NKG2D

23ME-01473 inhibited tumor growth in a patient-derived xenograft mouse model of non-small cell lung cancer Elevated levels of soluble and tumor-bound ULBP6 confirmed in squamous cell carcinomas and a subset of adenocarcinomas, offering potential indications to assess clinical activity Phase 1 trial ongoing with first patient dosed in March 2024 SUNNYVALE, CA, USA I September 15, 2024 I 23andMe Holding Co. (Nasdaq: ME) (“23andMe”), a leading human genetics and biopharmaceutical company, announced nonclinical data supporting the anti-tumor activity of its first-in-class 23ME-01473 (’1473) antibody targeting the NKG2D ligand ULBP6 at the European Society of Medical Oncology (ESMO) Congress 2024 in Barcelona, September 13-17. In a poster presentation at the 2024 ESMO Congress, 23andMe Therapeutics presented new data showing that 23ME-01473 inhibits growth of non-small cell lung cancer in a patient-derived xenograft mouse model. The presentation also included data showing elevated plasma soluble and tumor expression levels of ULBP6 in squamous cell carcinomas and a subset of adenocarcinomas. These findings have led to the prioritization of four expansion cohort cancer types for potential further investigation during the Phase 2a dose expansion portion of the Phase 1/2a trial, which began in March 2024: head and neck squamous cell carcinoma, squamous non-small cell lung cancer, colorectal cancer and triple-negative breast cancer. The design of this Phase 1/2a trial was presented in a second Trials-In-Progress presentation at the ESMO Congress. (The 23andMe ESMO posters are available on the 23andMe Therapeutics and Investor websites). “We are excited to share this new preclinical data that support our ongoing clinical trial,” said Jennifer Low, M.D., Ph.D., Head of Therapeutics Development. “This additional data, coupled with our ongoing clinical studies, demonstrates the potential utility of human genetics to identify new targets and develop promising new drugs in the immuno-oncology space.” About 23ME-01473 ’1473 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 ULBP ligands from their cell surface, which act as immunosuppressive molecular decoys. Blocking the binding of soluble ULBP6 to NKG2D through ‘1473 may restore immune cell recognition and killing of cancers. Further, ‘1473 is Fc-effector enhanced, which provides an additional mechanism for 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 the Phase 1 ‘1473 Study The first-in-human, multi-center, open-label clinical trial will determine the safety and tolerability of ‘1473 in people with locally advanced or metastatic solid malignancies that have progressed after standard therapy. This study will also evaluate the pharmacokinetic and pharmacodynamic profile of ‘1473 to identify the optimal dose and schedule for further clinical studies. Clinical trials registry (clinicaltrials.gov): NCT06290388 . For information on enrolling on to this clinical trial contact 650-963-8997 or studyinquiry@23andme.com. About 23andMe 23andMe is a genetics-led consumer healthcare and therapeutics company empowering a healthier future. For more information, please https://therapeutics.23andme.com . SOURCE: 23andMe

Preliminary data from renal cancer and TMB-H/MSI-H cohorts in the Phase 1/2a clinical trial of 23ME-00610 to be presented Analysis of CD200 as an exploratory tissue-based biomarker associated with 23ME-00610 efficacy to be presented Preclinical murine data on 23ME-01473 to be presented; Phase 1/2a dose escalation study ongoing SOUTH SAN FRANCISCO, Calif., Sept. 03, 2024 (GLOBE NEWSWIRE) -- 23andMe Holding Co. (Nasdaq: ME) (“23andMe”), a leading human genetics and biopharmaceutical company, today announced that it will display three poster presentations on 23ME-00610, a first-in-class anti-CD200R1 antibody, and two on 23ME-01473, an anti-ULBP6 monoclonal antibody, at the European Society for Medical Oncology (ESMO) Congress 2024, taking place September 13 – September 17 in Barcelona, Spain. 23andMe will present additional preliminary clinical data, including efficacy data, for the clear-cell renal-cell carcinoma and high tumor microsatellite instability and/or high tumor mutational burden patient cohorts in the Phase 2a portion of its ongoing Phase 1/2a clinical trial evaluating 23ME-00610, as well as share further analyses on an exploratory tissue-based biomarker, CD200. In Phase 2 data presented at the American Society of Clinical Oncology (ASCO) in June, monotherapy 23ME-00610 demonstrated a continued acceptable safety and tolerability profile and preliminary evidence of clinical benefit in neuroendocrine and ovarian cohorts, including one confirmed partial response in a patient with well-differentiated pancreatic neuroendocrine cancer. Additionally, data showed early evidence pointing to CD200 as a potential tissue-based biomarker. The Company will present preclinical data on the 23ME-01473 program, as well as a trials in progress presentation on the Phase 1 clinical trial that began in March 2024. 