1stOncology™: Cancer Intelligence Service – Page 10775 – 1stOncology is recognized as a Top 10 Global Pharma Analytic Provider

Celldex Provides Corporate Update and Reports Third Quarter 2020 Results

On November 5, 2020 Celldex Therapeutics, Inc. (NASDAQ:CLDX) reported business and financial highlights for the third quarter ended September 30, 2020 (Press release, Celldex Therapeutics, NOV 5, 2020, View Source [SID1234570046]).

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!

"In the third quarter, building on the compelling CDX-0159 data presented at EAACI, we initiated two Phase 1b studies in chronic spontaneous urticaria and chronic inducible urticaria which will provide the foundation for several important data readouts in 2021," said Anthony Marucci, Co-founder, President and Chief Executive Officer of Celldex Therapeutics. "We also advanced the first candidate from our bispecific program, CDX-527, into the clinic in solid tumors and continued to expand the ongoing CDX-1140 program, adding a combination cohort with chemotherapy in pancreatic cancer.

In addition, we are completing our work prioritizing opportunities to expand development of CDX-0159 into additional therapeutic areas. Our analysis supports that there are multiple mast cell driven indications that have the potential to be dramatically impacted by an agent that targets the root cause of the disease—the mast cell itself—and we remain on track to start a third study in a mast cell disease setting next summer. We are closing out a busy, successful year and look forward to continuing this momentum in 2021," concluded Marucci.

Recent Pipeline Highlights

While Celldex’s clinical development programs have not been significantly, negatively impacted by COVID-19 to date, the Company continues to carefully monitor the evolving situation closely across all development programs and work to minimize potential impact/disruptions.

CDX-0159—a humanized monoclonal antibody developed by Celldex that binds the KIT receptor with high specificity and potently inhibits its activity. The KIT receptor tyrosine kinase is expressed in a variety of cells, including mast cells, which mediate inflammatory responses such as hypersensitivity and allergic reactions. KIT signaling controls the differentiation, tissue recruitment, survival and activity of mast cells. Results from a Phase 1a dose escalation study of CDX-0159 were featured in a late breaking presentation in June at the EAACI Annual Congress 2020. CDX-0159 demonstrated a favorable safety profile as well as profound and durable reductions of plasma tryptase, indicative of systemic mast cell ablation.

Celldex initiated dosing in a Phase 1b multi-center study of CDX-0159 in chronic spontaneous urticaria (CSU) in October. This study is a randomized, double-blind, placebo-controlled clinical trial designed to assess the safety of multiple ascending doses of CDX-0159 in up to 40 patients with CSU who remain symptomatic despite treatment with antihistamines. Secondary and exploratory objectives include pharmacokinetic and pharmacodynamic assessments, including measurement of tryptase and stem cell factor levels and clinical activity outcomes (impact on urticaria symptoms, disease control, clinical response) as well as quality of life assessments. Results from the study are expected in the second half of 2021.

Patient screening has begun in a second Phase 1b study in chronic inducible urticaria (CIndU). This study, which is being conducted by Dr. Marcus Maurer, Professor of Dermatology and Allergy and Director of Research at the Department of Dermatology and Allergy at the Allergie-Centrum-Charité of the Charité – Universitätsmedizin in Berlin, is exploring cold-induced urticaria and symptomatic dermographism (scratch-induced urticaria). The initiation of the study was slowed by the need to incorporate, align and obtain approval on COVID-19 screening and management protocols with the responsible Ethics Committee and German Health Authority. The Company plans to present data from the study at the end of the first quarter.

Celldex is also exploring additional mast cell driven diseases for potential future development, including mast cell activation syndromes, asthma, allergic conditions and mast cell driven gastrointestinal disorders.
CDX-1140—a potent CD40 human agonist antibody developed by Celldex that the Company believes has the potential to successfully balance systemic doses for good tissue and tumor penetration with an acceptable safety profile.

