NKG2D

Mont-Saint-Guibert, Belgium; April 02, 2025, 7:00 pm CET; regulated information – Celyad Oncology (Euronext: CYAD) (the “Company”), today announces its financial results for the fiscal year ended December 31, 2024, and provides a business update. Matt Kane, Chief Executive Officer of Celyad Oncology, commented: “2024 was an important and highly productive year for the Company as it emerged with a lean and efficient new structure. I am incredibly proud of the resilience and ingenuity demonstrated by the team throughout the year.” 2024 business highlights Monetization of its innovative approaches and technologies is a key objective. Celyad Oncology is progressing in this regard and is currently in discussion with potential partners for selected out-licensing of its technologies; The Company continues to address current deficiencies in CAR-T approaches. It has published a review highlighting non-gene editing technologies for allogeneic CAR T-cell therapies in Cells[1] and a review providing an overview of engineering strategies to safely drive CAR T-cells into the future in Frontiers in Immunology [2]; In response to the request expressed by several companies and academic institutions engaged in gene and cell therapies for cardiac applications, the Company has re-initiated the manufacturing and commercialization of C-Cath®, an intra-myocardial injection catheter developed and owned by the Company. 2024 operational highlights Multiplex micro ribonucleic acid (miRNA)-based short hairpin RNA (shRNA) non-gene edited technology platform Last year, the company introduced a chimeric micro-RNA (miRNA) cluster to enable multiplexing of shRNAs, and downregulation of up to four target genes simultaneously in CAR T-cells. In 2024, we further advanced this technology by expanding the platform to a 5-plex system. The novel chimeric cluster demonstrated high efficiency in knocking down five highly relevant genes in CAR T-cells simultaneously. Notably, our non-gene editing technology enabled independent modulation of each target gene to achieve the desired expression levels, thus fine-tuning the functional outcomes based on the specific biology of each target. The feasibility and effectiveness of our multiplex approach to improve allogeneic CAR T-cell viability by avoiding graft-versus-host disease (GvHD) and host-versus-graft (HvG) reaction and promoting cell persistence was demonstrated. Additionally, the feasibility of this platform to withstand the immunosuppressive tumor microenvironment was further demonstrated. Lastly, the secretion of specific cytokines was modulated as a way to reduce the risk of CAR T-cell-related toxicity, and cytokine release syndrome, thus enhancing CAR T-cell safety. Multispecific NKG2D-based CAR T-cell platformPSMA/NKG2DL tandem CAR T-cells, that encompass the extracellular domain of the natural NKG2D receptor fused to an anti-PSMA CAR to overcome antigen heterogeneity were developed and demonstrated these CAR constructs are fully functional in vitro against prostate cancer cell lines that are positive or negative for the tumor-associated antigen PSMA. In vivo data confirmed the superiority of both PSMA/NKG2DL tandem CAR T-cells and NKG2DL single CAR T-cells over PSMA single CAR T-cells in a heterogeneous model of prostate cancer. These data provide a proof-of-concept that NKG2DL are valuable targets in a multispecific CAR approach to treat solid cancer indications; In addition, the in vivo proof-of-concept of the previously developed CD19/NKG2DL tandem CAR T-cell candidate was provided in a B-ALL relapse model, showing that the Company’s multispecific CAR T-cell candidate has an enhanced anti-tumor efficacy in a lymphoma model of antigen-loss as compared to currently existing treatment options. Last year, the company introduced a chimeric micro-RNA (miRNA) cluster to enable multiplexing of shRNAs, and downregulation of up to four target genes simultaneously in CAR T-cells. In 2024, we further advanced this technology by expanding the platform to a 5-plex system. The novel chimeric cluster demonstrated high efficiency in knocking down five highly relevant genes in CAR T-cells simultaneously. Notably, our non-gene editing technology enabled independent modulation of each target gene to achieve the desired expression levels, thus fine-tuning the functional outcomes based on the specific biology of each target. The feasibility and effectiveness of our multiplex approach to improve allogeneic CAR T-cell viability by avoiding graft-versus-host disease (GvHD) and host-versus-graft (HvG) reaction and promoting cell persistence was demonstrated. Additionally, the feasibility of this platform to withstand the immunosuppressive tumor microenvironment was further demonstrated. Lastly, the secretion of specific cytokines was modulated as a way to reduce the risk of CAR T-cell-related toxicity, and cytokine release syndrome, thus enhancing CAR T-cell safety. PSMA/NKG2DL tandem CAR T-cells, that encompass the extracellular domain of the natural NKG2D receptor fused to an anti-PSMA CAR to overcome antigen heterogeneity were developed and demonstrated these CAR constructs are fully functional in vitro against prostate cancer cell lines that are positive or negative for