Geneos Therapeutics Announces Eight of 34 Patients to Achieve Complete Response, Complete Molecular Response

--By RECIST1.1, Three Complete Responses and Seven Durable Partial Responses Achieved to Date--

--Three of the Seven Patients With Durable Partial Responses, and One With Stable Disease, Have Now Achieved Complete Molecular Response By Ultrasensitive ctDNA Analysis--

--No Serious Adverse Events Related to Cancer Vaccine, Related Adverse Events Grades 1 and 2 Only--

PLYMOUTH MEETING, Pa., Aug. 22, 2023 /PRNewswire/ -- GeneOS Therapeutics, a clinical stage biotherapeutics company focused on the development of personalized therapeutic cancer vaccines (PTCV), today announced updated data from GT-30, an ongoing single-arm open-label multi-center Phase 1b/2a study in second-line advanced hepatocellular carcinoma (HCC). Previously, Geneos reported three patients to have achieved a complete response (CR) and a fourth patient to be cancer-free, whose liver and lung lesions shrank to become fully responsive to surgery and radiation (secondary resectability).

Geneos reports today that four additional patients have achieved a complete molecular response (CMR) by ultrasensitive, third-generation, circulating tumor DNA (ctDNA) analysis. The ctDNA dropped below the limit of detection in all four patients. By RECIST1.1, three of these four patients are durable partial responses (PR) and one a durable stable disease (SD). Applying mRECIST criteria as additional evaluation, each of the three PR patients is a CR and the SD patient is a PR.

Among all CR and PR patients for whom ctDNA data is available, the reductions in ctDNA level (molecular response) have preceded improvement by MRI.

To date, among 32 evaluable patients from the first 34 enrolled, by RECIST1.1 the study has achieved 3 complete responses, 7 partial responses, 9 stable disease and 13 progressive disease.

By either RECIST1.1 or by ctDNA response, 11 of 32 evaluable have achieved either a complete response, partial response, or complete molecular response.

There have been no vaccination-related serious adverse events (SAEs). Vaccination-related AEs, mostly injection site reactions, have been transient, mild, and all Grades 1 and 2.

GT-30 is evaluating the safety, immunogenicity, and efficacy of PTCV (GNOS-PV02 plus plasmid-encoded IL-12) administered in combination with the immune checkpoint inhibitor pembrolizumab, in 36 patients with unresectable or metastatic hepatocellular carcinoma (HCC) who progress on, or are intolerant to, first-line tyrosine kinase inhibitors (sorafenib or lenvatinib). HCC is characterized by a low tumor mutational burden and is resistant to immune checkpoint monotherapy in the majority of patients due to the immune-excluded tumor microenvironment. The study is fully enrolled. https://classic.clinicaltrials.gov/ct2/show/NCT04251117

“As hepatologists and oncologists treating patients with HCC, we’re increasingly using ctDNA to monitor tumour response to therapy. In this study, the ctDNA improvements all preceded the MRI improvements, which shows ctDNA’s prognostic importance, especially since HCC lesions sometimes never fully resolve on MRI despite patients having no clinical evidence of residual viable cancer,” said Dr Ed Gane, professor of medicine at the University of Auckland, New Zealand, hepatologist and deputy director of the New Zealand Liver Unit at Auckland City Hospital. “Historically, CRs in advanced HCC from checkpoint inhibitor treatment alone are virtually unheard of. The numerous CRs and CMRs seen here are remarkable and emphasize the role Geneos’ vaccines may have to treat seriously ill patients with late-stage HCC. I’m excited for what these vaccines may mean for these patients, who may now be able to hope, realistically, for a complete response to treatment,” Dr Gane added.

