TC Biopharm Announces Closing of $4 Million Underwritten Public Offering

On June 7, 2022 TC Biopharm (Holdings) PLC ("TC Biopharm" or the "Company") (NASDAQ: TCBP) (NASDAQ: TCBPW), a clinical stage biotechnology company developing platform allogeneic gamma-delta T cell therapies for cancer indications, reported the closing of its previously announced underwritten public offering of 10,000,000 American Depositary Shares (the "ADSs"), each ADS representing one ordinary share of the Company, at a public offering price of $0.40 per ADS, for aggregate gross proceeds of $4 million, prior to deducting underwriting discounts and commissions, and other offering expenses (Press release, TC Biopharm, JUN 7, 2022, View Source [SID1234615729]). In addition, the Company has granted the underwriters a 45-day option to purchase up to an additional 1.5 million ADSs at the public offering price per share, less the underwriting discounts and commissions, to cover over-allotments, if any.

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EF Hutton, division of Benchmark Investments, LLC, acted as sole book-running manager for the offering.

A registration statement on Form F-1 (File No. 333-265159), was filed with the Securities and Exchange Commission ("SEC") and was declared effective on June 2, 2022. A final prospectus relating to the offering was filed with the SEC and is available on the SEC’s website at View Source Electronic copies of the final prospectus relating to this offering may be obtained from EF Hutton, division of Benchmark Investments, LLC, 590 Madison Avenue, 39th Floor, New York, NY 10022, Attention: Syndicate Department, or via email at [email protected] or telephone at (212) 404-7002.

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

ASCO 2022 | Ascentage Pharma Releases for the First Time Results of its FAK/ALK/ROS1 inhibitor APG-2449 Demonstrating Safety and Efficacy in Patients with Advanced NSCLC

On June 7, 2022 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that it has released the results from its Phase I first-in-human (FIH) study of the company’s novel FAK inhibitor and third-generation ALK/ROS1 tyrosine kinase inhibitor (TKI) APG-2449 in patients with second-generation TKI-resistant ALK/ROS1+ non-small-cell lung cancer (NSCLC) or mesothelioma in a Poster Presentation at the 58th American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Ascentage Pharma, JUN 7, 2022, View Source;ascentage-pharma-releases-for-the-first-time-results-of-its-fakalkros1-inhibitor-apg-2449-demonstrating-safety-and-efficacy-in-patients-with-advanced-nsclc-301563283.html [SID1234615727]). APG-2449 is the first China-developed third-generation ALK inhibitor entering clinical studies.

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Entering the fifth consecutive year in which its abstracts were selected for presentations by the ASCO (Free ASCO Whitepaper) Annual Meeting, Ascentage Pharma showcased results from multiple clinical trials of its five drug candidates, including the first-time results of APG-2449 highlighting the company’s promising pipeline in solid tumors. APG-2449 demonstrated preliminary efficacy in TKI-naïve patients or those whose disease was resistant to second-generation TKIs, with 4 partial responses (PRs) observed in the 14 patients with second-generation-TKI resistant and ALK-positive NSCLC. In the 10 TKI-naïve ALK/ROS1+ patients, the objective response rate (ORR) was 80%, and the disease control rate (DCR) was 100%.

Discovered and developed by Ascentage Pharma, APG-2449 is a novel, orally-available FAK/ALK/ROS1 inhibitor and the first China-developed third-generation ALK inhibitor entering clinical studies.

Prof. Hongyun Zhao of Sun Yat-sen University Cancer Center, who is the principal investigator of this study, said, "APG-2449 is a potent FAK/ALK/ROS1 inhibitor that can address drug resistance to second-generation ALK TKIs. In this FIH study, APG-2449 demonstrated favorable safety and antitumor activity in patients with advanced NSCLC, and showed on-target pharmacodynamic effects. Building on results from this Phase I study, we look forward to further evaluate APG-2449’s efficacy in advanced NSCLC patients resistant to second-generation ALK inhibitor.

