CLL-1

Next trem-cel (VOR33) clinical data update expected by Relapse After Transplant and Cellular Therapy (HSCT2) Conference Nov 10-11Three oral abstracts and two poster presentations accepted at ASH 2023 Dec 9-12 CAMBRIDGE, Mass., Nov. 07, 2023 (GLOBE NEWSWIRE) -- Vor Bio (Nasdaq: VOR), a clinical-stage cell and genome engineering company, today reported financial results for the three-month period ended September 30, 2023, and provided a business update. “We look forward to imminent data releases by HSCT2 and ASH demonstrating progress across our clinical programs and platform. Following successful clearance of our IND application in June, we are pleased that the VBP301 clinical trial of VCAR33ALLO is now actively enrolling patients,” said Dr. Robert Ang, Vor Bio’s President and Chief Executive Officer. Corporate Updates VBP101 trem-cel clinical data update expected by the ASTCT-EBMT 6th International Conference on Relapse After Transplant and Cellular Therapy (HSCT2), Nov 10-11 The planned update will include engraftment data for additional patients receiving a trem-cel transplant and further data from patients treated with multiple doses of MylotargTM.The data was selected for an oral presentation at ASH 2023. Trem-cel is a genome-edited allogeneic hematopoietic cell transplant (HCT) that is lacking the CD33 protein. It is designed to replace standard of care transplants for patients with acute myeloid leukemia (AML) and potentially other blood cancers. Trem-cel has the potential to enable powerful targeted therapies in the post-transplant setting including Mylotarg and CD33-targeted CAR-Ts. VCAR33AUTO (CD33CART) data released by PTCTC in ASH abstract supports Vor Bio’s VCAR33ALLO Data from the Pediatric Transplantation and Cellular Therapy Consortium (PTCTC)1 regarding the ongoing Phase 1/2 pediatric bridge-to-transplant trial evaluating CD33CART (also known as VCAR33AUTO) in adolescent and young adult relapsed/refractory AML patients was recently released in an abstract accepted for oral presentation at ASH 2023. Nineteen patients were treated in the Phase 1 portion of the study. The data showed that 2 out of 5 (40%) evaluable patients achieved complete remission at the highest dose level (DL4, 1 x 107 CAR+ cells/kg), suggesting that this is a potentially active CAR-T product candidate. Four of 19 total patients treated had cytokine release syndrome (CRS) ≥ Grade 3.Vor Bio’s VCAR33ALLO uses the same CAR-T construct used in CD33CART. However, VCAR33ALLO uses a potentially superior T cell source from healthy transplant donors, which are likely to have a more stem-like phenotype and greater potential for expansion, persistence, and anti-leukemic activity compared to a product derived from autologous sources.Enrollment is ongoing in VBP301, a Phase 1/2, multicenter, open-label, first-in-human study of VCAR33ALLO, a transplant donor-derived anti-CD33 CAR-T cell therapy in patients with post-transplant relapsed or refractory AML. Continuing to build industry-leading engineered HSC platform The preclinical and process development research that supported Vor Bio’s Investigational New Drug (IND) application for trem-cel demonstrating the potential for next generation transplants in AML using CRISPR/Cas9 CD33-edited hematopoietic stems cells was published in Molecular Therapy - Methods & Clinical Development online on October 12, 2023. The full manuscript can be accessed HERE.Data presented at the SITC 38th Annual Meeting, held November 3-5, 2023, in San Diego, CA showed potent in vitro and in vivo cytolytic activity of Vor Bio’s antigen-specific CLL-1-directed CAR-T cells, supporting further clinical development of the company’s lead CLL-1 CAR candidate either as a stand-alone treatment or in combination with its eHSC platform.Data presented at the 30th Annual ESGCT Congress, held October 24-27, 2023, highlighted Vor Bio’s advanced computational biology expertise, showing development of a proprietary computational workflow known as GUMM (Genotyping Using Mixture Models) that interprets single-cell DNA sequencing data from gene editing experiments and confirms the edits were correctly made. GUMM addresses existing analytical challenges in using single-cell DNA sequencing by streamlining the genotyping process, adopting an automated data-driven approach which requires minimal user intervention. Expanding scientific advisory board The Company is adding academic pioneers in engineering stem cell transplants to protect against on-target toxicity to its scientific advisory board. Saar Gill, MD, PhD, Scientific Co-Director, Cell Therapy and Transplant Program and Associate Professor of Medicine (Hematology-Oncology) at the Hospital of the University of Pennsylvania.Pietro Genovese, PhD, Assistant Professor in Pediatrics at the Harvard Medical School and Principal Investigator at the Gene Therapy Program at Dana-Farber/Boston Children's Cancer and Blood Disorders Center. Upcoming Milestones VBP101 clinical data update including engraftment data for additional patients and further Mylotarg hematologic protection expected by HSCT2, Nov 10-11In-house manufacturing of trem-cel operational by year-end 2023 Third Quarter 2023 Financial Results Cash Position: Cash, cash equivalents and marketable securities were $160.1 million as of September 30, 2023, which is projected to fund operations into the first quarter of 2025. Research & Development (R&D) Expenses: R&D expenses for the third quarter of 2023 were $27.6 million, compared to $16.9 million for the third quarter of 2022. The increase in R&D expenses of $10.7 million was primarily due to an increase in external research and development costs of $5.1 million driven by the execution of our non-exclusive license agreement with Editas Medicine and continued development of our platform, an increase in external manufacturing expenses of $1.8 million, an increase in clinical expenses of $0.8 million related to our ongoing trem-cel clinical trial and the development of our VCAR33 programs, and an increase in personnel expenses of $1.9 million.General & Administrative (G&A) Expenses: G&A expenses for the third quarter of 2023 were $7.7 million, compared to $7.2 million for the third quarter of 2022. The increase in G&A expense of $0.5 million was primarily due to an increase in personnel costs of $0.8 million, including an increase in stock-based compensation expense of $0.3 million, offset by a decrease in facilities and other expenses of $0.3 million. Net Loss: Net loss for the third quarter of 2023 was $33.2 million, compared to $23.8 million for the third quarter of 2022. Condensed Consolidated Balance Sheet Data (Unaudited) (in thousands) September 30, December 31, 2023 2022 Cash, cash equivalents and marketable securities $160,098 $230,245 Total assets 223,023 299,366 Total liabilities 48,242 48,759 Total stockholders' equity 174,781 250,607 Condensed Consolidated Statement of Operations (Unaudited) (in thousands, except share and per share data) Three Months Ended Nine Months Ended September 30, September 30, 2023 2022 2023 2022 Operating expenses: Research and development $27,606 $16,875 $73,418 $47,488 General and administrative 7,710 7,226 24,494 21,205 Total operating expenses $35,316 $24,101 -$97,912 $68,693 Loss from operations $(35,316) $(24,101) $(97,912) $(68,693) Other income: Interest income 2,126 313 6,310 509 Total other income 2,126 313 6,310 509 Net loss $(33,190) $(23,788) $(91,602) $(68,184) Net loss per share attributable to common stockholders, basic and diluted $(0.49) $(0.63) $(1.37) $(1.81) Weighted-average common shares outstanding, basic and diluted 67,607,713 38,009,022 66,973,771 37,582,463 About Vor Bio Vor Bio is a clinical-stage cell and genome engineering company that aims to change the standard of care for patients with blood cancers by engineering hematopoietic stem cells to enable targeted therapies post-transplant. For more information, visit: www.vorbio.com. Forward-Looking StatementsThis press release contains forward-looking statements within the meaning of the Private Securities Litigation Reform Act of 1995. The words “aim,” “anticipate,” “can,” “continue,” “could,” “design,” “enable,” “expect,” “initiate,” “intend,” “may,” “on-track,” “ongoing,” “plan,” “potential,” “should,” “target,” “update,” “will,” “would,” and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. Forward-looking statements in this press release include Vor Bio’s statements regarding the potential of its product candidates to positively impact quality of life and alter the course of disease in the patients it seeks to treat, the timing and pace of patient enrollment in clinical trials and the availability of data therefrom, the success and timing of manufacturing clinical supply for its product candidates at its in-house manufacturing facility, its intentions to use VCAR33ALLO in combination with trem-cel as a Treatment System and the potential benefits of such a Treatment System, the potential of trem-cel to enable targeted therapies in the post-transplant setting including Mylotarg and CD33-targeted CAR-Ts, the potential superiority of the T-cell source of VCAR33ALLO compared to VCAR33AUTO, its potential upcoming milestones, and its cash runway and expected capital requirements. Vor Bio may not actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. Actual results or events could differ materially from the plans, intentions and expectations disclosed in these forward-looking statements as a result of various factors, including: uncertainties inherent in the initiation and completion of preclinical studies and clinical trials and clinical development of Vor Bio’s product candidates; availability and timing of results from preclinical studies and clinical trials; whether interim results from a clinical trial will be predictive of the final results of the trial or the results of future trials; expectations for regulatory approvals to conduct trials or to market products; the success of Vor Bio’s in-house manufacturing capabilities and efforts; and availability of funding sufficient for its foreseeable and unforeseeable operating expenses and capital expenditure requirements. These and other risks are described in greater detail under the caption “Risk Factors” included in Vor Bio’s most recent annual or quarterly report and in other reports it has filed or may file with the Securities and Exchange Commission. Any forward-looking statements contained in this press release speak only as of the date hereof, and Vor Bio expressly disclaims any obligation to update any forward-looking statements, whether because of new information, future events or otherwise, except as may be required by law. Contact:Investors & MediaSarah Spencer +1 857-242-6076sspencer@vorbio.com 1 Sponsored by the National Marrow Donor Program (NMDP) and Center for International Blood and Marrow Transplant Research (CIBMTR). Funding by St. Baldrick’s Foundation.

