On July 8, 2019 McKesson, an independent specialty pharmacy for oncology and other complex therapeutic areas, reported that it has been selected by Karyopharm Therapeutics, Inc. to be in the limited distribution network for XPOVIO (selinexor) (Press release, McKesson, JUL 8, 2019, View Source [SID1234537408]).

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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

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XPOVIO is the first and only nuclear export inhibitor that blocks XPO1 and is indicated in combination with dexamethasone for the treatment of adult patients with relapsed refractory multiple myeloma (RRMM) who have received at least five prior therapies and whose disease is refractory or intolerant to at least two proteasome inhibitors (PI), at least two immunomodulatory agents (IMiD), and an anti-CD38 monoclonal antibody (mAb).1,2 Approved on July 3, XPOVIO was previously granted both Orphan Drug designation and Fast Track designation by the FDA.

"We are excited that Biologics is included in the limited network distribution for XPOVIO," said Ann Steagall, director of Clinical Policy at Biologics. "We are pleased to be included in the distribution of a first in class XPO inhibitor. Patients who have exhausted the current standard of care therapies now have another option. It is important to us as a premier oncology pharmacy to offer patients and prescribers the newest therapies available."

Biologics is committed to and recognized for its high level of customer service as well as its innovative, high-touch and multidisciplinary patient-centric approach. Each team includes a pharmacist with in-depth knowledge of disease states and oncology therapies available, an experienced oncology nurse and a financial counselor who is familiar with various financial assistance programs and organizations that help cancer patients. This highly-skilled care team works together to develop individualized care plans that address each patient’s unique clinical, financial and emotional needs and streamlines communication back to the treating provider, enabling high-quality care and differentiated outcomes. In addition, the Biologics team works closely with payers to ensure patients can access the specialty medications they need.

Physicians may submit prescriptions to Biologics via phone (800.850.4306), fax (800.823.4506) or eScribe. For electronic prescribing systems, physicians may search for Biologics within their EMR system.

On July 8, 2019 AmerisourceBergen, a global healthcare solutions leader, reported that it has entered a long-term strategic relationship with OneOncology, the national partnership of community oncologists driving the future of cancer care in the U.S. OneOncology has selected ION Solutions and Oncology Supply to provide a suite of services and solutions to community oncology practices across the nation. ION Solutions has been selected for GPO contracting and Oncology Supply for the distribution of chemotherapy and supportive care products to OneOncology members (Press release, AmerisourceBergen, JUL 8, 2019, View Source [SID1234537407]).

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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

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OneOncology partners with the nation’s top community oncology practices and their physicians to support delivery of comprehensive cancer care to patients, close to home. Since its public launch in September 2018, the organization is now comprised of four large practices across the U.S., representing nearly 250 physicians practicing at more than 70 sites of care.

"At ION Solutions and AmerisourceBergen, we’re dedicated to supporting community-based care. This commitment aligns nicely with OneOncology’s mission to drive the future of cancer care through a physician-led, data-driven, technology-powered and patient-centric model and we’re excited to have them in our network," said Brian Ansay, President, Physician Group Purchasing Organizations, AmerisourceBergen. "We look forward to supporting OneOncology with the full power of our ION GPO and AmerisourceBergen’s integrated service offerings, and we’ll continue to enhance value, provide more efficiencies and offer more clinical-decision support to all of our esteemed GPO members and customers."

OneOncology partners will have dedicated account teams that act as an extension of the practice and actively consult on inventory and creating operational efficiencies. OneOncology members will have access to Oncology Supply’s robust inventory of specialty and full-line oral, infusible and injectable products. AmerisourceBergen will provide OneOncology practices with tools and resources, practice management technologies, analytics and reports for better insight and education, and consultants, business coaches, and advisors who will assist with maximizing operating efficiencies.

"We look forward to a collaborative relationship with AmerisourceBergen that delivers value to all of our stakeholders," said Dr. Jeffrey Patton, President of Physician Services at OneOncology and CEO Of Tennessee Oncology, a OneOncology practice. "We believe this strategic partnership will help to optimize clinical and financial efficiencies for all of our partners during an era of unprecedented innovation in oncology."

To support the shift to value-based care, ION Solutions’ network members can leverage technology, analytics and informatics solutions to drive higher-quality and lower-cost care in every community. Tools like InfoDive, a web-based business intelligence solution, allows practices to quickly and easily analyze internal and comparative data in the areas of coding, productivity, marketing, revenue collection and more. ION is supporting the standardization of treatment protocols. For example, network members have full access to a centralized library of precision medicine testing recommendations and resources through the Precision Medicine Center.

