1stOncology™: Cancer Intelligence Service – Page 16112 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Pipeline Review Check

OSE-172 (Effi-DEM) is a monoclonal antibody: a new generation checkpoint inhibitor which blocks the generation of pro-tumor suppressor cells and restores their effector function.

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!

OSE-172 blocks SIRP-alpha (Signal Regulatory Protein Alpha), on strategic SIRP-alpha/CD47 pathway, a receptor strongly expressed by myeloid and macrophage suppressor cells. It restores effector functions of these suppressor cells, an activity which promotes the immunosurveillance (Hanna R.N. et al ; Science 2015). OSE-172 may also be combined with other immunotherapies, in particular with checkpoint inhibitors acting on T lymphocytes, e.g. checkpoint inhibitors targeting the PD-1/PD-L1 axis or products triggering a stimulation of the immune system.

This innovative product helps modifying Tumor Associated Macrophages (TAM) and Myeloid Derived Suppressor Cells (MDSC) associated with a poor prognosis, by blocking and transforming them into cells with a good prognosis (in blue in the above diagram).
Proof of concept obtained in in vivo models

Proof of concept has been obtained in models of aggressive cancers such as primary liver cancer, melanoma and breast cancer. These studies have confirmed a therapeutic effect of OSE-172 (Effi-DEM) as well as a potential long-lasting effect, in both monotherapy or combined with another checkpoint inhibitor, or with an immune system stimulator.

The therapeutic effect can be considered as long-lasting as reinsertion of a new tumor in animals treated by OSE-172 shown to be impossible : animals had developed an anti-tumor immunization. A treatment with OSE-172 as a monotherapy and combined with other immunotherapies induces a strong and long-lasting anti-tumor effect.

OSE-172 could be developed in all cancers involving TAM and MDSC cells, key cells in the progression of inflammatory cancers. Cytokines secreted by suppressor cells foster this mechanism (IL-10, IL-1β, TGFβ). This therapeutic strategy could be applied to cancers linked to a chronic inflammation such as primary liver cancer or colon cancer (Zamarron B.F. et 2011) (Mallmann MR et al. 2012).

Rubius Therapeutics Closes $120 Million Financing

On June 21, 2017 Rubius Therapeutics, a biotechnology company pioneering the development of a new class of extraordinarily active and differentiated cell therapies reported that it has raised $120 million in a highly oversubscribed private financing (Press release, Rubius Therapeutics, JUN 21, 2017, View Source [SID1234520731]).

