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CD38^KO NK cell therapy has the potential to maximize the efficacy of anti-CD38 against multiple myeloma

Amsterdam, The Netherlands, July 22, 2020 – Kiadis Pharma N.V. (“Kiadis” or the “Company”) (Euronext Amsterdam and Brussels: KDS), a clinical stage biopharmaceutical company developing innovative cell therapeutics for life-threatening diseases, today announces publication of an article in Blood, Journal of the American Society of Hematology. The article describes the synergy of mbIL21 expanded NK cells (FC21-NK) modified with a CD38 gene knockout together with an anti-CD38 monoclonal antibody (mAb) for enhanced killing of multiple myeloma cells.

The publication describes the use of the CRISPR/Cas9 system to delete CD38 (CD38^KO) in ex vivo expanded peripheral blood K-NK cells, with 82% knock out efficiency. These CD38^KO K-NK cells were completely resistant to anti-CD38 antibody-induced fratricide. In addition, as compared to wild type NK cells, the CD38^KO K-NK cells showed superior persistence in immune deficient mice pre-treated with anti-CD38 antibody, and enhanced ADCC activity against CD38-expressing multiple myeloma cell lines and primary multiple myeloma cells. Additionally, analysis demonstrated that CD38^KO K-NK cells have unique metabolic reprogramming with higher mitochondrial respiratory capacity, important in a hypoxic tumor micro-environment. Taken together, these findings provide proof-of-concept that adoptive immunotherapy using ex vivo expanded CD38^KO K-NK cells has the potential to boost anti-CD38 antibody activity in multiple myeloma.

Dean Lee, MD, PhD, co-author of the article, Director of the Cellular Therapy and Cancer Immunology Program at Nationwide Children’s Hospital and The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard Solove Research Institute commented, “This work was a great opportunity to collaborate with Gabriel Ghiaur, MD, PhD, co-author of the article and Assistant Professor of Oncology at The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University. By combining the CRISPR/Cas9 technology with the FC21-NK cell platform we were able to produce and test an engineered NK cell therapeutic to address a recognized hurdle in immunotherapy of multiple myeloma. The ease and efficiency of this approach increases its potential to be translated to the clinic.”

Robert Friesen, chief scientific officer of Kiadis commented, “We are excited to see the published results of this scientific study, the proof-of-concept that targeted knockout of CD38 in highly stimulated NK cells can be synergistically applied to antibody treatments for the potential benefit of patients with multiple myeloma.”

Arthur Lahr, chief executive officer of Kiadis, added “This publication demonstrates that CD38^KO K-NK cells are resistant to killing by anti-CD38 antibodies, and demonstrates how CD38^KO K-NK cells improve potency of anti-CD38 antibodies. This data drove Sanofi’s excitement to license KNK004 for combination with Sarclisa®, to provide better treatment options for multiple myeloma patients. This data showcases the scientific rationale underpinning the collaboration with Sanofi, and should enhance the understanding of the potential of this combination.”

• Senior executives with extensive biotechnology and pharmaceutical industry, science, innovation and business development experience 
• Bringing unique capabilities to unlock broad potential of Kiadis platform 

Amsterdam, The Netherlands, July 13, 2020 – Kiadis Pharma N.V. (“Kiadis” or the “Company”) (Euronext Amsterdam and Brussels: KDS), a clinical stage biopharmaceutical company developing innovative NK-cell therapeutics for patients with life-threatening diseases, today announces that it has appointed Ray Barlow, Ph.D. as chief business officer and Govert Schouten, Ph.D. as head of innovation. As of today, Barlow and Schouten will report to Kiadis’ CEO, Arthur Lahr, and will be members of the Company’s Management Team. Marcel Zwaal, the Company’s senior vice president of corporate development, will be leaving the Company to pursue other opportunities.

Dr. Barlow is responsible for all corporate business development initiatives, including out-licensing, pharma and biotech partnerships, development and commercialization collaborations, and potential mergers and acquisitions. Dr. Schouten is responsible for Kiadis’ intellectual property, scientific and academic collaborations, government grants and in-licensing of science and IP to build Kiadis’ K-NK technology platform.

Arthur Lahr, chief executive officer of Kiadis, commented, “Kiadis’ K-NK-cell therapy platform has almost unlimited potential for the treatment of cancers, infectious diseases and other life-threatening diseases. Ray and Govert have throughout their careers led hundreds of deals with pharma, biotech and academia, and brought in hundreds of millions in licensing fees and government grants. They can make a huge contribution to unlock the value of our platform, for products that we bring to market on our own or with the help of a bigger pharmaceutical company. I want to thank Marcel for all of his contributions to acquire and position our K-NK technology and wish him all the best in his future endeavors. We welcome Ray and Govert and look forward to their contributions to build our pipeline and our K-NK-cell therapy platform.”