Through the power of the ION GPO and AmerisourceBergen’s relationships with pharmaceutical manufacturers, members have access to the newest therapies entering the market. ION also advocates for community practices and their access to new research opportunities. Through solutions like AdvanceIQ, ION Solutions can help match independent community oncology practices with national clinical trials and research opportunities.

OneOncology partners will also have access to ION’s ongoing educational conference series. ION hosts nine annual conferences for its members; these events are designed to facilitate peer-to-peer learning and networking and strengthen the community of independent oncologists. Each conference features expert speakers, clinical reviews and best practices for business operations.

About ION Solutions & Oncology Supply

ION Solutions, a part of AmerisourceBergen Corporation, is the largest physician service organization and GPO specializing in the support of community oncology. ION provides GPO procurement services, technologies, advocacy resources and expertise to more than half of the community-based oncology practices in the nation to help improve their clinical and operational management. For more information, go to www.iononline.com. For over 35 years, Oncology Supply has been a trusted partner and supplier of chemotherapy and supportive care products to independent oncology practices nationwide from our office/distribution center in Dothan, AL. For more information about Oncology Supply, www.oncologysupply.com/OSCHome.

On July 8, 2019 Compass Therapeutics, a clinical-stage biotechnology company targeting the human immune synapse with a new generation of monoclonal and multispecific antibody therapeutics, reported the first patient has been dosed in its multi-center, open-label, first-in-human Phase 1 trial of CTX-471, a fully human monoclonal antibody that binds and activates a unique epitope of the co-stimulatory receptor CD137 expressed on T cells and NK cells (Press release, Compass Therapeutics, JUL 8, 2019, View Source [SID1234537406]). Enrollment in the trial is open to patients with metastatic or locally advanced solid cancers that have progressed while receiving an approved PD-1 or PD-L1 inhibitor for at least three months.

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"The field of oncology is greatly in need of novel ways to engage the immune system to fight cancer beyond PD-1/PD-L1 checkpoint inhibitors. We currently have very limited options for treating patients in whom PD-1 or PD-L1 inhibitors fail," said F. Stephen Hodi, MD, a member of the Compass Scientific Advisory Board, director of the Melanoma Center and the Center for Immuno-Oncology at Dana-Farber/Brigham and Women’s Cancer Center, and professor of medicine at Harvard Medical School.

The study is a multiple ascending dose (MAD) study with the potential for a dose expansion phase. The primary objective of the MAD portion of the study is to assess the safety and tolerability of CTX-471 monotherapy at various doses. The dose expansion stage will then evaluate a larger cohort of patients to determine an optimized dose for the future Phase 2 studies. Secondary endpoints will include measures of overall response rate and progression- free survival, among others.

"We are immensely gratified to have reached this milestone to begin to bring this treatment to patients," said Thomas Schuetz, MD, PhD, the scientific founder and chief executive officer of Compass. "We believe CTX-471 has the potential to be a best-in-class CD137 agonist due to its very promising preclinical data, which include the total eradication of established tumors in syngeneic mouse models and the generation of long-term, functional immunological memory in these models."

Further information is available at View Source

About CTX-471
CTX-471 is a fully human monoclonal antibody that binds and activates a novel epitope of the co-stimulatory receptor CD137, also known as 4-1BB, a member of the tumor necrosis factor receptor superfamily. CTX-471 has demonstrated potent monotherapy activity against multiple syngeneic tumor models including the generation of long-term functional immunological memory. Most notably, CTX-471 shows a unique ability to completely eradicate large, established tumors where other preclinical CD137 antibodies and antibodies against PD-1, PD-L1, CTLA-4 and OX40 have minimal effects in these models. In contrast to other CD137 antibodies, CTX-471 shows no evidence of hepatic toxicity in both mice and non-human primates, supporting the potential for a wide therapeutic window in patients.

On July 8, 2019 Horizon Discovery Group plc (LSE: HZD) ("Horizon"), a company driving the application of gene editing and gene modulation within the global life science market, reported that Celyad (Euronext Brussels and Paris, and Nasdaq: CYAD), a clinical-stage biopharmaceutical company focused on the development of CAR-T cell-based therapies, received FDA Acceptance of Investigational New Drug (IND) application for the autologous NKG2D based CAR-T cell therapy CYAD-02 that deploys Horizon’s optimized SMARTvector shRNA technology (Press release, Horizon Discovery, JUL 8, 2019, View Source [SID1234537405]). The Phase 1 trial will be the first CAR-T cell therapy to employ the SMARTvector platform. Horizon will receive an undisclosed milestone payment for the successful IND filing.

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Celyad has been investigating the use of shRNAs to support the clinical development of its CAR-T cell platform. The FDA approved IND application involves CYAD-02, a next generation CAR-T cell therapy in which shRNA is employed to suppress two genes. Celyad has pre-clinical data indicating that this improves in vivo engraftment and efficacy of CYAD-02.