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, commented, "APG-2449 is one of our key drug candidates, outside our pipeline of apoptosis-targeting assets. The data presented at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting demonstrated APG-2449’s therapeutic potential in patients with advanced NSCLC and are indicative of our progress in the field of solid tumors. We will continue to take firm steps to advance this clinical development program. Furthermore, we are proud to be able to present clinical development progress for a number of Ascentage Pharma’s drug candidates at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting, which highlight our capabilities in global innovation. Honoring our mission of addressing unmet clinical needs in China and around the world, we are now accelerating our clinical programs to bring more safe and effective therapeutics to patients in need."

The highlights of this abstract on APG-2449 are as follows:

First-in-human phase I results of APG-2449, a novel FAK and third-generation ALK/ ROS1 tyrosine kinase inhibitor (TKI), in patients (pts) with second-generation TKI-resistant ALK/ROS1 non-small-cell lung cancer (NSCLC) or mesothelioma.

Abstract: #9071

This dose-escalation and dose-expansion study was designed to assess the safety, tolerability, recommended Phase II dose (RP2D), pharmacokinetics (PK), pharmacodynamics (PD), and efficacy of APG-2449 in patients with second-generation TKI-resistant ALK/ROS1+ NSCLC or mesothelioma.
As of December 30, 2021, 84 Chinese patients with NSCLC or mesothelioma enrolled were treated with APG-2449 at doses ranging from 150 to 1,500 mg. APG-2449 was administered orally once daily on a 28-day cycle using a "3+3" dose escalation design.
4 PRs were observed in 14 ALK+ patients resistant to second-generation TKIs treated at the RP2D. Among 8 patients with brain metastases, 1 complete response (CR) and 3 PRs were observed intracranially. In 10 TKI-naïve patients, the ORR was 80% (ALK+, 6/8; ROS1+, 2/2) and the DCR was 100%.
In addition, AGP-2449 demonstrated a favorable safety profile. The preliminary biomarker data showed decreased FAK phosphorylation in peripheral blood mononuclear cells and increased IFN-γ levels in serum after multiple doses of APG-2449.
Conclusions: APG-2449 has a favorable safety and PK profile. Preliminary efficacy was observed in patients whose disease was resistant to second-generation or TKI-naïve. Biomarker data indicated potential target engagement on FAK and the immunomodulatory effects of APG-2449.

ASCO 2022 | Ascentage Pharma Releases Updated Data Demonstrating Lisaftoclax’s (APG-2575) Therapeutic Potential in Patients with R/R CLL/SLL

On June 7, 2022 Ascentage Pharma (6855.HK), a global biopharmaceutical company engaged in developing novel therapies for cancers, chronic hepatitis B (CHB), and age-related diseases, reported that it has released the updated results from a Phase Ib/II study of the Bcl-2 inhibitor lisaftoclax (APG-2575) in patients with relapsed/refractory chronic lymphocytic leukemia/small lymphocytic lymphoma (R/R CLL/SLL) in a Poster Presentation at the 58th American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (Press release, Ascentage Pharma, JUN 7, 2022, View Source;ascentage-pharma-releases-updated-data-demonstrating-lisaftoclaxs-apg-2575-therapeutic-potential-in-patients-with-rr-cllsll-301563282.html [SID1234615726]).

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Entering the fifth consecutive year in which company’s abstracts were selected for presentations by the ASCO (Free ASCO Whitepaper) Annual Meeting, Ascentage Pharma showcased results from multiple clinical trials of its five drug candidates, including favorable data of lisaftoclax, a key drug candidate of the company’s apoptosis-targeted pipeline, in Chinese patients with R/R CLL/SLL showing an objective response rate (ORR) of 67.4%. Lisaftoclax was well tolerated, and all adverse events were manageable. No dose-limiting toxicity (DLT) were observed at up to 800 mg/day. The risk of clinical tumor lysis syndrome (TLS) in patients on daily dose ramp-up was minimal.