In the Phase 1 dose escalation study of CDX-1140 in patients with recurrent, locally advanced or metastatic solid tumors and B cell lymphomas, both the monotherapy and combination with CDX-301 dose escalation portions of the trial are complete with an identified maximum tolerated dose (MTD) and recommended dose of CDX-1140 at 1.5 mg/kg—one of the highest systemic dose levels in the CD40 agonist class. Expansion cohorts are actively recruiting including:

CDX-1140 with KEYTRUDA (pembrolizumab) in patients who have progressed on checkpoint therapy; and,

A combination of CDX-1140 with standard of care chemotherapy in first line metastatic pancreatic cancer.
Updated interim data from the ongoing Phase 1 study has been accepted for poster presentation at the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper)’s (SITC) (Free SITC Whitepaper) 35th Anniversary Annual Meeting & Pre-Conference Programs (SITC 2020) and will include updated data from the monotherapy and CDX-301 combination cohorts focusing on the MTD level (1.5 mg/kg), as well as preliminary safety data from the combination cohort with pembrolizumab.
CDX-527—the first candidate developed by Celldex from its bispecific platform which utilizes the Company’s proprietary highly active anti-PD-L1 and CD27 human antibodies to couple CD27 co-stimulation with blockade of the PD-L1/PD-1 pathway.

In August, Celldex initiated a Phase 1 dose escalation study in up to ~90 patients with advanced or metastatic solid tumors that have progressed during or after standard of care therapy to be followed by tumor-specific expansion cohorts. The study is designed to determine the MTD during a dose escalation phase and to recommend a dose level for further study in the subsequent expansion phase. The expansion is designed to further evaluate the tolerability, and biologic and anti-tumor effects of selected dose level(s) of CDX-527 in specific tumor types. Initial data from the Phase 1 study are anticipated in the first half of 2021.

The CDX-527 Phase 1 study design will be presented as a clinical trial in progress poster at SITC (Free SITC Whitepaper) 2020.
In addition to the CDX-1140 and CDX-527 presentations, the Company will also present preclinical data from its Axl discovery program at SITC (Free SITC Whitepaper) 2020. Axl is a member of the TAM (Tyro3/Axl/MerTK) family of receptor tyrosine kinases and a negative regulator of innate immunity.

Third Quarter 2020 Financial Highlights and 2020 Guidance

Cash Position: Cash, cash equivalents and marketable securities as of September 30, 2020 were $199.6 million compared to $206.9 million as of June 30, 2020. The decrease was primarily driven by third quarter cash used in operating activities of $11.9 million, partially offset by net proceeds of $4.3 million from sales of common stock under Celldex’s Controlled Equity OfferingSM agreement with Cantor. At September 30, 2020, Celldex had 39.6 million shares outstanding.

Revenues: Total revenue was $0.7 million in the third quarter of 2020 and $3.6 million for the nine months ended September 30, 2020, compared to $0.5 million and $2.7 million for the comparable periods in 2019. The increase in revenue was primarily due to the $1.8 million milestone payment from Rockefeller University related to Celldex’s manufacturing and development services agreement, partially offset by a decrease in services performed under the Company’s manufacturing and research and development agreement with Duke University.

R&D Expenses: Research and development (R&D) expenses were $10.7 million in the third quarter of 2020 and $32.1 million for the nine months ended September 30, 2020, compared to $11.1 million and $32.3 million for the comparable periods in 2019. The decrease in R&D expense was primarily due to a decrease in contract research and stock-based compensation expenses, partially offset by an increase in clinical trials and contract manufacturing expenses.

G&A Expenses: General and administrative (G&A) expenses were $3.6 million in the third quarter of 2020 and $10.8 million for the nine months ended September 30, 2020, compared to $3.4 million and $12.2 million for the comparable periods in 2019. The decrease in G&A expenses was primarily due to a decrease in stock-based compensation and facility expenses.

Intangible Asset Impairment: The $3.5 million non-cash impairment charge recorded during the second quarter of 2020 was due to the discontinuation of the CDX-3379 program.

Changes in Fair Value Remeasurement of Contingent Consideration: The $0.7 million loss on fair value remeasurement of contingent consideration recorded during the third quarter of 2020 and the $4.2 million gain on fair value remeasurement of contingent consideration recorded during the nine months ended September 30, 2020 were primarily due to updated assumptions for CDX-3379 related milestones due to the discontinuation of the CDX-3379 program in the second quarter of 2020, changes in discount rates and the passage of time.

