T cell replacement therapy (Kiadis Pharma)

Amsterdam, The Netherlands, April 17, 2019 - Kiadis Pharma N.V. (“Kiadis” or the “Company”) (Euronext Amsterdam and Brussels: KDS), a clinical stage biopharmaceutical company, today announced that it has entered a definitive agreement to acquire US-based CytoSen Therapeutics, Inc. (“CytoSen”), subject to Kiadis’ shareholder approval and customary closing conditions. Privately held CytoSen has developed a proprietary natural killer (NK)-cell platform to enable NK-cell therapy with broad anti-cancer potential. It was founded on technology exclusively licensed from the University of Central Florida (UCF) and further developed at Nationwide Children’s Hospital (NCH). The company’s founders, including Dean Lee, Stefan Ciurea and Robert Igarashi, are leading physicians and scientists at NCH, MDACC and UCF, respectively. Following the transaction, Dr. Carl June, a pioneer in the development of CAR T-cell therapy and current scientific advisor to CytoSen, will join Kiadis’ Scientific Advisory Board. The transaction creates a leader in cell-based cancer immunotherapy. The combined company has a complementary development pipeline focused on improving outcomes for patients undergoing hematopoietic stem cell transplants (HSCT). Kiadis’ lead T-cell product ATIR101 is in EU registration and a global Phase 3 clinical trial; CytoSen’s lead NK-cell product candidate, CSDT002-NK, building on promising clinical proof-of-concept studies in 25 patients carried out at MD Anderson Cancer Center, is expected to enter the clinic in the US in 2020. The unique combination of proprietary and synergistic NK-cell and T-cell therapy platforms has the potential to revolutionize HSCT and enables Kiadis to create a pipeline with novel cancer treatments. Arthur Lahr, CEO of Kiadis commented: “Our vision is to leverage the strengths of the human immune system to help patients with life-threatening diseases. With the addition of CytoSen, we can create cell therapy treatments that combine the innate and adaptive arms of the immune system. The ATIR T-cell and CSDT002-NK-cell programs each have the potential to make transplants safer and more effective. In combination, they have the potential to revolutionize HSCT, making it suitable for an even wider group of patients. This transaction will transform Kiadis into a unique company with two synergistic proprietary cell-based immunotherapy platforms and the opportunity to create a pipeline of innovative treatments for cancer patients.” Carl H. June, MD, Richard W. Vague Professor in Immunotherapy in the Department of Pathology and Laboratory Medicine at the University of Pennsylvania, commented: “NK-cell therapy could significantly advance the field of immuno-oncology. Also, I believe the fields of NK-cells and T-cells are enormously synergistic and the combination could potentially help patients with devastating diseases. I am pleased to be joining the Scientific Advisory Board of Kiadis.” Dean A. Lee, MD, PhD, co-founder of CytoSen and director of the Cellular Therapy and Cancer Immunology Program at Nationwide Children’s Hospital (NCH), commented: “CytoSen has the most advanced NK-cell technology to enable NK-cell therapy with broad anti-cancer potential. The strong experience, infrastructure, and competencies of Kiadis in cell therapy will accelerate our delivery of NK-cells to patients, and the new opportunities for exploring NK-cell and T-cell synergies will enable disruptive innovation in the cell therapy space. I am excited to collaborate with Kiadis to bring this innovation to patients.” NK-cells are one of the body’s first lines of immunological defense with an innate ability to rapidly and selectively destroy abnormal cells, such as cancer or virally-infected cells. Advancing research into the biology of NK-cells, as well as emerging early-stage clinical evidence, has increasingly shown that NK-cell immunotherapy has the potential to be at the forefront of cancer immunotherapy. CytoSen’s patented nanoparticle processing technology enables improved ex vivo expansion and activation of NK-cells supporting multiple high dose infusions with potent anti-cancer cytotoxicity. CytoSen’s lead program, CSTD002-NK in HSCT, is built on proof-of-concept studies in 25 patients carried out at MDACC. First results of these studies demonstrated a relapse rate of 