On January 4, 2018 ChemoCentryx, Inc., (Nasdaq:CCXI) reported that it will receive a $50 million milestone payment from Vifor Fresenius Medical Care Renal Pharma (VFMCRP), a company of the Vifor Pharma Group and Fresenius Medical Care (Press release, ChemoCentryx, JAN 4, 2018, View Source [SID1234522888]). The milestone was triggered by the European Medicines Agency (EMA)’s validation of the Company’s Conditional Marketing Authorization (CMA) application for avacopan in the treatment of patients with anti-neutrophil cytoplasmic auto-antibody-associated vasculitis (ANCA-associated vasculitis), announced earlier today. In addition to the $50 million milestone from VFMCRP, the Company also entered into a $50 million growth capital financing agreement with Hercules Capital, Inc. (NYSE:HTGC), bringing total new capital commitments of up to $100 million to ChemoCentryx. Such additional capital is expected to provide funding to advance avacopan through topline data from the Phase III ADVOCATE trial as well as potential registration filings in the U.S. and EU.

"The validation of our CMA application by the EMA is a pivotal milestone in our Kidney Health Alliance with Vifor. It is also a major advance in heightening the awareness of the plight of ANCA vasculitis patients," said Thomas J. Schall, Ph.D., President and Chief Executive Officer of ChemoCentryx. "The status quo is simply not good enough for ANCA patients and new therapies are desperately needed. The decision of the EMA to validate our conditional marketing application will enable a thorough examination of how we at CCXI and our partners at Vifor may create just such a valuable new paradigm for ANCA treatment."

ChemoCentryx, which is responsible for the discovery and development of avacopan, owns and retains the commercial rights to the drug in the United States and China, and VFMCRP has licensed the rights to commercialize the drug in all other countries. Under the terms of the Kidney Health Alliance with Vifor Pharma, which comprises both avacopan and CCX140, ChemoCentryx has received a total of $155 million in upfront cash and cash commitments in addition to the $50 million milestone announced today. ChemoCentryx is eligible to receive additional payments upon the achievement of certain development, regulatory and sales-based milestones, as well as tiered double-digit royalties on potential net sales of avacopan and CCX140 in the Vifor licensed territories.

The $50 million credit facility from Hercules Capital comprises three tranches. The first tranche of $15 million, of which $5.0 million was funded upon closing of the agreement, is available through June 2018. The remaining $35 million is available in two additional tranches, subject to certain conditions. The term loan has a 24-month interest-only period from initial funding, which is extendable to 30 months upon the achievement of certain milestones and matures in 48 months. Further information with respect to the growth capital financing agreement with Hercules is contained on a Form 8-K to be filed by ChemoCentryx with the Securities and Exchange Commission.

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On January 4, 2018 Celsion Corporation (NASDAQ: CLSN), an oncology drug development company, reported that the U.S. Food and Drug Administration (FDA), following the customary 30 day review period, has accepted its submission without comment, providing clearance for the OVATION II Study, the Company’s planned Phase I/II clinical trial of GEN-1, its DNA-based immunotherapy for the localized treatment of ovarian cancer (Press release, Celsion, JAN 4, 2018, View Source [SID1234522887]). The Phase I/II trial was developed with extensive input from the Company’s Medical Advisory Board. The OVATION II Study builds on the highly promising clinical and translational research data from the Phase IB dose-escalating OVATION Study where enrolled patients received escalating weekly doses of GEN-1, from levels beginning at 36mg/m², to 47mg/m², 61mg/m² and 79mg/m² weekly for 8 treatments in total, in combination with neoadjuvant chemotherapy, followed by interval debulking surgery.

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This next Phase I/II study is designed with a single dose escalation phase to 100 mg/m² to identify a safe and tolerable dose of GEN-1 while maximizing an immune response, followed by a continuation at the selected dose in Phase II in an open label, 1:1 randomized design up to 90 patients with Stage III/IV ovarian cancer at up to fifteen U.S. centers. The study is powered to show a 33% improvement in the primary endpoint, progression-free survival (PFS), when comparing GEN-1 with neoadjuvant chemotherapy versus neoadjuvant chemotherapy alone.

