On July 1, 2020 EpicentRx Inc. ("EpicentRx"), a San Diego-based clinical cancer immunotherapy company and SciClone Pharmaceuticals International Ltd., ("SciClone") reported that they have entered into a licensing agreement for RRx-001, a small molecule immunotherapy targeting CD47 – SIRPα with ongoing Phase III trial in Small Cell Lung Cancer ("SCLC") (Press release, EpicentRx, JUL 1, 2020, View Source [SID1234561624]).

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Under the terms of the agreement, SciClone will obtain exclusive licensing rights to co-develop and commercialize RRx-001, for the treatment of cancer in humans, within Greater China territory, including mainland China, Hong Kong, Macau and Taiwan. SciClone will be responsible for development, product registration and commercialization in these territories. Per the agreement, SciClone will pay EpicentRx an undisclosed upfront payment and conditionally agrees to invest in EpicentRx this year. EpicentRx will be eligible to receive an aggregate amount of up to $120 million upon achieving certain development, approval, and commercial milestones. In addition, EpicentRx is eligible to receive double-digit royalties in the Greater China territory. SciClone has the option to solely develop RRx-001 for Hepatocellular Carcinoma indication in Greater China, and is eligible to receive royalties from EpicentRx upon the approval of such indication in EpicentRx’s territory.

"SciClone is a dynamic, innovative and forward-thinking company with whom we have excellent personal chemistry and are fully aligned as we seek to improve cancer outcomes in the US, China and around the world," said Tony Reid, CEO of EpicentRx.

"This agreement marks our next phase of growth, expanding development of our Phase 3 study as a global trial and strengthening the company financially to support a number of exciting programs," added EpicentRx’s CFO, Franck Brinkhaus.

"RRx-001 was initially identified and sourced from the aerospace industry and has been developed by EpicentRx as a novel first-in-class therapy. This small molecule drug acts to normalize the tumor microenvironment, activate the tumor associated macrophages (TAMs) of the innate immune system, and sensitize solid tumors to standard therapies," said Hong Zhao, President and Chief Executive Officer of SciClone. "We are excited to partner with EpicentRx team to develop and commercialize RRx-001 for the treatment of various types of cancer. This strategic partnership recognizes SciClone’s capability as a leading biotech company with integrated platform of development and commercialization."

RRx-001 is a well-tolerated next generation small molecule immunotherapeutic that targets the CD47 – SIRPα axis and repolarizes tumor associated macrophages (TAMs) and other immunosuppressive cells in the tumor microenvironment to an immunostimulatory phenotype as well as improves tumor blood flow to enhance oxygen supply and drug delivery. As an immunotherapeutic with a non-overlapping mechanism of action and the potential to convert "treatment-resistant" tumors into "treatment sensitive" tumors, RRx-001 may be used as monotherapy or in combination with chemotherapy, immunotherapy, radiation and targeted agents. RRx-001 is currently a Phase 3 trial called REPLATINUM trial for the treatment of third-line and beyond SCLC. Clinical studies for the drug have also been conducted for the treatment of colorectal cancer, brain metastases and glioblastoma and are planned in leukemia and myelodysplastic syndrome.

On July 1, 2020 Cellectar Biosciences, Inc. (NASDAQ: CLRB), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of drugs for the treatment of cancer, reported that it has appointed Dr. John Friend as chief medical officer, effective immediately (Press release, Cellectar Biosciences, JUL 1, 2020, View Source [SID1234561623]).

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"We are pleased to welcome John back to Cellectar to oversee CLR 131’s late-stage oncology clinical development plans and FDA engagement for our adult and pediatric programs" said Jim Caruso, president and CEO of Cellectar Biosciences. "John’s understanding and prior involvement with CLR 131 combined with his extensive experience in oncology drug development will prove invaluable to our overall development program and near-term pivotal study registration strategies."

Dr. Friend returns to Cellectar bringing more than 17 years of global drug development and medical affairs expertise in hematology/oncology as well as a variety of other therapeutic indications. Most recently, he was chief medical officer of DRGT and prior to his earlier tenure at Cellectar, Dr. Friend served as Senior Vice President of Research and Development at Helsinn Therapeutics (U.S.), Inc. leading its research and development, clinical, medical affairs and regulatory affairs divisions. Prior to his time at Helsinn, Dr. Friend held executive responsibility for clinical research, medical affairs, pharmacovigilance and risk management at various pharmaceutical companies including Akros Pharma, Actavis, Alpharma, Hospira and Abbott.