“While we welcome the advances currently observed with mRNA-based cancer vaccines, they are being deployed almost exclusively in the adjuvant setting, to prevent cancer recurrence in patients who have had surgery to remove their tumor. As a result, some are even suggesting that personalized therapeutic vaccines may only be effective in the adjuvant setting and ineffective at reducing advanced, unresectable, and metastatic tumors.” stated Niranjan Sardesai, PhD, president and chief executive officer of Geneos. “We feel these latest data should set the record straight. Cancer vaccines based on our DNA vaccine platform are showing complete responses in patients with late-stage, advanced cancer. We look forward to continuing to develop in the advanced setting with the goal to offer this profoundly important treatment option to patients with advanced cancer, one with a side effect profile, as seen to date, as benign as that for the typical seasonal flu shot,” added Dr. Sardesai.

GT-30 Trial of Geneos’ Personalized Therapeutic Cancer Vaccines
In the GT-30 trial, DNA plasmid-encoded personalized therapeutic cancer vaccine (PTCV) together with plasmid-encoded interleukin-12 (pIL12, a T cell-stimulating cytokine) adjuvant are administered via intradermal injection followed by electroporation (EP) in combination with pembrolizumab. The potential utility of this combination was suggested by preclinical studies which demonstrate Geneos’ PTCV to rescue PD-1 in murine tumor therapeutic challenge models. Geneos’ PTCVs have been engineered to drive a strong CD8+ T cell response against the tumor. CD8 cells are the killing machines of the immune system, seeking out and destroying cancer cells, but have been difficult to induce using prior vaccine approaches. Adjuvant pIL12 and EP serve to optimize the effectiveness of peripheral vaccination, and their utility is seen by the effective CD4+/CD8+ T cell responses observed to the delivered neoantigens in the GT-30 patients. Each patient’s PTCV is designed based on their unique tumor neoantigens (abnormal mutations and genomic variations produced by cancer cells), and unlike other personalized platforms, in almost every case, Geneos’ PTCVs include all of a patient’s specific neoantigens. This removes any requirement to try to pre-select the “high value” neoantigens accurately and, instead, leaves it to nature to decide which ones will matter for triggering the desired immune response. PTCV manufacturing “needle to needle” time, i.e., from biopsy to treatment, is six to eight weeks and is in the process of being reduced to three to four weeks.

Circulating tumor DNA (ctDNA) has enabled non-invasive detection and monitoring of potentially actionable mutations and can identify therapeutic response/resistance prior to confirmation by MRI imaging. For the data announced here, the NeXT Personal^® platform (Personalis, Inc.) was used to longitudinally monitor molecular residual disease (MRD). NeXT Personal™ platform is an ultra-sensitive tumor-informed ctDNA assay that leverages whole genome sequencing of tumor/normal samples to generate personalized liquid biopsy panels. Each panel includes up to 1,800 selected variants of the highest value specific to each patient, enabling detection of ultra-low traces of residual cancer, as low as 1 - 3 parts per million (PPM).

About Geneos Therapeutics
Geneos Therapeutics, a privately held, clinical stage biotherapeutics company, believes that the company’s personalized therapeutic cancer vaccines (PTCVs) may serve an important role in new immunotherapeutic paradigms for cancer. The company’s approach, using its proprietary GT-EPIC™ platform, is to target neoantigens (abnormal mutations produced by cancer cells) from individual patient tumors to develop novel and uniquely personalized treatments for cancer. Planning is underway for a potentially registrational clinical trial in advanced hepatocellular carcinoma. Geneos’ experienced management team has a track record of success in building immunotherapy-based companies. For more information, please visit www.geneostx.com.

This press release contains certain forward-looking statements relating to our business, including our plans regarding the development of personalized therapeutic cancer vaccines, our expectations regarding our research and development programs, including the planned expansion and conduct of clinical trials and the availability and timing of data from those trials, and the use of our capital resources. Actual events or results may differ from the expectations set forth herein. There can be no assurance that any product candidate in Geneos’ pipeline will be successfully developed, manufactured or commercialized, that final results of clinical trials will be supportive of regulatory approvals required to market licensed products, or that any of the forward-looking information provided herein will be proven accurate. Forward-looking statements speak only as of the date of this release, and Geneos undertakes no obligation to update or revise these statements, except as may be required by law.

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SOURCE Geneos Therapeutics, Inc.