Rubius has developed the technology to grow, genetically engineer and mature long-circulating red cell therapeutics which will provide transformational clinical benefits to a wide range of patients across multiple therapeutic areas. These allogeneic, off-the-shelf products offer the additional advantage of extended stability and storage to allow for rapid, universal access by the medical community. Proceeds will be used to accelerate the advancement of Rubius’ breakthrough Red-Cell Therapeutics (RCT) product portfolio, to further build out the team and to prepare to enter human clinical trials in 2018. This financing follows the successful achievement of several key milestones, including the clinical scale production of cultured red cells in bioreactors and the generation of preclinical proof-of-concept data for several lead programs.
"With this financing, Rubius is well positioned to focus on the continued development of our platform to advance a broad range of therapeutic candidates that have the potential to make a significant difference in the lives of patients," said Torben Straight Nissen, Ph.D., President of Rubius Therapeutics.
"Rubius has achieved multiple scientific and manufacturing milestones in the first six months of this year. Those achievements plus the trust that Flagship and our new investors have put in Rubius with this financing sets us up to turn our RCTs into important new treatment options," said David Epstein, Chairman of Rubius Therapeutics and Executive Partner of Flagship Pioneering.
The RCT platform allows Rubius to express enzymes, agonists, antagonists, binders and combinations in their natural conformation on or inside of red cells. Lead RCT programs include enzyme replacement therapies as well as therapies targeting solid tumors and hematological cancers. Further, Rubius has demonstrated that RCTs provide potential applications across additional therapeutic areas, such as autoimmune disease, infectious disease, metabolic disease and rare diseases, including hemophilia.
"We are excited to expand our support of Rubius in this next round of funding as the company continues to advance its technology and programs — following in the footsteps of Flagship’s family of successful multiproduct platform companies," said Noubar Afeyan, CEO of Flagship Pioneering and Co-Founder of Rubius. "The team at Rubius has made great strides over the past three years and we are pleased to support the company’s continued growth. This new financing, together with a leadership team with unparalleled expertise, positions Rubius to deliver on the promise of the RCT platform and bring transformative therapies to patients."
Rubius was conceived, launched and funded by Flagship VentureLabs, the innovation foundry of Flagship Pioneering. Joined by undisclosed large institutional investors, Flagship Pioneering significantly increased its investment in this financing.
About Red-Cell Therapeutics Red-Cell Therapeutics are genetically engineered, enucleated red cells that provide allogeneic, off-the-shelf therapies to patients across multiple therapeutic areas. RCT advantages over other therapies include immuno-privileged presentation of proteins within or on the red cell, high target avidity and affinity resulting in highly potent and selective therapies, and long circulation half-life. Rubius RCTs exhibit fundamentally unique biology and have been engineered to replace missing enzymes for patients living with a variety of rare diseases, to kill tumors, and upregulate or downregulate the immune system to treat both cancer and autoimmune disorders.
About Rubius Therapeutics Rubius Therapeutics is developing Red-Cell Therapeutics (RCTs) as a new class of medicines to address a wide array of indications, with leading applications in cancer, rare and autoimmune disease, as well as additional potential in hemophilia, infectious and metabolic diseases. The company was founded and launched in 2014 by Flagship VentureLabs, the innovation foundry of Flagship Pioneering. Rubius has successfully engineered and manufactured red cells that express therapeutic proteins for use in the treatment of serious diseases. The company is now demonstrating that these newly equipped high performing, off-the-shelf Red-Cell Therapeutics have pre-clinical activity across a spectrum of medical applications. Rubius has generated more than 200 prototypes to date.

OncoArendi Therapeutics Announces Selection of Its Second Clinical Development Candidate: OATD-02 For the Treatment of Multiple Cancers

On June 21, 2017 / B3C newswire / — During the first Company Presentation at the global BIO Conference in San Diego OncoArendi Therapeutics SA reported that it has selected OATD‑02 as its clinical development candidate for cancer immunotherapy. Submission of the Company’s second Investigational New Drug (“IND”) application is expected by the third quarter of 2018.

OATD-02 is a highly potent and selective small molecule inhibitor of two arginase isoforms (Arg-1 and Arg-2) in both biochemical and cell-based-assays. OATD-02 is the second arginase inhibitor to enter development.

OATD-02 has been shown to be effective in vivo in three different mouse models of cancer (colorectal, lung and melanoma) and demonstrated superior antitumor efficacy in combinations with the PD-L1 checkpoint inhibitor and with gemcitabine; resulting in a controlled tumor growth, and, in some cases in a full regression.

Pilot studies also suggested a therapeutic potential of OATD-02 in glioblastoma multiforme (GBM), the most malignant brain tumor with no effective treatment.

“We believe that small molecule drugs preventing cancer cells from escaping from the immune surveillance have great potential in combination therapies and to be transformational medicines in the treatment of many types of cancer. The increasing number of clinical trials with multiple IDO inhibitors and various check-point inhibitor combinations additionally validate this approach. At OncoArendi, we are dedicated to research and development of the first-in-class or best-in-class small molecule-based therapies that in combination with other modalities, could significantly improve the treatment of unmet medical needs in many solid and hematopoietic cancers ” said Marcin Szumowski, PhD, CEO of OncoArendi Therapeutics. “We are particularly excited about the potential of arginase as an additional new target in cancer immunotherapy and the potential of OATD-02 to become the best-in-class arginase inhibitor on the market. This compound demonstrated a potent extracellular and cellular activity while its pharmacological profile makes it suitable for oral dosing.”