23ME-01473 targets soluble ULBP6, which is released by cancer cells to promote an immunosuppressive tumor microenvironment. It is also Fc-effector enhanced to provide an additional mechanism for NK cells to induce cell death of ULBP6-expressing cancer cells. 23andMe scientists discovered the targets for 23ME-00610 and 23ME-01473 through the Company’s proprietary database of human genetic and health information. 23andMe has more than 15 million genotyped customers, roughly 80 percent of whom consent to participate in research. 23andMe is able to study the de-identified genetic information of research participants in combination with billions of health data points to identify potential pathways for novel therapeutic targets rooted in human genetic information. Details on the ESMO posters are below. Posters will be available on the 23andMe Therapeutics and Investor websites following the presentations. Abstract: 1069TiPTitle: A Phase 1/2a Dose Escalation and Expansion Study of 23ME-01473, an anti-ULBP6/2/5 Antibody, for Patients with Advanced Solid MalignanciesSession Type: Poster Session – Investigational ImmunotherapyDate and Time: September 14, 9:00-17:00 Central European Summer Time (CEST) Abstract: 620PTitle: Efficacy, safety and PKPD of 23ME-00610, a first-in class anti-CD200R1 antibody, in patients with tumor mutational burden-high (TMB-H) and/or microsatellite instability-high (MSI-H) cancers: Results from an expansion cohortSession Type: Poster Session – Developmental TherapeuticsDate and Time: September 14, 9:00-17:00 Central European Summer Time (CEST) Abstract: 153PTitle: 23ME-01473, an Fc-enhanced anti-ULBP6/2/5 antibody, restores anti-tumor NK cell function through NKG2D and FcgRIIIa activation Session Type: Poster Session – Biomarkers and Translational Research (agnostic)Date and Time: September 15, 9:00-17:00 Central European Summer Time (CEST) Abstract: 1706PTitle: Efficacy, safety and PKPD of 23ME-00610, a first-in-class anti-CD200R1 antibody, in patients with advanced or metastatic clear-cell renal cell carcinoma (ccRCC): Results from a multi-center multi-country Phase 1/2a expansion cohortSession Type: Poster Session – Renal CancerDate and Time: September 15, 9:00-17:00 Central European Summer Time (CEST) Abstract: 150PTitle: Phase 1/2a trial of CD200R1 inhibitor 23ME-00610; exploratory analyses of tissue-based and genetic biomarkersSession Type: Poster Session – Biomarkers and Translational Research (agnostic)Date and Time: September 15, 9:00-17:00 Central European Summer Time (CEST) About 23ME-0061023ME-00610 is a first-in-class anti-CD200R1 monoclonal antibody in the Phase 2a portion of Phase 1/2a clinical development for advanced solid malignancies. CD200R1 was identified as an immuno-oncology (I/O) target from the 23andMe database, with pleiotropic causal variants that have opposing effect on risks for cancer and immune diseases, referred to as an I/O signature, observed in 3 components in this pathway. 23ME-00610 is designed to bind to CD200R1 and prevent the interaction of CD200R1 with CD200. The CD200–CD200R1 axis is an immunological checkpoint that plays a pivotal role in maintenance of immune tolerance. CD200R1 is an inhibitory receptor expressed on T cells and myeloid cells while CD200, the ligand for CD200R1, is highly expressed on certain tumors. In preclinical studies, binding of tumor-associated CD200 to CD200R1 leads to immune suppression and decreased immune cell killing of cancer cells. Preclinical data indicate that this mechanism has the potential to restore the ability for both T-cells and myeloid cells to kill cancer cells. Clinical trials registry (clinicaltrials.gov): NCT05199272. About 23ME-0147323ME-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 ULBP ligands from their cell surface, which act as immunosuppressive molecular decoys. Blocking the binding of soluble ULBP6 to NKG2D through 23ME-01473 may restore immune cell recognition and killing of cancers. Further, 23ME-01473 is Fc-effector enhanced, which provides an additional mechanism for 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 and biopharmaceutical company empowering a healthier future. For more information, please visit www.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, including. 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 our 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, 23andMe undertakes no obligation to update them, whether as a result of new information, developments, or otherwise. Contacts:Investor Relations Contact: investors@23andMe.comMedia Contact: press@23andMe.com

