Geneos Therapeutics Announces Another Complete Response in Ongoing Clinical Trial of Personalized Therapeutic Cancer Vaccination in Second Line Advanced Liver Cancer

--To Date, Four Patients Are Now Cancer Free Out of 23 Evaluable--

--No Serious Adverse Events Related to Cancer Vaccine Reported, While Adverse Events Continue to be Limited to Grades 1 and 2--

--Planning Underway for Potentially Registrational Clinical Trial--

PLYMOUTH MEETING, Pa., Dec. 14, 2022 /PRNewswire/ -- Geneos Therapeutics, a clinical stage biotherapeutics company focused on the development of personalized therapeutic cancer vaccines (PTCV), today announced that a third patient has achieved a complete response (CR) among the first 24 patients (23 evaluable) enrolled in GT-30, an ongoing single-arm open-label multi-center Phase 1b/2a study. Overall response rate by RECIST 1.1 is 30.4% in the evaluable patients consisting of three complete responses, four partial responses, six stable disease, and ten progressive disease.

GT-30 is evaluating safety, immunogenicity, and efficacy of PTCV (GNOS-PV02 plus plasmid-encoded IL-12) administered in combination with the immune checkpoint inhibitor pembrolizumab, in 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.

In addition to the three CRs, a fourth patient is also cancer-free after liver and lung lesions shrank to become fully responsive to surgery and radiation, thereby achieving secondary resectability.

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

The Geneos PTCV approach is distinguished from other cancer vaccine platforms in offering a means to vaccinate virtually all patients with all of their neoantigens, and to do so rapidly. PTCVs are DNA-based rather than mRNA, viral vector, or peptide. Unlike these alternatives, Geneos DNA vaccines have the capacity to include up to 40 neoantigens in each vaccine, and up to 80 neoantigens merely by combining two DNA plasmids for each patient.

The most recent CR, a 72 year old male with stage IVa HCC whose PTCV included 40 neoantigens, highlights the value of vaccinating with as many neoantigens as possible. The patient developed therapeutically useful T cell responses to 38 of the 40 vaccine neoantigens, as confirmed by ELISpot analysis. In contrast to the large neoantigen capacity of Geneos' PTCVs, a vaccine based on a platform with a limited neoantigen capacity would have had to compromise on the vaccine neoantigens delivered, thereby likely limiting efficacy. 

"We were confident going into this study of the potential of Geneos PTCVs to offer a level of efficacy never seen previously with a cancer vaccine," stated Niranjan Sardesai, PhD, president and chief executive officer of Geneos. "This latest complete response confirms just how groundbreaking our approach is, not only among cancer vaccines but more broadly among oncology therapeutics. We know of no other cancer treatment which offers the potential for such profound efficacy, even in patients with advanced cancers, with the side effect profile, as seen to date, of a typical seasonal flu shot," added Dr. Sardesai.

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 for other personalized platforms, in most 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 process of being reduced to three to four weeks.

Based on the full 24-patient data, which were presented at the Society for Immunotherapy of Cancer (SITC) 37^th Annual Meeting last month, Geneos has expanded GT-30 to enroll a further 12 patients, with first reports on benchmark overall survival (OS) from the full cohort of 36 anticipated in mid-2023. In parallel, the company is developing plans with its medical advisors for a potential registrational trial in advanced HCC and preparing for discussions with regulatory agencies.   

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. Encouraging clinical data from a Phase 1b/2a clinical trial in hepatocellular carcinoma has prompted planning for a potentially registrational clinical trial. 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. 

SOURCE Geneos Therapeutics, Inc.