trial of ALLO-501A in R/R Large B Cell Lymphoma (LBCL), which Allogene reports to be on track to begin mid-year 2022 subject to ongoing discussions with the FDA.
As part of a concurrent development plan, Allogene intends to launch a separate registrational trial for ALLO-647, Allogene’s anti-CD52 monoclonal antibody, at the time of the ALLO-501A pivotal Phase 2 trial. This trial is intended to demonstrate the safety of ALLO-647 along with its contribution to the overall benefit of the lymphodepletion regimen.
Allogene: anti-BCMA and anti-CD70 programs
Following the FDA’s clinical hold, Allogene had announced that it has resumed clinical study activities on ALLO-715 and ALLO-605 for r/r MM, and ALLO-316 for advanced or metastatic clear cell renal cell carcinoma (RCC), and began enrolling patients earlier in February 2022.
Allogene’s anti-BCMA strategy includes its Phase 1 UNIVERSAL trial, which has cohorts evaluating ALLO-715 as a monotherapy, consolidated dosing of ALLO-715 using ALLO-647 to selectively extend the window of lymphodepletion, and ALLO-715 in combination with SpringWorks Therapeutics’ investigational gamma secretase inhibitor, nirogacestat.
Data from Allogene’s UNIVERSAL trial with ALLO-715 as a monotherapy for the treatment of r/r MM was also presented at ASH (Free ASH Whitepaper) 2021, with Allogene reporting that response rates that are similar to the approved autologous CAR T therapy.
Manufacturing Facilities
Cellectis’ starting materials manufacturing facility in Paris, France is now fully operational, focusing on the production of starting materials including plasmids and mRNA for our TALEN gene editing technology, and viral vectors for use in clinical manufacturing.
Cellectis’ UCART GMP manufacturing facility in Raleigh, North Carolina is now fully operational, focusing on Cellectis’ clinical and commercial UCART manufacturing operations as well as manufacturing and release testing of batches of product candidates UCART22 and UCART20x22.
Partnerships
Cytovia Therapeutics
On February 12, 2021, we entered into a research collaboration and non-exclusive license agreement with Cytovia Therapeutics, Inc., or Cytovia to develop induced Pluripotent Stem Cell (iPSC) iPSCderived Natural Killer (NK) and CAR-NK cells edited with our TALEN (the "Cytovia Agreement").
Pursuant to the Cytovia Agreement, as expanded in November 2021 to include a new CAR target and development in China by Cytovia’s joint venture entity, CytoLynx Therapeutics, Cellectis is eligible to receive an upfront cash payment or equity stake in Cytovia of $20 million, if certain conditions (the "Cytovia Conditions") were met by December 31, 2021, as well as aggregate additional payments of up to $805 million of development, regulatory and sales milestones from Cytovia. Cellectis is also eligible to receive single-digit royalty payments on the net sales of the partnered products commercialized by Cytovia. Cellectis also received an option to participate in certain future financing rounds by Cytovia. Cellectis is currently in discussions with Cytovia to grant a waiver and to extend the deadline for the Cytovia Conditions, which had not yet been achieved as of December 31, 2021.
Following Cellectis’ previously announced partnership with Iovance Biotherapeutics in tumor-infiltrating lymphocytes, the collaboration with Cytovia in another cell therapy modality highlights TALEN as a gene editing technology of choice for cell therapy applications.
2021 Corporate Highlights
Cellectis’ Innovation Days
In May 2021, Cellectis held a week-long virtual event, providing an inside look into the Company’s current and new product candidates pipeline, manufacturing and technologies. To watch a replay of all Cellectis Innovation Days episodes, click here.
Appointments
On November 4, 2021, Cellectis announced the appointment of Donald A Bergstrom, M.D., Ph.D., as an Observer on the Company’s Board of Directors. Dr. Bergstrom, serves as Executive Vice President, Head of Research and Development at Relay Therapeutics, Inc., a clinical-stage precision medicines company. He brings with him over 15 years of experience in the biopharmaceutical and medical industries.