Dr. Friend noted, "I am excited to rejoin the Cellectar team and to lead the clinical development, global regulatory submission and post-approval support of CLR 131. The recent results from the company’s phase 2a B-cell study demonstrating 40% plus response rates for relapsed and refractory multiple myeloma and non-hodgkin’s lymphomas as well as a 100% response rate to date in Waldenstrom Macroglobulinemia validates my early belief in CLR 131 and the PDC technology platform. I look forward to working to bring CLR 131 to market for the many cancer patients that may benefit from its treatment."

Dr. Friend completed his post-graduate residency program in family medicine and subsequently served as Clinical Director and faculty attending physician at Cabarrus Family Medicine Residency Program in North Carolina. He earned his medical degree from UMDNJ-Robert Wood Johnson Medical School (now Rutgers, RWJMS) and received his undergraduate degree in Chemistry from Southern Methodist University,

Grant of Inducement Option

In connection with his hiring, Cellectar has granted to Dr. Friend, effective as of his first day of employment with Cellectar, an option to purchase 100,000 shares of Cellectar’s common stock at an exercise price per share equal to the closing price of Cellectar’s common stock on the grant date as reported by Nasdaq. This grant was approved by the Compensation Committee of Cellectar’s Board of Directors and made as an inducement material to Dr. Friend entering into employment with Cellectar as contemplated by Nasdaq Listing Rule 5635(c)(4).

The stock option, which has a 10-year term, vests and becomes exercisable in three equal annual installments beginning on the first anniversary from the date of Dr. Friend’s first day of employment.

Cellectar provides this information in accordance with Nasdaq Listing Rule 5635(c)(4).

Resignation of Dr. Igor Grachev

Dr. Igor Grachev announced his resignation to pursue other opportunities. "We acknowledge and thank Igor for his contributions to our programs and wish him the very best in his future endeavors," said Jim Caruso, president and CEO of Cellectar Biosciences.

About CLR 131

CLR 131 is a small-molecule Phospholipid Drug Conjugate designed to provide targeted delivery of iodine-131 (radioisotope) directly to cancer cells, while limiting exposure to healthy cells unlike many traditional on-market treatment options. CLR 131 is the company’s lead product candidate and is currently being evaluated in a Phase 2 study in B-cell lymphomas, and a Phase 1 dose-escalating clinical study in pediatric solid tumors and lymphomas. The company recently completed a Phase 1 dose-escalation clinical study in r/r multiple myeloma. The FDA granted CLR 131 Fast Track Designation for both r/r multiple myeloma and r/r diffuse large b-cell lymphoma and Orphan Drug Designation (ODD) for the treatment of multiple myeloma, lymphoplasmacytic lymphoma/Waldenstrom’s macroglobulinemia, neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma. CLR 131 was also granted Rare Pediatric Disease Designations for the treatment of neuroblastoma, rhabdomyosarcoma, Ewing’s sarcoma and osteosarcoma. Most recently, the European Commission granted an ODD for r/r multiple myeloma.

On July 1, 2020 Daiichi Sankyo Company, Limited (hereafter, Daiichi Sankyo) reported the first patient with triple negative breast cancer (TNBC) has been dosed in the ongoing phase 1 study assessing DS-1062, a TROP2 directed DXd antibody drug conjugate (ADC) (Press release, Daiichi Sankyo, JUL 1, 2020, View Source [SID1234561622]).

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Patients with TNBC, an aggressive subtype of breast cancer, have limited treatment options beyond standard chemotherapy.[1] High TROP2 expression has been reported in up to 80 percent of patients with TNBC.[2],[3]

"Following the promising preliminary results reported with DS-1062 in patients with non-small cell lung cancer, we have expanded the study to include patients with triple negative breast cancer," said Gilles Gallant, BPharm, PhD, FOPQ, Senior Vice President, Global Head, Oncology Development, Oncology R&D, Daiichi Sankyo. "We continue to follow the science to determine whether DS-1062, designed with our proprietary DXd ADC technology, could serve as a new TROP2 directed therapy option for patients with TNBC and other cancers."

About the Phase 1 Study

The first-in-human, open-label, two-part, multi-center phase 1 study is designed to evaluate the safety, tolerability and preliminary efficacy of DS-1062 in patients with TROP2 unselected advanced solid tumors, which are refractory to or relapsed from standard treatment or for whom no standard treatment is available.

