Kiadis Buying CytoSen Will Combine Natural Killer And T-Cell Immunotherapies
Executive Summary
An all-stock transaction will see Europe’s Kiadis and US’s CytoSen bring together complementary approaches to improving stem cell transplants and cancer immunotherapy.
The proposed acquisition of the private US biotech, CytoSen Therapeutics Inc., by the Amsterdam, Netherlands-based Kiadis Pharma Netherlands BV will produce a new company with two synergistic immunotherapy platforms, involving natural killer cells and T-cells, a cell therapy for graft-versus-host disease (GVHD) in leukemia patients nearing the market, and a strengthened position in the key US market.
“No other company has platform technologies targeting both arms of the immune system, innate and adaptive,” believes Kiadis CEO Arthur Lahr. “The immune system is the best protection out there. It’s a better source of innovation than anything people can create,” he told a 17 May briefing on the proposed transaction. And CytoSen is known to the US Blood and Marrow Transplant Clinical Trial Network, which could help the clinical development of the new company’s products in that market.
Natural killer (NK) cells are being researched for their therapeutic potential by several other biotechs, including US/Israeli Gamida Cell Ltd., which has struck a deal with Editas Medicine Inc. to enhance the efficacy of its NAM-NK cells and is in Phase I. (Also see "Deal Watch: Novartis Opts In On Lipoprotein A Candidate From Akcea" - Scrip, 25 Feb, 2019.) Others in the field include NKarta Therapeutics Inc. and Dragonfly Therapeutics Inc.. (Also see "Deal Watch: Boehringer, Epizyme Team Up To Develop Epigenetic Cancer Therapies" - Scrip, 21 Nov, 2018.) There are numerous companies developing T-cell based therapies. (Also see "J.P. Morgan Roundtable: Financing Challenges, And Opportunities, For Complex Therapies" - Scrip, 7 Feb, 2019.)
The belief in the potential benefits of the technologies has led to a slightly unusual structure for the current deal, with CytoSen shareholders receiving Kiadis stock rather than cash, “as they believed in the fundamental potential of their own programs and the synergies of a combination. They also agreed on a two-year lock-up for their Kiadis shares with the same reasoning,” Lahr said.
Under the acquisition, CytoSen shareholders will receive 1.94 million shares of Kiadis stock and will be eligible to receive up to 5.82 million additional shares upon the achievement of six clinical development and regulatory milestones, with the final milestone being US FDA approval of an NK-cell product based on CytoSen’s technology.
Despite the potential of the field, Kiadis and CytoSen have been cautious about outcomes, with a sizable chunk of the value tied to future milestones, and CytoSen being entitled to receive a $1m break-up fee from Euronext-quoted Kiadis if the European company’s shareholders vote against the deal. The acquisition is expected to complete after a meeting of Kiadis shareholders on 29 May.
Cell Therapy Technologies
The acquisition will bring together two cell therapy technologies: Kiadis has a T-cell based immunotherapy, ATIR101, which has been submitted for approval in the EU for use during hematopoietic stem cell transplantation (HSCT), while CytoSen has developed an NK cell therapy candidate, CSDT002-NK in HSCT, which is expected to enter clinical development in 2020, based on a previous proof-of-concept study conducted in 25 patients at the MD Anderson Cancer Center in the US.
The technologies being developed by CytoSen and Kiadis have the potential to make transplants safer and more effective and be used together in future cell-based treatment strategies for cancers and leukemias.
CytoSen’s approach is based on technology exclusively licensed from the University of Central Florida and developed at Nationwide Children’s Hospital. It involves culturing and activating NK cells ex vivo with nanoparticles containing certain antigens and infusing them back into cancer patients.
“With NK cells, numbers matter and it’s crucial to have high doses of NK cells because they don’t follow the same biology as T-cells,” explained Lehr.
In an academic proof-of-concept study, the infusion of CytoSen’s NK cells was associated with a 66% progression-free survival rate and an 8% relapse rate in 25 patients. In a clinical trial set to start in 2020, high-risk acute myeloid leukemia patients will undergo a haploidentical (partially mismatched) HSCT at US transplant centers. Also, the NK cells will be evaluated for other cancer treatments based on an eight-patient proof of concept study conducted at MD Anderson in refractory AML. Dr Carl June, a pioneer of CAR-T cell therapy and a scientific advisor to CytoSen, will join Kiadis’s scientific advisory board.
Kiadis’s lead cell therapy product, ATIR101, is designed to be an adjunct to allogeneic HSCT, and may be of particular benefit when a haploidentical family member is being used as a donor to treat blood cancers – matching donors will not be found in time for many cancer patients who need them, while a haploidentical family member is available for around 95% of patients, although there is a risk of graft-versus-host disease (GVHD).
With ATIR101, the T-cells causing GVHD are removed from a donor T-cell lymphocyte culture by an ex vivo process involving incubating donor cells with cells from the patient, and then adding an agent, TH9402, which is taken up by GVHD-causing T cells and then activated into a cytotoxic agent by light irradiation. This produces a preparation which when given to the patient after HSCT will fight infections and kill any remaining tumor cells while the patient’s immune system takes a number of months to recover via the stem cells in the transplanted graft. It is hoped that prophylactic immunosuppression, with its associated side effects, will not be necessary in ATIR101-treated patients.
An EU marketing application for ATIR101 has been submitted on the strength of a Phase II clinical study, CR-AIR-007, and Kiadis plans to respond to day-180 outstanding issues by the end of May, with EU approval and launch expected by the end of 2019, Lehr said. Kiadis intends to launch ATIR101 in Europe through its own commercialization organization. A global Phase III study is also underway with ATIR1010, with an interim analysis expected in 2021, comparing ATIR101 with post-transplant cyclophosphamide (PTCy), also called the Baltimore protocol.
Kiadis is preparing for EU launch of ATIR101, building up its medical and commercial teams, and establishing a manufacturing facility in Amsterdam, and a patient specific supply chain.