On February 10, 2022, Cellectis announced the appointment of Bing Wang, Ph.D, MBA as Chief Financial Officer and member of Cellectis’ executive committee. Dr. Wang is a highly accomplished biotechnology executive who brings extensive global finance experience in the biotechnology industry including a background with global public companies in corporate finance, mergers and acquisitions, operations management systems, and financial planning and analysis. He joins Cellectis to oversee the company’s global finance team reporting directly to Chief Executive Officer, André Choulika, PhD.
ATM program
On March 29, 2021, Cellectis announced the commencement of an At-The-Market (ATM) program, pursuant to which it may, from time to time, offer and sell to eligible investors a total gross amount of up to $125.0 million of American Depositary Shares ("ADS"). Each ADS represents one ordinary share of the Company.
On April 9, 2021, the Company announced that it completed sales of approximately $47 million of ADS pursuant to the ATM program, comprising an aggregate of 2,415,630 new ADSs and the same number of underlying new ordinary shares were issued to existing and new investors at an at-the-market price of $19.50 per new ADS.
2021 Financial Results
The condensed consolidated financial statements of Cellectis, which consolidate the results of Calyxt, Inc. of which Cellectis is a 61.8% stockholder (as of December 31, 2021) and 56.1% as of March 3, 2022, have been prepared in accordance with International Financial Reporting Standards, as issued by the International Accounting Standards Board ("IFRS").
We present certain financial metrics broken out between our two reportable segments – Therapeutics and Plants – in the appendices of this Q4 2021 and Full Year 2021 financial results press release.
Fourth Quarter and Full Year 2021 Financial Results
Cash: As of December 31, 2021, Cellectis, including Calyxt, had $191 million in consolidated cash, cash equivalents, current financial assets and restricted cash of which $177 million are attributable to Cellectis on a stand-alone basis. This compares to $274 million in consolidated cash, cash equivalents, current financial assets and restricted cash as of December 31, 2020, of which $244 million was attributable to Cellectis on a stand-alone basis. This net decrease of $83 million primarily reflects (i) $116 million of net cash flows used in operating, investing and lease financing activities of Cellectis, (ii) $20 million of net cash flows used in operating, capital expenditures and lease financing activities of Calyxt and (iii) $6 million of unfavorable FOREX impact which was partially offset by (iv) $49 million of equity proceeds raised from sales under the Company’s "At-The-Market" (ATM) program in April 2021 and Calyxt ATM program during the fourth quarter of 2021 and (v) $10 million of proceeds from stock options exercises at Cellectis. Based on the current operating plan and financial projections, Cellectis excluding Calyxt anticipates that the cash, cash equivalents, and restricted cash of $177 million as of December 31, 2021 will fund its operations into early 2024.
Revenues and Other Income: Consolidated revenues and other income were $14 million for the three months ended December 31, 2021 compared to $16 million for the three months ended December 31, 2020. Consolidated revenues and other income were $67 million for the year ended December 31, 2021 compared to $82 million for the year ended December 31, 2020. 58% of consolidated revenues and other income was attributable to Cellectis in the full year of 2021. This decrease between the year ended December 31, 2021 and 2020 was mainly attributable to a $29 million upfront payment received in March 2020 and the recognition of $20 million of other previously-received upfront and milestone payments on the five released targets based on the March 2020 amendment of the License, Development and Commercialization Agreement signed with Servier. That was partially offset by (i) the recognition of a $20.0 trade receivable obtained as consideration for a license granted to Cytovia, (ii) $10.0 million related to the recognition of two Allogene milestones, (iii) the increase in sales of soybean products at Calyxt for $4 million, and (iv) Calyxt’s Paycheck Protection Program loan forgiveness obtained in April 2021 for 1.5 million, and is partially offset by a decrease in licenses revenues of $2 million.
Cost of Revenues: Consolidated cost of revenues were $2 million for the three months ended December 31, 2021 compared to $19 million for the three months ended December 31, 2020. Consolidated cost of revenues was $31 million for the year ended December 31, 2021 compared to $36 million for the year ended December 31, 2020. This decrease was primarily explained by the cost of products sold during the period by Calyxt.