Net Loss: Net loss was $14.2 million, or ($0.36) per share, for the third quarter of 2020, and $37.9 million, or ($1.44) per share, for the nine months ended September 30, 2020, compared to a net loss of $11.4 million, or ($0.75) per share, for the third quarter of 2019 and $40.4 million, or ($2.92) per share, for the nine months ended September 30, 2019.

Financial Guidance: Celldex believes that the cash, cash equivalents and marketable securities at September 30, 2020 are sufficient to meet estimated working capital requirements and fund planned operations through 2023.

KEYTRUDA is a registered trademark of Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ USA.

Navidea Biopharmaceuticals to Host Third Quarter 2020 Earnings Conference Call and Corporate Update

On November 5, 2020 Navidea Biopharmaceuticals, Inc. (NYSE American: NAVB) ("Navidea" or the "Company"), a company focused on the development of precision immunodiagnostic agents and immunotherapeutics, reported it will host a conference call and webcast on Thursday, November 12, 2020 at 5:00 p.m. (EST) to discuss financial results and corporate developments for the third quarter ended September 30, 2020 (Press release, Navidea Biopharmaceuticals, NOV 5, 2020, View Source [SID1234570045]).

Jed Latkin, Chief Executive Officer, Dr. Michael Rosol, Chief Medical Officer, and Erika Eves, Senior Director of Finance and Administration, will host the call and webcast to discuss the financial results and provide an update on recent developments and clinical progress. Management will be available to answer questions live immediately following the earnings announcement and prepared remarks portion of the call.

To participate in the call and webcast, please refer to the information below:

Event: Q3 2020 Earnings and Business Update Conference Call

Date: Thursday, November 12, 2020

Time: 5:00 p.m. (EST)

Webcast Link: View Source

A live audio webcast of the conference call will also be available on the investor relations page of Navidea’s corporate website at www.navidea.com. In addition, the recorded conference call can be replayed and will be available for 90 days following the call on Navidea’s website.

Fate Therapeutics Reports Third Quarter 2020 Financial Results and Highlights Operational Progress

On November 5, 2020 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for cancer and immune disorders, reported business highlights and financial results for the third quarter ended September 30, 2020 (Press release, Fate Therapeutics, NOV 5, 2020, View Source [SID1234570043]).

"The clinical data across our iPSC product platform continue to solidify our conviction that multiple doses of iPSC-derived NK cells can be administered off-the-shelf in the outpatient setting, are well-tolerated, and can drive anti-tumor activity, including in combination with monoclonal antibody therapy," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "We have now expanded the scope of clinical investigation for FT516 to solid tumors as well as for FT596 to chronic lymphocytic leukemia after observing clinical activity in diffuse large B-cell lymphoma at the first dose level. In addition, we have initiated first-in-human investigation of the first-ever CRISPR-edited, iPSC-derived cell therapy FT538, which incorporates three engineered elements to enhance multiple mechanisms of innate immunity, in acute myeloid leukemia and multiple myeloma."

Clinical Programs

FT596 (CAR19 + hnCD16 + IL-15RF) NK Cell Product Candidate

First Patients Treated with Dual-Antigen Targeting Regimen of FT596 in Combination with Rituximab. The Company is conducting a multi-center Phase 1 clinical trial of FT596, its universal, off-the-shelf, chimeric antigen receptor (CAR) natural killer (NK) cell product candidate, as a monotherapy and in combination with CD20-targeted monoclonal antibody therapy for the treatment of relapsed / refractory B-cell lymphoma (NCT04245722). The first patients have been treated at the first dose level (30 million cells) in combination with rituximab, which enables dual-antigen targeting of both CD19 and CD20 antigens expressed on malignant B cells. In addition, the Company has initiated enrollment at the second dose level (90 million cells) as monotherapy. FT596 is derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three anti-tumor functional modalities: a proprietary CAR optimized for NK cell biology that targets CD19 (CAR19); a novel high-affinity, non-cleavable CD16 (hnCD16) Fc receptor that enhances antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells; and an IL-15 receptor fusion (IL-15RF) that augments NK cell activity.
Clinical Scope of FT596 Phase 1 Study Expanded to CLL. In August, the Company amended the clinical protocol of its FT596 Phase 1 clinical trial to include treatment of relapsed / refractory chronic lymphocytic leukemia (CLL). Under the amended protocol, the Company has initiated enrollment at the first dose level (30 million cells) as monotherapy, and plans to begin enrollment of FT596 in combination with obinutuzumab upon dose-limiting toxicity clearance of monotherapy at the first dose level.
Investigator-initiated Clinical Trial of FT596 for Relapse Prevention Opened to Enrollment. The Phase 1 study, which is sponsored by investigators from the Masonic Cancer Center, University of Minnesota, is designed to assess the potential of FT596 to prevent relapse for patients with B-cell lymphoma who have undergone autologous hematopoietic stem cell transplant and are considered high risk for early relapse (NCT04555811). Up to three dose levels of FT596, beginning at 90 million cells per dose, in combination with rituximab will be evaluated.
FT516 (hnCD16) NK Cell Product Candidate