the tumor-associated antigen PSMA. In vivo data confirmed the superiority of both PSMA/NKG2DL tandem CAR T-cells and NKG2DL single CAR T-cells over PSMA single CAR T-cells in a heterogeneous model of prostate cancer. These data provide a proof-of-concept that NKG2DL are valuable targets in a multispecific CAR approach to treat solid cancer indications; In addition, the in vivo proof-of-concept of the previously developed CD19/NKG2DL tandem CAR T-cell candidate was provided in a B-ALL relapse model, showing that the Company’s multispecific CAR T-cell candidate has an enhanced anti-tumor efficacy in a lymphoma model of antigen-loss as compared to currently existing treatment options. Full year 2024 financial review As of December 31, 2024, the Company’s Treasury position amounts to €4.2 million. The Company projects that its existing cash and cash equivalents should be sufficient to fund operating expenses and capital expenditure requirements into the third quarter of 2025. Hence, its existing cash and cash equivalents will not be sufficient to fund its estimated operating and capital expenditures over at least the next 12 months from the date that the financial statements are issued. Refinancing discussions are ongoing. Key financial figures for full-year 2024, compared with full-year 2023, are summarized below: (1) “Treasury position” is an alternative performance measure determined by adding Short-term investments and Cash and cash equivalents from the statement of financial position prepared in accordance with IFRS. Management’s purpose of this measure is to identify the level of cash available internally (excluding external sources of financing) within 12 months. Research and Development (R&D) expenses were €3.2 million in 2024 as compared to €4.6 million in 2023, a year-over-year decrease of €1.4 million. The decrease in the Company’s R&D expenses is primarily driven by the Company’s continuous efforts to reduce significantly the preclinical and clinical costs following the change of business strategy by the Company end of 2022. Furthermore, employee expenses have decreased compared with the year 2023 as a consequence of the Company’s reorganization for the new business model in 2022 and 2023. General and Administrative (G&A) expenses were €3.2 million in 2024 as compared to €6.0 million in 2023, a decrease of €2.8 million. This decrease is primarily related to the decrease of insurances costs, the decrease of employee and consulting fees expenses due to headcount reduction and management changes. Until December 31, 2024, Management has determined that there has been no event (such as a firm sublicense or collaboration contract) that led to a change in fair value of the contingent consideration and other financial liabilities towards Dartmouth and Celdara. The Company’s other income decrease of €1.9 million is mainly related to lower grants income from the Walloon Region of €0.8 million coupled to a one-time income of €1.1 million generated by the sale of certain fixed assets to Cellistic in 2023. Net loss for the year ended December 31, 2024, was €5.8 million, or €0.14 per share, compared to a net loss of €8.5 million, or €0.34 per share, for the same period in 2023. As noted above, the decrease in net loss between periods was primarily due to the decrease of R&D and General and administrative expenses in 2024. Net cash used in operations for the year ended December 31, 2024, which excludes non-cash effects, amounted to €5.7 million, which is far below the net cash used in operations of €15.2 million for the year ended December 31, 2023. Alarm bell status The net assets of the Company per 31 December 2024, on a BE-GAAP non-consolidated basis, having fallen below twenty-five percent of the Company’s capital, the board of directors will submit to the ordinary shareholders meeting on the 20th of May 2025 the proposal to continue the Company’s activities in accordance with article 7:228 of the Belgian Code for Companies and Associations. The board of directors will publish a special report in this respect, by the 18th of April 2024 together with the convening notice with proposed resolutions for the shareholders’ meeting. Annual Report 2024 The Annual Report for the year ended December 31, 2024 will be published on April 04, 2025, and will be available on the Company’s website, www.celyad.com. The Company’s statutory auditor, BDO Réviseurs d’Entreprises SRL, has confirmed that the completed audit has not revealed any material misstatement in the consolidated financial statements. BDO also confirmed that the accounting data reported in the press release are consistent, in all material respects, with the consolidated financial statements from which it has been derived. Financial Calendar 2025 The financial calendar is communicated on an indicative basis and may be subject to change. [1] Cells 2024;13(2):146 [2] Front Immunol. 2024:15:1411393

