On September 21, 2021 Provectus (OTCQB: PVCT) reported that data from an ongoing clinical trial of investigational cancer immunotherapy PV-10 (rose bengal disodium) for the treatment of neuroendocrine tumors (NET) metastatic to the liver (mNET) refractory to somatostatin analogs (SSAs) and peptide receptor radionuclide therapy (PRRT) (NCT02693067) was presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress, held online from September 16-21, 2021 (Press release, Provectus Biopharmaceuticals, SEP 21, 2021, View Source [SID1234590071]).

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Highlights from the ESMO (Free ESMO Whitepaper) 2021mNET Presentation:

Baseline disease characteristics
N = 12 patients: 50% male; median age of 66 years (range 47-79)
Primary tumor sites: 7 small bowel (58%), 2 pancreas (17%), 1 caecal (8%), and 2 unknown (17%)
NET grades: 5 Grade 1 (42%) and 7 Grade 2 (58%)
Refractory to SSA and PRRT; all symptomatic progressive disease
Chromogranin A (CgA): median 1,585 μg/L (35-10,370)
PV-10 treatment
Median number of injected lesions: 1 (1-4)
Median number of injection cycles: 1 (1-4); 8 patients (67%) received 1 PV-10 cycle; 4 patients received multiple cycles
Safety
Injection site pain in 9 of 12 patients (75%)
Grade 3 photosensitivity reaction in 1 patient; Grade 3 elevation of hepatic enzymes in 1 patient (resolved by Day 7); carcinoid flare in 2 patients
Injected-lesion efficacy (RECIST)
42% partial response (PR) and 42% objective response rate (ORR)
Patient-level efficacy (RECIST)
83%a disease control rate (DCR) (10 of 12 patients)
Median progression-free survival (PFS): 9.2 months (1.0-41.8)
Median overall survival (OS): 22.5 months (5.5-41.8); 6 patients (50%) undergoing response follow-up (data cut-off: April 30, 2021)
Immune response
Upregulation of NK cells and activated CD4+ T cells observed in peripheral blood collected 7-28 days post-PV-10 injection
Biomarkers and quality of life (QOL)
CgA stable in 10 patients (83%)
Health-related QOL assessments stable or improved at one month in 8 of 11 patients (73%); maintained at 3 months in 6 of 10 patients (60%)
a Typographical error on the poster

A copy of the poster is available on Provectus’ website at View Source

Simone Leyden, Chief Executive Officer and Co-Founder of NeuroEndocrine Cancer Australia, and International Neuroendocrine Cancer Alliance (INCA) Research Chair, said "The safety and efficacy data from this Phase 1 clinical trial of single-agent PV-10 present a promising therapy for refractory, symptomatic, neuroendocrine cancer patients with liver metastases, a patient population who are underrepresented when it comes to new medical research and treatment options. We look forward to seeing PV-10’s future use in this refractory setting, and also in Phase 2 combination therapy testing for earlier lines of neuroendocrine cancer treatment."

Dominic Rodrigues, Vice Chair of the Company’s Board of Directors, added, "These data may initially position single-agent PV-10 behind somatostatin analogs and peptide receptor radionuclide therapy in the Australian patient treatment setting. Our clinical trial database should lock in the fourth quarter of 2021, providing us the opportunity to finalize data collection and analysis prior to assessing PV-10’s regulatory prospects and options."

This clinical trial, a single-center study at The Queen Elizabeth Hospital (TQEH) in Adelaide, Australia that completed enrollment in 2020, is led by Tim Price, MBBS, DHlthSc (Medicine), FRACP, Head of Clinical Oncology Research and Chair of the combined Hematology and Medical Oncology Unit at TQEH and Clinical Professor in the Faculty of Medicine at the University of Adelaide. The primary endpoint of the trial is safety. Secondary endpoints include ORR of injected target and measurable bystander lesions, target lesion somatostatin receptor expression, and biochemical response. Disease response assessments are conducted by independent review using Response Evaluation Criteria in Solid Tumors (RECIST) criteria. Six patients in the first cohort each received one percutaneously-administered injection of PV-10 to one target lesion per treatment cycle. Patients in the six-person second cohort can receive PV-10 injections of multiple lesions per cycle.

About PV-10

Intralesional (IL) administration of PV-10 for the treatment of solid tumor cancers can yield immunogenic cell death within hours of tumor injection, and induce tumor-specific reactivity in circulating T cells within days. This IL PV-10-induced functional T cell response may be enhanced and boosted in combination with immune checkpoint blockade (CB). In CB-refractory advanced cutaneous melanoma, IL PV-10 may restore disease-specific T cell function, which may also be prognostic of clinical response. IL PV-10 has been administered to over 450 patients with cancers of the skin and of the liver. It is administered under visual, tactile or ultrasound guidance to superficial malignancies, and under CT or ultrasound guidance to tumors of the liver. Systemic administration of PV-10 is also undergoing preclinical study as prophylactic and therapeutic treatments for refractory and high-risk adult solid tumor cancers, and as a treatment for relapsed and refractory blood cancers.

About NeuroEndocrine Cancer Australia

NeuroEndocrine Cancer Australia is the only Australian not-for-profit medical charity focused on neuroendocrine tumors. It was co-founded in 2009 by Simone Leyden and her brother Dr. John Leyden through shared experiences with their sister Kate’s diagnosis of pancreatic neuroendocrine carcinoma and liver metastases. For more information, please visit NeuroEndocrine Cancer Australia’s website at www.neuroendocrine.org.au.

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]).

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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."

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.

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"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.

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]).

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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.

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.

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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.