Prof. Jianyong Li, Director of the Hematology Department, Jiangsu People’s Hospital, and the principal investigator of this study, said, "Lisaftoclax is a Bcl-2 selective inhibitor that can induce apoptosis and suppress the growth of tumor cells. In this Phase Ib/II study, lisaftoclax as a single agent showed favorable preliminary efficacy and safety, and a daily ramp-up schedule that is patients’ friendly. We look forward to further evaluating the efficacy of lisaftoclax as a single agent and in combinations in patients with R/R CLL/SLL."

Dr. Yifan Zhai, Chief Medical Officer of Ascentage Pharma, commented, "Lisaftoclax is the first China-developed Bcl-2 inhibitor entering clinical development in China, also the world’s second and China’s first Bcl-2 inhibitor being investigated in pivotal trials. Data released at this year’s ASCO (Free ASCO Whitepaper) Annual Meeting suggest that lisaftoclax may offer an effective, safe, and more ‘user friendly’ treatment alternative to patients with R/R CLL/SLL. We are taking firm steps forward with this clinical development program to allow patients to benefit from this novel therapeutic as soon as possible. Meanwhile, we are also evaluating lisaftoclax monotherapy and combinations in patients with solid tumors."

Dr. Zhai continued, "Furthermore, we are proud to be able to present clinical development progress for a number of Ascentage Pharma’s drug candidates, which highlight our capabilities in global innovation. Honoring our mission of addressing unmet clinical needs in China and around the world, we are now accelerating our clinical programs to bring more safe and effective therapeutics to patients in need."

The highlights of this abstract on lisaftoclax are as follows:

A phase Ib/II study of lisaftoclax (APG-2575), a novel BCL-2 inhibitor (BCL-2i), in patients (pts) with relapsed/refractory chronic lymphocytic leukemia or small lymphocytic lymphoma (R/R CLL/SLL).

Abstract: #7543

The aim of this multicenter, open-label study was to evaluate the safety, antitumor activity, PK, and pharmacodynamics (PD) of lisaftoclax in Chinese patients with R/R CLL/SLL.

As of January 25, 2022, 45 patients had been enrolled. Lisaftoclax was administered orally once daily at 3 dose cohorts (400, 600, or 800 mg) in 28-day cycles, with 15 patients in each cohort.

Lisaftoclax monotherapy demonstrated favorable safety profiles in all three dose cohorts, and no DLT was observed during the Phase I study.

The risk of TLS in patients on daily dose ramp-up was extremely low, which was consistent with the observations of the Phase I study. The median duration of treatment was 7 cycles. and the ORR in the 43 efficacy evaluable patients with R/R CLL/SLL was 67.4%, including 1 complete response (CR) and 28 partial responses (PRs).

BCL-2i lisaftoclax was well tolerated up to 800 mg/day. There were no significant new or unmanageable safety findings. The recommended Phase II dose (RP2D) of lisaftoclax was determined as 600 mg. Lisaftoclax may offer a treatment alternative for patients with R/R CLL/SLL, with a daily ramp-up schedule that may be more convenient and "user friendly".
Appendix: A list of Ascentage Pharma’s abstracts selected by this year’s ASCO (Free ASCO Whitepaper) Annual Meeting

Antengene Announces First Patient Dosed in the Phase I STAMINA-001 Study of ATG-037 for the Treatment of Patients with Locally Advanced or Metastatic Solid Tumors

On June 7, 2022 Antengene Corporation Limited ("Antengene" SEHK: 6996.HK), a leading innovative, commercial-stage global biopharmaceutical company dedicated to discovering, developing and commercializing first-in-class and/or best-in-class therapeutics in hematology and oncology, reported that the first patient has been dosed in the Phase I STAMINA-001 trial to evaluate ATG-037 as a monotherapy or in combination with pembrolizumab in patients with locally advanced or metastatic solid tumors in Australia (Press release, Antengene, JUN 7, 2022, View Source [SID1234615725]).

