On March 4, 2020 Cellectis (Paris:ALCLS) (NASDAQ:CLLS) (Euronext Growth: ALCLS – Nasdaq: CLLS), a clinical-stage biopharmaceutical company focused on developing immunotherapies based on gene-edited allogeneic CAR T-cells (UCART), reported its results for the fourth quarter 2019 and full year ended December 31, 2019 (Press release, Cellectis, MAR 4, 2020, View Source [SID1234555173]).
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Earnings Call Details
Cellectis to hold a conference call for investors on March 5, 2020 at 7:30 a.m. EST – 1:30 p.m. CET. The call will include the Company’s fourth quarter 2019 and year-end financial results.
US & Canada only: +1 877-407-3104
International: +1 201-493-6792
In addition, a replay of the call will be available until March 19, 2020 by calling +1 877-660-6853 (Toll Free US & Canada); +1 201-612-7415 (Toll Free International)
Conference ID: 13688263
"Cellectis had strong achievements in 2019, as we are moving forward with the first three Phase 1 clinical trials for our wholly controlled product candidates which started in the fourth quarter – AMELI-01, BALLI-01 and MELANI-01 – in relapsed/refractory Acute Myeloid Leukemia (r/r AML), B-cell Acute Lymphoblastic Leukemia (r/r B-ALL) and Multiple Myeloma (r/r MM) patients, respectively," said Dr. André Choulika, Chairman and CEO, Cellectis. "We further established Cellectis’ position as a leader in the allogeneic and gene-edited cell therapy field through a series of new partnerships, publications and patents. 2020 will be a pivotal year for Cellectis, as we believe our clinical progress will start to show proof-of-concept for our wholly-owned allogeneic CAR T-cell product candidates. Hand-in-hand with our clinical advancements, we are on track with the construction of our in-house manufacturing sites, which are designed to deliver independence and protect our two decades of know-how and expertise in gene editing and cell therapy."
Fourth Quarter 2019 and Recent Highlights
Proprietary Allogeneic CAR T-Cell Development Programs
UCART123 in relapsed/refractory AML patients
In January 2020, the first patient was dosed in our AMELI-01 study, the Phase 1 dose escalation clinical trial evaluating a new version of our UCART123 product candidate in r/r AML. This trial is part of an Investigational New Drug (IND) from the US Food and Drug Administration (FDA) for a new UCART123 construct and an optimized production process, and is evaluating the safety, expansion, persistence and clinical activity of the product candidate in patients with relapsed/refractory AML. AMELI-01 replaces the first US clinical trial assessing the first version of UCART123 product candidate.
AMELI-01 is designed to find the safe and optimal therapeutic dose for UCART123 exploring four different dose levels.
UCART22 in relapsed/refractory B-ALL patients
In December 2019, Cellectis announced the first patient was dosed in our BALLI-01 study, the Phase 1 dose escalation clinical trial evaluating the safety, expansion, persistence and clinical activity of UCART22 in patients with r/r B-ALL.
BALLI-01 is designed to find the safe and optimal therapeutic dose for UCART22 exploring three different dose levels.
Cellectis is planning on filing a protocol amendment with the US FDA to evaluate the addition of alemtuzumab to the lymphodepletion regimen compared to the current regimen with UCART22 in B-ALL. The optimal lymphodepletion regimen prior to the administration of CAR-T product candidates remains an area of investigation in the field of CAR T-cell therapy. As the inventor of the CD52 knockout concept that is already incorporated in the current UCART123, UCART19 and UCART22 constructs to make them compatible with alemtuzumab treatment, Cellectis would explore an alemtuzumab-based lymphodepletion regimen in a separate cohort of patients to guide the future development of UCART22 therapy in CD22+ B-ALL.
This comparative study might not start before the completion of the second cohort of the current BALLI-01 study.
UCARTCS1 in relapsed/refractory MM patients
In October 2019, the first patient was dosed in our MELANI-01 study, the Phase 1 dose escalation clinical trial evaluating the safety, expansion, persistence and clinical activity of UCARTCS1 in patients with relapsed/refractory multiple myeloma (r/r MM).
MELANI-01 is designed to find the safe and optimal therapeutic dose for UCARTCS1 exploring three different dose levels.
Enrollment in the AMELI-01, BALLI-01 and MELANI-01 studies is ongoing as planned. As of today, Cellectis is enrolling patients in the first cohort of all three Phase 1 dose escalation clinical studies.
Partnered Allogeneic CAR T-Cell Development Programs
Cellectis and Servier announced today the execution of the amendment confirming the terms of the term sheet signed on February 18, 2020. Under this amendment, Cellectis grants Servier an expanded exclusive worldwide license to develop and commercialize all next generation gene-edited allogeneic CAR T-cell products targeting CD19, including rights to UCART19/ALLO-501, and ALLO-501A, an anti-CD19 candidate in which the rituximab recognition domains have been removed, either directly or through its US sublicensee Allogene Therapeutics.