Progression-free survival for patients treated per protocol in the Phase IB OVATION Study continues to be followed. Of the thirteen patients who received GEN-1 treatment in all four dose escalating cohorts, only four patients’ cancer has progressed to-date. This compares favorably to the historical median progression-free survival of 12 months for newly-diagnosed patients with Stage III and IV ovarian cancer that undergo neoadjuvant chemotherapy followed by interval debulking surgery. Summarized below are the latest PFS results for all patients treated per protocol in the Phase IB OVATION Study:

Cohort 1 (36 mg/m²) – All patients have progressed; Average PFS was 19.25 months; Longest progression-free patient in 1st cohort was 24.8 months.

Cohort 2 (47 mg/m²) – No patients have progressed after 21 months.

Cohort 3 (61 mg/m²) – One patient has progressed after 14 months; Two other patients in 3rd cohort are progression free over 17 months.

Cohort 4 (79 mg/m²) – No patients have progressed; Average PFS for these five patients in 4th cohort is 14 months.
"In previous clinical studies performed to date, GEN-1 has demonstrated excellent safety and impressive clinical activity supported with dose dependent, pro-immune improvement in the tumor micro environment. A onetime dose escalation may prove to be even more impressive," stated Dr. Nicholas Borys, Celsion’s senior vice president and chief medical officer. "As we continue to follow patients, the latest PFS analysis from the OVATION Study is showing a median of at least 15.4 months in the as-treated group which compares favorably to a historical control of 12 months. Our highest dose cohort has not demonstrated any progressions at our current 14 month follow up. This same cohort also had a 100% R0 surgical resection rate. One of our patients in the OVATION Study even had a complete pathological response."

The Company expects to initiate enrollment of the Phase I portion of the OVATION II Study in the first half of 2018. The Company expects to have 25% of the study enrolled by the end of 2018. Due to the open label design, clinical data will be disclosed throughout the execution of the trial as it is released by the study’s investigators.

"GEN-1 holds the potential for tremendous promise as a cancer treatment in the rapidly emerging area of immunotherapy. This new trial will evaluate GEN-1’s value as an adjuvant to current standard of care in newly diagnosed Stage III/IV ovarian cancer patients with a relatively healthy immune system. We look forward to initiating the study in the first half of 2018," said Michael H. Tardugno, Celsion’s chairman, president and chief executive officer. "Designed in consultation with leading medical experts, this Phase I/II trial is expected to define an optimal dose, demonstrate GEN-1’s clinical benefit when compared with current standard of care, and provide insights on powering for a registration program as the candidate progresses through development."

About GEN-1 Immunotherapy

GEN-1, designed using Celsion’s proprietary TheraPlas platform technology, is an IL-12 DNA plasmid vector encased in a nanoparticle delivery system, which enables cell transfection followed by persistent, local secretion of the IL-12 protein. IL-12 is one of the most active cytokines for the induction of potent anti-cancer immunity acting through the induction of T-lymphocyte and natural killer (NK) cell proliferation. The Company has previously reported positive safety and encouraging Phase I results with GEN-1 given as monotherapy in patients with peritoneally metastasized ovarian cancer, and a Phase Ib trial of GEN-1 in combination with PEGylated doxorubicin in patients with platinum-resistant ovarian cancer.

On January 4, 2018 ImmunoGen, Inc. (Nasdaq: IMGN), a leader in the expanding field of antibody-drug conjugates (ADCs) for the treatment of cancer, reported that the first patient has been treated with IMGN632 in a Phase 1 clinical trial of patients with CD123-positive hematological malignancies, including acute myeloid leukemia (AML) and blastic plasmacytoid dendritic cell neoplasm (BPDCN) (Press release, ImmunoGen, JAN 4, 2018, View Source [SID1234522879]).

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IMGN632 uses ImmunoGen’s novel indolino-benzodiazepine payload, DGN549, which alkylates DNA without crosslinking, as well as novel linker technology with a CD123-targeting antibody. In preclinical studies with IMGN632, ImmunoGen has reported potent and selective activity against AML cells with lower cytotoxicity to normal myeloid progenitor cells than an ADC designed to crosslink DNA.1 Supporting preclinical data for IMGN632 have also shown compelling activity in AML and acute lymphoblastic leukemia (ALL) models with single and multi-dose regimens.2,3 These data suggest that IMGN632 has the potential to be a highly effective, yet tolerable ADC.