SNK02 has the potential to be a first-in-class cryopreserved allogeneic NK cell therapy for solid tumors that does not require lymphodepletion before administration, which may lead to better overall synergy in future combination regimens with immune checkpoint inhibitors. In this Phase 1 trial, the best objective response of stable disease was demonstrated in 100% of patients that completed 8 treatment cycles of SNK02. SNK02 was well tolerated as a monotherapy and appears to have some clinical activity against pretreated solid tumors despite the lack of lymphodepletion. SANTA ANA, Calif., May 23, 2024 (GLOBE NEWSWIRE) -- NKGen Biotech, Inc. (Nasdaq: NKGN) (“NKGen” or the “Company”), a clinical-stage biotechnology company focused on the development and commercialization of innovative autologous, allogeneic and CAR-NK natural killer (“NK”) cell therapeutics, today announced an online publication, titled “Interim Analysis of a Phase I Study using Cryopreserved Non-genetically Modified Allogeneic Natural Killer Cells With Enhanced Cytotoxicity (SNK02) in Patients with Advanced Solid Tumors without Lymphodepletion” at the 2024 American Society of Clinical Oncology (“ASCO”) Annual Meeting to be held virtually and at the McCormick Place Convention Center in Chicago, Illinois from May 31–June 4, 2024. This Phase 1 clinical trial is a multi-center, open-label study evaluating the safety and tolerability of SNK02 in participants with pathologically confirmed solid tumors refractory to standard of care therapy. The study drug, SNK02, is a first-in-kind, cryopreserved allogeneic non-genetically modified NK cell product with significant anti-tumor cytotoxicity and over 90% expression of CD16, NKG2D, NKp46, and DNAM-1, that can be consistently produced on a large commercial scale. SNK02 was administered as an intravenous infusion (IV), weekly for eight weeks in patients with advanced solid tumors. The starting dose was 6x109 SNK02 cells. We hypothesized that higher doses of SNK02 (to overcome autodigestion) could be delivered frequently without the need for lymphodepletion and that it might demonstrate activity against solid tumors that have failed multiple prior standard-of-care treatment options. The primary endpoint was safety based on adverse events (AEs), vitals, laboratory tests, and physical exams. Tolerability of SNK02 and maximum tolerated dose were also evaluated. “Interim data from our Phase 1 clinical study utilizing our second NK cell therapy product, SNK02, demonstrated that the treatment was well-tolerated as a monotherapy in patients with solid tumors refractory to standard of care therapy,” said Paul Y. Song, MD, Chairman and CEO of NKGen. “We are particularly excited because SNK02 has the potential to be a first-in-class cryopreserved allogeneic NK cell therapy for solid tumors that does not require lymphodepletion before administration, which may lead to better overall synergy in future combination regimens especially with immune checkpoint inhibitors where a robust T-cell response is needed. Using our proprietary allogeneic manufacturing and cryopreservation processes, we are capable of producing hundreds of thousands of potential doses of enhanced NK cell therapies from materials collected from a single donor. Thus, our potential to treat a significant number of cancer patients with SNK02 is remarkably high. We are pleased to see such promising Phase 1 trial results for both of our unique cell therapy candidates: autologous SNK01 for neurodegenerative disease and allogeneic SNK02 for cancer.” For additional information on the SNK02 clinical trial, please visit https://www.clinicaltrials.gov/ using the identifier NCT05990920. Highlights from the online publication include: Five patients with advanced refractory solid tumors were enrolled in the trial.Patients had received an average of 4 lines of prior therapy.Median age was 64 (range 44 – 71) and 3 were male.The subtypes were 1 leiomyosarcoma, 1 angiosarcoma, 1 endometrial adenocarcinoma, 1 undifferentiated pleomorphic sarcoma, and 1 colorectal adenocarcinoma.Four of five patients completed 8 cycles of SNK02. The best objective response of stable disease (tumor stopped growing) was demonstrated in 100% of patients