First Patient Treated with FT516 in Combination with Avelumab for Advanced Solid Tumors. FT516 is the Company’s universal, off-the-shelf NK cell product candidate derived from a clonal master iPSC line engineered to express its novel hnCD16 Fc receptor. The Company has treated the first patient in a multi-center Phase 1 clinical trial of FT516 in combination with avelumab, an FDA-approved monoclonal antibody targeting PD-L1 (NCT04551885). Each patient is to receive three once-weekly doses of FT516, beginning at 90 million cells per dose, for up to two 30-day cycles in combination with avelumab. The Company is also continuing to enroll its multi-center Phase 1 clinical trial of FT516 as a monotherapy for the treatment of acute myeloid leukemia (AML) and in combination with CD20-targeted monoclonal antibody therapy for the treatment of relapsed / refractory B-cell lymphoma (NCT04023071).
First Patients Treated with FT516 for COVID-19. Investigators from the Division of Infectious Diseases and International Medicine, University of Minnesota have treated the first patients with FT516 for Coronavirus Disease 2019 (COVID-19). The investigator-initiated Phase 1 clinical trial is evaluating up to three escalating doses of FT516 administered over one week for patients with COVID-19 at high risk of developing critical life-threatening illness (NCT04363346).
FT538 (hnCD16 + IL-15RF + CD38KO) NK Cell Product Candidate

Enrollment Initiated with FT538 in Phase 1 Clinical Trial. The multi-center Phase 1 study of FT538, the first-ever CRISPR-edited, iPSC-derived cell therapy, is designed to assess the safety and efficacy of three once-weekly doses of FT538 as a monotherapy for patients with relapsed / refractory AML and in combination with the CD38-targeted monoclonal antibody daratumumab for patients with relapsed / refractory multiple myeloma. Up to four dose levels of FT538, beginning at 100 million cells per dose, will be evaluated. FT538 is derived from a clonal master iPSC line engineered with three functional components to enhance innate immunity: a novel hnCD16 Fc receptor that enhances ADCC; an IL-15RF that augments NK cell activity; and the deletion of the CD38 gene (CD38KO), which promotes persistence under oxidative stress and prevents NK cell fratricide in combination with CD38-targeted monoclonal antibody therapy.
FT500 NK Cell Product Candidate

FT500 Dose Expansion Ongoing in Solid Tumors Resistant to Checkpoint Inhibitor Therapy. At the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) annual meeting being held virtually from November 9-14, 2020, the Company plans to present previously disclosed clinical data from the dose-escalation stage of the Company’s Phase 1 clinical trial of FT500 (NCT03841110). Fifteen heavily pre-treated patients, ten of whom were refractory to their last prior therapy, were administered up to six doses of FT500 as a salvage treatment for patients with advanced solid tumors. No dose-limiting toxicities, and no FT500-related severe adverse events (AEs) or Grade ≥ 3 AEs, were observed. In addition, there were no reported cases of cytokine release syndrome, immune effector cell-associated neurotoxicity syndrome, or graft-versus-host disease. Eleven patients had a best overall response of stable disease. The Company is currently enrolling the dose-expansion stage of the FT500 Phase 1 clinical trial for patients with non-small cell lung cancer or classical Hodgkin lymphoma who are refractory to, or have relapsed on, checkpoint inhibitor therapy.
FT819 (TRAC-integrated 1XX-CAR19) T-Cell Product Candidate

