GenVivo, Inc.

GEN2 was studied in patients with hepatocellular carcinoma or advanced solid tumors metastatic to the liver and was well-tolerated at all dose levels administered21% of patients remained on study for >6 months, with half at the highest administered doses and the longest up to 21 monthsA Maximum Tolerated Dose (MTD) was not defined in this studyA second Phase 1 study, in the US, exploring a different dosing schedule is underway; once a recommended dose in this study is defined, 3 expansion cohorts will be initiated PASADENA, Calif., Nov. 08, 2024 (GLOBE NEWSWIRE) -- GenVivo, Inc. (GVO) a private, clinical stage biopharmaceutical company with breakthrough “off-the-shelf” gene vector immunotherapies to treat cancer, announces the presentation of GEN2 Phase 1 clinical trial results in adult patients with hepatocellular carcinoma or tumors metastatic to the liver (NCT04313868), at the 2024 Society for Immunotherapy of Cancer (SITC) Annual Meeting, November 8-10, in Houston, TX. GEN2, a non-replicating mRNA vector, delivers two payload genes that provide dual-mechanisms of action: an enhanced prodrug-activated enzyme (HSV-eTK) and an immunostimulatory cytokine (GM-CSF). After valganciclovir administration, GEN2 triggers the local release of tumor-specific antigens (including neoantigens) to stimulate an immune response. This novel therapy enables faster treatment, as it does not require tumor biopsies or tumor-specific genomic sequencing to identify patient-specific neoantigens prior to commencing therapy. GEN2 was evaluated intravenously (IV) in combination with valganciclovir (VGCV) in 48 patients in this dose-escalation Phase 1 trial. GEN2 was administered on Days 1, 2, and 3 with VGCV on days 8 to 12 on a three-week cycle. GEN2 demonstrated tolerability and minimal toxicity, with no dose-dependent Treatment Emergent Adverse Events (TEAEs). Linear exposure was observed across the 1000-fold dose range. Twenty-one percent of patients remained on therapy for longer than 6 months with the longest up to 21 months. A toxicity-defined maximum tolerated dose (MTD) has not been identified. A second Phase 1 trial, initiated in the US earlier this year under protocol NCT06391918, will identify the Recommended Phase 2 Dose (RP2D) on a different IV schedule and expand into additional tumor types. This trial includes a variety of exploratory objectives including validation of receptor binding, pre- and post-tumor biopsy analyses, cytokine assessment, immunophenotyping and analysis of presence or absence of neutralizing antibodies to optimize the dosing schedule. Once the RP2D has been defined, expansion cohorts will enroll patients with hepatocellular carcinoma (HCC), hormone receptor positive breast cancer and skin cancers. An additional cohort of patients (also with skin cancers) will investigate intratumoral (IT) dosing, with the goal of obtaining paired biopsies and tissue correlative studies. GEN2’s IV administration represents a major advancement over alternative therapies limited by IT or Intralesional (IL) approaches, as the use of local administration is usually restricted to readily accessible tumors. While clinical trials of oncolytic viruses or replication-deficient vectors have demonstrated encouraging results in skin, bladder, prostate, pancreatic, and lung cancers (sometimes showing effects in both injected and non-injected tumors), there are practical limitations to IT or IL administration. By contrast, GEN2’s IV administration allows for the treatment of advanced disease with malignancies that have spread widely throughout the body. Poster 1 Abstract Title: “A phase 1 clinical trial of GEN2, a personalizing immunotherapy gene vector product, in combination with valganciclovir in adult patients with hepatocellular carcinoma or tumors metastatic to liver”Session Date and Time for Poster Presentation: Friday, November 8, 2024, from 9:00 AM to 7:00 PM CT, Poster HallAbstract Number: 609Presenter: Alison L. Hannah, M.D. Chief Medical Officer, GenVivo, Inc. About GenVivo GenVivo (GVO) is a private, vertically integrated biotechnology company founded to develop novel gene delivery and immune stimulation therapies, which activate the patient’s immune system to treat cancers. GenVivo is committed to developing and manufacturing products that are rapidly deployed, and easily administered, with the goal of increasing cancer patient survival and improving quality of life. GEN2, GVO’s first clinical candidate, is currently in a Phase 1 clinical trial in the US (NCT06391918). For more information about GenVivo, visit https://genvivoinc.com/ Forward-Looking Statements This press release contains forward-looking statements of GenVivo, Inc. (“GenVivo”) that involve substantial risks and uncertainties. The words ‘‘anticipate,’’ ‘‘believe,’’ ‘‘continue,’’ ‘‘could,’’ ‘‘estimate,’’ ‘‘expect,’’ ‘‘intend,’’ ‘‘may,’’ ‘‘plan,’’ ‘‘potential,’’ ‘‘predict,’’ ‘‘project,’’ ‘‘target,’’ ‘‘should,’’ ‘‘would,’’ and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These statements are based on current scientifically-based mechanisms, understandings, and expectations and are not guarantees of future performance. GenVivo 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. In addition, the forward-looking statements included in this press release represent GenVivo’s views as of the date of this press release. GenVivo anticipates that subsequent events and developments will cause its views to change. However, while GenVivo may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. “GenVivo,” the GenVivo logo and other trademarks, trade names or service marks of GenVivo appearing in this press release are the property of GenVivo. All other trademarks, trade names and service marks appearing in this press release are the property of their respective owners and are used for reference purposes only. Such use should not be construed as an endorsement of such products or companies.