A Phase 1 dose-escalation trial evaluating the safety and clinical activity of CYAD-02 is planned for early 2020 and will involve a preconditioning chemotherapy (CyFlu) in patients with relapse/refractory (r/r) acute myeloid leukemia (AML) or myelodysplastic syndromes (MDS).

Terry Pizzie, Chief Executive Officer, Horizon Discovery Group plc, commented: "We see great potential for shRNA technology in the optimization of next-generation cell therapies. The success of this IND filing is testament to the strength of our relationship with Celyad, and the powerful combination of Horizon’s SMARTvector shRNA platform with Celyad’s CAR-T expertise."

Filippo Petti, Chief Executive Officer, Celyad, said: "Over the past few years Celyad has made great strides in evaluating our NKG2D-based CAR-T therapy for the treatment of relapsed/refractory acute myeloid leukemia and myelodysplastic syndrome. The FDA approval for the CYAD-02 IND application will allow us to evaluate new therapies in this difficult to treat population and the inclusion of an optimized shRNA developed using Horizon’s SMARTvector technology represents the output of a strong collaboration. We look forward to a continued successful relationship."

On July 8, 2019 Provectus (OTCQB: PVCT) reported an update on the Company’s gastrointestinal (GI) tumor clinical development program for its lead investigational cancer drug PV-10, which is administered percutaneously when targeting primary or metastatic tumors of the liver, such as hepatocellular carcinoma (HCC), metastatic neuroendocrine tumors (mNET), and metastatic uveal melanoma (mUM) (Press release, Provectus Biopharmaceuticals, JUL 8, 2019, View Source [SID1234537404]). Intratumoral injection of oncolytic immunotherapy PV-10 can yield immunogenic cell death in solid tumor cancers that results in tumor-specific reactivity in circulating T cells.1-5

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The Company’s oncology drug development strategy includes:

Further demonstrating PV-10’s activity in non-T cell and T cell inflamed and low and high tumor mutation burden tumor types,
Further demonstrating the T cell response generated by PV-10 treatment, and
Contrasting and comparing PV-10 treatment – activity and induced immune response – with that of checkpoint inhibitor (CI) and other drug classes in monotherapy and combination therapy settings.
Provectus believes this strategy should quicken the advancement of single-agent PV-10 along a pathway-to-approval in solid tumor cancer indications where there is high unmet need, limited activity from other therapies, and the opportunity to further display a functional immune response from PV-10 treatment, such as for mNET (NCT02693067).

Provectus also believes this approach should permit the Company to develop and advance a combination therapy involving a CI or other drug class along a pathway-to-approval in an indication where there is high unmet need, limited activity from standard of care (SOC) treatment, and the opportunity to display how PV-10 augments clinical response to existing or emerging SOCs, such as for mUM (i.e., combination therapy with anti-CTLA-4 and anti-PD-1 agents) (NCT00986661).

Update #1 (mNET): The Company plans to present further lesion-level (i.e., local) efficacy, preliminary patient-level (i.e., systemic) efficacy, further clinical and biomarker outcome, and preliminary T cell response data from single-agent PV-10 treatment of mNET at a regional annual scientific meeting in the third quarter of 2019 and a global GI-focused medical conference in the first quarter of 2020.

Update #2 (mNET): Investigators and researchers collaborating with Provectus plan to present the design of a Phase 2 mNET study combining PV-10 and an agent from a class of CI drugs at the abovementioned scientific meeting. The Company would seek partial or total sponsored-financial support for this trial.

Update #3 (mNET): The Company is exploring possible collaboration with another group of investigators to develop a Phase 2 mNET study design of PV-10 and an agent from another class of CI drugs. The Company would also seek partial or total sponsored-financial support for this trial.

Dominic Rodrigues, Vice Chair of Provectus’ Board of Directors stated, "We believe PV-10 monotherapy treatment of metastatic neuroendocrine tumors has yielded encouraging clinical data of single-agent drug activity that include both local and systemic disease control. Checkpoint inhibitor drugs have thus far shown limited or no monotherapy activity in this non-T cell inflamed and low tumor mutation burden tumor type. While we believe single-agent PV-10 can help fill this unmet medical need, we also think there is a meaningful rationale to combine a tumor-specific immunotherapy like PV-10 with a non-specific immunotherapy like a checkpoint inhibitor drug for this patient population."

Update #4 (mUM): The Company plans to present preliminary lesion- and patient-level efficacy data from PV-10 treatment of mUM at a global immuno-oncology-focused medical conference in the fourth quarter of 2019. mUM patients have received PV-10 monotherapy and PV-10 in combination with two CI drugs, anti-CTLA-4 and anti-PD-1 agents.

