1stOncology™: Cancer Intelligence Service – Page 8216 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Black Diamond Therapeutics and OpenEye Scientific Announce Collaboration to Expand MAP Drug Discovery Platform

On September 21, 2021 Black Diamond Therapeutics, a precision oncology medicine company pioneering the discovery and development of MasterKey therapies, and OpenEye Scientific, a leader in computational molecular design, reported that they are entering into a strategic partnership incorporating OpenEye’s Orion molecular design platform into Black Diamond’s proprietary Mutation-Allostery-Pharmacology (MAP) drug discovery engine to advance Black Diamond’s efforts to develop MasterKey inhibitor cancer therapies (Press release, Black Diamond Therapeutics, SEP 21, 2021, View Source [SID1234590070]).

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!

OpenEye’s Orion Software-as-a-Service platform will enable Black Diamond to perform rapid simulations and analysis of protein motion through Orion’s powerful combination of a high-performance compute facility, scientific development environment, and browser-based analysis and collaboration tools. Black Diamond and OpenEye will collaborate to co-develop enhanced-sampling capabilities designed to deliver information on an accelerated time scale. With the increased capability to model large and complex systems, Black Diamond will enhance its ability to discover mutant selective MasterKey therapies that target families of oncogenic mutations.

"Our proprietary MAP drug discovery engine combines computational and experimental techniques to identify, validate, and aggregate oncogenic mutations, rendering them actionable by a single MasterKey inhibitor," said David M. Epstein, PhD, Co-Founder, President and CEO of Black Diamond Therapeutics. "Complementing our expertise in cancer genomics, protein function and medicinal chemistry, we believe our work with OpenEye will enable the expansion of Black Diamond’s therapeutic pipeline by enhancing a molecular understanding of intact, full-length oncoproteins activated by a diverse array of driver mutations."

OpenEye’s Orion molecular design platform integrated with Amazon Web Services’ Cloud environment allows Black Diamond to pursue scalable and parallel analyses of the conformational states of families of mutant oncogenes. The deployment of these large-scale perturbations provides Black Diamond with detailed structural and dynamic information on target proteins to guide drug discovery efforts. The arrangement between OpenEye and Black Diamond involves an upfront payment and potential downstream economics resulting from select Black Diamond products for OpenEye.

"We are beginning to see the marriage of computation and genomics not just through sequence analysis, but at the structural level," said Anthony Nicholls, CEO and Founder of OpenEye Scientific. "This shift is being hastened by the Cloud and its democratization of large-scale computation. We’re very proud to be able to work with Black Diamond to combine molecular simulation on our cloud platform, Orion, with their MAP drug discovery engine to accelerate their search for novel cancer therapeutics."

Acquisition expands research in cancer immunology

On September 21, 2021 Boehringer Ingelheim reported the acquisition of Abexxa Biologics Inc., a biopharmaceutical company taking a new approach in the fields of immuno-oncology and oncology research to develop the next generation of precision medicines designed to revolutionize cancer treatments (Press release, Boehringer Ingelheim, SEP 21, 2021, View Source [SID1234590068]). The acquisition will allow Boehringer Ingelheim to access Abexxa’s expertise in targeting cancer-specific proteins that are located inside the cell, rather than those expressed on the cell membrane. This enlarges the pool of potential cancer antigen targets. In particular, Abexxa’s technology could lead to the development of cancer immunotherapies that are effective in a broader range of patients and cancer types.

"The acquisition of Abexxa bolsters our commitment to tumor-antigen discovery and new ways of targeting intracellular antigens. Their cutting-edge know-how and technologies for antigen discovery and novel antibody generation strongly complement the current approaches we have been applying successfully to enable immune-targeting of cancer cells," said Clive R. Wood, Ph.D., corporate senior vice president and global head of discovery research, Boehringer Ingelheim. "By expanding our portfolio of antibodies binding novel intracellular tumor antigens, we are striving to develop unique and broadly applicable new immunotherapeutic approaches for cancer patients," added Wood.

