Elenagen

In a preprint paper published on MedRxiv, a team of scientists at CureLab Oncology and their international collaborators have demonstrated a clear clinical benefit of a new biological agent against the deadliest form of ovarian cancer. The results were derived from a clinical study that evaluated the safety and efficacy of Elenagen, a novel anticancer therapeutic (plasmid DNA encoding p62/SQSTM1 protein), as an adjuvant to platinum-based chemotherapy, gemcitabine, in patients with advanced platinum-resistant ovarian cancer BOSTON, Nov. 30, 2023 /PRNewswire/ -- Major scientific breakthroughs are sometimes the result of a combination of serendipity and human error. One such example is platinum-based chemotherapy, which was discovered by accident. Using a special device, researchers were testing how cancer cells responded to electricity. During the study, they observed that the cancer cells were indeed affected — but it was only later that they realized that they had forgotten to plug in the device. What they had stumbled upon is that the cancer cells were in fact responding to the platinum electrodes and platinum ions in the media. Today, the majority of newly diagnosed ovarian cancer patients are initially treated with platinum-based chemotherapy (such as cisplatin and carboplatin), a therapy that keeps many of them free of disease progression over a prolonged period. Sooner or later, however, most patients stop responding to platinum therapies, joining those who had a platinum-resistant form of ovarian cancer from the very beginning. Treatment options for these patients are limited, which makes it especially important to improve the efficacy of platinum-based chemotherapies. "Almost 1 in 80 women will be diagnosed with ovarian cancer during her lifetime, and almost 1 in 110 will die of it," said Dr. Alex Shneider, founder and CEO of CureLab Oncology. "I doubt that we can significantly change these numbers anytime soon. But these numbers would be less tragic if we could say to a diagnosed woman: 'We can give you an extended period of a high-quality life.' Our team has been focused on giving patients diagnosed with platinum-resistant ovarian cancer additional life — a life full of energy and free of pain." One of the commonly used treatments for platinum-resistant ovarian cancer (PROC) patients is gemcitabine. Originally, it was thought that gemcitabine 'tricks' rapidly dividing cancer cells because the molecule looks very similar to the natural nucleotides required for cell propagation while making cell division impossible. Later, it turned out that gemcitabine also works through a patient's immune system, and possibly other mechanisms that are yet to be discovered. In a study published on MedRxiv, a team of scientists from CureLab Oncology, the N.N. Alexandrov National Cancer Center, and Minsk City Oncology Center set out to establish whether an investigational new drug, Elenagen, can safely enhance gemcitabine PROC treatment. Elenagen is a plasmid, a circular DNA that encodes a gene known as p62/SQSTM1 (p62). Originally, Dr. Shneider and his team decided to inject this plasmid into cancer patients because elevated levels of p62 were reported for cancer cells, distinguishing them from normal cells. Could injecting p62-encoding DNA into a muscle could result in a specific immune response against overly abundant p62, thereby selectively eliminating cancer cells? In other words, a classic vaccine mechanism of action. However, to their great surprise, CureLab researchers and their academic collaborators observed Elenagen effects that could not be explained solely by their original hypothesis. For example, in response to an intramuscular injection of Elenagen, tumors changed their internal structure, permitting immune cells to enter the tumors more efficiently while making it harder for metastatic cells to exit. Importantly, Elenagen also reduced systemic chronic inflammation in the organism. Chronic inflammation plays a detrimental role in many diseases, including cancer. "When we began our study, we were concerned that the mechanism of action of this novel drug is not clear," said co-author of the study, Professor Sergey Krasny, M.D., Ph.D., Sc.D. "In fact, it may be years or even decades before it is entirely understood. Then we thought, what if our predecessors had waited for the mechanism of action of penicillin to be entirely clear in the lab before testing in the clinic? We were also compelled by the strong published evidence of Elenagen's effects obtained during Phase I clinical studies and in laboratory dogs." In a clinical trial, 40 PROC patients were randomly divided into two groups. One received standard gemcitabine regimen while another received a combination of the same gemcitabine treatment coupled with weekly injections of Elenagen. No serious adverse events (SAE) due to Elenagen were reported. Note: SAE have often observed during immune oncology studies, which sets Elenagen apart. In addition to safety, the study used the standard primary endpoint of progression-free survival (PFS). PFS is the duration of time between the moment when a patient is enrolled in a study and the moment of relapse of a primary tumor and/or metastatic lesions, as confirmed by radiographic scans. As in other published reports, the average PFS for gemcitabine-treated group was just 2.8 months. However, the group receiving the chemotherapy supplemented with Elenagen demonstrated a PFS of 7.2 months, a statistically significant increase. Importantly, 9 out of 20 patients receiving Elenagen did not demonstrate any disease progression, with a longest recorded observation of 24 months. At the same time, all patients receiving only the chemotherapy had disease progression within less than one year. Although the fact that 45% of patients in the Elenagen-treated group did not show a disease progression is itself remarkable, additional truly counterintuitive data appeared through a subgroup analysis. CA 125 is a protein circulating in blood and is used by oncologists as an ovarian oncomarker. The higher the level of CA 125, the worse the prognosis. One might expect that Elenagen + gemcitabine treatment would show reduced benefits for patients with elevated CA 125, since their disease is more severe and is thus harder to treat. However, compared to the control group, the patients with elevated CA 125 patients were the most responsive to Elenagen regimens. Another prognosis factor for a patient is the number of platinum chemotherapy courses received prior to becoming platinum resistant. Indeed, if disease progresses after just one course of platinum treatment, it is often more severe and harder to treat than in cases where the patient remains progression-free over multiple courses. Also of note: the most obvious effect of Elenagen treatment was observed in patients whose disease progressed after just one course of platinum chemotherapy. Encouraged by these ex-US results, CureLab Oncology has submitted its pre-IND package to the FDA. The company plans to expand the study in the USA as Phase II/III study. The principal investigator for the study will be Prof. Bhavana Pothuri, MD of NYU. The same combination of Elenagen with gemcitabine will be explored. Meanwhile, non-pivotal studies will continue abroad to test if Elenagen also enhances anti-PROC effects of paclitaxel, doxil, and other treatments. About CureLab Oncology CureLab Oncology Inc. is a pre-IPO, clinical-stage biotech company headquartered in the greater Boston area, Massachusetts. CureLab is dedicated to advancing new and safer therapeutics for solid tumors and other oncology and inflammatory indications. CureLab's lead investigational compound is code-named Elenagen, an experimental DNA therapy that consists of a circular piece of DNA called a plasmid that includes a gene for a human protein called p62/SQSTM1. To learn more, visit curelab.com. Media contact: Tim Cox | ZingPR | [email protected] SOURCE CureLab Oncology Inc.

