1stOncology™: Cancer Intelligence Service – Page 10752 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Therapeutic Solutions International Uses StemVacs™ Platform to Generate Personalized Adoptive T Cell Therapy Targeting Cancer Stem Cells

On February 22, 2021 Therapeutic Solutions International, Inc., (OTC Markets: TSOI), reported today novel data and filing of a patent application demonstrating that StemVacs cells carrying proprietary sequences from the cancer-specific antigen Brother of the Regulator of Imprinted Sites (BORIS), were able to elicit the generation of T cells capable of selectively killing cancer stem cells (Press release, Therapeutics Solutions International, FEB 22, 2021, View Source [SID1234575405]).

Schedule your 30 min Free 1stOncology Demo!
Discover why more than 1,500 members use 1stOncology™ to excel in:

Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

Schedule Your 30 min Free Demo!

In contrast to other markers associated with cancer, BORIS is not simply a "flag" that is recognized by the immune system, but it is essential for cancer to be cancer. Dr. Thomas Ichim, Board Member of the Company, published that gene silencing of BORIS resulted in the death of cancer cells.1 National Institutes of Health Scientist Dr. Dmitri Loukinov, as well as other collaborators, published with Dr. Ichim that DNA immunization with BORIS resulted in suppression of aggressive breast cancer,2 as well as induction of T cells capable of killing glioma, leukemia, and mastocytoma.3

"Despite living in what is called the Golden Age of Immunotherapy, the majority of cancers still do not undergo substantial responses to current treatments," said Dr. James Veltmeyer, Chief Medical Officer of the Company and co-inventor of the patent application. "What is impressive about the StemVacs approach is that it can generate personalized T cells that selectively seek and destroy cancer stem cells. It is the cancer stem cells that are the ‘roots’ of the cancer. They are resistant to chemotherapy and radiotherapy and to my knowledge the only possible way of eliminating cancer stem cells is through immunotherapy."

"Having worked in the area of cellular therapy and vaccine development, the possibility of using an allogeneic dendritic cell-based approach to ex vivo generate cancer stem cell killing T effector cells is tantalizing," said Feng Lin, MD, Ph.D., Chief Scientific Officer of the Company. "I look forward to continuation of these studies and eventual clinical utilization."

Researchers believe current cancer treatments sometimes fail because they don’t destroy the cancer stem cells. Think of cancer as a weed: the stem cells are the root while the remaining majority of the cells are the part of the weed above ground. If you remove only the leaves but not the root, the weed will grow back. The same is true for cancer: if you do not kill the cancer stem cells, the cancer is likely to return.4

"Cellular therapy is the future of medicine," said Famela Ramos, Vice President of Business Development of the Company and co-inventor of the patent. "This demonstration that StemVacs can generate "patient specific" killer cells that can be reinfused in patients offers a new area of product development for us, as well as an ability to implement a two-punch attack on the tumor."

"At Therapeutic Solutions International we are focused on researching, patenting, and implementing the most innovative and potentially effective immunotherapies we can develop," said Timothy Dixon, President and CEO of the Company and co-inventor of the patent. "The ability to generate tailor-made killer T cells that appear to selectively target cancer stem cells provides yet another complementary cellular immunotherapy in our growing armamentarium against this terrible disease."

ESSA Pharma Announces Closing of $130 Million Public Offering of Common Stock

On February 22, 2021 ESSA Pharma Inc. ("ESSA", or the "Company") (Nasdaq: EPIX), a clinical-stage pharmaceutical company focused on developing novel therapies for the treatment of prostate cancer, reported the closing of an underwritten public offering of 4,830,918 of its common shares at a public offering price of $27.00 per share before underwriting discounts (the "Offering") (Press release, ESSA, FEB 22, 2021, View Source [SID1234575404]). ESSA granted the underwriters a 30-day option to purchase up to an additional 724,637 common shares. The gross proceeds from the Offering were approximately $130 million.

ESSA intends to use the net proceeds from the Offering to fund clinical activities, chemistry, manufacturing and controls, and research and development, as well as working capital and general corporate purposes. Clinical activities include supporting multiple combination studies with EPI-7386 and anti-androgens, a Phase 2 clinical study, and preparatory work on a Phase 3 confirmatory study.

Jefferies and Piper Sandler acted as joint book-running managers for the Offering. Oppenheimer & Co. acted as lead manager for the Offering and Bloom Burton Securities Inc. acted as co-manager for the Offering.

The securities described above were offered by ESSA in the United States pursuant to a shelf registration statement on Form S-3 (File No. 333-250971) that was previously filed by ESSA with the Securities and Exchange Commission (the "SEC") and became effective on December 29, 2020 and in Canada pursuant to ESSA’s Canadian short form base shelf prospectus (the "Canadian Base Shelf Prospectus") dated August 24, 2020 that was previously filed with the securities regulatory authorities in each of the provinces of British Columbia, Alberta and Ontario.