Abexxa’s innovative platform unlocks the ability to target intracellular antigens of cancer cells by recognizing their presentation on the cell surface by MHC class 1 molecules. While the Abexxa platform addresses the more common HLA-A2 peptide presentation, the company has developed specific expertise in the nonclassical MHC class 1 molecule HLA-E, which has the potential to impact a broader set of cancer patients’ antigens. More specifically, Abexxa has developed a first-in-class T-cell receptor (TCR)-like antibody that can be used to disrupt the NKG2A:HLA-E immune checkpoint axis in oncology. Abexxa molecules are also being formulated to recruit immune cells targeting HLA-E peptide complexes on tumors.

In 2016, Boehringer Ingelheim’s Venture Fund, the arm of the company that invests in ground-breaking therapeutic and digital health approaches, awarded Abexxa initial investment funding. Later that year, Abexxa won Boehringer Ingelheim’s Innovation Prize, which facilitates business growth and rewards new companies for their dedication to innovation. The prize allowed Abexxa to expand operations into a shared lab space in Cambridge, Massachusetts, to continue its research. Boehringer Ingelheim’s investment in Abexxa demonstrates how the company is seeking to foster innovation across leading biotech communities, including the Dallas-Fort Worth, Texas, area.

"The investment by Boehringer Ingelheim’s Venture Fund in 2016 was a defining moment for Abexxa," said Debra Wawro Weidanz, co-founder and CEO of Abexxa. "The acquisition by Boehringer Ingelheim allows our team to access the company’s expertise and capabilities in immuno-oncology and antibody development and to have the opportunity to translate Abexxa technology into a clinical asset," said Jon Weidanz, Ph.D., co-founder and CSO of Abexxa.

This transaction is the latest in a series of strategic acquisitions and collaborations that reinforce Boehringer Ingelheim’s overall oncology strategy, bringing together cancer immunology and cancer cell directed therapies to fight cancer. This strategy has further strengthened Boehringer Ingelheim’s position in oncology through the development of leading assets and robust capabilities in cancer vaccines, oncolytic viruses, T-cell engagers, antibody drug conjugates (ADCs) and myeloid and stromal cell modulators. By combining its world-class in-house research and development with that of highly innovative biotechnology companies like Abexxa, Boehringer Ingelheim is developing innovative cancer immunology therapies and accelerating the delivery of the next generation of cancer treatments.

Learn more about Boehringer Ingelheim’s innovation in oncology here.

The total transaction includes an upfront payment, milestones and other consideration payments. Abexxa will continue to operate in the Arlington, Texas, area as a Boehringer Ingelheim family company, collaborating extensively with the colleagues at Boehringer Ingelheim’s U.S. research site in Ridgefield, Connecticut.

Magenta Therapeutics to Participate in 2021 Cantor Virtual Global Healthcare Conference

On September 21, 2021 Magenta Therapeutics, Inc. (Nasdaq:MGTA), a clinical-stage biotechnology company developing novel medicines designed to bring the curative power of stem cell transplants to more patients, reported that the company will participate in a fireside chat at the 2021 Cantor Virtual Global Healthcare Conference on Tuesday, September 28 at 4:40 p.m. ET (Press release, Magenta Therapeutics, SEP 21, 2021, View Source [SID1234590067]).

A live webcast of the fireside chat can be accessed on the Magenta Therapeutics website at View Source The webcast replay will be available for 90 days following the event.

Galectin Therapeutics Announces $20 Million Convertible Debt Financing from Its Chairman, Richard E. Uihlein

On September 21, 2021 Galectin Therapeutics Inc. (NASDAQ:GALT), the leading developer of therapeutics that target galectin proteins, reported that it has entered into a $20 million convertible debt financing agreement with Richard E. Uihlein, the Company’s Chairman and largest individual stockholder (Press release, Galectin Therapeutics, SEP 21, 2021, View Source [SID1234590066]). This $20 million convertible debt is in addition to a $10 million convertible debt financing from Mr. Uihlein completed in April 2021.