"We continue to rapidly advance our novel IGN portfolio in a number of hematological malignancies and are pleased to be moving our second IGN ADC, IMGN632, into the clinic," said Anna Berkenblit, M.D., VP and Chief Medical Officer of ImmunoGen. "Our IGN payloads were developed to meet the dual challenges of achieving high potency against target cells, while enabling continued patient treatment. We believe IMGN632 has the potential to be a highly effective therapy with favorable tolerability for the treatment of patients with CD123-positive hematologic malignancies, including AML and BPDCN, cancers where new therapies are desperately needed."

The Phase 1 trial in AML and BCPDN will follow a once every three week dosing schedule while in its dose-finding stage. The selected dose will then be used in expansion cohorts assessing IMGN632 in patients with BPDCN, AML, ALL, and other CD123-positive hematologic malignancies.

"We are excited to be leading off the clinical evaluation of IMGN632, a potential new treatment option for patients with CD123-positive hematologic malignancies," said Hagop M. Kantarjian, M.D., professor and chair of the Department of Leukemia at the University of Texas MD Anderson Cancer Center and principal investigator of the trial of IMGN632.

Data presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting (ASH) (Free ASH Whitepaper) 2017 demonstrated promising activity and safety with IMGN632 in preclinical models of B-cell ALL (B-ALL).4 CD123 expression is prevalent across ALL subtypes, including 90% of B-ALL and nearly half of T-cell acute lymphoblastic leukemia. IMGN632 demonstrated promising activity against B-ALL cell lines and patient samples in vitro, including the elimination of more than 90% of B-ALL blasts in 6 out of 8 patient samples. Normal cells were not affected by IMGN632 at 100-fold higher concentrations.

This is the second clinical trial using IGNs, a new class of cancer-killing agents developed by ImmunoGen for use in ADCs. ImmunoGen recently reported findings from the Company’s ongoing Phase 1 study of IMGN779 in patients with relapsed or refractory adult AML whose tumors express CD33.5 The data demonstrate that IMGN779 is well-tolerated with no dose-limiting toxicities, pharmacokinetic exposures and pharmacodynamic CD33 saturation increasing with dose, and anti-leukemia activity observed in patients with poor prognostic features.

About IMGN632
IMGN632 is a humanized anti-CD123 ADC that is a potential treatment for AML, BPDCN, myelodysplastic syndrome, B-cell ALL and other CD123-positive malignancies. IMGN632 uses a novel IGN payload, linker and antibody technology, and has demonstrated potent and selective activity, with minimal cytotoxic effects, in preclinical models of AML and ALL.6,7

About IGNs
Indolino-benzodiazepine agents, or IGNs, are a new class of cancer-killing agent developed by ImmunoGen for use in ADCs. IGN payloads were designed to meet the dual challenges of achieving high potency against target cells, while having a tolerability profile that can enable continued patient treatment. These ultra-potent, DNA-acting IGNs alkylate DNA without crosslinking, which preclinically has resulted in potent anti-leukemia activity with relative sparing of healthy cells.8,9

About Acute Myeloid Leukemia (AML)
AML is a cancer of the bone marrow cells that produce white blood cells. It causes the marrow to increasingly generate abnormal, immature white blood cells (blasts) that do not mature into effective infection-fighting cells. The blasts quickly fill the bone marrow, impacting the production of normal platelets and red blood cells. The resulting deficiencies in normal blood cells leave the patient vulnerable to infections, bleeding problems and anemia.

It is estimated that, in the U.S. alone, 21,380 patients will be diagnosed with AML this year and 10,590 patients will die from the disease.10

About Blastic Plasmacytoid Dendritic Cell Neoplasm (BPDCN)

BPDCN is a disease of the bone marrow and blood that affects multiple organs, including the lymph nodes and the skin. It often presents as leukemia or lymphoma. There are little data about BPDCN and there is no established treatment. The average age at diagnosis is 60 to 70 years. There are more men than women who are diagnosed with BPDCN.11,12

On January 4, 2018 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH), a clinical-stage biopharmaceutical company focused on addressing key mechanisms of tumor drug resistance, reported that it has initiated a Phase 3 clinical study to evaluate the safety and efficacy of DCC-2618, a pan-KIT and PDGFRα inhibitor, in patients with advanced gastrointestinal stromal tumors (GIST) (Press release, Deciphera Pharmaceuticals, JAN 4, 2018, View Source [SID1234522871]).