GEN2’s dose-escalation trial, GVO-1102, will establish the Recommended Phase 2 Dose (RP2D), followed immediately by an expansion phase into 3 solid tumor types. GEN2 has a dual mechanism: 1) initial suicide gene killing, independent of the tumor’s antigens, and 2) the release of patient-specific tumor antigens which in the presence of the payload-encoded cytokine results in the generation and activation of immune effector cells. Each cycle of GEN2 maintains and continually amplifies therapeutic immune cytolytic responses as more tumor cells are killed and release antigen (including mutating neoantigens). GEN2 is an off-the-shelf, non-replicating immunotherapy vector administered by intravenous infusion; it enables immediate treatment without the time delays and expense associated with tumor biopsies and genomic sequencing. PASADENA, Calif., June 27, 2024 (GLOBE NEWSWIRE) -- GenVivo, Inc., a private, clinical-stage biopharmaceutical company with breakthrough off-the-shelf platforms for cancer gene medicine immunotherapies, announced that it has dosed the first US patient in a Phase I/Ib, open-label, dose-escalation and expansion clinical trial of GEN2. GEN2, GenVivo’s first product candidate to enter clinical development, is a non-replicating mRNA gene therapy vector being developed as a cancer immunotherapy to both kill tumors and activate a patient’s immune system against their individual cancer antigens (neoantigens). GEN2 is an off-the-shelf medicine, providing the advantages of a personalizing therapy without the time delays and expense associated with autologous products or tumor genome sequencing. This GEN2 Phase I/Ib, dose-escalation clinical trial (NCT06391918) is currently enrolling US patients with advanced solid tumors who have progressed or were non-responsive to prior therapies. The clinical trial is primarily designed to assess the safety and tolerability of GEN2 and to establish the recommended Phase II dose (RP2D). Following the initial dose-escalation phase, the expansion phase will explore the RP2D in 3 arms with defined solid tumor types, to further demonstrate safety, tolerability, and signs of clinical activity. Pharmacokinetic and exploratory biomarker endpoints will be assessed. Additional data relevant to efficacy will be obtained from paired-tumor biopsies, measuring payload expression, immune cell infiltration and activation, and tumor killing. “The initiation of this US trial represents an important milestone in our efforts to systemically administer our off-the-shelf personalizing gene medicine platform to activate a cancer patient’s immune system against the full breadth of their unique tumor antigens,” said Robert G. Johnson, M.D., Ph.D., Chief Operating Officer of GenVivo, Inc. “We are encouraged by the potential of GEN2 (demonstrated in a prior phase 1 trial, NCT04313868) and look forward to advancing to the expansion phase once the appropriate dose is identified.” Daneng Li, M.D., Associate Professor, Department of Medical Oncology & Therapeutics Research, Hepatobiliary Lead and Co-Director, Neuroendocrine Tumor Program, City of Hope, Duarte, CA added “We are excited to be working with the GenVivo team on GEN2, an innovative dual-payload targeted vector, with the goal to improve therapies for our patients with refractory disease.” About GEN2 GenVivo’s product candidate, GEN2, is designed to kill the tumor and trigger direct tumor release of patient specific neoantigens in the presence of a locally produced cytokine. The vector mRNA payload encodes an optimized prodrug-activated enzyme (enhanced viral thymidine kinase (HSV-eTK)) and an immunostimulatory cytokine (GM-CSF). The orally administered prodrug, modified by the HSV-eTK, directly kills tumor cells, releasing the patient’s full complement of unique tumor antigens in the presence of the immunostimulatory cytokine, to then directly stimulate tumor-specific killer cells. These tumor-lytic immune cells amplify and maintain ongoing tumor cell killing, including subsequently arising tumor mutations (neoantigens) and tumors at metastatic sites. Data from 59 patients in a Phase 1 trial in Asia, demonstrated safety and tolerability with signs of clinical benefit (NCT04313868). GVO-1102 (NCT06391918) will complete the intravenous dose escalation started in the Phase 1 trial in Asia. About GenVivo GenVivo is a private, vertically-integrated biotechnology company with cGMP manufacturing capabilities, founded to develop the latest novel gene delivery and immune stimulation therapies, which activate the patient’s immune system to treat cancers and prevent infectious diseases. GenVivo is committed to developing and manufacturing products that are rapidly deployed, and easily administered, with the goal of increasing patient survival and improving quality of life. For more information about GenVivo, visit Forward-Looking Statements This press release contains forward-looking statements of GenVivo, Inc. (“GenVivo”) that involve substantial risks and uncertainties. The words ‘‘anticipate,’’ ‘‘believe,’’ ‘‘continue,’’ ‘‘could,’’ ‘‘estimate,’’ ‘‘expect,’’ ‘‘intend,’’ ‘‘may,’’ ‘‘plan,’’ ‘‘potential,’’ ‘‘predict,’’ ‘‘project,’’ ‘‘target,’’ ‘‘should,’’ ‘‘would,’’ and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. These statements are based on current beliefs and expectations and are not guarantees of future performance. GenVivo 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. In addition, the forward-looking statements included in this press release represent GenVivo’s views as of the date of this press release. GenVivo anticipates that subsequent events and developments will cause its views to change. However, while GenVivo may elect to update these forward-looking statements at some point in the future, it specifically disclaims any obligation to do so. “GenVivo,” the GenVivo logo and other trademarks, trade names or service marks of GenVivo appearing in this press release are the property of GenVivo. All other trademarks, trade names and service marks appearing in this press release are the property of their respective owners and are used for reference purposes only. Such use should not be construed as an endorsement of such products or companies. Contact Victor Constantinescu, M.Eng Head of Business Development BD@genvivoinc.com 626-768-5162