The loan agreement comprises two separate $10 million convertible notes, the first of which closed and funded on September 17, 2021 and the second which will close on or before December 17, 2021. The convertible notes are unsecured and bear interest at a rate of 2% compounded annually. Additional interest of 2.5% per quarter will accrue but will only be paid if the debt and interest are converted into shares of the Company’s common stock, at Mr. Uihlein’s option, on or prior to maturity, which is four years from the date of each loan closing. The conversion price of the debt and interest is fixed at 228% above the price per share of common stock on the day prior to each closing or $5.00 per share, whichever is greater.

Richard E. Uihlein, Chairman of Galectin Therapeutics, commented on his $20 million investment, "I remain deeply committed to the Company’s success and our goal of addressing large, unmet medical needs. We are the only Company addressing NASH cirrhosis using a clinically relevant endpoint to measure efficacy. Additionally, the results from a phase 1 trial using belapectin in combination with KEYTRUDA, a checkpoint inhibitor, were very encouraging, particularly in patients with metastatic melanoma. This financing demonstrates my confidence in our team and our science, and I look forward to advancing our programs."

"I want to thank Mr. Uihlein for his unwavering commitment to the Company. The impact of his financial backing and leadership as Chairman cannot be overstated," said Joel Lewis, president and Chief Executive Officer of Galectin Therapeutics. "We continue to make progress in our NAVIGATE trial for patients with NASH cirrhosis and we also are exploring how to best move forward in the treatment of metastatic melanoma, where we have seen promising early results of belapectin in combination with KEYTRUDA in the treatment of advanced melanoma. This financing, as well as the recent addition of several accomplished and experienced professionals to our management team, provide resources that will help us pursue our goals."

About Belapectin

Belapectin is a complex carbohydrate drug that targets galectin-3, a critical protein in the pathogenesis of NASH and fibrosis. Galectin-3 plays a major role in diseases that involve scarring of organs including fibrotic disorders of the liver, lung, kidney, heart and vascular system. Belapectin binds to galectin-3 and disrupts its function. Preclinical data in animals have shown that belapectin has robust treatment effects in reversing liver fibrosis and cirrhosis. A Phase 2 study showed belapectin may prevent the development of esophageal varices in NASH cirrhosis, and these results provide the basis for the conduct of the NAVIGATE trial. The NAVIGATE trial (NAVIGATEnash.com), entitled "A Seamless Adaptive Phase 2b/3, Double-Blind, Randomized, Placebo-controlled Multicenter, International Study Evaluating

the Efficacy and Safety of Belapectin (GR-MD-02) for the Prevention of Esophageal Varices in NASH Cirrhosis" began randomization of patients in August, 2020, and is posted on www.clinicaltrials.gov (NCT04365868). Galectin-3 has a significant role in cancer, and the Company has supported a Phase 1b study in combined immunotherapy of belapectin and KEYTRUDA in advanced melanoma and in head and neck cancer. This trial provided a strong rationale for moving forward into a Phase 2 development program which the company is considering.

About Fatty Liver Disease with Advanced Fibrosis and Cirrhosis

Non-alcoholic steatohepatitis (NASH) has become a common disease of the liver with the rise in obesity and other metabolic diseases. NASH is estimated to affect up to 28 million people in the U.S. It is characterized by the presence of excess fat in the liver along with inflammation and hepatocyte damage (ballooning) in people who consume little or no alcohol. Over time, patients with NASH can develop excessive fibrosis, or scarring of the liver, and ultimately liver cirrhosis. It is estimated that as many as 1 to 2 million individuals in the U.S. will develop cirrhosis as a result of NASH, for which liver transplantation is the only curative treatment available. Approximately 8,890 liver transplants are performed annually in the U.S. There are no drug therapies approved for the treatment of liver fibrosis or cirrhosis.