While the disease has progressed in all patients receiving standard of care, it did not progress in 40% of the patients receiving standard chemotherapy together with the experimental drug, Elenagen — and for half of the patients in the group, Elenagen has increased the time to disease progression by more than 2.5 times BOSTON, Sept. 9, 2022 /PRNewswire/ -- CureLab Oncology, a clinical-stage, pre-IPO biotech company, is presenting the results of its ongoing ex-US clinical trial at this year's meeting of the European Society for Medical Oncology (ESMO). The trial is assessing an experimental DNA plasmid encoding the human protein, p62 (affectionately codenamed Elenagen), at the N.N. Alexandrov National Cancer Centre, one of the leading cancer centers in Eastern Europe. Continue Reading CureLab Oncology, a clinical-stage, pre-IPO biotech company, is presenting the results of its ongoing ex-US clinical trial at this year’s meeting of the European Society for Medical Oncology (ESMO). Platinum-resistant ovarian cancer (PROC) is one of the deadliest forms of ovarian cancer and has a very poor prognosis. The FDA approved other novel treatments for PROC based on statistically significant improvements for the delay of progression of the cancer, assessed by the increasing size of a primary tumor and/or the appearance of new metastatic lesions or growth of the existing ones; i.e., progression-free survival (PFS). A statistically significant prolongation of PFS was clearly demonstrated in the trial and continues to extend as the trial continues. Summary of what CureLab Oncology is presenting at ESMO 2022 In the ex-US clinical trial, CureLab Oncology is assessing its experimental plasmid DNA therapeutic, Elenagen, for its ability to extend progression-free survival (PFS) in patients with PROC receiving standard chemotherapy, gemcitabine. For all patients in the trial receiving the standard of care only, the disease progressed during the first year of observations, with 50% of patients progressing within 2.7 months. In contrast, the disease did not progress at all for almost 40% of patients receiving the same gemcitabine in combination with weekly intramuscular injections of Elenagen. In 50% of patients receiving standard of care only, the disease has progressed within 2.7 months, while the time to progression for 50% of patients in the "chemo plus Elenagen" group has increased to 7.2 months. To date, no patient receiving Elenagen demonstrated any adverse event (AE) or significant adverse event (SAE) greater than grade 1, and all resolved quickly without impact. So far, the longest PFS in the gemcitabine + Elenagen treatment group is 27 months (and continues to grow), while the disease has progressed in all patients in the gemcitabine-only group within less than 12 months. "While our data on increasing progression-free survival are already statistically significant (P=0.01), it will take a little longer to reach a statistical significance on overall survival of the patients," said Professor Sergey Krasny, M.D., D.Sc., co-author of the ESMO presentation, and a medical director of the study. "However, so far, no single patient receiving gemcitabine alone has lived longer than 18 months, while over 50 percent of patients receiving gemcitabine and Elenagen live longer than that. Also of note is that no person who survived to live 18 months has died at this point in the study." "Our presentation at ESMO 2022 is a great step forward compared to what we presented at ESMO 2021. Now, we are certain that Elenagen is increasing progression-free survival for platinum-resistant ovarian cancer patients in the trial," said Alexander Shneider, Ph.D., CEO of CureLab Oncology. About Elenagen CureLab's lead investigational compound is code-named Elenagen, an experimental DNA therapy that consists of a circular piece of DNA called a plasmid that includes a gene for a human protein called p62/SQSTM1. In animal studies and Phase I/II human trials conducted ex-US, Elenagen demonstrated promise in reversing tumor grade, changing the tumor microenvironment, and enhancing the anti-cancer effects of chemotherapy. Experimental results also indicate mitigation of chronic inflammation and stimulation of an immune response to the tumor. About CureLab Oncology CureLab Oncology Inc. is a pre-IPO, clinical-stage immuno-oncology biotech company headquartered in the greater Boston area, Massachusetts. CureLab is dedicated to advancing new and safer therapeutics for solid tumors and other oncology and inflammatory indications. To learn more, visit curelab.com. Media contact: Tim Cox, ZingPR, [email protected] SOURCE CureLab Oncology Inc.