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"We are extremely pleased to initiate the INVICTUS study with DCC-2618 in heavily pretreated GIST patients, specifically fourth-line and fourth-line plus patients," said Michael D. Taylor, Ph.D., President and Chief Executive Officer of Deciphera. "We expect to report top-line results in 2019 and, if successful, this pivotal Phase 3 study could serve as the basis for a New Drug Application (NDA), providing a much-needed therapeutic option for these patients for whom there are no approved treatments. We also plan to initiate a second Phase 3 study later this year evaluating DCC-2618 in second-line GIST patients who have progressed or are intolerant to front-line therapy with imitanib."

"While effective treatments are available for patients with early-stage GIST, in 9 out 10 patients the disease will eventually progress due to the development of secondary drug resistance mutations," said Professor Jean-Yves Blay, Medical Oncologist, General Director Centre Léon Bérard, Comprehensive cancer Centre of Lyon, France. "A therapy with the potential to provide broad coverage across the full spectrum of KIT and PDGFRα mutations would represent a much-needed improvement over currently approved treatment options for patients with later-stage GIST."

Initiation of the INVICTUS study follows results from the ongoing Phase 1 clinical trial presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress in September 2017, in which durable disease control by DCC-2618 was observed in heavily pretreated patients with GIST.

INVICTUSPhase 3 Study
The INVICTUS Phase 3 clinical study is a randomized, double-blind, placebo-controlled, international, multicenter trial to evaluate the safety, tolerability, and efficacy of DCC-2618 compared to placebo in patients with advanced GIST patients whose previous therapies have included imatinib, sunitinib, and regorafenib. The trial is expected to enroll approximately 120 patients randomized 2:1 to either 150 mg once daily of DCC-2618 or placebo. The primary efficacy endpoint is median progression free survival (PFS) as determined by independent radiologic review using modified Response Evaluation Criteria in Solid Tumors (RECIST). Secondary endpoints as determined by independent radiologic review using modified RECIST include Objective Response Rate (ORR); Time to Tumor Progression (TTP); and Overall Survival (OS). See www.clinicaltrials.gov for further information (NCT03353753).

About DCC-2618
DCC-2618 is a pan-KIT and PDGFRα kinase switch control inhibitor in clinical development for the treatment of KIT and/or PDGFRα-driven cancers, including gastrointestinal stromal tumors, glioblastoma multiforme and systemic mastocytosis. DCC-2618 was specifically designed to improve the treatment of GIST patients by inhibiting the full spectrum of mutations in KIT and PDGFRα. DCC-2618 is a pan-KIT and pan-PDGFRα inhibitor that blocks initiating KIT mutations in exons 9, 11, 13, 14, 17, and 18, known to be present in GIST patients and the D816V exon 17 mutation known to be present in ASM patients. DCC-2618 inhibits PDGFRα mutations in exon 18, including the D842V mutation that drives a subset of GIST.

On January 4, 2018 NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products, and Riken Genesis, a subsidiary of Sysmex Corporation (TOKYO, 6869), reported that they have entered into a partnership to introduce nCounter-based diagnostic assays in Japan (Press release, NanoString Technologies, JAN 4, 2018, View Source [SID1234522864]).

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Under this agreement, NanoString and Riken Genesis will collaborate to register, obtain reimbursement and commercialize companion diagnostic assays in Japan, including NanoString’s Lymphoma Subtyping Test which will be marketed as the nCounter Dx LymphMarkTM assay.

LymphMark is a 20-gene signature that classifies cell-of-origin subtypes of Diffuse Large B-cell Lymphoma (DLBCL) tumors. The initial indication for the LymphMark assay is expected to be a potential companion diagnostic to aid in identifying DLBCL patients for treatment. The LymphMark assay is based on the Lymph2Cx gene signature that was originally developed by the Lymphoma/Leukemia Molecular Profiling Project (LLMPP) and has demonstrated analytical robustness and potential clinical utility.

The LymphMark assay was used to select patients in a Phase III clinical trial. The LymphMark assay is being evaluated in more than 40 research studies that are being conducted with 23 companies.

"Through this collaboration, we will work closely with Riken Genesis to launch novel diagnostic products on the nCounter platform that have the potential to guide decision making in the Japanese oncology community," said Brad Gray, chief executive officer of NanoString.

"We are pleased to partner with NanoString to bring new highly multiplexed molecular assays to clinicians and patients in Japan," said Dr. Naoto Kondo, president and chief executive officer of Riken Genesis. "These innovative assays will be an important addition to our portfolio of diagnostic tests."