The first part of the study (dose escalation) assessed the safety and tolerability of increasing doses of DS-1062 to determine the maximum tolerated dose (MTD) and/or recommended dose for expansion (RDE) in patients with unresectable advanced NSCLC. The second part of the study (dose expansion) is further assessing the safety and tolerability of DS-1062 at selected dose levels for NSCLC. A cohort of patients with unresectable/advanced or metastatic TNBC has been added.

The study is currently enrolling approximately 180 patients in the U.S. and Japan with advanced unresectable NSCLC to receive DS-1062 at doses of 4, 6, and 8 mg/kg, and approximately 40 patients with advanced/unresectable or metastatic TNBC will receive DS-1062 at the 8 mg/kg dose. Patient enrollment in the dose expansion part of the study may be further expanded to include additional tumor types.

Safety endpoints include dose limiting toxicities and serious adverse events. Efficacy endpoints include objective response rate, duration of response, disease control rate, time to response, progression-free survival and overall survival. Pharmacokinetic, biomarker and immunogenicity endpoints also will be evaluated.

Updated data from this study in patients with heavily pre-treated advanced non-small cell lung cancer (NSCLC) were recently presented at the 2020 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Virtual Scientific Program (#ASCO20).

About TROP2

TROP2 (trophoblast cell-surface antigen 2) is a transmembrane glycoprotein that is overexpressed in many cancers including up to 80 percent of patients with triple negative breast cancer.2,3 High TROP2 expression also has been identified in a majority of NSCLCs.[4] Research indicates that high TROP2 expression is associated with cancer cell growth and proliferation and poor patient survival.[5] TROP2 is recognized as a promising molecular target for therapeutic development in various cancers.5

About Triple Negative Breast Cancer

Approximately 10 to 20 percent of breast cancers are considered triple negative because the tumors test negative for estrogen and progesterone hormone receptors (HRs) and for human epidermal growth factor 2 receptor (HER2).[6] Patients with TNBC have limited treatment options beyond standard chemotherapy.6 An aggressive breast cancer subtype, TNBC is more likely to recur following initial chemotherapy compared to other breast cancers.[7] Overall, prognosis for patients with metastatic TNBC is worse than for the other breast cancer subtypes, and more effective therapeutic options are needed.6

About DS-1062

DS-1062 is one of three lead DXd antibody drug conjugates (ADCs) in the oncology pipeline of Daiichi Sankyo. ADCs are targeted cancer medicines that deliver cytotoxic chemotherapy ("payload") to cancer cells via a linker attached to a monoclonal antibody that binds to a specific target expressed on cancer cells.

Designed using Daiichi Sankyo’s proprietary DXd ADC technology, DS-1062 is comprised of a humanized anti-TROP2 monoclonal antibody attached to a topoisomerase I inhibitor payload by a tetrapeptide-based linker with a customized drug-to-antibody ratio (DAR) of four to optimize the benefit-risk ratio for the intended patient population.

Preclinical studies have demonstrated that DS-1062 selectively binds to the TROP2 receptor on the surface of a tumor cell. It is proposed that DS-1062 is then internalized into the cancer cell where lysosomal enzymes break down the tetrapeptide-based linker and release the DXd payload.

DS-1062 is an investigational agent that has not been approved for any indication in any country. Safety and efficacy have not been established.

On July 1, 2020 Xenetic Biosciences, Inc. (NASDAQ:XBIO) ("Xenetic" or the "Company"), a biopharmaceutical company focused on advancing XCART, a personalized CAR T platform technology engineered to target patient- and tumor-specific neoantigens, reported a development update for its XCART technology platform (Press release, Xenetic Biosciences, JUL 1, 2020, View Source [SID1234561619]).

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The Company entered into agreements with Scripps Research on May 19, 2020 and with PJSC Pharmsynthez on June 16, 2020 to advance the development of the XCART technology for B-cell malignancies. Both Scripps Research as well as Pharmsynthez and its collaborators have extensive experience with XCART, having co-invented the technology, and will have integral roles in the preclinical development activities.

"Our recently announced collaborations with Scripps Research, Pharmsynthez and multiple academic institutions in Russia and Belarus are critical components of our overall development plan for XCART. These agreements provide us access to partners that have the capability and capacity to expeditiously and cost-effectively advance XCART through preclinical development. We will also have access to patients and CART T clinical manufacturing suites which will potentially allow us to enter into a Phase 1 dosing study," commented Jeffrey Eisenberg, Chief Executive Officer of Xenetic.