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The primary objective of the study is to evaluate the safety, tolerability, recommended Phase II dose and preliminary antitumor efficacy of ATG-037 as a monotherapy and in combination with pembrolizumab. Secondary objectives include characterization of the pharmacology of ATG-037.

ATG-037 is an orally available, small molecule CD73 inhibitor. CD73 is an "immune checkpoint mediator"1 that interferes with anti-tumor immune responses by generating adenosine, which leads to immunosuppression in the tumor microenvironment. ATG-037 can reverse adenosine-mediated immunosuppression2. It has demonstrated promising preclinical efficacy as a monotherapy and in combination with ICIs and chemotherapy agents. In preclinical studies, this compound overcomes the "hook effect" that is common in anti-CD73 antibodies. In addition, GLP toxicology studies indicate the compound has a potentially wide therapeutic window.

"While ICIs are widely used in the treatment of various cancers, many patients have resistant or refractory disease, which has created a large unmet need," said Dr. Ganessan Kichenadasse, principal investigator, Southern Oncology Clinical Research Unit in Adelaide, Australia. "Mounting evidence suggests that adenosine plays a critical role in suppressing anti-tumor immunoactivity. CD73 can convert adenosine monophosphate (AMP) to adenosine. ATG-037, an orally available, small molecule CD73 inhibitor, can block the generation of adenosine. We are excited to be a part of the STAMINA-001 Trial. This Phase I study brings together a group of highly experienced Australian investigators to collaborate with Antengene. We are excited to assess the therapeutic potential of ATG-037 for patients with solid tumors as a single agent as well the exploring the opportunity for benefit with the addition of an ICIs."

"Developing agents that can act in the tumor microenvironment to reverse immunosuppression is one of the key focus areas for Antengene, " said Dr. Kevin Lynch, Antengene’s Chief Medical Officer. "Preclinical data presented at the 2022 American Association of Cancer Research Annual Meeting (AACR 2022) showed that ATG-037 had a stronger ability to restore T-cell function in higher-AMP environments compared with anti-CD73 monoclonal antibodies. These data highlighted the potential therapeutic advantages of small molecule inhibitors of CD73 over blocking antibodies, either as a monotherapy, or in combination with other immune-oncological treatments. We have been very pleased with the drug’s performance in preclinical studies and are hopeful that in this Phase I study ATG-037 can demonstrate the tolerability and signals of activity that will allow us to move forward into a broader development program. We are very excited about the start of this first in human clinical trial and look forward to next steps with ATG-037."

About the STAMINA-001 Trial

The STAMINA-001 trial is a Phase I multi-center, open-label, dose finding study of ATG-037 monotherapy or combination therapy with pembrolizumab in patients with locally advanced and metastatic solid tumors. Subjects will begin with two monotherapy cycles and then be allowed to receive the addition of pembrolizumab. The primary objective of the study is to evaluate the safety and tolerability of ATG-037 and to determine the maximum tolerated dose (MTD) and/or recommended Phase II dose (RP2D) and/or optimal biological dose of ATG-037 monotherapy and preliminary efficacy. Secondary objectives include characterization of the pharmacology of ATG-037. As a Phase I study, there will be intensive safety monitoring throughout the trial.

About ATG-037

ATG-037 is an orally-available, highly selective small molecule that completely blocks the activity of CD73. CD73, an ecto-5′-nucleotidase, catalyzes the conversion of adenosine monophosphate (AMP) to adenosine. Adenosine production leads to significant immunosuppression in the tumor microenvironment, now recognized as one of the most important immunomodulatory pathways in the tumor microenvironment.

Many human tumors overexpress CD73 and this expression is frequently associated with poor prognosis. Blocking CD73 has been shown to be effective in controlling tumor growth and metastases and CD73 inhibitors may increase the therapeutic activity of ICIs and chemotherapy agents. Clinical data so far indicate that CD73 inhibitors add little additional toxicity to standard of care treatments.