8% and progression-free survival (PFS) of 66% (published in Blood, with follow up data presented at the American Society of Hematology (ASH) annual meeting in 2018). The upcoming clinical study with CSDT002-NK, expected to start in 2020, has been designed with and will be supported by the Blood and Marrow Transplant Clinical Trials Network (BMT CTN). The study will enroll high-risk acute myeloid leukemia (AML) patients undergoing a haploidentical HSCT at a consortium of leading US transplant centers in the BMT CTN network. Additionally, CytoSen’s NK-cell therapy will be investigated for other cancer treatments based on an 8-patient proof-of-concept study conducted at MDACC in refractory AML. Transaction Details: At closing, CytoSen shareholders will receive upfront consideration of 1.94 million shares of Kiadis stock. The upfront consideration constitutes approximately 7.4% of Kiadis’ shares outstanding after the transaction. In addition, CytoSen shareholders are eligible to receive potential future consideration of up to 5.82 million additional shares of Kiadis stock upon the achievement of six clinical development and regulatory milestones, with the final milestone being first FDA approval of an NK-cell product based on CytoSen’s technology. The majority of the Kiadis shares issued to the CytoSen shareholders, including to its Executive Chairman and founders, will be subject to a lock-up for a period of two years from closing. At signing, CytoSen held approximately USD 6 million in net cash, which will remain in the combined company. Saola Healthcare Partners acted as financial advisor to Kiadis in the transaction. Shareholder Approval: The transaction is subject to the approval of Kiadis’ shareholders. The Company has called an extraordinary meeting of shareholders (EGM) to be held on Wednesday, May 29, 2019, at which the proposal supporting the transaction will be voted upon. Kiadis’ two largest shareholders (funds represented by and/or affiliated with Life Sciences Partners and Draper Esprit), together representing 31.5% of Kiadis stock, have executed voting agreements in favor of the transaction. In the event that the transaction does not complete because the General Meeting withholds its approval, CytoSen is entitled to a USD 1 million break fee to be paid in cash or Kiadis shares. Kiadis Business Update: Conference Call / Webcast Information: Kiadis’ management will host a webcast / conference call for analysts and investors today, April 17, 2019 at 3:00pm CEST / 2:00pm BST / 9:00am EDT. To participate in the conference call, please call one of the following numbers ten minutes prior to commencement of the call: Confirmation Code: 5737097 Participant dial-ins: Belgium: +32 (0)2 400 6926, Norway: +47 2350 0296, Finland: +358 (0)9 7479 0404, Sweden: +46 (0)8 5065 3942, France: +33 (0)1 76 77 22 57, Switzerland: +41 (0)22 567 5750, Germany: +49 (0)69 2222 2018, United Kingdom: +44 (0)330 336 9411, Netherlands: +31 (0)20 703 8261, United States: +1 323-794-2093. Webcast: https://webcasts.eqs.com/osc20190417 A question and answer session will follow the presentation. The presentation may be accessed by visiting http://www.kiadis.com/financial-news. About CytoSen Therapeutics, Inc.: CytoSen is a private biopharmaceutical company on the front line of advancing development of next generation NK-cells with the first scalable, therapeutic platform for high dose, cancer-killing NK-cells calibrated to each cancer target while reinforcing immune defenses. Born from the intersection of cellular immunotherapy and nanotechnology, CytoSen’s NK-cell therapy harnesses the power of the immune system to treat cancer. About the BMT CTN: The Blood and Marrow Transplant Clinical Trials Network (BMT CTN) conducts multi-institutional clinical trials of high scientific merit, focused on improving survival for patients undergoing hematopoietic cell transplantation (HCT) and/or receiving cellular therapies. The BMT CTN is funded by the National Heart, Lung, and Blood Institute and National Cancer Institute at the National Institutes of Health (NIH) and is a collaborative effort of 20 Core Transplant Centers/Consortia, The Center for International Blood and Marrow Transplant Research (CIBMTR), the National Marrow Donor Program (NMDP)/Be The Match and Emmes, a clinical research organization. CIBMTR is a research collaboration between