In this amendment, financial terms are improved to include an additional USD 27.6 million (EUR 25 million) upfront payment, as well as up to USD 410 million (EUR 370 million) in clinical and commercial milestones. The royalty rate is increased from tiered high single-digit royalties to flat low double-digit royalties based on net sales of products.
In addition, Cellectis regains exclusive control over the five undisclosed allogeneic CAR T-cell targets previously covered by the initial agreement.
GMP Manufacturing
In March 2019, Cellectis executed a lease agreement for an 82,000 square foot commercial-scale manufacturing facility in Raleigh, North Carolina. This new site is being designed to provide GMP manufacturing for clinical supplies and commercial manufacturing upon regulatory approval. In addition, Cellectis is building a 14,000 square foot manufacturing facility in Paris, France. This facility is designed to produce Cellectis’ critical raw and starting material supplies for UCART clinical studies and commercial products. Construction of Cellectis’ in-house GMP Paris and GMP Raleigh manufacturing facilities are on track for their anticipated go-live dates.
Cellectis also announced in October 2019 that it had entered into a manufacturing service agreement with Lonza, covering clinical manufacturing of Cellectis’ allogeneic UCART product candidates. Lonza is responsible for implementing Cellectis’ manufacturing processes at their GMP facility in Geleen, Netherlands, as per current Good Manufacturing Practices (cGMP) that meet the highest quality and safety standards outlined by the FDA.
Scientific publications
Cellectis published a paper in November 2019 in Nature Communications that describes a proof-of-concept for rewiring the cell pathway to create highly intelligent T-cells that can recognize cancerous tumors and cause a micro secretion of therapeutic proteins onto these tumors, which ultimately reshapes the tumor microenvironment and improves the T-cells ability to fight cancer. By utilizing gene editing techniques to rewire the TCRα, CD25 and PD1 genes, the study enabled CAR T-cells to micro secrete the pro-inflammatory cytokine, IL-12, in a tumor and time-dependent manner, paving the way for a next generation of tightly controlled, highly active and potentially safer CAR T-cell treatments.
In January 2020, Cellectis announced the publication of a review titled "Off-the-shelf’ allogeneic CAR T cells: development and challenges" in Nature Reviews Drug Discovery by Prof. Stéphane Depil, Dr. Philippe Duchateau, Prof. Stephan Grupp, Prof. Ghulam Mufti and Dr. Laurent Poirot. The authors review the opportunities and challenges presented by universal allogeneic CAR T-cell therapies, such as the potential of taking T-cells from a healthy donor instead of using patient-derived cells and the challenge that graft-versus-host-disease (GvHD) poses during treatment.
Patent
In November 2019, Cellectis announced that European Patent EP3004337, which claims a method of preparing T-cells for immunotherapy using the CRISPR-Cas9 system, initially granted on August 2, 2017, has been upheld by the European Patent Office (EPO) following an opposition procedure initiated in May 2018.
European Patent EP3004337 claims a method of genetically modifying T-cells by introduction into the cells and/or expression in the cells of an RNA-guided endonuclease, and a specific guide RNA that directs an endonuclease to at least one targeted locus in the T-cell genome, where it is expressed from transfected mRNA and guide RNA is expressed in the cells as a transcript from a DNA vector. The patent also covers the expansion phase of the resulting cells in vitro.
Other Partnerships
In January 2020, Cellectis and Iovance entered into a research collaboration and exclusive worldwide license agreement whereby Cellectis grants Iovance an exclusive license under certain TALEN technology in order to develop tumor infiltrating lymphocytes (TIL) that have been genetically edited to create more potent cancer therapeutics. This license enables Iovance Biotherapeutics’ use of TALEN technology addressing multiple gene targets to modify TIL for therapeutic use in several cancer indications. Financial terms of the license include development, regulatory and sales milestone payments from Iovance Biotherapeutics to Cellectis, as well as royalty payments based on net sales of TALEN-modified TIL products.
Financial Results
The consolidated financial statements of Cellectis, which consolidate the results of Calyxt, Inc. of which Cellectis is a 68.9% stockholder, have been prepared in accordance with International Financial Reporting Standards, or IFRS, as issued by the International Accounting Standards Board ("GAAP").
We present certain financial metrics broken out between our two reportable segments – Therapeutics and Plants – in the appendices of this Q4 2019 and Full Year 2019 financial results press release.
