On November 11, 2018 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported new clinical data for FATE-NK100, an investigational, first-in-class, allogeneic donor-derived natural killer (NK) cell cancer immunotherapy, and provided a regulatory update on the development of FT500, a universal, off-the-shelf NK cell product candidate derived from a master induced pluripotent stem cell (iPSC) line, on November 10, 2018.

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Twenty heavily pre-treated subjects, each presenting with progressive disease at the time of enrollment, have been treated with FATE-NK100 in the dose-escalation phases of three Phase 1 clinical trials. As of a October 22, 2018 data cutoff, one-month follow-up data were available on fourteen subjects1, with clinical benefit indicated in seven of these fourteen subjects:

In the DIMENSION study for the treatment of advanced solid tumors (n=5 in the monotherapy regimen; n=1 in the monoclonal antibody combination regimen1), one subject at the second dose level (1-3×107 cells per kg) and two subjects at the third dose level (3-10×107 cells per kg) treated with a single intravenous infusion of FATE-NK100 in the monotherapy regimen had stable disease at one month. These two subjects at the third dose level were each subsequently treated with a second dose of FATE-NK100 and remain on study (3.1 and 5.0 months, respectively) with ongoing disease control. The study is currently enrolling at the third dose level in the monotherapy regimen, at the second dose level in the cetuximab combination regimen (1-3×107 cells per kg) and at the run-in dose level in the trastuzumab combination regimen (1×106 cells per kg).
In the APOLLO study for the treatment of recurrent ovarian cancer (n=4), one subject treated with a single intraperitoneal infusion of FATE-NK100 at the second dose level (1-3×107 cells per kg) had stable disease at one month. The subject was subsequently treated with a second dose of FATE-NK100 and maintained disease control for 6.2 months. The study is currently enrolling at the third dose level (3-10×107 cells per kg).
In the VOYAGE study for the treatment of refractory or relapsed acute myelogenous leukemia (n=4), all three subjects treated with a single intravenous infusion of FATE-NK100 at the second dose level (1-3×107 cells/kg) showed complete clearance of leukemic blasts in the bone marrow and achieved a morphologic leukemia-free state at Day 14 following treatment. Each of these three subjects received a single dose of FATE-NK100 only, and the anti-leukemic response in each of these subjects was transient. The study is currently enrolling at the second dose level.
No dose limiting toxicities related to FATE-NK100 were reported. One serious adverse event related to FATE-NK100 was reported (Grade 3: abdominal pain) in the APOLLO study.

"The safety and clinical benefit observed with a single infusion of FATE-NK100 as a monotherapy in heavily pre-treated cancer patients, including in refractory AML patients that have high leukemic blast burden in the marrow and in advanced solid tumor patients with progressive disease, are encouraging," said Sarah Cooley, M.D., Associate Professor of Medicine, Division of Hematology, Oncology and Transplantation at the University of Minnesota and the lead investigator of the VOYAGE study. "We are particularly excited that a repeat dose of FATE-NK100 was well-tolerated and showed persistence. Importantly, all three subjects re-treated with a second dose have demonstrated disease control. These data provide compelling proof-of-concept for FATE-NK100 and support earlier intervention with NK cell therapy using a multi-dose treatment cycle."

In addition, the Company announced that adventitious agents testing of the master iPSC bank for the clinical production of FT500, a universal, off-the-shelf NK cell product candidate, has been completed. The FT500 master iPSC bank was found to be free of adventitious agents as determined by in vivo and in vitro testing. The Company has submitted these results to the U.S. Food and Drug Administration (FDA) in furtherance of the agency’s review of the Company’s FT500 Investigational New Drug (IND) application. Upon allowance by the FDA of the FT500 IND, the Company plans to initiate Phase 1 clinical testing of FT500 as a monotherapy and in combination with checkpoint inhibitor therapy for the treatment of advanced solid tumors. This first-in-human study is expected to evaluate the safety and tolerability of multiple doses of FT500 in multiple dosing cycles.

An updated presentation on the Company’s NK cell cancer immunotherapy franchise can be found under "Events & Presentations" in the Investors and Media section of the Company’s website at www.fatetherapeutics.com.