Formal pre-clinical development of OATD-02 will be initiated next month with GLP toxicology studies expected in Q4 of this year and first in human studies anticipated in the third quarter of 2018. OncoArendi Therapeutics’ arginase inhibitors, including OATD-02, are protected by two pending patents covering two structurally different groups of compounds.

About Arginase Science
Arginase has been recently validated as a promising target in immuno-oncology. Arginase is an enzyme that catalyzes the final step in the urea cycle, during which the body disposes of harmful ammonia. However, in cancer, arginase through its capacity to decrease arginine levels, blocks the natural antitumor immunity by suppressing activation and proliferation of T cells. Even a moderate decrease of arginine levels is immunosuppressive. T-cells deprived of arginine do not die – they retain the ability to expand when arginine is replenished. Since the majority of human cancers exhibit a highly increased arginase activity and decreased plasma arginine levels, arginase inhibitors are expected to exhibit a wide clinical utility, in particular in combinations with other therapeutic modalities, such as checkpoints inhibitors and immunogenic therapies.
With a decade-long expertise in the type of chemistry required to synthesize and optimize arginase inhibitors, promising initial data and a strong development team, OncoArendi has laid out a clear strategy to bring to the clinic the best in class arginase inhibitor.

Adaptive Biotechnologies Announces a Collaboration with Janssen Biotech, Inc. to use the clonoSEQ® Assay to Measure Minimal Residual Disease in Ongoing and Future DARZALEX® Multiple Myeloma Trials

On June 21, 2017 Adaptive Biotechnologies, the leader in combining Next Generation Sequencing (NGS) and expert bioinformatics to profile T- and B-cell receptors of the adaptive immune system, reported it has partnered with Janssen Biotech, Inc. to utilize Adaptive’s NGS-based clonoSEQ Assay for measuring minimal residual disease (MRD) in patients with Multiple Myeloma (MM) who have been treated with DARZALEX (daratumumab) (Press release, Adaptive Biotechnologies, JUN 21, 2017, View Source [SID1234519651]). DARZALEX is a CD38-directed cytolytic antibody approved for the treatment of patients with relapsed or refractory MM. Under the terms of the collaboration, Adaptive will receive an undisclosed upfront technology access payment in addition to development funding and potential future milestone payments. Adaptive will be responsible for seeking regulatory approvals for and commercialization of the clonoSEQ Assay in MM.

"Adaptive is thrilled to develop the technology to help measure the depth of response generated by DARZALEX in patients with MM," said Chad Robins, CEO and co-founder of Adaptive Biotechnologies. "We look forward to advancing our strategic partnership with Janssen by incorporating the highly sensitive and quantitative clonoSEQ Assay into more trials with DARZALEX."

Through this collaboration, the parties will work together to demonstrate the clinical utility of monitoring MRD negativity by the clonoSEQ Assay in MM patients who have been treated with DARZALEX, and to assess the medication’s ability to achieve MRD.

"Incorporating novel, proven molecular diagnostic tools into drug development and regulatory processes can enable clinicians to treat patients with the optimal interventions at the right time," said Charles Sang, Adaptive’s Senior Vice President, Diagnostics. "Adaptive’s clonoSEQ Assay can help accomplish this goal due to the robust validation of the assay. We believe the shared commitment of both companies to monitor MRD negativity in patients with MM will drive the success of this collaboration."

About Minimal/Measurable Residual Disease 

Minimal/measurable residual disease (MRD) refers to cancer cells that remain in the body of a person with lymphoid cancer after treatment. These cells can be present at levels undetectable by traditional morphologic, microscopic examination of blood, bone marrow or a lymph node biopsy. Sensitive molecular technologies, such as next-generation sequencing utilized by the Adaptive Biotechnologies clonoSEQ Assay, are needed for reliable detection of MRD at levels below the limits of traditional assessment.