Astellas remains committed to Xyphos’ Advanced Cellular Control through Engineered Ligands (ACCEL) technology, a company spokesperson said. \n On Astellas Pharma’s mission to develop new cell therapies in cancers and other diseases, not all candidates are destined to reach the finish line. Now, following a review of its pipeline, the Japan-based drugmaker has jettisoned an early CAR-T prospect leveraging technology from its subsidiary Xyphos.The asset in question, an autologous CAR-T dubbed ASP2802 aimed at CD20-positive B-cell lymphomas, had been undergoing a phase 1 trial to determine a suitable dose for further studies as well as the candidate’s tolerability and safety. But an Astellas spokesperson confirmed to Fierce Biotech that “as a result of our prioritization efforts, we have made the difficult decision to terminate ASP2802.”“Astellas is continually evaluating how to streamline its operations and prioritize its resources in our continuous effort to deliver meaningful solutions to our patients,” the spokesperson added.They also noted that the work done on ASP2802 has yielded “important progress” and “drug development knowledge” that will benefit the company’s efforts in other disease areas. Additionally, Astellas remains committed to Xyphos’ Advanced Cellular Control through Engineered Ligands (ACCEL) technology, the spokesperson said.Word of the study\'s termination was first reported by Endpoints News.  Astellas paid $120 million upfront to acquire Xyphos in 2019. As part of the pact, Xyphos is also in line to receive potential development milestone payments that could work out to a total deal value of $665 million, Astellas said at the time.The transaction allowed Astellas to get its hands on Xyphos’ synthetic biology platform, which, in the case of CAR cells, leverages an engineered modification to a natural human receptor known as NKG2D. Through protein engineering, Xyphos has modified several natural ligands of NKG2D, allowing them to be wed with tumor-seeking antibodies among other functional molecules.In turn, CAR cells leveraging this approach can be directed by the ligand-bound antibody to seek, become activated and attack a targeted cancer cell, Astellas and Xyphos have said previously.In the case of ASP2802, which was developed using Xyphos’ technology, the CAR-T prospect was accompanied by a so-called MicAbody protein designed to direct and activate the CAR-T component.Despite the decision to scrap ASP2802, Astellas has stayed busy inking cell therapy deals through Xyphos in recent months. Xyphos linked arms with Kelonia in February 2024 for a research and licensing deal worth more than $800 million. The accord saw the companies combine their technologies to work on up to two programs in immuno-oncology, with the second contingent upon Xyphos opting in.Three months later, Xyphos signed a deal with Poseida Therapeutics to develop two cell therapy candidates for solid tumors that will fuse Poseida’s allogeneic CAR-T platform with Xyphos’ ACCEL technology.Aside from ASP2802, Astellas is working on a wide range of cell therapies seeking to tackle cancers, vascular disease, autoimmune diseases and more. 

Reduces workforce by roughly 40%; expects annualized cost savings of more than $35 million Discontinues development of therapeutics division and commences strategic alternatives process for all in-house therapeutic programs SUNNYVALE, Calif., Nov. 11, 2024 (GLOBE NEWSWIRE) -- 23andMe Holding Co. (Nasdaq: ME) (the “Company” or “23andMe”), a leading human genetics and preventive health company, today announced a business restructuring to streamline operations and reduce costs. In addition, 23andMe is discontinuing further development of all its therapeutics programs, while evaluating strategic alternatives for its clinical and preclinical assets. The Company is reducing its overall headcount by over 200 employees, representing approximately 40% of the workforce. The business restructuring is expected to substantially reduce operating expenses and result in annualized cost savings of more than $35 million. The Company expects to incur up to $12 million in costs and expenses primarily related to one-time severance, transition and termination-related costs. “We are taking these difficult but necessary actions as we restructure 23andMe and focus on the long-term success of our core consumer business and research partnerships,” said Anne Wojcicki, 23andMe’s CEO, Co-Founder, and Chair of the Board. “I want to thank our team for their hard work and dedication to our mission. We are fully committed to supporting the employees impacted by this transition.” Strategic Alternatives Process for Therapeutics Programs In parallel with the discontinuation of its therapeutics division, the Company is actively exploring all strategic options for a limited time to maximize the value of its therapeutics programs, including licensing agreements, asset sales or other transactions. 23andMe intends to wind-down its ongoing clinical trials as quickly as practical, while the strategic alternatives process is ongoing. “We continue to believe in the promise shown by our clinical and preclinical stage pipeline and will continue to pursue strategic opportunities to continue their development. We remain deeply grateful to the patients, investigators and study staff for their participation in our clinical trials,” said Wojcicki. The Company’s therapeutic programs include 23ME-00610 (a Phase 1/2a therapeutic antibody that is designed to restore the immune system’s ability to kill cancer cells by blocking the immune checkpoint CD200R1), 23ME-01473 (a Phase 1 therapeutic antibody that targets ULBP6, which can be expressed and secreted by tumor cells to suppress immune activity), and other preclinical immunology and inflammation programs. 