With more than 20 years of experience in the biopharmaceutical industry, Ray Barlow has served in various leadership roles including most recently as chief executive officer at e-therapeutics PLC where he led the turnaround of the business and generated its first commercial deals. Previously, Dr. Barlow worked at Amgen as executive director of corporate development and prior to that at Crucell Vaccines where he managed business deals in infectious diseases and vaccines. Prior to joining Crucell, Ray founded and led his own business, BD Solutions Ltd, advising clients on corporate development and commercialization strategies. Dr. Barlow started his career at AstraZeneca where he held a number of senior R&D, Business Development and Commercial roles over a 12-year period. Dr. Barlow holds a Ph.D. in macromolecular science from the University of Manchester, UK, a BSc in Chemistry from the University of Leeds, UK, and an MBA from Manchester Business School, UK.

Govert Schouten brings nearly 25 years of experience in the pharmaceutical and biotechnology industry to Kiadis. Most recently, Dr. Schouten was the founder of Idmon Consulting B.V., a consulting firm providing corporate development, strategy and business development services. Prior to that, Dr. Schouten was co-founder and chief business officer of myTomorrows (Impatients N.V.), chief executive officer of Mucosis B.V., and vice president, head of business development and member of the executive committee of Crucell Vaccines. Dr. Schouten holds a Master’s degree in behavioral sciences and a Ph.D. in tumor virology from Leiden University, The Netherlands.

• Combination of Kiadis’ CD38 knock out K-NK cells with Sanofi’s anti-CD38 antibody Sarclisa® enables optimal tumor cell killing, and offers a potential first-in-class treatment for patients with multiple myeloma
• Kiadis receives €17.5 million up front payment; potential for up to €857.5 million in preclinical, clinical, regulatory and commercial milestone payments, and up to double-digit royalties 
• Kiadis to hold conference call with investors and analysts at 16:00 CET today

Amsterdam, The Netherlands, July 8, 2020 – Kiadis Pharma N.V. (“Kiadis” or the “Company”) (Euronext Amsterdam and Brussels: KDS), a clinical-stage biopharmaceutical company developing innovative natural killer cell therapies for patients with life-threatening diseases, today announces the exclusive license of Kiadis’ previously undisclosed K-NK004 program to Sanofi. The agreement covers Kiadis’ proprietary CD38 knock out (CD38KO) K-NK therapeutic for combination with anti-CD38 monoclonal antibodies, including Sarclisa®, Sanofi’s recently approved therapy for patients with multiple myeloma. Additionally, Sanofi has obtained exclusive rights to use Kiadis’ K-NK platform for two undisclosed pre-clinical programs.

As part of the agreement, Kiadis will receive a €17.5 million up front payment and will be entitled to receive up to €857.5 million upon Sanofi’s achievement of preclinical, clinical, regulatory and commercial milestones. Kiadis will also receive up to low double-digit royalties based on commercial sales of approved products resulting from this agreement.  

Natural killer (NK) cells are the human body’s first line of defense against cancer and infections. Antibodies work synergistically with NK cells to kill tumor cells in a process called antibody-dependent cell-mediated cytotoxicity (ADCC). Treatment of multiple myeloma with anti-CD38 antibodies, such as Sarclisa®, deplete the patients’ own NK cells, as natural NK cells also express CD38. Kiadis’ CD38KO K-NK cells are NK cells that have been modified to prevent expression of CD38, and are thus resistant to this effect. Therefore, adjunctive infusion of CD38KO K-NK cells will reinvigorate the natural synergy between NK cells and antibodies to kill tumor cells, optimizing efficacy.

Arthur Lahr, chief executive officer of Kiadis, commented, “We are proud to announce this collaboration with Sanofi, which marks the start of the previously undisclosed K-NK004 program and expands the application of our K-NK platform into multiple myeloma. The agreement with Sanofi –  with their world-class expertise and approved anti-CD38 monoclonal antibody, Sarclisa, in multiple myeloma and deep understanding of NK-cell biology – is a testament to the groundbreaking potential of our K-NK natural killer cell platform to treat life-threatening diseases.”

John Reed, Global Head of Research and Development at Sanofi, commented, “The licensing of Kiadis’ CD38KO K-NK cells is particularly exciting for Sanofi since we will be studying this cell-based therapeutic with our recently FDA approved treatment for patients with difficult-to-treat multiple myeloma, in hopes of bringing even more options to these patients with this hematologic cancer. At Sanofi, we are committed to pioneering treatments that address unmet healthcare challenges. Innovative collaborations, such as this partnership with Kiadis, have the potential to expand the clinical benefits of our medicines by combining them with synergistic partnered therapeutics to deliver improved outcomes for patients.”