FT819 GMP Manufacturing Campaign Completed. In the fourth quarter of 2020, the Company plans to initiate a multi-center Phase 1 clinical trial of FT819, the first-ever off-the-shelf, allogeneic CAR T-cell therapy derived from a clonal master iPSC line, for patients with B-cell lymphoma, chronic lymphocytic leukemia, or acute lymphoblastic leukemia. The Company has now completed its first GMP manufacturing campaign for FT819 and is conducting final release testing to enable clinical disposition and off-the-shelf availability. FT819 is engineered with several first-of-kind features designed to improve the safety and efficacy of CAR T-cell therapy including a novel 1XX CAR signaling domain targeting CD19+ malignancies (1XX-CAR19) that extends T-cell effector function without eliciting exhaustion; integration of the CAR transgene directly into the T-cell receptor alpha constant (TRAC) locus, which promotes uniform CAR expression and enhances T-cell potency; and complete bi-allelic disruption of T-cell receptor expression to prevent graft-versus-host disease, a potentially life-threatening complication associated with allogeneic T-cell therapy.
Corporate Highlights

Twelve Abstracts Accepted for Presentation at ASH (Free ASH Whitepaper). At the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition being held virtually from December 5-8, 2020, the Company plans to present 12 abstracts, including four oral presentations, for the Company’s iPSC product platform. In addition, the Company plans to host a virtual investor event entitled "The Power of hnCD16" to highlight the unique features and functionality of its novel hnCD16 Fc receptor, which is incorporated into the Company’s FT516, FT596, FT538 and FT576 product candidates.
Five Abstracts Accepted for Presentation at SITC (Free SITC Whitepaper). At SITC (Free SITC Whitepaper), the Company plans to present five abstracts including an oral presentation highlighting a new iPSC-derived CAR immune cell program targeting the pan-tumor associated antigen B7-H3, which is commonly expressed on hematological and solid tumors and is associated with metastasis and poor patient prognosis.
Preclinical Data Published in Science Translational Medicine Demonstrate iPSC-derived NK Cells Augment Checkpoint Inhibitor Therapy. Under a research collaboration between the University of Minnesota and the Company, scientists demonstrated that iPSC-derived NK (iNK) cells have the potential to overcome mechanisms of resistance to checkpoint inhibitor therapy. In preclinical studies, iNK cells were shown to rapidly infiltrate and kill solid tumors including those having alterations in antigen presentation or HLA downregulation, which are primary mechanisms of resistance to checkpoint inhibitor therapy. In addition, iNK cells in concert with T cells and anti-PD-1 antibody were shown to significantly improve anti-tumor activity in vivo compared to T cells and anti-PD-1 antibody either alone or in combination. The peer-reviewed findings were published online in Science Translational Medicine on November 4 (Cichocki et al).
Appointed Edward Dulac as Chief Financial Officer. In August, Mr. Dulac joined the Company from Celgene Corporation, where he most recently served as Vice President, Business Development & Strategy and was responsible for business development opportunities in the therapeutic areas of hematology and oncology, inflammation and immunology, and neuroscience. Mr. Dulac has extensive biopharmaceutical experience, having served for over 20 years in positions in finance, business development, and product portfolio strategy.
Third Quarter 2020 Financial Results