A preliminary prospectus supplement related to the Offering was filed with the SEC on February 16, 2021, and a final prospectus supplement related to the Offering was filed with the SEC on February 18, 2021, and each are available on the SEC’s website at View Source A preliminary prospectus supplement to ESSA’s Canadian Base Shelf Prospectus was also filed with the securities regulatory authorities in each of the provinces of British Columbia, Alberta and Ontario on February 16, 2021 and is available at View Source and a final prospectus related to the Offering was filed with the securities regulatory authorities in each of the provinces of British Columbia, Alberta and Ontario on February 18, 2021 and is available at View Source.

This press release shall not constitute an offer to sell or the solicitation of an offer to buy, nor shall there be any sale of, the shares in any state or other jurisdiction which such offer, solicitation or sale would be unlawful prior to the registration or qualification under the securities laws of any such state or other jurisdiction.

SHEPHERD Therapeutics Announces Research Collaboration with National Institutes of Health’s (NIH) National Center for Advancing Translational Sciences (NCATS) in Adenoid Cystic Carcinoma (ACC)

On February 22, 2021 SHEPHERD Therapeutics, a company dedicated to catalyzing lifesaving treatments for rare cancer patients, reported a collaboration with the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH) (Press release, SHEPHERD Therapeutics, FEB 22, 2021, View Source [SID1234575403]). The research collaboration will leverage NCATS and SHEPHERD’s collective technology and scientific capabilities, including SHEPHERD’s DELVE computational platform, to identify drugs and drug combinations from NCATS’ annotated compound libraries that may have the potential to significantly improve treatment options and outcomes for patients with adenoid cystic carcinoma (ACC), a rare head and neck cancer.

ACC is a rare secretory gland cancer that affects approximately 1,200 Americans each year. There is an urgent need for therapies for ACC: Currently, no effective therapies currently exist, and the tumors are resistant to conventional chemotherapy. The standard of care is surgical resection and radiation therapy. While complete resection can be curative, it is difficult to achieve, and there is a high rate of recurrence with metastasis to the lungs, bone, and liver. Median survival is approximately 21 months once metastasis occurs. Discovering new uses for U.S. Food and Drug Administration (FDA)-approved drugs, or drug repurposing, offers a rapid path to potential therapeutic options, and NCATS is developing approaches to advance this strategy across diseases.

As part of the organizations’ three-year collaboration, NCATS will conduct high throughput screening and other laboratory and research-based activities, including but not limited to those conducted on an ACC cell line. SHEPHERD will use its AI-enabled DELVE drug positioning and development platform, laboratory resources, and other research-based assays to inform and build upon NCATS’ screening and laboratory activities.

"Many people with rare cancers are given few options, as a result of a lack of funding, research, and data," said Katherine Arline, Chief Strategy of Officer of SHEPHERD and investigator on the project. "We are fueled at SHEPHERD by the belief that having a rare cancer diagnosis shouldn’t mean that you lack a standard of care or have fewer treatment options than patients with common cancer diagnoses."

Precigen to Announce Fourth Quarter and Full Year 2020 Financial Results on March 1st

On February 22, 2021 Precigen, Inc. (Nasdaq: PGEN), a biopharmaceutical company specializing in the development of innovative gene and cell therapies to improve the lives of patients, reported the Company will release fourth quarter and full year 2020 financial results after the market closes on Monday, March 1, 2021 (Press release, Precigen, FEB 22, 2021, View Source [SID1234575402]). The Company will host a conference call that day at 4:30 PM ET to discuss financial results and provide a general business update.

The conference call may be accessed by dialing 1-888-317-6003 (Domestic US), 1-866-284-3684 (Canada) or 1-412-317-6061 (International) and providing the number 9387943 to join the Precigen Conference Call. Participants are asked to dial in 10-15 minutes in advance of the scheduled call time to facilitate timely connection to the call.

Helen Sabzevari, PhD, President and CEO, will also present at the H.C. Wainwright Virtual Global Life Sciences Conference and the on-demand webcast will be available starting Tuesday, March 9, 2021 at 7:00 AM ET.

Participants may register and access the webcasts for both events through Precigen’s website in the Events & Presentations section at investors.precigen.com/events-presentations.