AUA2021 Presentation Highlights Results from a Phase 1/2 Clinical Trial of Intramural/Intravesical NanoDoce® Suspension in High-Risk Nonmuscle Invasive Bladder Cancer

On September 21, 2021 NanOlogy LLC, a clinical-stage interventional oncology drug company, reported that initial results from a Phase 1/2 clinical trial of intramural/intravesical (IMI/IVT) NanoDoce (large surface area microparticle [LSAM] docetaxel) suspension in high-risk nonmuscle invasive bladder cancer (hrNMIBC) were presented by Max Kates, MD (Johns Hopkins Medicine) at the American Urological Association annual meeting (AUA2021) via virtual platform on September 12, 2021 (Press release, NanOlogy, SEP 21, 2021, View Source;utm_medium=rss&utm_campaign=aus2021_presentation_highlights_pr [SID1234590065]).

The oral presentation entitled Initial Results from a Phase 1/2 Trial of Large Surface Area Microparticle Docetaxel for High-Risk Non-Muscle Invasive Bladder highlighted safety and preliminary efficacy data from the multicenter dose-rising/confirmation clinical trial that enrolled 19 subjects. In addition to Dr. Kates, contributing clinical investigators were Ahmed Mansour, MD (UT Health San Antonio), Donald Lamm, MD (BCG Oncology), and Neal Shore, MD (Carolina Urologic Research Center).

Highlights from the presentation:

Overall, NanoDoce was well tolerated. Most treatment emergent adverse events were mild to moderate, and no severe adverse events were attributable to the study drug.
Systemic absorption of docetaxel was negligible and below the threshold for systemic toxicity in all subjects.
Across all doses and subjects (n=19), complete response (CR) at 3 months as 68% (13/19) and durability for responding subjects at 12 months was CR of 31% (4/13).
In the high-dose cohort (n=6), 6/6 maintained CR > 6 months with 4 subjects showing durability at 12 months, 1 subject showing recurrence, and 1 subject lost to follow up.
Tissue biopsies suitable for multiplexed immunofluorescence were obtained pre/post NanoDoce in 5 subjects. Analysis revealed directional increases in density of T Cells, macrophages (including PD-L1), and NK cells, and decreases in myeloid and MDSC cells.
NanoDoce (LSAM docetaxel) suspension is composed of large surface area microparticles of pure docetaxel designed for local administration and sustained drug release over time. In the dose-rising phase of the study (n=13), 3mg to 15mg of investigational drug were delivered IMI into and around the tumor resection bed post transurethral resection of bladder tumor (TURBT) followed by multiple periodic IVT of 50mg to 75mg. No dose limiting toxicities were encountered allowing target of 15mg IMI and 75mg IVT NanoDoce to continue into dose confirmation (n=6). Subjects were followed for up to one year. A separate study arm evaluated a post-TURBT single IMI/IVT administration of NanoDoce for safety over a 45-day period in 17 patients with muscle invasive bladder cancer. These data will be reported separately once final.

The American Cancer Society estimates 83,730 new cases of bladder cancer in the United States for 2021 with more than 20,000 presenting with hrNMIBC. For these patients, bladder removal often follows, which results in among the highest lifetime treatment costs and negative impact to quality of life of any cancer. NanOlogy is in planning of a later phase clinical trial in hrNMIBC.

In addition to this trial, NanOlogy clinical programs have advanced in lung, pancreatic, and other cancers. Data from preclinical and clinical studies in a variety of solid tumors have shown evidence of tumor kill, minimal local or systemic toxicity, and favorable antitumoral immune effects, which includes published preclinical research of NanoDoce synergy in combination with an immune checkpoint inhibitor.

The NanOlogy therapeutic platform is based on a proprietary supercritical precipitation technology that converts taxane API crystals into stable LSAMs of pure drug for tumor-directed therapy and sustained drug release. The taxane particles are covered by composition of matter patents issued in the US (US 9,814,685, US 10,507,195, & US 10,993,927), Canada, Europe, Japan, Russia, and Australia all valid through June 2036, plus applications pending globally. These composition of matter patents form the foundation of an extensive intellectual property portfolio protecting NanOlogy investigational drugs, methods, and technology.