About the Sanofi-Kiadis License Agreement
Sanofi has received exclusive worldwide rights to research, develop and commercialize K-NK004 based on Kiadis’ CD38KO K-NK cells in combination with CD38-targeting molecules for the treatment of multiple myeloma and other CD38 positive blood cancers. Recently, Sanofi received U.S. Food and Drug Administration (FDA) approval for Sarclisa, a monoclonal antibody that targets CD38, for the treatment of multiple myeloma.  Additionally, Sanofi has obtained exclusive rights to use Kiadis’ K-NK platform for two other previously undisclosed pre-clinical programs. The license does not include rights to K-NK002 and K-NK003 or to any other current and future Kiadis programs.

Under the terms of this agreement, Sanofi will be responsible for and bear all costs related to the research and development, manufacturing, regulatory and commercial activities related to the licensed K-NK programs. Kiadis has retained exclusive rights to and will supply PM21 particles and select universal donors for Sanofi, paid for by Sanofi.

About Multiple Myeloma
Multiple myeloma is the second most common hematologic malignancy,¹ affecting more than 130,000 patients in the United States; approximately 32,000 Americans² are diagnosed with multiple myeloma each year. Despite available treatments, multiple myeloma remains an incurable malignancy, and is associated with significant patient burden. As patients relapse, they can become refractory to therapies they have received. There is a need for new agents so that patients and physicians can have options as the disease progresses over time.

IND supports the Company’s planned NK-REALM Phase 1/2 study which will evaluate K-NK002 in 63 patients with blood cancer undergoing a haploidentical hematopoietic stem cell transplant (HSCT)

Amsterdam, The Netherlands, April 9, 2020 – Kiadis Pharma N.V. (“Kiadis Pharma” or the “Company”) (Euronext Amsterdam and Brussels: KDS), a clinical stage biopharmaceutical company, today announced that it has filed an Investigational New Drug (IND) application with the U.S. Food and Drug Administration (FDA) for the Company’s natural killer cell therapy product K-NK002. The IND covers the production of K-NK002 using Kiadis Pharma’s proprietary PM21 technology platform that enables high dose, low cost, scalable and industrial production of NK-cell therapy without the risk of residual tumor cells in the final product. The Company plans to initiate a Phase 1/2 study with leading transplant centers in the U.S. to evaluate K-NK002 once it receives FDA approval for the IND.  

Kiadis Pharma is developing K-NK002 as an adjunctive therapy to the current haploidentical HSCT standard of care with the goal of improving relapse rates. The Phase 1/2 study, called NK-REALM (haploidentical NK-cells to prevent post-transplant RElapse in AML and MDS), will evaluate the use of K-NK002 as an adjunctive therapy for blood cancer patients undergoing a haploidentical HSCT with the current standard of care, post-transplant cyclophosphamide (PTCy) protocol. The study, which will be conducted with the Blood and Marrow Transplant Clinical Trials Network (BMT CTN), will enroll 63 patients at leading transplant centers in the U.S. The study is designed to confirm earlier proof-of-concept data in 24 patients, which showed that adjunctive treatment with K-NK002 has the potential to substantially improve outcomes for patients in need of HSCT.

Arthur Lahr, CEO of Kiadis Pharma, commented, “The filing of this IND is an important step forward for Kiadis in bringing K-NK cell therapy to patients in need. Under normal circumstances, the FDA would take 30 to 60 days to review an IND, but given the current environment it is difficult to project a date for IND approval. Once approved, we are ready to immediately initiate the trial with the BMT CTN, and ramp up production of clinical materials.”

About Kiadis Pharma’s K-NK-Cell Therapies 
Kiadis Pharma’s K-NK platform is designed to deliver potent NK cells to help each patient, without the need for genetic engineering. Kiadis Pharma’s programs consist of off-the-shelf and haploidentical donor NK-cell therapy products for the treatment of liquid and solid tumors as adjunctive and stand-alone therapies. 

The Company’s PM21 particle technology enables improved ex vivo expansion and activation of cytotoxic NK cells supporting multiple high-dose infusions. Kiadis Pharma’s proprietary off-the-shelf NK-cell platform is based on NK cells from unique universal donors and can make NK-cell therapy product rapidly and economically available for a broad patient population across a potentially wide range of indications.

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 Pharma has pre-clinical programs evaluating NK-cell therapy for the treatment of solid tumors. 

• Kiadis will focus all future investments on developing off-the-shelf and haplo donor NK-cell therapies for the treatment of solid and liquid tumors
• Discontinues development of ATIR101, stopping phase 3 trial 
• Restructures organization; reducing workforce by approximately half 

Amsterdam, The Netherlands, 12 November 2019 – Kiadis Pharma N.V. (“Kiadis Pharma” or the “Company”) (Euronext Amsterdam and Brussels: KDS), a clinical-stage biopharmaceutical company, today announced that it has completed a strategic portfolio review and has decided to change its strategy and focus all resources and investments on the company’s NK-cell therapy platform and product candidates. The company will discontinue development of ATIR101 and stop its ongoing phase 3 trial.   