Cash & Investment Position: Cash, cash equivalents and investments as of September 30, 2020 were $502.0 million.
Total Revenue: Revenue was $7.6 million for the third quarter of 2020, which was derived from the Company’s collaborations with Janssen and Ono Pharmaceutical.
R&D Expenses: Research and development expenses were $30.7 million for the third quarter of 2020, which includes $4.7 million of non-cash stock-based compensation expense.
G&A Expenses: General and administrative expenses were $8.4 million for the third quarter of 2020, which includes $3.1 million of non-cash stock-based compensation expense.
Other Expenses: Other expenses, net were $27.2M, which includes a $27.6M non-cash charge equal to the fair value of certain contingent milestone payments that will be owed to Memorial Sloan Kettering Cancer Center upon the Company’s achievement of a specified clinical milestone with an iPSC-derived CAR T-cell product candidate and the subsequent appreciation of the Company’s common stock price per share.
Shares Outstanding: Common shares outstanding were 87.0 million, and preferred shares outstanding were 2.8 million, as of September 30, 2020. Each preferred share is convertible into five common shares.
Today’s Conference Call and Webcast
The Company will conduct a conference call today, Thursday, November 5, 2020 at 5:00 p.m. ET to review financial and operating results for the quarter ended September 30, 2020. In order to participate in the conference call, please dial 877-303-6235 (domestic) or 631-291-4837 (international) and refer to conference ID 1060606. The live webcast can be accessed under "Events & Presentations" in the Investors & Media section of the Company’s website at www.fatetherapeutics.com. The archived webcast will be available on the Company’s website beginning approximately two hours after the event.

About Fate Therapeutics’ iPSC Product Platform
The Company’s proprietary induced pluripotent stem cell (iPSC) product platform enables mass production of off-the-shelf, engineered, homogeneous cell products that can be administered with multiple doses to deliver more effective pharmacologic activity, including in combination with other cancer treatments. Human iPSCs possess the unique dual properties of unlimited self-renewal and differentiation potential into all cell types of the body. The Company’s first-of-kind approach involves engineering human iPSCs in a one-time genetic modification event and selecting a single engineered iPSC for maintenance as a clonal master iPSC line. Analogous to master cell lines used to manufacture biopharmaceutical drug products such as monoclonal antibodies, clonal master iPSC lines are a renewable source for manufacturing cell therapy products which are well-defined and uniform in composition, can be mass produced at significant scale in a cost-effective manner, and can be delivered off-the-shelf for patient treatment. As a result, the Company’s platform is uniquely capable of overcoming numerous limitations associated with the production of cell therapies using patient- or donor-sourced cells, which is logistically complex and expensive and is subject to batch-to-batch and cell-to-cell variability that can affect clinical safety and efficacy. Fate Therapeutics’ iPSC product platform is supported by an intellectual property portfolio of over 300 issued patents and 150 pending patent applications.

About FT500

FT500 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line. The product candidate is being investigated in an open-label, multi-dose Phase 1 clinical trial for the treatment of advanced solid tumors (NCT03841110). The study is designed to assess the safety and tolerability of FT500 as a monotherapy and in combination with one of three FDA-approved immune checkpoint inhibitor (ICI) therapies – nivolumab, pembrolizumab or atezolizumab – in patients that have failed prior ICI therapy. Despite the clinical benefit conferred by approved ICI therapy against a variety of tumor types, these therapies are not curative and, in most cases, patients either fail to respond or their disease progresses on these agents. One common mechanism of resistance to ICI therapy is associated with mutations in genes that disrupt antigen presentation and/or down-regulate HLA Class I proteins on cancer cells, which enables T-cell evasion. A potential strategy to overcome resistance is through the administration of allogeneic NK cells, which have the inherent capability to recognize and directly kill cancer cells with these mutations.

About FT516
FT516 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered to express a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies. CD16 mediates antibody-dependent cellular cytotoxicity (ADCC), a potent anti-tumor mechanism by which NK cells recognize, bind and kill antibody-coated cancer cells. ADCC is dependent on NK cells maintaining stable and effective expression of CD16, which has been shown to undergo considerable down-regulation in cancer patients. In addition, CD16 occurs in two variants, 158V or 158F, that elicit high or low binding affinity, respectively, to the Fc domain of IgG1 antibodies. Numerous clinical studies with FDA-approved tumor-targeting antibodies, including rituximab, trastuzumab and cetuximab, have demonstrated that patients homozygous for the 158V variant, which is present in only about 15% of patients, have improved clinical outcomes. FT516 is being investigated in an open-label, multi-dose Phase 1 clinical trial as a monotherapy for the treatment of acute myeloid leukemia and in combination with CD20-targeted monoclonal antibodies for the treatment of advanced B-cell lymphoma (NCT04023071). Additionally, FT516 is being investigated in an open-label, multi-dose Phase 1 clinical trial in combination with avelumab for the treatment of advanced solid tumor resistant to anti-PDL1 checkpoint inhibitor therapy (NCT04551885).

