On November 12, 2018 Unum Therapeutics Inc. (NASDAQ: UMRX), a clinical-stage biopharmaceutical company focused on the development of novel cellular immunotherapies, reported financial results and provided a corporate update for the third quarter ended September 30, 2018 and recent activities (Press release, Unum Therapeutics, NOV 12, 2018, View Source [SID1234531239]).

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"In the third quarter of 2018, we continued to make significant progress advancing our clinical pipeline," said Chuck Wilson, CEO of Unum. "We are excited to announce today that we have selected ACTR707 in combination with rituximab for further development in patients with relapsed or refractory non-Hodgkin lymphoma. Early data from the ATTCK-20-03 trial continue to support our novel ACTR platform and potential best-in-class product profile. In addition, we remain on track with our two additional clinical studies, ATTCK-17-01 in multiple myeloma and ATTCK-34-01 in HER2+ solid tumors, and are looking forward to presenting further updates on all trials at upcoming scientific conferences in December. Finally, we are pleased with our significant progress in developing a second novel technology platform, BOXR, which is designed to improve T cell functionality in solid tumors, and we look forward to developing future products based on this platform."

Recent Highlights

Selected ACTR707 as Lead Candidate for Further Development in r/r NHL: Unum has elected to advance ACTR707 in combination with rituximab as its lead product candidate to treat patients with relapsed or refractory CD20-positive B cell non-Hodgkin lymphoma (r/r NHL). As a result of this decision, Unum intends to conclude enrollment in the ATTCK-20-2 study, in the first half of 2019. The selection of ACTR707 as the lead construct in r/r NHL was based on the emerging clinical data from the Phase I ATTCK-20-03 clinical trial, the continuing progress in the ATTCK-20-03 study, and the Company’s desire to efficiently manage resources. At the first dose level of that trial, three out of six treated patients achieved a complete response, two of which remained ongoing at the time of the September 4 data cut off. Additionally, no dose-limiting toxicities (DLTs), serious or severe adverse events of cytokine release syndrome or neurotoxicity were observed in any patients. The findings in ATTCK-20-03 build on the encouraging data observed in cohort 1 of the ATTCK-20-2 trial, which evaluated ACTR087 in combination with

rituximab in patients with r/r NHL. Updated data from the ATTCK-20-03 trial will be presented at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) meeting in December.

Continued Progress with ATTCK-17-01 Phase I trial: Unum is continuing to enroll and dose patients in ATTCK-17-01, a Phase I, multi-center, open-label clinical trial designed to test the safety, tolerability, and anti-myeloma activity of ACTR087 used in combination with SEA-BCMA in patients with r/r multiple myeloma through the dose escalation phase of the trial. This is the first clinical trial conducted under the strategic collaboration with Seattle Genetics. Unum plans to report preliminary data from early dose cohorts at the upcoming ASH (Free ASH Whitepaper) meeting in December 2018.

On Track to Initiate ATTCK-34-01 Trial by Year End in Solid Tumors: Unum’s investigational new drug (IND) application for ACTR T cells in combination with trastuzumab for the treatment of patients with HER2+ advanced cancers has been accepted, and Unum plans to initiate the multi-center Phase I ATTCK-34-01 trial by the end of 2018, and announce preliminary data in 2019. ATTCK-34-01, Unum’s first ACTR combination study in solid tumors, is a multicenter, single-arm, open-label dose escalation study evaluating ACTR T cells in combination with trastuzumab and includes a planned expansion at the recommended Phase 2 dose. The primary study objectives are to assess the safety and tolerability of the combination, and to define dose recommendations for further study. Additional objectives include assessment of anti-tumor activity, ACTR T cell persistence and trastuzumab pharmacokinetics. Unum expects to present updated preclinical data along with the clinical trial design at the San Antonio Breast Cancer Symposium in December 2018.

Announced New Technology Platform to Expand Clinical Development Efforts in Solid Tumors: At the Society for Immunotherapy (SITC) (Free SITC Whitepaper) meeting in November, Unum presented preclinical data on a new technology platform called "BOXR," or Bolt-On Chimeric Receptor, that improves the functionality of T cells, enabling them to be more effective in solid tumor cancers. BOXR works with ACTR T cells or CAR T cells to significantly improve T cell functionality. Unum will disclose more details on this new platform, as well as its broader efforts in solid tumors, at the upcoming investor event on November 19, 2018, in New York, featuring guest speaker Charles S. Fuchs, MD, MPH, of Yale Cancer Center. The event will be available also via live webcast.

Third Quarter 2018 Financial Results

Collaboration Revenue: Collaboration revenue recognized during the third quarter ended September 30, 2018 and 2017, of $2.0 million and $2.3 million, respectively, reflects the recognition of a portion of the $25.0 million upfront payment received from Seattle Genetics under Unum’s collaboration agreement as well as reimbursements of research and development costs by Seattle Genetics. Effective January 1, 2018, Unum adopted the new revenue recognition standard, ASC 606, which changed the manner in which the Company recognizes revenue from this collaboration agreement compared to the prior year period.

