CYAD-01(Dartmouth College)

This week, researchers delivered insights and breakthroughs in regenerative medicine, Long COVID, immuno-oncology and inflammatory diseases. Epigenetic Treatment Shows Potential in Spinal Cord Regeneration Researchers reported that activation of the CBP/p300 protein family led to increased axon growth, regenerative signaling and synaptic plasticity in the spinal cord after injury in mice. The study, led by Imperial College London, used a molecule called TTK21 to activate the genetic program to induce axon regeneration in neurons. During this process, TTK21 changes the epigenetic state by activating the CBP/p300 family of co-activator proteins, effectively leading to increased axon regeneration. In the study, researchers began treating the mice 12 weeks after severe spinal cord injury and continued for 10 weeks. They found axon sprouting in the spinal cord and retraction of motor neurons above the injury. These changes are believed to have been spurred by increased gene expression related to regeneration, which the researchers attributed to the TTK21 treatment. The results, while early and limited, are a step toward potential treatments for spinal cord injury. The next steps will be to enhance the effects of the treatments and trigger the regenerated axons to connect to the rest of the nervous system. The ultimate goal is to enable animals, and eventually people, to regain movement lost from their injuries. Neurological Consequences Evident in Long-Term COVID Study In a recent attempt to decode the long-term impacts of COVID-19, researchers built a dataset from the national healthcare databases of the US Department of Veterans Affairs. The study, led by the Clinical Epidemiology Center, Research and Development Service at VA St. Louis Health Care System, included 154,068 individuals with COVID-19, 5,638,795 contemporary controls and 5,859,621 historical controls. Results were published Thursday in Nature Medicine. Upon examination of the data sets, the researchers noted an increased risk in a series of neurological consequences. These included: ischemic and hemorrhagic strokes, episodic disorders, extrapyramidal and movement disorders, mental health disorders, musculoskeletal disorders, sensory disorders, Guillain-Barré syndrome and encephalitis or encephalopathy. They estimated a hazard ratio of 1.42 neurological sequelae per thousand COVID-19 cases, and 70.69 burdens per 1,000 cases. These numbers were not impacted by the severity of the infection or the need for hospitalization. The researchers note the sample set comprised a majority of white men, so further exploration into other demographic groups may be necessary for future studies. Novo Nordisk and Octagon Unite on Inflammatory R&D Octagon Therapeutics, a pre-clinical biopharmaceutical focused on autoimmune disease, announced the initiation of a multi-year research collaboration with Novo Nordisk to study potential treatments for inflammatory diseases. Octagon will bring its functional target discovery approach and novel chemistry approach, while Novo will contribute its specific disease expertise. Uli Stilz, vice president of the Bio-Innovation Hub at Novo Nordisk, commented on the synergies. “Combined with our disease understanding in the cardiometabolic space and Octagon´s approach in targeting specific lymphocyte populations that drive disease progression, it will be exciting to see what therapeutic discoveries the collaboration can lead to,” he said. Regen's RNA/DNA-Based Cancer Immunotherapy Regen BioPharma announced the filing of a provisional patent application for its RNA/DNA-based approach to cancer immunotherapy. The patent pertains to what Regen believes is “the first combination of an immunotherapy and a gene silencing agent in a single drug.” The novel composition acts as a checkpoint inhibitor drug that also silences the genes that regulate T-cells and cancer cells such as NR2F6 and Survivin. The new drug takes advantage of aptamers - a short RNA or DNA sequence that can also function as an antibody, recognizing specific proteins and binding to them. The proprietary sequence codes for inhibitory RNA, while keeping the aptamer intact on the other side. When it binds to a checkpoint such as PD-1, that RNA is converted within the cell, thus killing it. Used to target cancer cells, this could lead to better disease control and treatment. There is also hope that this process could be used to activate T cells, improving their immunotherapeutic potential. Toronto-Based Researchers Uncover Potential Solve for CAR T Toxicities Allogeneic double-negative (DN) chimeric antigen receptor (CAR)-T cells inhibit tumor growth without off-tumor toxicities, a new study found. Current CAR-T therapies approved by the FDA in treating blood cancers are limited by their level of toxicity and cost of production. Researchers from the Toronto General Hospital Research Institute, University Health Network, reported a new version of these therapies that did not have these drawbacks. The researchers found healthy donor-derived allogeneic DNTs as a CAR-T cell therapy platform had high levels of efficacy in both the human and mouse models. The researchers found the DN CAR-T cells were as effective as previously studied CAR-T cells but did not have the associated toxicity levels. They also come with the advantage of being made from mixed donors and remained effective even after being frozen for long periods of time. This feature could potentially overcome manufacturing challenges in the space. The authors noted these features make “DN CAR-T cells…an attractive “off-the-shelf” CAR-T cell therapy option.”