The Pershing Square Sohn Cancer Research Alliance Awards $4.2M to Seven Emerging Trailblazers in Cancer Research

On June 7, 2022 The Pershing Square Sohn Cancer Research Alliance reported the seven winners of the 2022 Pershing Square Sohn Prize for Young Investigators in Cancer Research, awarded annually to cancer research scientists and physician-scientists based in the greater New York City area (Press release, The Pershing Square Sohn Cancer Research Alliance, JUN 7, 2022, View Source [SID1234615724]). The Prize, totaling $4.2 million, empowers investigators early in their independent careers to pursue their most exciting research projects at a critical stage when traditional funding is lacking. Recipients receive $200,000 per year for three years.

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Over the past nine years, the Alliance has awarded over $35 million to 59 scientists at 12 institutions in New York, New Jersey, and Connecticut. With this funding, the recipients have contributed greatly to the New York City area’s growing biomedical research hub. In addition to funding, the Alliance provides Prize winners with opportunities to present their work to scientific and business audiences to encourage collaboration and help bridge the gap between academia and industry.

"Tackling the ‘frontline science’ of cancer research at record speeds demands the bold innovation and rigor embodied by this year’s cohort of Prize winners," said The Pershing Square Foundation Trustee Neri Oxman. "Young investigators lead the way in asking hard questions that hold the greatest potential for transformative impact, and we remain committed to empowering their groundbreaking work."

The winners of the 2022 Pershing Square Sohn Prize are:

Karuna Ganesh, MD, PhD, Memorial Sloan Kettering Cancer Center: The laboratory of Dr. Ganesh aims to figure out how metastatic cancer cells, particularly those of colorectal cancer, gain the ability to adapt to new environments as they spread to distant organs. As a physician-scientist, Dr. Ganesh studies metastatic cancer cells from patient surgical samples using interdisciplinary computational, genetic, and organoid culture approaches to accelerate clinical impact.
Richard Hite, PhD, Memorial Sloan Kettering Cancer Center: Dr. Hite and his lab will make 3D structures of transporters that move nutrients from the part of the cell where they are made, to the other part of the cell where they are needed to supply energy. All cells need nutrients for energy, but cancer cells rewire their metabolism to become dependent on a few key amino acids needed for rapid growth and survival. The transporter 3D structures will enable Dr. Hite to understand how they function and how they can be manipulated therapeutically to starve cancer cells by no longer providing them these vital nutrients.
Nikhil Joshi, PhD, Yale School of Medicine: Dr. Joshi’s laboratory aims to determine why immunotherapies don’t work for most cancer patients and how to fix this. Some of the best immune cells for fighting cancer are reserves of tumor-"killer" T cells that are in our lymph nodes, which are outside of the tumor. In lymph nodes, these killer T cells can talk with another immune cell—a "follicular helper"—which makes them better at fighting once the killer T cell travels from the lymph node and into the tumor. In his project, Dr. Joshi will determine how the killer T cells and follicular helpers interact in the lymph node and if their communication can be increased, with the goal of using this knowledge to develop therapies that will boost the number of follicular helpers as well as bring more killer T cells from the lymph node and into the tumor to successfully defeat cancer.
Piro Lito, MD, PhD, Memorial Sloan Kettering Cancer Center: Dr. Lito and his lab study proteins that drive cancer growth, focusing particularly on KRAS, a small enzyme that acts as an ‘on’/‘off’ switch to control a number of cellular functions. Mutations of the KRAS protein are found in nearly a third of cancer patients and lead to uncontrolled cancer growth. It is believed that genetic mutations result in keeping KRAS "locked" in an ‘on’ state, but new data from the Lito lab suggest the presence of certain cellular proteins that physiologically inactivate mutant KRAS. Through his project, Dr. Lito aims to explore this further and identify novel regulators of KRAS activity, thus opening new directions for potential therapeutics.
Michael Pacold, MD, PhD, NYU Grossman School of Medicine: A physician-scientist, Dr. Pacold’s project strives to determine how two of the most aggressive cancers—pancreatic cancer and glioblastoma—survive and proliferate when they have extremely little oxygen, which is required for many processes that enable cancer cells to grow. Using novel techniques to trace oxygen in cells, his lab will decipher how oxygen is efficiently utilized and how this process can be therapeutically targeted to stop cancer cell growth.
Maria Soledad Sosa, PhD, The Tisch Cancer Institute at Mount Sinai: The laboratory of Dr. Sosa believes that by targeting cells that have left the primary tumor and arrived at distant organs, metastatic tumor formation can be prevented. These disseminated cancer cells often come from invasive primary tumors but can even spread from pre-malignant cancer cell lesions and remain dormant for an extended period of time, so when a tumor is detected, patients may have already both types. The Sosa lab aims to understand how each type of disseminated cancer cell communicates with the other and the immune microenvironment, and how it contributes to metastasis formation, with the goal of identifying targets for therapeutic intervention and biomarkers to predict relapse.
Siyuan Wang, PhD, Yale School of Medicine: Using cutting-edge technologies that enable extremely detailed characterization of the 3D genome, the Wang lab aims to invent a novel methodology to discover genes that regulate DNA folding architectures and gene expression patterns in a variety of cancers. Disease occurs when DNA isn’t properly folded into the cell nucleus and is a hallmark of cancer. The genes that regulate this could lead to an entirely new class of therapeutics, as manipulating them could affect (even fix) abnormal DNA folding structures, enabling a novel approach towards future cures.
"We are continually inspired by the superb quality of the proposals we receive as well as the exceptionally talented researchers that are working in the greater New York area institutions," said Olivia Tournay Flatto, PhD, Co-Founder and Executive Director of the Pershing Square Sohn Cancer Research Alliance and President of The Pershing Square Foundation. "It is our goal to build a community of creative and talented individuals, and to connect them with like-minded peers in pursuit of novel ideas, therapies, technologies, and, ultimately, knowledge that can further our understanding of disease and fundamental human biology."