Mr. Rodrigues added, "Currently, there is no consensus on standard of care for the treatment of metastatic uveal melanoma. Treatment varies from medical center to medical center. In working with current and prospective principal investigators, we feel strongly that the combination of PV-10 with an anti-CTLA-4 agent and an anti-PD-1 agent, an approach that appears to leverage the unique clinical characteristics of each drug and drug candidate, may benefit this patient population who are in dire need of better therapeutic solutions."

Update #5 (HCC): Provectus has extended its long-standing scientific research relationship with the laboratory of Shari Pilon-Thomas, PhD at Moffitt Cancer Center in Tampa, Florida. A key aim of her new research initiative is to elucidate PV-10’s mechanism of action (MOA) in HCC, where the MOA hypothesis is the release of damage associated molecular patterns (DAMPs) from PV-10 treatment. Dr. Pilon-Thomas’ team have previously elucidated PV-10’s DAMP pathway in both a murine model of and clinical work on cutaneous melanoma.2

Ajay Maker, MD and his team at the University of Illinois at Chicago have previously elucidated a comparable DAMP pathway for PV-10 in colon cancer.3

PV-10, a lysosome-targeting treatment, may trigger several different pathways to achieve the death of cancer. Aru Narendran, MD, PhD and his team at the University of Calgary in Alberta, Canada have shown that PV-10 treatment leads to poly-ADP ribose polymerase (PARP) cleavage and tumor cell apoptosis in refractory neuroblastoma cell lines.5 Dr. Narendran’s team is currently pursuing the hypothesis of a third distinct PV-10-mediated cancer cell death pathway through an ongoing scientific research initiative with the Company.

Update #6 (HCC): As of the first quarter of 2019, an analysis of six patients who have received PV-10 monotherapy treatment for HCC displayed a median overall survival of 2.5 years (mean 3.1 years; range 0-8.3+ years).

Mr. Rodrigues concluded, "Dr. Pilon-Thomas and past and present team members at Moffitt Cancer Center have undertaken a significant amount of consequential translational research on PV-10 treatment, ranging from melanoma and breast cancer to monotherapy and combination therapy. This work has resulted in a critical understanding of the drug candidate’s underlying medical science and the publication of seminal journal articles. Recent failures by OPDIVO and KEYTRUDA to meet primary overall survival endpoints in their respective clinical trials for the treatment of hepatocellular carcinoma highlight the importance of our new mechanism of action study of PV-10 treatment for this disease, which may better help characterize a potential PV-10-checkpoint inhibitor drug combination solution."

About PV-10

PV-10 causes acute oncolytic destruction of injected tumors, releasing DAMPs and tumor antigens that initiate an immunologic cascade where local response by the innate immune system facilitates systemic anti-tumor immunity by the adaptive immune system. The DAMP release-mediated adaptive immune response activates lymphocytes, including CD8+ T cells, CD4+ T cells, and NKT cells, based on clinical and preclinical experience in multiple tumor types. T cell function can be further augmented by combining PV-10 with CI drugs.

PV-10 is undergoing clinical study for adult solid tumor cancers like melanoma and cancers of the liver (including metastatic neuroendocrine tumors and metastatic uveal melanoma) and preclinical study for pediatric cancers like neuroblastoma5, Ewing sarcoma, rhabdomyosarcoma, and osteosarcoma.

Orphan drug designation status has been granted to PV-10 by the U.S. Food and Drug Administration for the treatments of metastatic melanoma in 2006, hepatocellular carcinoma in 2011, neuroblastoma in 2018, and ocular melanoma (including uveal melanoma) in 2019.

PV-10 is an injectable formulation of rose bengal disodium (RB) (4,5,6,7-tetrachloro-2’,4’,5’,7’-tetraiodofluorescein disodium salt), which is a small molecule halogenated xanthene and PV-10’s active pharmaceutical ingredient. PV-10 drug product is a bright rose red solution containing 10% w/v RB in 0.9% saline for injection, which is supplied in single-use glass vials containing 5 mL (to deliver) of solution and administered without dilution to solid tumors via intratumoral injection.

Provectus’ intellectual property includes a family of US and international patents that protect the process by which pharmaceutical grade RB and related xanthenes are produced, reducing the formation of previously unknown transhalogenated impurities that exist in commercial grade RB in uncontrolled amounts. The requirement to control these impurities is in accordance with International Conference on Harmonisation (ICH) guidelines for the manufacturing of an injectable pharmaceutical. US patent numbers are 8,530,675, 9,273,022, and 9,422,260, with expirations ranging from 2030 to 2031.