Celyad achieves important milestone in CYAD-01 treatment evaluation of metastatic colorectal cancer: No toxicity observed to date in first patient enrolled in the SHRINK1 trial (concurrent administration of CYAD-01  with standard chemotherapy) No toxicity observed to date in first patient enrolled in the LINK2 trial (hepatic transarterial administrations) MONT-SAINT-GUIBERT, Belgium, May 03, 2018 (GLOBE NEWSWIRE) -- Celyad (Euronext Brussels:CYAD) (Paris:CYAD) (NASDAQ:CYAD) a clinical-stage biopharmaceutical company focused on the development of CAR-T cell therapies, today announced the successful injection of the first patients in the SHRINK trial and the LINK trial, both targeting metastatic colorectal patients. Dr. Christian Homsy, CEO of Celyad commented: “The infusion of a first patient in a new trial is always an important moment. CYAD-01, concurrently administered with standard chemotherapy FOLFOX in SHRINK, or administered through hepatic transarterial injections in LINK appears to have been well–tolerated to date. We are particularly satisfied with the lack of on target/off tumor toxicity observed to date in the context of the combination of CYAD-01 with chemotherapy. This bolstered our belief that, based on a careful and exhaustive clinical development plan, our product candidate will lead the path towards a therapy for cancer patients.” After the promising signals of clinical activity of CYAD-01 reported in 2017 and validation of the use of the NKG2D receptor, Celyad designed a clinical development plan which aims at defining the best of the following approaches for CYAD-01 in patients with Acute Myeloid Leukemia (AML) and colorectal (CRC) cancers: CYAD-01 as a stand-alone investigational therapy, currently being evaluated in the THINK trial with relapsed refractory AML and CRC patients. Results have already been reported: the world’s first complete response by a CAR-T cell therapy in a patient with refractory and relapsed AML as well as stable diseases reported in colorectal and ovarian cancer patients.CYAD-01 administered concurrently with standard of care treatments. The SHRINK trial was initiated with CRC patients earlier in 2018. We expect that the EPITHINK trial will be initiated soon with AML patients. CYAD-01 administered after preconditioning of the patients using lymphodepletion. We expect trials in AML (DEPLETHINK AML) and CRC (DEPLETHINK CRC) patients to be initiated in the coming weeks. Our objective is to continue with the above approach that offers the best observed safety/efficacy profile and to move forward in later phase clinical trials in both AML and CRC indications. Dr. Frédéric Lehmann, VP Clinical Development and Medical Affairs at Celyad added: “Today’s announcement reflects Celyad’s commitment to develop the potential of CYAD-01 and is the result of our strong collaborations with key academic institutions in both the USA and Europe. Our clinical strategy aims to build on the favorable tolerability profile of CYAD-01 observed to date, and evaluate CYAD-01 in multiple settings to find the best approach for cancer patients. We are making good progress and look forward to sharing further results on SHRINK, LINK and other trials.“ SHRINK is an open-label Phase I trial evaluating the safety and clinical activity of multiple doses of CYAD-01, administered concurrently with the neoadjuvant FOLFOX treatment in patients with resectable liver metastases from colorectal cancer. The dose escalation design of SHRINK includes three dose levels: 1x108, 3x108 and 1x109 of CYAD-01. At each dose, the patients will receive three successive administrations, two weeks apart at the specified dose. No adverse events have been reported in the first injection of the first patient enrolled. LINK is an open-label Phase I trial evaluating the safety and clinical activity of CYAD-01, adopting a loco-regional approach in treating patients with multiple CYAD-01 administration through hepatic transarterial injections to colorectal cancer patients diagnosed with unresectable liver metastases. The dose escalation design of LINK includes three dose levels: 3x108, 1x109 and 3x109 of CYAD-01. At each dose, the patients will receive three successive administrations, two weeks apart at the specified dose. No  adverse events have been reported in the first patient enrolled, who has received his three consecutive CYAD-01 administrations. 