23ME-00610 has demonstrated early monotherapy responses, potential patient selection biomarkers, and combination potential for patients across multiple difficult-to-treat solid tumors and 23ME-01473 has yielded promising preclinical data with a novel NK-cell-activating mechanism. There can be no assurance that the strategic alternatives process for the therapeutics assets will result in any course of action and there is no definitive timeline for completion. About 23ME-00610 (Phase 1/2a)23ME-00610 is a monoclonal antibody that binds to CD200R1 to prevent the interaction of CD200R1 with CD200. Using the world’s largest proprietary database of health and genetic information, 23andMe identified genetic variants of CD200R1, CD200, and DOK2, the downstream signaling protein, associated with higher risks of immune disease and lower risks of cancer, pinpointing CD200R1 as a promising immuno-oncology target. 23ME-00610 has demonstrated preliminary evidence of clinical benefit as monotherapy, including partial responses by RECIST criteria in patients with neuroendocrine tumors and clear-cell renal-cell carcinomas in the Phase 1/2a clinical trial. Additional preclinical data and recent literature validate the CD200-CD200R1 pathway as a potential oncology target for reversing immune tolerance, as a monotherapy or in combination (e.g., with anti-PD-1, anti-VEGF, CAR-T cell therapies). Higher tumor expression of CD200 and human genetics correlated with increased clinical benefit, suggesting potential value as patient selection biomarkers. 23ME-00610 has shown favorable pharmacokinetics (PK) for dosing once every three weeks, expected on-target pharmacologic activity, and a promising safety and tolerability profile suggesting amenability to combination therapies. About 23ME-01473 (Phase 1)23ME-01473 targets ULBP6 to restore anti-tumor immunity through NK and T cells. ULBPs are stress-induced ligands found on the surface of cancer cells that bind to their receptor, NKG2D, on NK and T cells. Cancers escape immune cell recognition by shedding decoy ULBP ligands from their cell surface. ULBP6 has the highest binding affinity to NKG2D, potentially 30 times higher than MICA. Blocking the binding of soluble ULBP6 to NKG2D through ‘1473 may restore immune cell recognition and killing of cancer cells. ‘1473 is also Fc-effector enhanced, which further enables NK cells to induce cell death of ULBP6-expressing cancer cells. ULBP6 was identified as a potential cancer drug target using the 23andMe immuno-oncology (I/O) genetic signature, an approach developed by 23andMe to identify evidence for genetic variants that increase immune function while decreasing cancer risk. Using genetic data, 23andMe can identify immune-related genes that are expected to have an impact on cancer biology. Specifically, germline genetics can reveal which of the immune-related genes harbor genetic variants that also alter an individual's predisposition for developing cancer. About 23andMe23andMe is a genetics-led consumer healthcare company empowering a healthier future. For more information, please visit www.23andMe.com. Contactpress@23andme.cominvestors@23andme.combd@23andme.com Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements, other than statements of historical fact, included or incorporated in this press release are forward-looking statements. The words “believes,” “anticipates,” “estimates,” “plans,” “expects,” “intends,” “may,” “could,” “should,” “potential,” “likely,” “projects,” “predicts,” “continue,” “will,” “schedule,” and “would” or, in each case, their negative or other variations or comparable terminology, are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These forward-looking statements are predictions based on 23andMe’s current expectations and projections about future events and various assumptions. 23andMe cannot guarantee that it will actually achieve the plans, intentions, or expectations disclosed in its forward-looking statements and you should not place undue reliance on 23andMe’s forward-looking statements. These forward-looking statements involve a number of risks, uncertainties (many of which are beyond the control of 23andMe), or other assumptions that may cause actual results or performance to differ materially from those expressed or implied by these forward-looking statements. The forward-looking statements contained herein are also subject generally to other risks and uncertainties that are described from time to time in the Company’s filings with the Securities and Exchange Commission, including under Item 1A, “Risk Factors” in the Company’s most recent Annual Report on Form 10-K, as filed with the Securities and Exchange Commission, and as revised and updated by the Company’s Quarterly Reports on Form 10-Q and Current Reports on Form 8-K. The statements made herein are made as of the date of this press release and, except as may be required by law, the Company undertakes no obligation to update them, whether as a result of new information, developments, or otherwise.