CALGARY, Alberta, May 10, 2022 (GLOBE NEWSWIRE) -- Zenith Epigenetics Ltd. (Zenith or the Company) announced today the initiation of a Phase 2b Triple Negative Breast Cancer (TNBC) clinical trial combining ZEN-3694 + Pfizer Inc.s Talzenna (talazoparib). The trial will continue to evaluate the efficacy and safety of this combination in patients with locally advanced or metastatic germline wild type BRCA1/2 TNBC. This Phase 2b trial is an extension of the recently completed Phase 1b/2 trial which met its primary efficacy endpoint of clinical benefit rate comprised of objective responses plus stable disease and which showed that the combination regimen was well tolerated. The Phase 2b extension will enroll patients who have previously been treated with a TROP2 antibody drug conjugate for locally advanced or metastatic disease.

The data from the Phase 1b/2 trial has shown that the ZEN-3694 plus talazoparib combination regimen induced durable responses in tumors of TNBC patients which do not harbor mutations in BRCA1/2," said Dr. Mark Robson, a principal investigator and medical oncologist at The Memorial Sloan Kettering Cancer Center. These clinical results confirm the rationale and data from pre-clinical experiments which have shown that BET inhibition can sensitize wild type BRCA1/2 TNBC tumors to PARP inhibition. This interesting data warrants the continued clinical evaluation of this combination.

In the United States, talazoparib is currently approved under the brand name TALZENNA, which is a poly (ADP-ribose) polymerase (PARP) inhibitor indicated for the treatment of adult patients with deleterious or suspected deleterious germline BRCA-mutated (gBRCAm) HER2-negative locally advanced or metastatic breast cancer.

Single agent PARPi are approved for gBRCAm HER2-negative locally advanced or metastatic breast cancer, as both PARP inhibition and non-functioning DNA repair proteins BRCA1/2 are required to block DNA repair and kill tumor cells (synthetic lethality). Preclinical and clinical data has shown that BET inhibition may reduce the levels of DNA repair proteins such as BRCA1/2 and RAD51 and thus create synthetic lethality in wildtype BRCA1/2 TNBC tumors when combined with PARP inhibition.

We are very pleased to advance our TNBC program to Phase 2b and closer to possible registration, said Donald J. McCaffery, President and CEO of Zenith. There is a significant unmet need in this aggressive cancer with few non cytotoxic therapy options available for the patient.

The data from the completed Phase 1b/2 part of the clinical trial will be presented in an oral poster discussion section at the annual ASCO conference in Chicago, Illinois on Monday, June 6, 2022. The abstract for this presentation will be released by ASCO on May 26, 2022, at 5:00 PM EDT on ASCO.org/Abstracts.

Abstract Number:1023

Abstract Title:A phase 1b/2 study of the BET inhibitor ZEN-3694 in combination with talazoparib for treatment of patients with TNBC without gBRCA1/2 mutations.

Session Type/Title:Poster Discussion Session/Breast CancerMetastatic

Session Date and Time:Monday, June 6, 2022, 11:30 AM-1:00 PM; 8:00 AM-11:00 AM CDT

About Zenith and ZEN-3694

Zenith Epigenetics Ltd., a wholly-owned subsidiary of Zenith Capital Corp., is a clinical stage biotechnology company focused on the discovery and development of novel therapeutics for the treatment of cancer and other disorders with significant unmet medical need. Zenith Epigenetics is developing various novel combinations of BET inhibitors with other targeted agents. The lead compound, ZEN-3694, is in clinical development for various oncologic indications, specifically:

About Triple Negative Breast Cancer (TNBC)

TNBC is an aggressive form of breast cancer with low survival rates. TNBC accounts for about 10-15%of all breast cancers and it differs from other types of invasive breast cancer in that it tends to grow and spread faster, has fewer treatment options, and tends to have a worse prognosis. The termtriple-negative breast cancerrefers to the fact that the cancer cells have only low or no amount of the receptors ER, PR, and HER2. Approximately 75,000 women in the US, Japan and the major EU countries are diagnosed with TNBC each year.

