Cellectis [NASDAQ: CLLS]: Pioneering Off-the-Shelf CAR-T Therapy for Cancer Treatment

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Cellectis [NASDAQ: CLLS]: Pioneering Off-the-Shelf CAR-T Therapy for Cancer Treatment

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André Choulika, Founder, Chairman & CEO, Cellectis [NASDAQ: CLLS]André Choulika, Founder, Chairman & CEO
In November 2015, Layla Richards, a one-year-old cancer patient in the U.K. was successfully treated of an aggressive form of cancer after researchers used ‘molecular scissors’ to edit genes and create designer immune cells to cure drug-resistant leukaemia. Diagnosed with acute lymphoblastic leukemia (ALL) when she was just three-months-old, Layla went through several rounds of chemotherapy and a bone marrow transplant in her first year. However, seven weeks after the treatment, Layla’s cancer relapsed and doctors declared that there was nothing more that could be done.

So, the question that arises is: how did her medical team at Great Ormond Street Hospital (GOSH) reverse such a bleak prognosis?

Researchers at GOSH were working in collaboration with the UCL Institute of Child Health (ICH) to develop treatments for some of the rarest and most intractable diseases, including drug resistant cancers such as Layla’s ALL. The team had developed a special type of alternative T-cells called UCART19 using a form of targeted genome editing technology, Transcription Activator-Like Effector Nuclease or TALEN. With special ethical approval, doctors gave this highly-experimental treatment to Layla and to everyone’s delight she responded well. The donor T-cells successfully overpowered her leukaemia and completely cured her of ALL.

The brain behind this breakthrough gene-edited cell treatment, TALEN, is Paris-based Cellectis [NASDAQ: CLLS], a biotech company that is pioneering the concept of off-the-shelf and ready-to-use gene-edited CAR T-cells to treat cancer patients. André Choulika, founder, chairman, and CEO of Cellectis says, “Our main objective is to provide cancer patients with accessible, cost-effective, off-the-shelf allogeneic CAR T-cell therapies across all geographies.”

Established in 1999 as a gene-editing company, today, Cellectis has evolved into a globally-recognized clinical-stage biopharmaceutical firm that is developing a new generation of immunotherapy product candidates equipped to resist mechanisms that inhibit immune system activity. “Gene editing is our biggest strength and the core expertise of the company. We know how to modify any gene in an extremely powerful, safe, and precise manner,” states Choulika.

Robust Allogeneic CAR-T Products

Cellectis has two major immuno-oncology CAR T-cell products known as Universal Chimeric Antigen Receptor T-cells (UCARTs), UCART123 and UCART22. Each of these allogeneic UCART products targets a selected tumor antigen and bears specific engineered attributes, such as compatibility with particular medical regimens that cancer patients may undergo.

UCART123, for instance, targets interleukin-3 receptor (CD123), an antigen expressed at the surface of leukemic cells in acute myeloid leukemia (AML), and other pathologies. Cellectis received the Investigational New Drug (IND) approval from the FDA in 2017 to conduct phase one clinical trials with UCART123 in patients with AML and BPDCN. UCART22, on the other hand, is designed for the treatment of B-cell acute lymphoblastic leukemia (B-ALL) in relapsed and refractory setting. It targets B-cell receptor CD22. In 2018, Cellectis received the FDA approval to initiate a phase one clinical trial for UCART22.

What truly makes Cellectis’ off-the-shelf CAR T-cells unique is they come with properties such as resistance to certain drugs, checkpoint inhibition, and cross-T-cell reaction suppression.
Cellectis aim with these product candidates is to deliver cost-effective treatments designed for optimal dosage as well as that are broadly available and compatible with current standards of cancer care.

Effective Electroporation System

Furthermore, to harness the power of the immune system in order to target and eradicate cancer cells, the firm also uses its pioneering electroporation system, PulseAgile. With the help of this effective treatment modality, Cellectis introduces nucleases inside targeted T-cells, where it can access the cell’s genomic DNA while maintaining high cell viability. A particularly effective combination of high voltage peaks and lower voltage pulses allows PulseAgile to create transient holes in the cell membrane and help mRNA migrate into the cells. “To simply put it, PulseAgile is used to introduce TALEN-encoding mRNA into T-cells to perform the required gene editing,” explains Choulika.

It is this proprietary technology combined with Cellectis’ 19 years of gene editing experience that make it possible to edit any gene with highly precise insertion, deletion, repair, and replacement of DNA sequences. The success of both TALEN and PulseAgile has prompted Cellectis to invest in advancing its gene editing technologies to design a new generation of personalized therapies to address viral infection. For example, the organization is currently working on developing innovative gene editing approaches to treat genetic diseases and metabolic disorders.

Driving Growth through Global Partnerships

Spearheading innovation through partnerships and strategic collaborations with leading companies has always been at the top of the agenda for Cellectis. As a matter of fact, Choulika strongly believes partnerships are fundamental to achieving results. In light of this, the firm has established long-standing partnerships with companies like Allogene Therapeutics, Pfizer, and Servier on CAR T-cells in oncology. “Our mission is to catalyze the next revolution in cancer treatment through the development of allogeneic CAR T-cell therapies. We believe these collaborations will fuel our mission and help us to accelerate the development of allogeneic cell therapies,” articulates Choulika.

Nevertheless, Cellectis is not just a CAR T-cell therapeutics company; the firm’s strong gene editing capabilities also open a vast space of new opportunities. Some of these opportunities are developed by Cellectis on a standalone basis, similar to its CART portfolio, UCART123, and UCART22. The company envisions pursuing new partnerships to expand the applications of its CAR T cell therapies to treat antiviral infections and or some metabolic diseases.

Building a Healthier Future

Recently, intending to enhance production of Cellectis’ UCART products, the company has entered into a lease agreement to build an 82,000 square foot commercial-scale manufacturing facility named Innovative Manufacturing Plant for Allogeneic Cellular Therapies (IMPACT) in Raleigh, North Carolina. In addition, the firm is also building a 14,000 square foot manufacturing facility in Paris named Starting Material Realization for CAR-T products (SMART) to produce Cellectis’ critical starting material supply for UCART clinical studies and commercial products. “By combining the state-of-the-art capabilities that IMPACT and SMART plants will provide, we will gain autonomy, control, and expertise in manufacturing operations, allowing us to continue to build competitive advantage and remain a leader in our field,” exclaims Choulika.

As part of its commitment to find a cure any type of cancer, Cellectis remains dedicated to its goal of coming up with life-saving UCART products to address the unmet needs of cancers such as multiple myeloma (MM), Hodgkin lymphoma (HL), and non-Hodgkin lymphoma (NHL). At the same time, the two-decade-old firm is also working on developing new therapies in the liquid tumor space. As a long-term vision, Cellectis has plans to diversify the company away from the CAR-T oncology space. “The future of cell therapy is in gene editing. Either you perform cell therapy and have a limited future, or you carry out gene editing with cell therapy, and the 21st century is yours,” proclaims Choulika.
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Cellectis [NASDAQ: CLLS]

Paris, France

André Choulika, Founder, Chairman & CEO

A clinical-stage biopharmaceutical company, Cellectis is developing a new generation of cancer immunotherapies based on gene-edited T-cells (UCART). By capitalizing on its 19 years of expertise in gene editing, built on its flagship TALEN technology and pioneering electroporation system, PulseAgile, Cellectis uses the power of the immune system to target and eradicate cancer cells. Using its life-science-focused, pioneering genome engineering technologies, Cellectis’ goal is to create innovative products in multiple fields and with various target markets. The organization is currently headquartered in Paris with additional offices in New York and North Carolina