1 Standard CHemotherapy Regimen and Immunotherapy with NKG2D 2 Loco-regional Immunotherapy with NKG2D About Celyad Celyad is a clinical-stage biopharmaceutical company focused on the development of specialized CAR-T cell-based therapies. Celyad utilizes its expertise in cell engineering to target cancer. Celyad’s CAR-T cell platform has the potential to treat a broad range of solid and hematologic tumors. Its lead oncology candidate, CYAD-01 (CAR-T NKG2D), has been evaluated in a single dose escalation Phase I clinical trial to assess the safety and clinical activity of multiple administrations of autologous CYAD-01 cells in seven refractory cancers including five solid tumors (colorectal, ovarian, bladder, triple-negative breast and pancreatic cancers) and two hematological tumors (acute myeloid leukemia and multiple myeloma). Celyad was founded in 2007 and is based in Mont-Saint-Guibert, Belgium, and New York, NY. Celyad’s ordinary shares are listed on the Euronext Brussels and Euronext Paris exchanges, and its American Depository Shares are listed on the NASDAQ Global Market, all under the ticker symbol CYAD. For more information, please contact:  CelyadChristian Homsy, CEO and Patrick Jeanmart CFO -  T: +32(0) 10 39 41 00 – investors@celyad.comNicolas Van Hoecke, Director, Investor Relations & Communications - T: +32(0) 10 39 41 48 – nvanhoecke@celyad.comFor Belgium: ComfiGunther De Backer and Sabine Leclercq - T: +32 (0)2 290 90 90 – celyad@comfi.beFor France: NewCapPierre Laurent and Nicolas Mérigeau -  T: + 33 (0)1 44 71 94 94  - celyad@newcap.euFor the rest of Europe and the USA: LifeSci AdvisorsInvestor Relations: Daniel Ferry -  T: +1 (617) 535 7746 – daniel@lifesciadvisors.comPublic Relations: Allison Blum – T:+1 (646) 627 8383 - allison@lifescipublicrelations.com  Subscribe to Celyad’s newsletter at www.celyad.comFollow us on LinkedIn & Twitter @CelyadSA Forward-looking statements In addition to historical facts or statements of current condition, this press release contains forward-looking statements, including statements about the potential safety, activity, efficacy and feasibility of CYAD-01 cell therapy and other product candidates, including current and planned preclinical studies and clinical trials and regulatory filings for Celyad’s product candidates; the clinical and commercial potential of these product candidates and the adequacy of Celyad’s financial resources; the strength of Celyad’s intellectual property portfolio and plans related thereto; Celyad’s expectations regarding its strategic collaborations and license agreements with third parties, including Novartis, Celdara Medical, and Dartmouth College, and the potential impact of such collaborations on Celyad’s future financial condition, including anticipated milestones and royalties and the timing thereof; Celyad’s expected cash burn, which reflect Celyad’s current expectations and projections about future events; and the anticipating timing of Celyad’s 2017 annual report, and involve certain known and unknown 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 forward-looking statements are further qualified by important factors and risks, which could cause actual results to differ materially from those in the forward-looking statements, including risks associated with conducting clinical trials; the risk that safety, bioactivity, feasibility and/or efficacy demonstrated in earlier clinical trials or preclinical studies may not be replicated in subsequent trials or studies; risks associated with the timely submission and approval of anticipated regulatory filings; the successful initiation and completion of clinical trials, including its clinical trials for CYAD-01; risks associated with the successful manufacture of drug product for its clinical trials; risks associated with the satisfaction of regulatory and other requirements; risks associated with the actions of regulatory bodies and other governmental authorities; risks associated with obtaining, maintaining and protecting intellectual property, Celyad’s ability to enforce its patents against infringers and defend its patent portfolio against challenges from third parties; risks associated with competition from others developing products for similar uses; risks associated with Celyad’s ability to manage operating expenses; and risks associated with Celyad’s ability to obtain additional funding to support its business activities and establish and maintain strategic business alliances and business initiatives. A further list and description of these risks, uncertainties and other risks can be found in Celyad’s U.S. Securities and Exchange Commission (SEC) filings and reports, including in its Annual Report on Form 20-F filed with the SEC on April 4, 2017 and subsequent filings and reports by Celyad. Given these uncertainties, the reader is advised not to place any undue reliance on such forward-looking statements. These forward-looking statements speak only as of the date of publication of this document. Celyad expressly disclaims any obligation to update any such forward-looking statements in this document to reflect any change in its expectations with regard thereto or any change in events, conditions or circumstances on which any such statement is based, unless required by law or regulation.