In vitro proof-of-concept data shows effective delivery of CpG to endosomal TLR9 via anti CLEC2D antibody, resulting in sustained myeloid and B cell activation, enabling induction of stronger T cell responses WALTHAM, Mass., Nov. 3, 2023 /PRNewswire/ -- Immunitas Therapeutics ("Immunitas"), a clinical stage precision immunotherapy company committed to discovering and developing novel, differentiated therapeutics for patients with cancer, today presented the first proof-of-concept data on its second program, a myeloid and B cell modulating anti CLEC2D-Toll-like receptor 9 (TLR9) agonist conjugate, at the Society for Immunotherapy of Cancer's 38th Annual Meeting (SITC 2023), held November 1-5 in San Diego, California. CLEC2D is a C-type lectin-like protein that is broadly expressed on a subset of immune cells and is naturally internalized by myeloid and B cells. Upon internalization, it can act as a vehicle to deliver histone/DNA complexes to endosomal TLR9, stimulating inflammatory responses. Harnessing this CLEC2D-mediated internalization offers a compelling immunotherapy approach of delivering CpG to TLR9 that can stimulate inflammatory responses with the potential to improve recruitment of functional T and NK cells into tumor tissues. "The inability to induce adequate responses in tumors with poor T and NK cell infiltration has limited the clinical impact of existing immunotherapies. At Immunitas, we prioritize targeting novel biological pathways with first-in-class molecules that have potential to show monotherapy efficacy in early clinical development. This program leverages our specialized knowledge of the CD161-CLEC2D pathway, and we are excited to be progressing a therapeutic with demonstrated potential to address the challenge of poor T and NK cell infiltration and truly benefit patients who lack immunotherapy options," said Amanda Wagner, President and Chief Executive Officer of Immunitas Therapeutics. "We are pleased to have our team present this data demonstrating in vitro proof-of-concept for our anti-CLEC2D antibody conjugated to a CpG oligonucleotide." The presented data showed that treatment with Immunitas' anti CLEC2D-TLR9 agonist immune stimulating antibody complex (ISAC) induced pro-inflammatory responses in THP1-TLR9 reporter cell lines and dramatically increased production of IFN-α, a critical cytokine for induction of anti-tumor T cells, in human plasmacytoid dendritic cells. Treatment of CLEC2D-expressing B cells with the ISAC molecule resulted in sustained B cell proliferation and upregulation of co-stimulatory molecules, enabling stronger induction of T cell immune responses. The results further confirmed that CLEC2D is expressed on tumor-associated macrophages (TAMs)—macrophages that strongly contribute to the immunosuppression in tumor microenvironments and can also directly promote tumor cell growth. Treatment of TAMs with Immunitas' anti CLEC2D-TLR9 agonist ISAC reversed TAM-mediated suppression of T cell proliferation and activation, indicating that TLR9 agonism can reprogram TAMs towards an inflammatory state. Studies in human peripheral blood mononuclear cells (PBMCs) has demonstrated that treatment with the anti CLEC2D-TLR9 agonist ISAC did not trigger release of inflammatory cytokines, providing a preliminary indication of safety. The presentation will be available on the Immunitas website following the meeting. Presentation Details for SITC 2023 Title: Anti CLEC2D-TLR9 agonist conjugate binds to and internalizes CLEC2D on myeloid cells, plasmacytoid DCs and B cells leading to robust TLR pathway activation and inflammatory cytokine production Abstract Number: 1131 Date/Time: Friday, November 3, 2023, 9:00am – 7:00pm PDT About CLEC2D CLEC2D is a C-type lectin-like protein broadly expressed on a subset of immune cells and tumor cells. It is also the ligand for CD161, target for Immunitas' lead investigational candidate, IMT-009. Additionally, CLEC2D naturally internalizes in TLR9 expressing myeloid and B cells. Building on this biology, Immunitas is developing a novel anti CLEC2D-TLR9 agonist immune stimulating antibody complex (ISAC) comprising a fully human anti-CLEC2D antibody conjugated to a CpG oligonucleotide. This CLEC2D-TLR9-ISAC molecule is capable of triggering TLR9 pathway activation in myeloid cells, B cells, and plasmacytoid dendritic cells and enabling induction of sustained T cell immunity. Harnessing this biology offers a compelling