The agreement with Scripps Research provides access to a team with extensive expertise in the CAR T space who will assist in the design and implementation of the preclinical development program for XCART. Xenetic will work with personnel in Dr. Richard Lerner’s lab, where the XCART technology was invented and where the preclinical proof of mechanism work was done. The agreement with Pharmsynthez provides access to the team that invented XCART in collaboration with Scripps Research, and also will involve institutions with extensive expertise in anti-idiotype approaches to lymphoma as well as CAR T development and manufacturing.

In collaboration with Pharmsynthez and multiple academic institutions in Russia and Belarus, the Company will conduct an exploratory trial to define and evaluate the XCART front-end process of target identification, screening and lead characterization in a real-world clinical setting. This exploratory stage entails enrollment of NHL patients, obtaining tumor biopsies and then refining the XCART front-end methods. Subsequently, the collaboration may be expanded to include development and qualification of manufacturing processes for producing autologous XCART T-cells. If successful, the Company has the potential to expand the clinical study component to dose a number of NHL patients in a Phase 1 dosing study. The data generated under the Belarus collaboration is expected to support an Investigational New Drug (IND) filing in the United States.

Curtis Lockshin, Ph.D., Chief Scientific Officer of Xenetic added, "As we move forward with these key partners, our team is focused on process development for autologous T cell manufacturing and generation of preclinical data covering the overall XCART workflow. These strategic collaborations provide us with highly cost-effective access to CAR T manufacturing and development suites, as well as clinical expertise and capabilities in the treatment of B-cell lymphomas. By augmenting preclinical data with insights gained from conduct of the XCART workflow in a human exploratory setting, we believe that we can strengthen the data sets with which we approach discussions with the United States Food and Drug Administration and, importantly, support our IND filing to advance our U.S. development strategy for XCART."

On July 1, 2020 Moleculin Biotech, Inc., (Nasdaq: MBRX) ("Moleculin" or the "Company"), a clinical stage pharmaceutical company with a broad portfolio of drug candidates targeting highly resistant tumors and viruses, reported that a peer-reviewed article published in Clinical Cancer Research (Clin Cancer Res June 30 2020 DOI:10.1158/1078-0432.CCR-19-4092) reported findings that Moleculin’s STAT3 inhibitor, WP1066, used in combination with traditional whole brain radiation therapy (WBRT) resulted in long-term survivors and enhanced median survival time relative to monotherapy in mice with implanted human brain tumors (Press release, Moleculin, JUL 1, 2020, View Source [SID1234561618]).

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The study was performed by lead author Martina Ott, Ph.D., Instructor of Neurosurgery, senior author Amy Heimberger, M.D., professor of Neurosurgery, and a team of researchers at The University of Texas MD Anderson Cancer Center. Heimberger also is the Principle Investigator of the current investigator-initiated clinical trial of WP1066 for brain tumors.

In the current study, C57BL/6 mice underwent intracerebral implantation of GL261 glioma cells, WBRT, and treatment with WP1066, a blood-brain barrier penetrant inhibitor of the STAT3 pathway, or the two in combination. The role of the immune system was evaluated using tumor rechallenge strategies, immune incompetent backgrounds, immunofluorescence, immune phenotyping of tumor-infiltrating immune cells (via flow cytometry), and nanostring gene expression analysis of 770 immune-related genes from immune cells, including those directly isolated from the tumor microenvironment.

The combination of WP1066 and WBRT resulted in long-term survivors and enhanced median survival time relative to monotherapy in the GL261 glioma model (combination vs. control p<0.0001). Immunological memory appeared to be induced, because mice were protected during subsequent tumor rechallenge. The therapeutic effect of the combination was completely lost in immune incompetent animals. Nanostring analysis and immunofluorescence revealed immunological reprograming in the brain tumor microenvironment specifically affecting dendritic-cell antigen presentation and T cell effector functions. The study indicates that the combination of STAT3 inhibition and WBRT enhances the therapeutic effect against gliomas in the CNS by inducing dendritic-cell and T cell interactions in the brain tumor, which seems to be a requirement for a fully functional immune response
"This impressive study confirms preliminary data we announced last year," commented Walter Klemp, Chairman and CEO of Moleculin. "Importantly, the study indicated that the combination of STAT3 inhibition with whole brain radiotherapy had the capacity to enhance the therapeutic effect against established tumors as well as developing immune memory that appears to prevent recurrence."

The research was supported by the Cancer Prevention & Research Institute of Texas (IIRA-RP160482), the National Institutes of Health (CA1208113, P50 CA093459, P50 CA127001 and P30 CA016672), the Ben and Catherine Ivy Foundation, MD Anderson’s Glioblastoma Moon Shot, and the Brockman Foundation.