R&D Expenses: Consolidated R&D expenses were $32 million for the three months ended December 31, 2021 compared to $23 million for the three months ended December 31, 2020. Consolidated R&D expenses were $129 million for the year ended December 31, 2021 compared to $87 million for the year ended December 31, 2020. 91% of consolidated R&D expenses was attributable to Cellectis in the full year of 2021. The $42 million increase between the full year of 2021 and 2020 was primarily attributable to (i) higher wages and salaries and social charges on stock option grants of $14 million, to (ii) higher purchases, external and other expenses of $25 million and to (iii) higher non-cash stock-based compensation expenses of $3 million.
SG&A Expenses: Consolidated SG&A expenses were $10 million for the three months ended December 31, 2021 compared to $12 million for the three months ended December 31, 2020. Consolidated SG&A expenses were $38 million for the year ended December 31, 2021 compared to $44 million for the year ended December 31, 2020. 60% of consolidated SG&A expenses was attributable to Cellectis in the full year of 2021. The $6 million decrease was mainly attributable to lower non-cash stock-based compensation expenses of $6 million and a decrease in wages and salaries of $1 million partially offset by an increase in social charges on stock option grants and purchases, external expenses and other of $1 million.
Net Income (loss) Attributable to Shareholders of Cellectis: The consolidated net loss attributable to shareholders of Cellectis was $25 million (or $0.55 per share) for the three months ended December 31, 2021, of which $21 million was attributed to Cellectis, compared to $41 million (or $0.95 per share) for the three months ended December 31, 2020, of which $34 million was attributed to Cellectis. The consolidated net loss attributable to shareholders of Cellectis was $114 million (or $2.55 per share) for the year ended December 31, 2021, of which $97 million loss was attributed to Cellectis, compared to a loss of $81 million (or $1.91 per share) for the year ended December 31, 2020, of which $54 million was attributable to Cellectis. This $33 million increase in net loss between full year 2021 and 2020 was primarily driven by a decrease in revenues and other income of $15 million and by an increase in operating expenses of $30 million and a decrease in non controlling interests of $5 million partially offset a by $18 million increase in net financial gain.
Adjusted Net Income (Loss) Attributable to Shareholders of Cellectis: The consolidated adjusted net loss attributable to shareholders of Cellectis was $22 million (or $0.48 per share) for the three months ended December 31, 2021, of which $19 million is attributed to Cellectis, compared to a net loss of $37 million (or $0.88 per share) for the three months ended December 31, 2020, of which $31 million was attributed to Cellectis. The consolidated adjusted net loss attributable to Shareholders of Cellectis was $102 million (or $2.27 per share) for the year ended December 31, 2021, of which $85 million loss was attributable to Cellectis, compared to a loss of $67 million (or $1.57 loss per share) for the year ended December 31, 2020, of which $44 million was attributable to Cellectis.
Please see "Note Regarding Use of Non-GAAP Financial Measures" for reconciliation of GAAP net income (loss) attributable to shareholders of Cellectis to adjusted net income (loss) attributable to shareholders of Cellectis.
We currently foresee focusing our cash spending at Cellectis for 2022 in the following areas:
Supporting the development of our pipeline of product candidates, including the manufacturing and clinical trial expenses of UCART123, UCART22, UCARTCS1, UCART20x22, and
Operating our manufacturing capabilities in Paris (France), and Raleigh (North Carolina, U.S.A);
and continuing to strengthen our manufacturing and clinical departments, including hiring talented, highly-qualified individuals
(1) When we have adjusted net loss, in accordance with IFRS, we use the Weighted average number of outstanding shares, basic to compute the Diluted adjusted net income (loss) attributable to shareholders of Cellectis ($/share). When we have adjusted net income, in accordance with IFRS, we use the weighted average number of outstanding shares, diluted to compute the diluted adjusted net income (loss) attributable to shareholders of Cellectis ($/share).
Conference Call and Webcast Details
Cellectis will host a live conference call and live audio webcast on March 4th, 2022 at 8AM EDT / 2:00PM CET to discuss fourth quarter and full year 2021 results and provide a business update.Webcast
Webcast link: View Source;tp_key=c23a20c39e
The webcast audio will be made available for one year on Cellectis’ website, linked here.