About FT596
FT596 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three anti-tumor functional modalities: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology that targets B-cell antigen CD19; a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; and an IL-15 receptor fusion (IL-15RF) that augments NK cell activity. In preclinical studies of FT596, the Company has demonstrated that dual activation of the CAR19 and hnCD16 targeting receptors enhances cytotoxic activity, indicating that multi-antigen engagement may elicit a deeper and more durable response. Additionally, in a humanized mouse model of lymphoma, FT596 in combination with the anti-CD20 monoclonal antibody rituximab showed enhanced killing of tumor cells in vivo as compared to rituximab alone. FT596 is being investigated in an open-label, multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell lymphoma as a monotherapy and in combination with rituximab and for the treatment of relapsed / refractory chronic lymphocytic leukemia (CLL) as a monotherapy and in combination with obinutuzumab (NCT04245722).

About FT538
FT538 is an investigational, universal, off-the-shelf natural killer (NK) cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line engineered with three functional components: a novel high-affinity 158V, non-cleavable CD16 (hnCD16) Fc receptor, which has been modified to prevent its down-regulation and to enhance its binding to tumor-targeting antibodies; an IL-15 receptor fusion (IL-15RF) that augments NK cell activity; and the deletion of the CD38 gene, which promotes persistence and function in high oxidative stress environments. FT538 is designed to enhance innate immunity in cancer patients, where endogenous NK cells are typically diminished in both number and function due to prior treatment regimens and tumor suppressive mechanisms. In preclinical studies, FT538 has shown superior NK cell effector function, as compared to peripheral blood NK cells, with the potential to confer significant anti-tumor activity to patients through multiple mechanisms of action. FT538 is being investigated in an open-label, multi-dose Phase 1 clinical trial for the treatment of acute myeloid leukemia (AML) and in combination with daratumumab, a CD38-targeted monoclonal antibody therapy, for the treatment of multiple myeloma (NCT04614636).

Deciphera Pharmaceuticals, Inc. Announces Third Quarter 2020 Financial Results

On November 5, 2020 Deciphera Pharmaceuticals, Inc. (NASDAQ:DCPH) reported financial results and provided a business update for the third quarter ended September 30, 2020 (Press release, Deciphera Pharmaceuticals, NOV 5, 2020, View Source [SID1234570042]).

"The strong U.S. commercial launch of QINLOCK, which is reflected in our first full quarter of results since the approval in May, is a testament to the potential for this new medicine to be a best-in-class treatment for people with GIST," said Steve Hoerter, President and Chief Executive Officer of Deciphera Pharmaceuticals. "During the third quarter, we also made substantial progress in preparing to bring QINLOCK to eligible patients around the world, including the submission and validation of the MAA by the EMA and the establishment of distribution agreements in Canada and Australia."

Mr. Hoerter continued, "In addition to executing on the successful launch of QINLOCK, we continue to advance our pipeline of promising product candidates. Notably, we look forward to presenting new data from our Phase 1/2 study of DCC-3014 in TGCT patients at the CTOS 2020 Virtual Meeting later this month."

Third Quarter 2020 Highlights and Recent Business Updates

QINLOCK (ripretinib) Commercialization
Recorded $15.2 million in net product revenue in the third quarter of 2020, including $14.7 million in U.S. net product revenue in the first full quarter of commercial launch following FDA approval in May 2020.
Submitted and received validation of a Marketing Authorisation Application (MAA) for QINLOCK in fourth-line gastrointestinal stromal tumor (GIST) by the European Medicines Agency (EMA). Validation of the MAA confirms that the application is sufficiently complete for the EMA to begin its formal review process.
Announced plans to establish a targeted commercial infrastructure in key European markets to support the potential launch of QINLOCK, as well as to support additional future product launches.
Entered into exclusive distribution agreements with the following partners to distribute QINLOCK in other territories:
Medison to distribute QINLOCK in Canada and Israel. Health Canada approved QINLOCK for fourth-line GIST in June 2020 under the U.S. FDA’s Project Orbis, an initiative that enables concurrent review of oncology products by international regulatory agencies.
Specialised Therapeutics Asia (STA) to distribute QINLOCK in Australia, New Zealand, Singapore, Malaysia, and Brunei. The Australian Therapeutic Goods Administration (TGA) approved QINLOCK in July 2020 under the U.S. FDA’s Project Orbis.
Presented two mini oral presentations on QINLOCK at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Virtual Congress 2020 in September. The first mini oral presentation was on the nine-month follow-up data from the Phase 3 INVICTUS study in patients with fourth-line and fourth-line plus GIST. The second mini oral presentation was on the ongoing Phase 1 study of QINLOCK in patients with second-line through fourth-line plus GIST. The presentation highlighted that the patients receiving QINLOCK who, upon disease progression, dose escalated to QINLOCK 150 mg twice daily (BID) experienced additional, clinically meaningful, progression-free survival benefit across all lines of therapy.

