Natural Killer Cells from Universal Donors

An Optimum Insight piece

Natural Killer Cells from Universal Donors: has Kiadis Found Immunotherapy’s Killer App?

In Amsterdam, there has just been a glimpse of the future of cellular medicine. Euronext listed Kiadis Pharma (Euronext Amsterdam and Brussels: KDS) recently received US FDA approval[1] to start its NK-REALM phase 2 clinical trial, which the Company submitted through an investigational new drug (IND) application in April 2020, as part of the process towards gaining a green light for the company’s pioneering natural killer (NK) cell platform to be used in clinical trials.

Kiadis’ NK platform, which uses a unique universal donor approach, is being adroitly lined up for regulatory approval for a Phase 1/2 US-based clinical trial in leading transplant centres, with up to 63 blood cancer patients undergoing a haploidentical hematopoietic stem cell transplant (HSCT). These are desperately ill cancer patients, with a high risk of relapse, and there is therefore a lot of interest in novel ways to substantially improve treatment outcomes for such patients with acute myeloid leukemia in need of HSCT. The NK-cells will help fight infections and remaining tumor cells, until the immune system has fully re-grown from stem cells in the transplanted graft.

Natural killer cells are a type of white blood cell and a component of the innate immune system, meaning that they respond to anything that appears to be non-self. NK cells play a major role in the host-rejection of both tumours and virally infected cells. As the name suggests, they are cytotoxic, and work by getting up close and personal with cancer cells, creating pores through the membrane of the target cell, through which they inject enzymes which induce cell death, like a deadly assassin armed with an envenomed blade.

The approach of using off-the-shelf and haploidentical donor NK-cell therapy is attracting significant attention, with some big deals in the space. Shares in San-Diego headquartered Fate Therapeutics (NASDAQ: FATE) surged over 20% early in April when it announced[2] a worldwide collaboration with Janssen for novel induced pluripotent stem cell-derived cell-based cancer immunotherapies, including NK cells. FATE has a market capitalisation of just over $2.6 billion (as of 10th June 2020), and has this past week announced an equity offering. Earlier in the quarter Gilead and its subsidiary Kite Pharma signed a deal to collaborate with Australian biotech Company oNKo-innate in programs to discover NK cell and drug therapies[3]. In November 2019, Takeda also licensed rights to 4 NK-cell programs from MD Anderson[4].

At Kiadis, its K-NK platform, specifically its PM21 particle technology, is designed to deliver potent NK cells to each patient, without the need for repeated harvesting, re-engineering and laborious, time-consuming, ex vivo growth of a patient’s own immune cells to allow multiple doses. The platform’s power as an off-the shelf technology means it can be used to avoid harvest and extensive genetic engineering altogether.

Kiadis’ PM21 particle technology enables improved ex vivo expansion and activation of cytotoxic NK cells supporting multiple high-dose infusions. Kiadis Pharma is developing K-NK002, which is administered as an adjunctive immunotherapeutic on top of HSCT, and K-NK003 for the treatment of relapse/refractory acute myeloid leukemia.  In addition, Kiadis has pre-clinical programs evaluating NK-cell therapy for the treatment of solid tumors.

The company’s technology builds on decades of fundamental research to lead today’s field of NK-cell therapy. Kiadis’ unique particle processing technology enables improved and sustained growth of high-dose NK cells that have a broad repertoire of “killer” anti-cancer functions, creating an immuno-oncology platform with the potential to address some of today’s most difficult cancers. Kiadis moved into the NK space last year through the acquisition[5] of CytoSen Therapeutics Inc., which gave Kiadis control of two NK cell therapy candidates. The deal also brought renowned immunologist and oncologist Carl June, MD, to Kiadis Scientific Advisory Board. Dr June is currently the Richard W. Vague Professor in Immunotherapy in the Department of Pathology and Laboratory Medicine at the Perelman School of Medicine of the University of Pennsylvania[6].

What Kiadis, Fate, and other pioneers developing personalized treatments are trying to do is find a way around one of the major limitations of cellular medicine approaches such as chimeric antigen receptor (CAR) T cell therapies. The problem is the logistically complex and expensive process of producing cell therapies which depend on using patient, or donor, sourced cells. This is like the assassin having to make a different venom for each patient. Several biotech companies are having a stab at this. Kiadis’ solution is a proprietary off-the-shelf NK-cell platform based on NK cells from unique universal donors. These can be used to make NK-cell therapy products rapidly and economically available for a broad patient population across a potentially wide range of cancers.

Such off-the-shelf immunotherapies should overcome the CAR T cell therapy problems of potentially severe side effects such as cytokine release syndrome, sticker-shock price tags, and slow manufacture. Making a life-saving treatment safer, cheaper, and faster is always going to attract interest and investment. Done well, such new approaches to serving patients, their families and care givers, offer hope, reduce suffering, and provide new life.

Investor interest in realising the potential of Kiadis’ NK technology is increasing rapidly. On 30th April 2020 Kiadis announced the closing of a €17 million financing in a private placement with two healthcare focussed investors to fund the business through near-term milestones with its K-NK programs.

The Company has also presented data, abstracts at ASGCT, ASCO 2020 and will be presenting posters at the 25th Congress of the European Hematology Association (EHA) on June 11-14[i].

Amsterdam is firmly on the map for immunotherapy’s killer app.