the NMDP/Be The Match and the Medical College of Wisconsin. More information about the BMT CTN can be found at www.bmtctn.net. About Kiadis Pharma: Kiadis is developing its lead product candidate, ATIR101, for use in conjunction with haploidentical HSCT for adult blood cancers to address key limitations of haploidentical HSCT, without prophylactic immunosuppression and its associated morbidity and mortality. Based on the positive results from the single dose Phase II CR-AIR-007 study, the Company submitted a marketing authorization application to the European Medicines Agency in April 2017 for approval of ATIR101 as an adjunctive treatment in haploidentical HSCT for high risk adult hematological malignancies. If the product is conditionally approved, Kiadis intends to launch ATIR101 in Europe through its own commercial organization by year end 2019. In December 2017, Kiadis commenced an international, multicenter, randomized and controlled Phase III clinical trial of ATIR101 against the Post-Transplant Cyclophosphamide, or PTCy protocol, the main protocol used to perform a haploidentical HSCT. The trial will be performed in 250 patients with acute leukemia and myelodysplastic syndrome at approximately 50 sites in the United States, Canada, Europe and certain additional countries. ATIR101 received regenerative medicine advanced therapy designation from the FDA in September 2017, which provides benefits that are materially equivalent to a breakthrough designation from the FDA. In addition, ATIR101 has been granted multiple orphan Drug designations both in the European Union and the United States. The Company’s shares are listed on Euronext Amsterdam and Brussels under the ticker KDS.

Potential CHMP opinion moved from Q4 2018 into H1 2019 Potential CHMP opinion moved from Q4 2018 into H1 2019 Guidance for initial EU commercial launch in H2 2019 unchanged FDA meeting held under RMAT status Phase 3 study on track with over 20 open sites expected by end 2018, of which several in US Amsterdam, The Netherlands, October 12, 2018 – Kiadis Pharma N.V. (“Kiadis Pharma” or the “Company”) (Euronext Amsterdam and Brussels: KDS ), a clinical-stage biopharmaceutical company, today announces a regulatory and clinical update for ATIR101. Europe EMA Following recent meetings of the Committee for Advanced Therapies (CAT) and the Committee for Medicinal Products for Human Use (CHMP) of the European Medicines Agency (EMA), Kiadis Pharma received a Day 180 second List of Outstanding Issues relating to its marketing authorization application (MAA) for ATIR101. Kiadis Pharma has completed its evaluation of these remaining Day 180 questions. Addressing the questions will require additional analyses of existing clinical data. As expected, no new experimental or new clinical data needs to be generated. EMA has accepted the Company’s request for the time needed to respond to the remaining questions. As a result, the timing of the expected CHMP opinion has moved from the fourth quarter of 2018 into the first half of 2019. Following potential EU approval, which typically follows a positive CHMP Opinion within 67 days, Kiadis Pharma intends to commercially launch ATIR101 in a first EU member state in the second half of 2019, which is unchanged versus previous guidance. US FDA In 2017, the US Food and Drug Administration (FDA) granted ATIR101 the Regenerative Medicine Advanced Therapy (RMAT) designation. Similar to a Breakthrough Therapy designation, RMAT status allows companies developing regenerative medicine therapies to interact with the FDA more frequently, and RMAT-designated products may be eligible for priority review and accelerated approval. As part of its RMAT status, Kiadis Pharma is benefitting from productive interactions with the US FDA, including a recent meeting. Phase 3 clinical trial The Company is on track with the ongoing Phase 3 clinical study to enroll 250 patients at leading transplant centers globally. The Company has now enrolled 22 patients and has 14 sites open in 7 countries. Kiadis Pharma expects to have over 20 sites open by the end of 2018, including several US sites. An interim analysis of the Phase 3 study is expected in the second half of 2020. Arthur Lahr, CEO of Kiadis Pharma, commented: “ We are pleased with our continued clinical and regulatory progress and remain on track for the initial commercial