1 Excludes one subject treated at the run-in dose level in the cetuximab combination regimen (1×106 cells per kg)

About FATE-NK100
FATE-NK100 is an investigational, first-in-class, allogeneic donor-derived natural killer (NK) cell cancer immunotherapy comprised of adaptive memory NK cells, a highly specialized and functionally distinct subset of activated NK cells expressing the maturation marker CD57. Higher frequencies of CD57+ NK cells in the peripheral blood or tumor microenvironment in cancer patients have been linked to better clinical outcomes. In August 2017, non-clinical data describing the unique properties and anti-tumor activity of FATE-NK100 were published by Cancer Research (doi:10.1158/0008-5472.CAN-17-0799), a peer-reviewed journal of the American Association of Cancer Research. Three clinical trials of FATE-NK100 are currently being conducted: VOYAGE for the treatment of refractory or relapsed acute myelogenous leukemia; APOLLO for the treatment of recurrent ovarian cancer; and DIMENSION for the treatment of advanced solid tumors, including in combination with monoclonal antibody therapy.

On November 11, 2018 Generon Corporation, a leading biopharmaceutical company in China, reported it received approval for the Company’s Investigational New Drug (IND) application from the State Food and Drug Administration (SFDA) of the People’s Republic of China to initiate a Phase I clinical trial for A-319 in patients with B cell malignancies (Press release, Generon (Shanghai), NOV 11, 2018, View Source [SID1234531111]). A-319 is Generon’s second bispecific antibody in clinical development.

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A-319 is the first CD19 engaging bispecific antibody approved by the SFDA for clinical trials in China. The CD3/CD19 bispecific antibody was developed using Generon’s Immuno-Therapy Antibody (ITab)TM technology platform. The IND approval enables Generon to commence Phase I clinical trials in China enrolling patients with B cell malignancies including acute lymphoblastic leukemia (ALL) and B cell lymphoma.

Dr. Mi Jian Qing, Professor at Ruijin Hospital, Shanghai Jiaotong University expressed his enthusiasm about the biology of A-319 and the potential benefits for ALL patients. He commented: "Obtaining the SFDA’s approval for the A-319 Phase I trial is a significant accomplishment for Generon’s ITabTM platform. The IND approval is another step in demonstrating Generon’s innovative capabilities".

Yifan Pharmaceuticals, Generon’s parent company, congratulated Generon’s team on the continued effort to develop innovative therapies. Dr. Xiao Qiang Yan, CEO and CSO of Generon, said, "Initiation of a Phase I study for A-319 in China is one of Generon’s goals this year. A-319 has a similar mechanism of action to eliminate malignant B cells to those of CAR-T and other CD19/CD3 bispecific antibodies, but it is more convenient for patient dosing and potentially with better safety. A-319 is our second T-cell activating bispecific antibody to enter clinical development. Generon is expanding its ITabTM pipeline for both liquid and solid tumors and committed to bringing innovative immune-oncology antibodies to cancer patients in China and the world".

B cell malignancies

B cell malignancies refer to the different types of cancers that form in B cells in the immune system, including B-cell lymphomas and B-cell leukemia. B-cell lymphoma may be either indolent (slow-growing) or aggressive (fast-growing). Most B-cell lymphomas are non-Hodgkin lymphomas (NHL). There are many different types of B-cell non-Hodgkin lymphomas including chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL), Burkitt lymphoma (BL), diffuse large B-cell lymphoma (DLBL), follicular lymphoma (FL), and mantle cell lymphoma (MCL). B-cell leukemia includes B-cell chronic lymphocytic leukemia (CLL), Acute lymphoblastic leukemia (ALL), B-cell prolymphocytic leukemia (PLL), and hairy cell leukemia (HCL). The prognosis and treatment of B cell malignancies depend on the specific type of the B cell lymphoma/leukemia, as well as the stage and grade. Recent immunotherapy (T-cell activating) approaches have demonstrated significant clinical benefits for patients.