that completed the 8 cycles.Out of the 36 doses administered through Cycle 8, there were 17 Grade 1, 3 Grade 2, and 1 Grade 3 adverse events (AEs) related to investigational product (IP). The Grade 3 AE of increased fatigue resolved after 1 day with no intervention required.There was 1 death on study, which was deemed unrelated to the IP.Auto-antibodies appeared to develop around cycle 5 and appeared to correlate with AEs.SNK02 was well tolerated as a monotherapy and appears to have some clinical activity against pretreated solid tumors despite the lack of lymphodepletion. SNK02 will continue to be studied as a monotherapy and in potential combination treatment regimens with monoclonal antibodies and immune checkpoint inhibitors. A copy of the ePublication will be available on the Scientific Publications page of the Company’s website at https://nkgenbiotech.com/. About SNK02 SNK02 is a novel cell-based, donor-derived ex vivo expanded allogeneic natural killer (“NK”) cell, immunotherapeutic drug candidate. NKGen Biotech, Inc. is developing SNK02 for the treatment of a broad range of cancers. About NKGen Biotech NKGen is a clinical-stage biotechnology company focused on the development and commercialization of innovative autologous, allogeneic, and CAR-NK NK cell therapeutics. NKGen is headquartered in Santa Ana, California, USA. For more information, please visit www.nkgenbiotech.com. Forward-Looking Statements Statements contained in this press release may contain “forward-looking statements” within the meaning of Section 27A of the Securities Act and Section 21E of the Securities Exchange Act of 1934, as amended. Forward-looking statements may be identified by the use of words such as “anticipate”, “believe”, “could”, “continue”, “expect”, “estimate”, “may”, “plan”, “outlook”, “future” and “project” and other similar expressions that predict or indicate future events or trends or that are not statements of historical matters. Because such statements are subject to risks and uncertainties, many of which are outside of the Company’s control, actual results may differ materially from those expressed or implied by such forward-looking statements. Such statements include, but are not limited to, statements regarding the Company’s plans and expected timing for developing SNK01, including the expected timing of completing and announcing further results from its ongoing clinical studies; statements regarding the Company’s plans and expected timing for developing SNK02, including the expected timing of completing and announcing further results from its ongoing clinical studies; and the Company’s expected timing for developing its product candidates and potential benefits of its product candidates. Risks that contribute to the uncertain nature of the forward-looking statements include: the Company’s ability to execute its plans and strategies; risks related to performing clinical studies; the risk that initial and interim results of a clinical study do not necessarily predict final results and that one or more of the clinical outcomes may materially change as patient enrollment continues, following more comprehensive reviews of the data, and as more patient data become available; potential delays in the commencement, enrollment and completion of clinical studies and the reporting of data therefrom; the risk that studies will not be completed as planned; the risk that the abstract will not be published as planned including delays in timing, format, or accessibility; and NKGen’s ability to raise additional funding to complete the development of its product candidates. These and other risks and uncertainties are described more fully under the caption “Risk Factors” and elsewhere in the Company’s filings and reports, which may be accessed for free by visiting the Securities and Exchange Commission’s website at www.sec.gov and on the Company’s website under the subheading “Investors—Financial and Filings”. Investors should take such risks into account and should not rely on forward-looking statements when making investment decisions. All forward-looking statements contained in this press release speak only as of the date on which they were made. The Company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made, except as required by law. Internal Contact:Denise Chua, MBA, CLS, MT (ASCP)Vice President, Investor Relations and Corporate Communications949-396-6830dchua@nkgenbiotech.com External Contacts:Chris CalabreseManaging DirectorLifeSci Advisors, LLCccalabrese@lifesciadvisors.com Kevin GardnerManaging DirectorLifeSci Advisors, LLCkgardner@lifesciadvisors.com