BioAtla Conditionally Active Biologic Antibody Design And Functionality For Cancer Treatment Described In Leading Scientific Journal Peer-Reviewed Paper

On February 22, 2021 BioAtla, Inc., a global clinical-stage biotechnology company focused on the development of Conditionally Active Biologic (CAB) antibody therapeutics, reported the publication by Proceedings of the National Academy of Sciences (PNAS) that describes the design and functionality of therapeutic antibody candidates utilizing BioAtla’s proprietary CAB technology making them active only in the acidic tumor microenvironment while binding is reversibly inhibited in healthy tissue (Press release, BioAtla, FEB 22, 2021, View Source [SID1234575401]). This improved tumor targeting utilizes a newly discovered chemical switch system and is shown in animal models to provide for potent anti-tumor activity with markedly reduced toxicity to normal tissue, indicating a widened therapeutic index.

The peer reviewed paper, "Generating Tumor-selective Conditionally Active Biologic Anti-CTLA4 Antibodies Via Protein-associated Chemical Switches" by Hwai Wen Chang, Ph.D., Gerhard Frey, Ph.D., Haizhen Liu, Ph.D., Charles Xing, M.S., Lawrence Steinman, M.D., William J. Boyle, Ph.D., and Jay M. Short, Ph.D., describes the application of CAB technology in the context of the preclinical development of BioAtla’s immuno-oncology based CAB-CTLA4 antibody candidates, as well as several CAB antibodies directed against other important oncology targets. "CAB antibodies utilize a newly discovered switch mechanism that allows them to be active only in the tumor microenvironment and not active under normal physiological conditions. CAB antibodies demonstrate reduced peripheral toxicity and therefore are expected to provide a wider therapeutic window compared to traditional antibodies currently available for cancer therapy, potentially enabling higher dosing and longer treatments for improved efficacy," stated co-inventor Jay M. Short, Ph.D., Chairman, Chief Executive Officer and co-founder of BioAtla, Inc.

The CAB technology capitalizes on the well-established Warburg Effect that through a glycolytic process leads to an acidic external tumor microenvironment. Extracellular pH levels in tumors have been measured to be as low as pH5.8 compared to the tightly controlled, alkaline, pH7.4 of blood, with even higher pH in healthy tissues. Glycolytic metabolism is also the basis of the established PET scanning technology for cancer detection for tumor types. CAB proteins have increased binding activity as the pH in the microenvironment becomes acidic, while being inactive in normal physiological environments. BioAtla scientists discovered a novel chemical switch mechanism involving physiological-occurring chemicals, such as bicarbonate and hydrogen sulfide. These molecules are negatively charged at physiological conditions and interact with positive charged areas on the protein surface. Under acidic conditions of the tumor microenvironment they are neutralized and released from the protein surface, uniquely allowing CAB antibodies to bind to their target and attack the tumor cell. BioAtla refers to this novel physiological mechanism, used for generating CABs, as Protein-associated Chemical Switch(es) or PaCS mechanism.

CAB antibodies belong to a novel class of tumor-selective therapeutics that do not require the addition of a protective group and irreversible enzymatic activation in the tumor that is used with prodrug designs. The CAB-CTLA4 candidates described in the paper showed substantially reduced binding at pH7.4 compared to binding at pH6.0, while the comparable Ipilimumab analogue (IpA) binding showed no dependence on pH, thereby leading IpA to bind and attack normal cells, which results in dangerous on-target off-tumor toxicity. In comparison, multiple CAB candidates demonstrated substantial binding differentials between pH6.0 and pH7.4 conditions ranging from 9-fold to over 175-fold by ELISA, which is expected to lead to an improved therapeutic index and the potential improved clinical risk benefit in future therapies. The ability to design CAB tumor target binding for a specific range of pH conditions demonstrates the flexibility provided by the PaCS mechanism and the CAB technologies. Selection of a CAB antibody candidate is based upon strong differential pH binding between tumor and normal cells that can lead to increased anti-tumor potency with reduced toxicity, while maintaining a low immunogenicity risk and efficient manufacturing characteristics.

In addition to the development of CAB-CTLA4 discussed in the paper, BioAtla has successfully generated several CAB antibodies against multiple targets including EpCAM, Her2, Nectin-4, and CD73. The proprietary technology has also successfully been used for the development of ADCs and T-cell engaging bispecific antibodies. The ability to design conditionally active therapeutics with stronger selectivity over narrower pH ranges using the PaCS mechanism offers the opportunity to greatly enhance both the safety and potency of future therapies for solid tumors.

Potential for additional therapeutic modalities and disease targets

It is expected from the studies described in the paper that there is a potential for other yet to be identified PaCS molecules in disease related microenvironments, whether controlled through pH, concentration, or other molecular characteristics (intra- or intermolecularly) for enhancing a drug’s therapeutic index. Potential new therapeutic candidates addressing these opportunities are not limited to antibodies, but also include small molecules, encompassing lipids, sugars and nucleic acid-based agents or drugs. Further, it is expected that PaCS protein-chemical systems are important naturally occurring regulatory systems linked to a range of disease-related microenvironments, including cancer, inflammation and cellular senescence.