"The work to find new treatments and cures for cancer continues to be an urgent global health priority so we are heartened by the research approaches of this year’s Prize winners," said Evan Sohn, Vice President of the Sohn Conference Foundation. "We are confident that with the passion, creativity, and insights we’ve seen from this group of scientists, they will make discoveries that will have a lasting impact for the patients for whom our Foundation fights."

As part of the selection process, the Pershing Square Sohn Cancer Research Alliance relied on and benefitted from the guidance of a highly accomplished advisory board.

Prize Advisory Board members include: Jeanne B. Ackman, MD, Director, Thoracic MRI, Radiologist, Massachusetts General Hospital, and Assistant Professor, Harvard Medical School; Mikael Dolsten, MD, PhD, Chief Scientific Officer and President, Worldwide Research, Development, and Medical, Pfizer, Inc.; Allan Goodman, PhD, Chief Executive Officer, The Institute of International Education; Pablo Legorreta, Founder and Chief Executive Officer, Royalty Pharma; Richard P. Lifton, MD, PhD, President, The Rockefeller University; Siddhartha Mukherjee, MD, PhD, Assistant Professor, Department of Medicine, Division of Oncology, Columbia University Medical Center, and Author of The Emperor of All Maladies: A Biography of Cancer and The Gene: An Intimate History; James E. Rothman, PhD, Sterling Professor of Cell Biology and Professor of Chemistry, Yale University and 2013 Nobel Prize Winner in Physiology or Medicine; Bruce Stillman, PhD, President and Chief Executive Officer, Cold Spring Harbor Laboratory; Craig Thompson, MD, President and Chief Executive Officer, Memorial Sloan Kettering Cancer Center; and George D. Yancopoulos, MD, PhD, President and Chief Scientific Officer, Regeneron.