Fourth Quarter and Full Year 2019 Financial Results
Cash: As of December 31, 2019, Cellectis, including Calyxt, had $364 million in consolidated cash, cash equivalents, current financial assets and restricted cash of which $304 million are attributable to Cellectis on a stand-alone basis. This compares to (i) $367 million in consolidated cash, cash equivalents, current financial assets and restricted cash as of September 30, 2019 of which $299 million was attributable to Cellectis on a stand-alone basis and (ii) $453 million in consolidated cash, cash equivalents, current financial assets and restricted cash as of December 31, 2018, of which $358 million were attributable to Cellectis on a stand-alone basis. This net decrease of $89 million for the twelve-month ended December 31, 2019 primarily reflects $69 million in net cash flows used by operating activities, of which $37 million are attributable to Cellectis, and $13 million in acquisitions of property, plant and equipment. We believe that the consolidated cash, cash equivalents, current financial assets and restricted cash position of Calyxt as of December 31, 2019 will be sufficient to fund their operations to mid-2021 while amounts attributable to Cellectis will be sufficient to fund operations into 2022.
Revenues and Other Income: Consolidated revenues and other income were $6 million for the three months ended December 31, 2019 compared to $3 million for the three months ended December 31, 2018. Consolidated revenues and other income were $23 million for the year ended December 31, 2019 compared to $21 million for the year ended December 31, 2018. 68% of consolidated revenues and other income was attributable to Cellectis in 2019. This increase of $2 million between the year ended December 31, 2019 and 2018 was mainly attributable to a milestone of $5 million related to ALLO-715 clinical development and higher Calyxt revenues due to the commercialization of their first products, High Oleic Soybean Oil and High Oleic Soybean Meal. That was partially offset by a decrease in recognition of upfront payments already received and R&D cost reimbursements in relation to the therapeutic collaborations, and other income.
R&D Expenses: Consolidated R&D expenses were $30 million for the three months ended December 31, 2019 compared to $21 million for the three months ended December 31, 2018. Consolidated R&D expenses were $92 million for the year ended December 31, 2019 compared to $77 million for the year ended December 31, 2018. 87% of consolidated R&D expenses was attributed to Cellectis in 2019. The $15 million increase between the year ended December 31, 2019 and 2018 was primarily attributed to higher employee expenses by $5 million, higher social charges on stock option grants by $1 million, higher purchases and external expenses by $9 million and higher other expenses by $6 million. This increase was partially offset by the reduction of non-cash stock-based compensation expenses by $6 million.
SG&A Expenses: Consolidated SG&A expenses were $9 million for the three months ended December 31, 2019 compared to $11 million for the three months ended December 31, 2018. Consolidated SG&A expenses were $43 million for the year ended December 31, 2019 compared to $47 million for the year ended December 31, 2018. 39% of consolidated SG&A expenses was attributed to Cellectis in 2019. The $4 million decrease between the year ended December 31, 2019 and 2018 was primarily attributed to the reduction of non-cash stock-based compensation expenses by $5 million and to lower purchases and external expenses by $3 million. This decrease was partially offset by higher employee expenses and higher social charges on stock option grants by $2 million and higher other expenses by $1 million.
Net Loss Attributable to Shareholders of Cellectis: The consolidated net loss attributable to shareholders of Cellectis was $37 million (or $0.88 per share) for the three months ended December 31, 2019, of which $29 million was attributed to Cellectis, compared to $23 million (or $0.54 per share) for the three months ended December 31, 2018, of which $17 million was attributed to Cellectis. The consolidated net loss attributable to Shareholders of Cellectis was $102 million (or $2.41 per share) for the year ended December 31, 2019, of which $75 million was attributed to Cellectis, compared to $79 million (or $1.93 per share) for the year ended December 31, 2018, of which $60 million was attributed to Cellectis. This $23 million increase in net loss between the full year 2019 and the corresponding prior-year period 2018 was primarily driven by an increase in operating losses of $18 million, of which $10 million was attributed to Calyxt.
Adjusted Net Loss Attributable to Shareholders of Cellectis: The consolidated adjusted net loss attributable to shareholders of Cellectis was $31 million (or $0.73 per share) for the three months ended December 31, 2019, of which $25 million is attributed to Cellectis, compared to $16 million (or $0.37 per share) for the three months ended December 31, 2018, of which $12 million was attributed to Cellectis. The consolidated adjusted net loss attributable to shareholders of Cellectis was $79 million (or $1.86 per share) for the year ended December 31, 2019, of which $60 million is attributed to Cellectis, compared to $44 million (or $1.08 per share) for the year ended December 31, 2018, of which $31 million was attributed 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 on our cash spending at Cellectis for 2020 in the following areas:
Supporting the development of our deep pipeline of product candidates, including the manufacturing and clinical trials expenses of UCART123, UCART22 and UCARTCS1;
Building our state-of-the-art manufacturing capabilities in Paris and Raleigh); and
Strengthening our manufacturing and clinical departments, including hiring talented personnel.
Calyxt plans to focus its cash spending for 2020 in the following areas:
Continuing to drive the commercialization of its High-Oleic Soybean products – High-Oleic Soybean Oil and High-Oleic Soybean Meal;
Supporting its innovative products pipeline; and
Strengthening its commercial and general and administrative support.