Cellectis SA, which last month disclosed plans to file for an IPO of American Depositary Shares (ADS) on the U.S. markets, dropped its paperwork, indicating it will seek to raise up to $115 million, including overallotments, and a listing on the Nasdaq Global Market under the ticker CLLS. The Paris-based company trades on the Alternext market of the Euronext Paris under the symbol ALCLS.

After two big U.S. IPOs in January, for Ascendis Pharma A/S and Spark Therapeutics Inc., and a smattering of smaller closings, the IPO market has taken a bit of a breather, although 20 companies remain in the IPO queue, according to BioWorld Snapshots. During the first two months of the year, six biotechs have raised $545.45 million in U.S. IPOs, with Spark topping the list at $185 million and Inotek Pharmaceuticals Corp. closing the smallest deal at $40.2 million. Bone Therapeutics SA, of Gosselies, Belgium, also completed a €32.2 million (US$36.4 million) IPO this month on the Euronext Exchange. (See BioWorld Today, Nov. 6, 2014, Feb. 2, 2015, and Feb. 5, 2015.)

In comparison, 17 biotechs closed U.S. IPOs during the first two months of 2014, raising a collective $1.2 billion, with deal sizes ranging from $120.97 million for Ultragenyx Pharmaceuticals Inc. down to $37.2 million for Nephrogenex Inc. Despite higher volume last year, the average deal size was lower, at $70.5 million, compared to $90.9 million for the six U.S. IPOs closed so far this year. (See BioWorld Today, Feb. 3, 2014.)

But trends are beside the point when looking at the red-hot chimeric antigen receptor T-cell, or CAR-T, space, where Cellectis already has several pharma deals.

CAR-T technology already is moving rapidly down a variety of promising paths. The Cellectis approach is based on the development of gene-edited T cells that express CAR to create allogeneic CAR-T cells that are derived from healthy donors rather than patients. If the strategy works, products could be manufactured, stored, distributed broadly and infused into patients in an off-the-shelf approach, according to Cellectis.

Pipelines associated with cancer immunotherapy have accelerated several biotechs into the fast lanes, producing stellar IPOs last year for Juno Therapeutics Inc. and Bellicum Pharmaceuticals Inc., which collected $304.8 million and $160.6 million, respectively, in December, and Kite Pharma Inc., which raised $146.6 million in June. (See BioWorld Today, June 23, 2014, and Dec. 22, 2014.)

Although the proposed Cellectis raise is a bit smaller by comparison, the company aims to leapfrog its rivals with its lead allogeneic program, UCART19, expected to begin trials in humans this year.

To that end, in February 2014 Cellectis inked a strategic collaboration with Les Laboratoires Servier SA, also of Paris, to develop and commercialize candidates targeting leukemia and solid tumors, including the UCART19 T-cell therapy, which carries a conventional, single-chain, CD19-directed CAR that targets B cells while activating its T-cell carrier. The genomes of the T cells are edited to remove their ability to express both the T-cell receptor alpha chain and the CD52 antigen – the target of the chronic lymphocytic leukemia drug alemtuzumab (Lemtrada, Genzyme Corp.). Those modifications eliminate the risk of graft-vs.-host disease arising through alloreactivity while leaving open the possible use of alemtuzumab without damaging the transferred T cells, according to Cellectis. (See BioWorld Today, April 2, 2014.)

The Servier deal also included research, development and potential commercialization of five additional candidates targeting solid tumors. Cellectis is responsible for R&D for certain candidates through phase I studies, with Servier granted an exclusive global option to license each candidate under the agreement and to assume responsibility for their clinical development, registration and commercialization.

The collaboration included an up-front payment of $10 million and up to $140 million for each of six candidates in the agreement, based on the achievement of development and commercialization milestones, plus sales royalties.

ENHANCING T-CELL RESPONSE STRENGTH

Cellectis followed up that agreement with an even larger strategic collaboration, in June, with New York-based Pfizer Inc. that included $80 million up front, a $32 million equity investment and up to $2.8 billion in milestone payments. (See BioWorld Today, June 19, 2014.)

The second deal gave Pfizer exclusive rights on CAR-T cell therapies directed at up to 15 oncology targets, for which it will provide research funding, plus another 12 targets selected by Cellectis. Pfizer gained first right of refusal on four of the Cellectis programs, for which it will provide research funding, with the two companies collaborating on preclinical development. Cellectis will work independently on the other eight internal programs.

Industrializing an allogeneic approach to the field would substantially reduce the costs and the logistical complexities associated with autologous or patient-specific approaches, according to Cellectis. Cancer immunotherapies currently in clinical trials are largely based on T cells that are modified ex vivo by the addition of a viral vector, which results in the T cell expressing an extracellular antigen-binding domain – typically an antibody fragment – that is connected, via a transmembrane domain, to a cytoplasmic signaling domain, such as the CD3 T-cell receptor zeta chain. Further iterations involve the addition of a second signaling domain and a co-stimulatory domain, to enhance the strength of the T-cell response.

Cellectis employs the Talens (transcription activator-like effector nucleases) protein-based genome-editing technology to reprogram T cells more comprehensively, using a tailored fusion protein that comprises a selective DNA-binding Tal effector protein with a DNA cleavage domain derived from the FokI bacterial endonuclease.

In its F-1 filing, the company said it plans to file this year for a clinical trial authorization in the UK for UCART19. To advance its strategic agreements, Cellectis also aims to file one investigational new drug application or foreign equivalent per year.

The company's investors include Pfizer and the French government.

Founded in 2000, Cellectis reported $28 million in cash as of June 30, 2014. Although pricing terms and the number of shares were not disclosed, the company's ordinary shares on the Euronext closed at €24.02 (US$27.40) apiece on Feb. 19, the day before the F-1 was filed.

BofA Merrill Lynch, Jefferies, Piper Jaffray and Oppenheimer are joint bookrunners on the deal.