For further information, please contact:

Investor Relations & Communications

Zenith EpigeneticsPhone: 587-390-7865Email: info@zenithepigenetics.comWebsite:www.zenithepigenetics.com

This news release may contain certain forward-looking information as defined under applicable Canadian securities legislation, that are not based on historical fact, including without limitation statements containing the words "believes", "anticipates", "plans", "intends", "will", "should", "expects", "continue", "estimate", "forecasts" and other similar expressions. In particular, this news release includes forward looking information relating to the Companys development activities involving ZEN-3694 in combination with Pfizers PARP inhibitor Talzenna, and other targeted agents used in precision oncology, as well as other planned PARPi based combination therapy clinical trials in other tumor types. Our actual results, events or developments could be materially different from those expressed or implied by these forward-looking statements. We can give no assurance that any of the events or expectations will occur or be realized. By their nature, forward-looking statements are subject to numerous assumptions and risk factors including those discussed in our most recent MD&A which are incorporated herein by reference and are available through SEDAR at http://www.sedar.com. The forward-looking statements contained in this news release are expressly qualified by this cautionary statement and are made as of the date hereof. Zenith disclaims any intention and has no obligation or responsibility, except as required by law, to update or revise any forward-looking statements, whether as a result of new information, future events or otherwise

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Zenith Epigenetics Announces Initiation of a Phase 2b Triple Negative Breast Cancer (TNBC) Clinical Trial - BioSpace

Watching Fear and Loathing in Las Vegas(now streaming on Peacock) with its frenetic pace, bizarre performances, and twisted cinematography is a visual experience akin to falling into a drug binge, and thats by design. The movie is constructed to give the feeling of living inside the minds of its two protagonists as they consume every illicit substance known to humanity, while supposedly on a work trip in Las Vegas. The result is an anxiety-laden two hours capturing a glimpse inside the mind of author Hunter S. Thompson.

While the movie has a certain amount of humor at the expense of its characters, driven mostly by the bombastic performances of Johnny Depp and Benicio del Toro, real-world substance dependence offers little to laugh about.

Long-term exposure to substances like alcohol, especially during adolescence not to mention the hard stuff found in the fictional Thompsons drug stash causes epigenetic changes to a persons brain chemistry which leads to dependence and anxiety disorders. According to a new study, gene editing by way of a modified version of CRISPR Cas9, might be able to reverse those changes in the brain.

Subhas Pandey from the Center for Alcohol Research in Epigenetics at the University of Illinois was the senior author of the study, now published in the journal Science Advances, which sought to reverse the negative effects of alcohol dependence in the brains of rats and, hopefully someday, in humans.

Adolescent binge drinking is a major public health concern, and it produces long lasting impacts on brain chemistry. So, its really important to catch the disease early and cure it before someone predisposes to substance abuse disorder, anxiety, and depression, Pandey told SYFY WIRE.

The research targeted the enhancer region of the activity-regulated cytoskeleton-associated protein, ARC for short, which is suppressed when individuals are exposed to chronic alcohol use in adolescence. According to Pandey, ARC is important for making connections between neurons so they can communicate with one another, and plays an important role in synaptic plasticity, learning, and memory. When its suppressed, alcohol consumption and anxiety behaviors increase.

Researchers used a modified version of CRISPER Cas9, known as dCAS9, which causes a functional change in a target gene without clipping it out. In this case, that meant researchers were able to increase ARC expression to undo the epigenetic damage caused by alcohol exposure.

In tests, rats were given alcohol between the 27th and 41st days of life, the equivalent of ages 10 to 18 in humans, which led to anxiety and increased alcohol consumption when the rats grew to adulthood. Then, they injected dCas9 into the amygdala to increase ARC expression. The process takes two weeks to go into full effect, but the results were impressive. Symptoms of anxiety as well as alcohol consumption decreased. The evidence suggests the relationship between gene expression and alcoholism or anxiety also holds for adults without early exposure to alcohol.

In a previous study, we found that chronic alcohol exposure in adulthood also leads to a reduction in the expression of this gene and causes anxiety-like behavior. In adult control animals, who are normal, if we do gene editing to suppress the expression of the ARC gene, they become anxious and start drinking more. So, it looks like this phenomenon is also important in adults, Pandey said.

Understanding the genetic and epigenetic drivers of anxiety and alcohol disorders, as well as gene editing strategies to address them, could lead researchers to novel therapies.

There are drugs which can manipulate this gene, but they may also affect several places in the brain, so we might get side effects because other genes are affected. Targeted manipulation of the gene, I personally feel, is the future of the medicine, Pandey said.

Hunter S. Thompson somehow straddled the line between brilliance and complete collapse, at least for a while. He was one of a kind, its unlikely there will ever be another like him. Especially now that gene editing can flip the off switch on our inner demons.

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Gene edited rats cured of anxiety and alcoholism | SYFY WIRE - Syfy