launch of ATIR101 in a first EU country in the second half of 2019. We are confident that we can address the remaining questions from EMA, allowing for a CHMP opinion in the first half of 2019. The FDA granting the RMAT status is a clear validation of the importance of ATIR101 and has resulted in productive interactions with the US FDA. We are very pleased with progress made in our Phase 3 clinical trial to date. We are again a step closer to bringing ATIR101 to patients.” For more information, please contact: Kiadis Pharma: Karl Hård, Head of IR & Communications Tel. +31 611 096 298 k.hard@kiadis.com Optimum Strategic Communications: Mary Clark, Supriya Mathur, Hollie Vile Tel: +44 203 714 1787 David Brilleslijper (Amsterdam) Tel: +31 610 942 514 kiadis@optimumcomms.com About Kiadis Pharma Kiadis Pharma is developing its lead product candidate, ATIR101, for use in conjunction with haploidentical (genetically half-matched) hematopoietic stem-cell transplantations (HSCT) for adult blood cancers to address key limitations of haploidentical HSCT, without prophylactic immunosuppression and its associated morbidity and mortality. Based on the positive results from the single dose Phase 2 CR-AIR-007 study, the Company submitted a marketing authorization application to the European Medicines Agency in April 2017 for approval of ATIR101 as an adjunctive treatment in haploidentical HSCT for high risk adult hematological malignancies. If the product is conditionally approved, Kiadis Pharma intends to launch ATIR101 through its own commercial organization in a first EU member state in the second half of 2019. In December 2017, Kiadis Pharma commenced an international, multicenter, randomized and controlled Phase 3 clinical trial of ATIR101 against the Post-Transplant Cyclophosphamide, (PTCy) protocol, the main protocol used to perform a haploidentical HSCT. The trial will be performed in 250 patients with acute leukemia and myelodysplastic syndrome at approximately 50 sites in the United States, Canada, Europe and certain additional countries. ATIR101 received regenerative medicine advanced therapy (RMAT) designation from the FDA in September 2017, which provides benefits that are materially equivalent to a Breakthrough Therapy designation from the FDA. In addition, ATIR101 has been granted multiple orphan drug designations both in the European Union and the United States. The Company’s shares are listed on Euronext Amsterdam and Brussels under the ticker KDS. Forward Looking Statements Certain statements, beliefs and opinions in this press release are forward-looking, which reflect Kiadis Pharma’s or, as appropriate, Kiadis Pharma’s directors’ current expectations and projections about future events. By their nature, forward-looking statements involve a number of risks, uncertainties and assumptions that could cause actual results or events to differ materially from those expressed or implied by the forward-looking statements. These risks, uncertainties and assumptions could adversely affect the outcome and financial effects of the plans and events described herein. A multitude of factors including, but not limited to, changes in demand, competition and technology, can cause actual events, performance or results to differ significantly from any anticipated development. Forward looking statements contained in this press release regarding past trends or activities should not be taken as a representation that such trends or activities will continue in the future. As a result, Kiadis Pharma expressly disclaims any obligation or undertaking to release any update or revisions to any forward-looking statements in this press release as a result of any change in expectations or any change in events, conditions, assumptions or circumstances on which these forward-looking statements are based. Neither Kiadis Pharma nor its advisers or representatives nor any of its subsidiary undertakings or any such person’s officers or employees guarantees that the assumptions underlying such forward-looking statements are free from errors nor does either accept any responsibility for the future accuracy of the forward-looking statements contained in this press release or the actual occurrence of the forecasted developments. You should not place undue reliance on forward-looking statements, which speak only as of the date of this press release.