About A-319

A-319 is a T-cell activating bispecific antibody (BsAb) designed to target CD19 and CD3 (anti-CD19, anti-CD3) and is under development for the treatment of patients with B cell malignancies including B-cell leukemia and B-cell lymphoma. A-319 activates T lymphocytes in a patient to kill CD19 expressing malignant B-cells.

On November 11, 2018 Harpoon Therapeutics, Inc. ("Harpoon"), a clinical-stage immunotherapy company developing a novel class of T cell engagers, reported the closing of a $70 million Series C equity financing (Press release, Harpoon Therapeutics, NOV 11, 2018, View Source [SID1234531110]). OrbiMed served as the lead new investor, along with new investors Cormorant, Ridgeback Capital Investments, Lilly Asia Ventures (LAV) and NS Investment. Harpoon’s existing investors MPM Capital, Oncology Impact Fund, Arix Bioscience, New Leaf Venture Partners and Taiho Ventures, LLC also participated in the Series C financing round. Harpoon intends to use the proceeds from the financing to support further advancement of its immunotherapy programs based on its TriTAC (Tri-specific T cell Activating Construct) and ProTriTAC (Protease-activated Tri-specific T Cell Activating Construct) platforms, which are designed to harness the natural power of the body’s immune system to fight cancer and other diseases.

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Harpoon’s TriTAC platform was designed to advance the therapeutic potential of T cell engagers, with a long half-life extended format. Harpoon is developing a pipeline of four wholly owned TriTAC product candidates. Harpoon’s lead product candidate, HPN424, is currently in a Phase 1 clinical trial for the treatment of metastatic castration-resistant prostate cancer, or mCRPC.

"This financing is a significant milestone for us as we continue to advance our pipeline, including HPN424, our lead product candidate, with which we initiated a Phase 1 trial this summer as a potential treatment for prostate cancer," said Jerry McMahon, Ph.D., President and Chief Executive Officer. "With these funds, we intend to pursue preclinical and clinical development of additional product candidates based on our TriTAC platform as well as our second technology platform, ProTriTAC, which we believe can expand access to a broader landscape of tumor targets and indications."

"Harpoon has assembled a world-class team to drive forward an ambitious pipeline across a range of indications and patient populations," said Luke Evnin, Ph.D., Co-Founder and Chairman of Harpoon and Founder and Managing Director at MPM Capital. "With this financing, we believe we have the capacity not only to advance those pipeline programs but also to continue to innovate in the immuno-oncology arena."

In addition, in 2019, Harpoon plans to initiate Phase 1 clinical trials for HPN536 (a mesothelin-targeting TriTAC) for the treatment of mesothelin-expressing tumors, and HPN217 (a BCMA-targeting TriTAC) for the treatment of multiple myeloma. The ProTriTAC platform effort is yielding T-cell engagers against additional targets based on tumor protease-dependent activation in the tumor microenvironment, and Harpoon expects to advance its first ProTriTAC product candidate to IND-enabling studies in 2019.

On November 10, 2018 Dendrogenix a company developing a innovative therapies, reported a first funding round of €3.6M, including €1.2M in capital and €2.4M in grants and recoverable advances from walloon region (Press release, Dendrogenix, NOV 10, 2018, View Source [SID1234539438]).

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On November 10, 2018 Jounce Therapeutics, Inc. (NASDAQ: JNCE), a clinical-stage company focused on the discovery and development of novel cancer immunotherapies and predictive biomarkers, reported that reverse translational and biomarker data derived from its ICONIC (ICOS AgONist Antibody for Immunotherapy in Cancer Patients) trial of JTX-2011 and preclinical data from the ICOS (Inducible T cell CO-Stimulator) program were presented at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 33rd Annual Meeting, being held November 9-11, 2018 in Washington, D.C (Press release, Jounce Therapeutics, NOV 10, 2018, View Source;p=RssLanding&cat=news&id=2376614 [SID1234531232]).