About the clonoSEQ Assay

The Adaptive Biotechnologies clonoSEQ Assay enables physicians to utilize next-generation sequencing-based minimal/measureable residual disease (MRD) detection to inform clinical decision making for patients with lymphoid malignancies. The clonoSEQ Assay detects and quantifies DNA sequences found in malignant cells which can be tracked throughout treatment. This robust assay provides consistent, accurate measurement of disease burden which potentially allows physicians to monitor response to treatment over time to optimize patient management. Adaptive will be seeking marketing authorization from the FDA for the clonoSEQ Assay.

Immune Pharmaceuticals Signs Agreement to Regain Worldwide Rights for Ceplene

On June 15, 2017 Immune Pharmaceuticals Inc. (NASDAQ: IMNP) (‘Immune’) reported that it has signed an agreement with Meda, a Mylan NV company (‘Mylan’) to repurchase assets relating to Ceplene, including the right to commercialize Ceplene in Europe and to register and commercialize Ceplene in certain other countries (Filing, 8-K, Immune Pharmaceuticals, JUN 21, 2017, View Source [SID1234519644]). Immune sold certain of these Ceplene-related assets to Meda AB in 2012. Immune intends, through its Immuno-Oncology subsidary, Cytovia, Inc. (‘Cytovia’) to undertake commercialization efforts in Europe, Asia and Latin America. In addition, Cytovia intends to pursue continued development of Ceplene towards potential regulatory approval in the United States.

"We are excited to regain Ceplene’s European and Asian rights from Mylan and to transition Immune, through Cytovia, into a revenue-generating phase of the company’s evolution. This agreement is an additional step forward towards our previously stated objective of executing a plan to establish an independent oncology business through Cytovia and follows the execution of the Letter of Intent with Pint Pharma related to licensing Ceplene in Latin America and investing in Cytovia", said Dr. Daniel Teper. "Proactive maintenance treatment for Acute Myeloid Leukemia (AML) has been recognized as highly essential for relapse prevention, and we are pleased for the potentail opportunity to become a leader in the AML remission maintenance space."

The assets acquired from Mylan include rights to marketing authorizations, trademarks, patents, and other intellectual property related to Ceplene and its use. Under the terms of the acquisition agreement, Immune has agreed to pay Mylan a fixed price, which is payable in installments, as well as additional amounts contingent on the achievement of certain milestones.

The market for AML therapeutics is steadily growing due to an aging population and medical need that has been unmet due to the complexity of AML. Unfortunately, most patients with AML who are able to achieve complete remission will eventually relapse, and survival following such a relapse is poor, with rates of 33% in younger patients but only 15-20% in patients over 60 years of age. In the therapeutic management of patients with AML, remission maintenance therapy is important for the prevention of relapse and the prolongation of disease-free survival.

About Ceplene

Ceplene (histamine dihydrochloride) is administered in conjunction with low dose interleukin-2 (IL-2), for maintenance of first remission in patients with Acute Myeloid Leukemia (AML). Ceplene has been shown in clinical studies to prevent leukemic relapses in AML patients in first remission and prolong leukemia-free survival while maintaining good quality of life during treatment. Ceplene acts by enhancing the immunostimulatory effect of IL-2 and countering ROS-induced dysfunction and apoptosis of T and NK cells, thereby inducing immune-mediated killing of leukemic cells, providing a strong pharmacological rationale for this combination therapy. A recent Phase IV study presented at the meeting of the American Association for Cancer Research (AACR) (Free AACR Whitepaper) in 2016 confirmed the safety and efficacy of Ceplene demonstrated in the international study that supported European approval.

About Acute Myeloid Leukemia (AML)

AML patients receive intensive induction treatment with chemotherapeutic drugs at diagnosis, and typically become free of detectable leukemia, achieving "complete remission." However, within 1-2 years the majority (75-80%) of adult patients will experience a relapse of leukemia, of which survival prognosis is 33% in younger patients but only 15-20% in patients over 60 years of age. According to the American Cancer Society, there will be approximately 21,380 new cases of AML and 10,590 deaths from AML in the US in 2017. The prognosis following first remission is poor and there are no other effective remission therapies currently available, AML represents an orphan indication with particularly high unmet need.