immunotherapy approach that stimulates inflammatory responses that may improve recruitment of functional T and NK cells in tumors with otherwise poor T cell infiltration. About Immunitas Therapeutics Immunitas is a clinical stage precision immunotherapy company committed to discovering and developing novel, differentiated treatments for patients with cancer. A focus on human data, combined with fully integrated internal R&D capabilities and parallel discovery efforts, allows Immunitas to start with and stay closer to the most relevant and translatable biology for patients, accelerating the timeline from discovery to the clinic. The Immunitas discovery engine combines deep expertise in single-cell genomics with customized machine learning approaches to elucidate immune cell populations that are key actors in immuno-oncology. The company was founded by Longwood Fund with leading scientists from Dana-Farber, MGH, the Broad, and MIT. Since being founded in 2019, Immunitas has raised a total of $97 million in venture funding from a strong syndicate of investors including Agent Capital, Alexandria Venture Investments, Evotec, Leaps by Bayer, Longwood Fund, M Ventures, Medical Excellence Capital, and Novartis Venture Fund. To learn more, visit . SOURCE Immunitas Therapeutics, Inc.

The companies will develop gene therapies for ocular diseases under the new deal. Credit: elenavolf / Shutterstock.com. Otsuka Pharmaceutical has entered a multi-target partnership with ShapeTX for the development of new adeno-associated viruses (AAV) gene therapies to treat ocular diseases. The parties will focus on developing intravitreally delivered AAVs. Recommended Reports Reports LOA and PTSR Model - Gene Therapy to Target BCMA for Relapsed and Refractory Multiple Myeloma GlobalData Reports LOA and PTSR Model - Gene Therapy To Target Cd33 And Cll1 For Oncology in Myeloproliferative Diso... GlobalData View all The AAVid capsid discovery platform and transgene engineering technology of ShapeTX will be combined with the capabilities of Otsuka in genetic payload design and ophthalmology. ShapeTX is entitled to receive an initial undisclosed payment from Otsuka. Otsuka will also make developmental, regulatory and sales-based milestone payments totalling more than $1.5bn. Based on potential sales of products developed by the partnership, ShapeTX will also receive tiered royalty payments. ShapeTX’s artificial intelligence (AI)-powered AAVid platform merges throughput screening of numerous AAV variants and machine learning to detect new AAV capsids for direct-to-NHP in vivo selection to enhance clinical translation. ShapeTX will also use its transgene engineering technology to optimise payloads of Otsuka for therapeutic gene expression levels in directed cell types. The collaboration offers options to include other targets and tissue types in the future. Otsuka Pharmaceutical Osaka Research Center for Drug Discovery executive director and head Toshiki Sudo stated: “Our recent research activities have led to the identification of target molecules and antibodies for specific ocular diseases of interest with high unmet medical needs. “Our collaboration with ShapeTX aims to enable the delivery of vectorised antibody drugs in combination with AAV, in order to target specific disease cell types in the eye and provide a once-in-a-lifetime and curative administration with stable lifetime expression. “This holds the potential to become dramatically beneficial to patients who have suffered from specific chronic ocular diseases.” Cell & Gene Therapy coverage on Pharmaceutical Technology is supported by Cytiva. Editorial content is independently produced and follows the highest standards of journalistic integrity. Topic sponsors are not involved in the creation of editorial content. Free Whitepaper Cell and gene therapies: Pipe dream to pipeline The cell and gene industry is gaining momentum, with a new wave of therapies promising to transform the way doctors treat, and even cure, disease. In this report, Cytiva and GlobalData have collaborated to explore the rise of the cell and gene therapy industries, the current state of the market, present and future opportunities for advancement, and the challenges that lie ahead. By Cytiva Thematic By downloading this case study, you acknowledge that GlobalData may share your information with Cytiva Thematic and that your personal data will be used as described in their Privacy Policy