R&D Expenses: Research and development expenses were $10.3 million for the third quarter ended September 30, 2018, compared to $8.2 million for the same period last year. The increase reflects higher clinical trial costs for the active Phase I clinical trials, as well as increased personnel-related costs, materials and facility-related costs related to scaling manufacturing processes, and increased consultant costs. This was partially offset primarily by a decrease in manufacturing costs incurred for the Phase I clinical trial of ACTR087 in combination with rituximab.

G&A Expenses: General and administrative expenses for the third quarter ended September 30, 2018, were $2.4 million, compared to $1.3 million for the same period last year. The increase is primarily due to expenses around operating as a public company and higher personnel related costs.

Net Loss: Net loss attributable to common stockholders was $10.2 million, or $0.34 per share, for the third quarter ended September 30, 2018, and $7.0 million, or $0.69 per share, for the same period last year.

Cash, Cash Equivalents and Marketable Securities: As of September 30, 2018, Unum had cash, cash equivalents, and marketable securities of $87.1 million. Today, the Company updated its cash runway and now believes that its existing cash, cash equivalents, and marketable securities will fund operating expenses and capital expenditure requirements through at least June 2020, without considering $15.0 million in available borrowings under its loan and security agreement, as a result of its decision to conclude enrollment in the ATTCK-20-2 study in the first half of 2019.

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 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 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 10, 2018 Brooklyn ImmunoTherapeutics, a biopharmaceutical company focused on exploring the role that cytokine-based therapy can have in treating patients with cancer, and Providence Cancer Institute reported the clinical results of IRX-2 therapy in resectable breast cancer and head and neck cancer that were presented in an oral presentation at the 2018 Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) on November 10th at the Walter E. Washington Convention Center in Washington, D.C (Press release, Brooklyn ImmunoTherapeutics, NOV 10, 2018, View Source [SID1234531112]).

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IRX-2 is an allogeneic, cell-derived biologic with multiple active cytokine components, including IL-2, that act on various parts of the immune system to activate the entire tumor microenvironment.

"The clinical results presented today demonstrate that treatment with IRX-2 was associated with a mean 116% increase in tumor-infiltrating lymphocytes in patients with early stage breast cancer and a mean increase of 58% in head and neck squamous cell carcinoma," said David B. Page, M.D., Earle A. Chiles Research Institute, a division of Providence Cancer Institute in Portland, Oregon, and the presenter at SITC (Free SITC Whitepaper)’s 33rd Annual Meeting. "Moreover, IRX-2 therapy was also associated with an increase in PD-L1 RNA upregulation in the early stage breast cancer patients and was well-tolerated in both the breast cancer and head and neck cancer patients enrolled in these clinical trials. Together these results support the further evaluation of IRX-2 with anti-PD-1 and neoadjuvant chemotherapy in stage II-III triple negative breast cancer as well as ongoing follow-up of a randomized Phase 2 INSPIRE trial in head and neck cancer."

"These highly encouraging clinical results support further study of IRX-2 as a potential important new immunotherapeutic drug candidate for the treatment of both breast cancer and head and neck cancer," said Mark Leuchtenberger, interim President and CEO of Brooklyn ImmunoTherapeutics. "We believe that IRX-2, both as a single agent and in combination with other anti-cancer agents, can potentially improve patient outcomes in these difficult-to-treat indications as well as in the treatment of other cancers. On-going studies, including the Phase 2B INSPIRE trial and an investigator-sponsored trial in squamous cervical intraepithelial neoplasia 3 or vulvar intraepithelial neoplasia 3, are further exploring the potential of IRX-2 in treating cancer."

Results

In the early stage breast cancer trial (ESBC), 16 patients were enrolled and evaluable for tumor-infiltrating lymphocyte (TIL) analysis, and the head and neck squamous cell carcinoma (HNSCC) trial is fully enrolled at 105 patients with 36 patients evaluable at the time of analysis. In both trials, all patients received all planned injections with no treatment-related surgical delays, complications, or treatment-related grade III/IV toxicities. Treatment was associated with a mean 116% relative increase in TILs (range –36% to +1275%, p = 0.02) in ESBC and a mean 58% relative increase (range –57 to +452%, p=0.01) in HNSCC. Treatment was associated with PD-L1 RNA upregulation in EBSC (mean +54%, range –53% to +185%, p=0.04). RNA analysis in ESBC and HNSCC revealed concordant increases in cytokine gene expression, including CXCL2, CCL4, CXCR4, and CXCL12 as well as transcription factors including FOS, ETS1, NFκB, EGR1/2 which are involved in T-cell activation and differentiation. Augmentation of ITGAE (CD103), a known marker of memory T-cell activation in EBSC cohort was also observed