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"The data presented at SITC (Free SITC Whitepaper)’s 33rd Annual Meeting demonstrate the role of JTX-2011 in the emergence and agonism of ICOS hi CD4 T effector cells and provide further evidence in support of the biological and clinical activity of JTX-2011. The regimens we are advancing, including ongoing combinations with ipilimumab, are grounded in these important scientific findings," said Elizabeth Trehu, M.D., chief medical officer of Jounce Therapeutics. "New insights from our Translational Science Platform continue to inform JTX-2011 clinical development. We believe our science-based approach is necessary to develop new immunotherapies to benefit cancer patients."

Data presented from ICONIC patients demonstrate the agonistic properties of JTX-2011. These data are in addition to the subset analysis data presented at ASCO (Free ASCO Whitepaper) 2018 demonstrating the emergence of ICOS hi CD4 T cells in the bloodstream in all patients with ≥30% target lesion tumor reductions, both in patients treated with JTX-2011 monotherapy and in combination with nivolumab. The ICOS hi CD4 T cells were not observed in patients with primary progressive disease.

"Through additional reverse translational studies presented today, we established two key insights that provide the scientific foundation for the next stage of development of JTX-2011," said Richard Murray, Ph.D., chief executive officer and president of Jounce Therapeutics. "First, the emergence of these ICOS hi CD4 T cells was related to JTX-2011, as it has not been detected in a separate study we conducted of responding and non-responding patients that received PD-1/L1 inhibitor monotherapy treatment; and second, in vitro experimental data showed that JTX-2011 only activates CD4 T cells if they already express high levels of ICOS. Additionally, new preclinical tumor model data presented in a separate poster, strengthens our belief that agents that induce ICOS hi CD4 T cells detectable in the bloodstream, such as anti-CTLA-4, may be attractive combination partners for JTX-2011."

In a poster titled "Emergence of an ICOS hi CD4 T cell subset correlates with tumor reductions in subjects treated with the ICOS agonist antibody JTX-2011," Jounce researchers describe the reverse translational efforts ongoing in the ICONIC trial including:

Follow-up on the initial observation of the emergence of ICOS hi CD4 T cells. Emergence of this cell population, which correlated with clinical benefit in patients treated with both JTX-2011 monotherapy and in combination with nivolumab, was presented at ASCO (Free ASCO Whitepaper) in June 2018. These data build upon the initial observation and provides further characterization of the emerging cell population as T effector and not T regulatory cells and includes evidence that the cells do not emerge in patients responding to PD-1 monotherapy.
Additional in vitro data presented demonstrate that JTX-2011 alone induces a cytokine response from CD4 T cells, only if the T cells have pre-existing ICOS hi characteristics.
CTLA-4 inhibition has been shown to induce a population of ICOS hi cells in the bloodstream, while PD-1 inhibitors do not, and these observations further support the biological rationale for the ongoing clinical development of JTX-2011 in combination with ipilimumab.
In a poster titled "Inducible T cell Co-stimulator (ICOS) is upregulated on lymphocytes following radiation of tumors and ICOS agonism in combination with radiation results in enhanced tumor control," Jounce collaborators at the Earle A. Chile’s Research Institute, Providence Portland Medical Center, highlight the benefit of upregulation of ICOS in circulating and intra-tumoral T cells by radiation and its role in effective combination treatment with an ICOS agonist antibody to mediate tumor reduction. The data presented demonstrate:

The combination of radiation therapy and treatment with an ICOS agonist antibody led to increased anti-tumor response in an immunogenic mouse tumor model.
In a less immunogenic tumor model, response required the combination of ICOS agonist and PD-1 antagonist with radiation, suggesting again that ICOS agonism in combination with modalities that upregulate ICOS, such as with radiation, may represent an attractive regimen for combination immunotherapy of anti-PD-1 resistant tumors.
Both posters are available on the Investors and Media section of the Jounce Therapeutics website under "Presentations & Publications" at www.jouncetx.com.

About JTX-2011
Jounce’s lead product candidate, JTX-2011, is a monoclonal antibody that binds to and activates ICOS, a protein on the surface of certain T cells. Preclinical data support that JTX-2011 may have a dual mechanism of action that stimulates anti-tumor T effector cells, and also reduces the immunosuppressive T regulatory cells in the tumor microenvironment. The company is developing JTX-2011 to treat solid tumors as a single agent and in combination with other therapies.