Kiadis’ NK-cell program consists of off-the-shelf and haplo donor cell therapy products for the treatment of liquid and solid tumors. Kiadis’ proprietary off-the-shelf NK-cell platform is based on NK-cells from unique universal donors, expanded and activated ex vivo using our PM21 particle technology. The Kiadis off-the-shelf platform has the potential to make NK-cell therapy products rapidly and economically available for a broad patient population across a potentially wide range of indications.

The company’s pipeline includes:

• K-NK002: A phase 1/2 study will begin in 2020 evaluating K-NK002 as an adjunctive treatment to the current standard-of-care haploidentical hematopoietic stem cell transplantation (HSCT) with post-transplant cyclophosphamide (PTCy). Relapse remains an issue with the PTCy protocol. The phase 1/2 study was designed based on promising clinical proof-of-concept data in 25 patients that demonstrated a reduction of long-term relapse rates from 45% in a matched contemporaneous control of patients treated with PTCy, to 8% of patients treated with PTCy and K-NK002 (Blood 2017, ASCO 2018). The 63 patient phase 1/2 study will be conducted in collaboration with the Bone Marrow Transplant Clinical Trial Network (BMT-CTN), which consists of the premier transplant clinics in the United States.
• K-NK003: A phase 1/2A study will begin in 2020 evaluating K-NK003 as a treatment for patients with relapse and refractory acute myeloid leukemia. The trial is designed based on clinical proof-of-concept data that showed a 69% complete response rate (Haplo 2018).
• Pre-clinical programs: Kiadis has multiple preclinical programs evaluating its K-NK-cell therapies for the treatment of solid tumors.

Arthur Lahr, CEO of Kiadis Pharma commented, “We believe that our proprietary NK-cell therapy platform has broad potential as stand-alone or adjunctive treatments for patients with both liquid and solid tumors. Our off-the-shelf NK-cell platform is based on NK-cells from unique universal donors, expanded and activated with our PM21 particle technology, to make our NK-cell therapy products rapidly and economically available for patients across a potentially broad range of indications. The proof-of-concept trials for our NK pipeline programs, in which 38 patients have been treated, is very promising and was the basis for our acquisition of Cytosen Therapeutics, Inc. earlier this year. To confirm findings from these trials, we will start two Phase 1/2 clinical trials in 2020. We believe that investing in our NK platform and rapidly advancing development of our off-the-shelf and haplo donor derived NK-cell therapies in solid and liquid tumors will bring value to patients and our investors.” 

Lahr continued, “As part of our strategic portfolio review, we reviewed progress of our phase 3 study, which was designed to show superiority of ATIR101 over the PTCy protocol. We identified that in the phase 3 a higher percentage of patients than expected dropped out of the study before receiving ATIR101. We subsequently collected additional recent external data, which show that outcomes with PTCy have better survival and lower severe GVHD than literature showed when we designed and started the phase 3 study. Based on these data, we no longer believe that the phase 3 ATIR study as currently designed with 250 patients can demonstrate superiority over PTCy and at a minimum would require a much larger trial. In the best interest of patients, we have therefore taken the decision to discontinue the ATIR101 study with immediate effect and are proceeding with close down activities.”

Restructuring
Kiadis is implementing a restructuring program to refocus the organization on its NK-cell therapy platform, which will result in a reduction of approximately half of its workforce, a reduction in external clinical trial costs associated with the phase 3 study, and a reduced company cash burn. The company ended the third quarter of 2019 with approximately €47 million of cash.

About Kiadis’ K-NK-Cell Therapies 
Kiadis’ NK-cell programs consist of off-the-shelf and haplo donor cell therapy products for the treatment of liquid and solid tumors as adjunctive and stand-alone therapies.  

Our NK-cell PM21 particle technology enables improved ex vivo expansion and activation of anti-cancer cytotoxic NK-cells supporting multiple high-dose infusions. Kiadis’ proprietary off-the-shelf NK-cell platform is based on NK-cells from unique universal donors. The Kiadis off-the-shelf K-NK platform can make NK-cell therapy product rapidly and economically available for a broad patient population across a potentially wide range of indications.

Administered as an adjunctive immunotherapeutic on top of HSCT, K-NK002 provides functional, mature and potent NK-cells from a haploidentical family member.  In addition, Kiadis is developing K-NK003 for the treatment of relapse/refractory acute myeloid leukemia and has pre-clinical programs evaluating NK-cell therapy for the treatment of solid tumors.