Rebastinib
Presented results from Part 2 (Stage 1) of the platinum-resistant ovarian cancer cohort in the ongoing Phase 1b/2 study of rebastinib in combination with paclitaxel in an E-poster presentation at the ESMO (Free ESMO Whitepaper) Virtual Congress 2020. Data presented demonstrated encouraging efficacy with an objective response rate of 38%, confirmed and unconfirmed, and a clinical benefit rate of 88% at eight weeks. Treatment with rebastinib 50 mg BID in combination with paclitaxel was generally well-tolerated. Enrollment in Stage 2 of the platinum-resistant ovarian cancer cohort at the rebastinib 50 mg BID dose is completed and further efficacy and safety evaluation is ongoing.
Presented results from Part 1 of the Phase 1b/2 study of rebastinib in combination with carboplatin in an E-poster presentation at the ESMO (Free ESMO Whitepaper) Virtual Congress 2020. The clinical benefit rate was 50% at six weeks and 36% at twelve weeks, and the median duration of treatment was 7.8 weeks. Rebastinib in combination with carboplatin was generally well-tolerated. The Part 2 portion of the ongoing Phase 1/2 study is currently enrolling patients and will evaluate the safety and efficacy of rebastinib at the recommended Phase 2 dose of 50 mg BID in combination with carboplatin.
Upcoming Scientific Congress Presentations

Connective Tissue Oncology Society (CTOS) 2020 Virtual Annual Meeting, November 18-21
DCC-3014
Oral Presentation: "Phase 1 dose-escalation study of the safety, tolerability, pharmacokinetics, and pharmacodynamics of DCC-3014 in advanced solid tumors and tenosynovial giant cell tumor"
QINLOCK (ripretinib)
Oral Presentation: "Characterization of the extensive heterogeneity of KIT/PDGFRA mutations in patients with fourth-line advanced gastrointestinal stromal tumor: genomic analysis of the phase 3 INVICTUS study"
Poster Presentation: "Ripretinib demonstrated activity across all KIT/PDGFRA mutations in patients with fourth-line advanced gastrointestinal stromal tumor: analysis from the phase 3 INVICTUS study"
Oral Presentation: "Ripretinib intra-patient dose escalation following disease progression provides clinically meaningful progression-free survival in gastrointestinal stromal tumor in phase 1 study"
Poster Presentation: "Clinical benefit with ripretinib as ≥4th line treatment in patients with advanced gastrointestinal stromal tumor: update from the phase 3 INVICTUS study"
Third Quarter 2020 Financial Results

Revenue: Total revenue for the third quarter of 2020 was $15.5 million, which includes $15.2 million of net product revenue from sales of QINLOCK and $0.3 million of collaboration revenue. Net product revenues for the third quarter of 2020 includes U.S. sales of QINLOCK of $14.7 million and ex-U.S. sales of QINLOCK of $0.5 million. In the third quarter of 2019, the Company did not generate revenue.
Cost of Sales: Cost of sales for the third quarter of 2020 was $0.1 million as the majority of the manufacturing costs related to third quarter QINLOCK sales were incurred prior to FDA approval, and thus, were recorded as R&D expense. Cost of sales will not be significant until the initial pre-launch inventory is depleted, and additional inventory is manufactured and sold. In the third quarter of 2019, there were no cost of sales as no product sales were generated during that period.
R&D Expenses: Research and development expenses for the third quarter of 2020 were $49.2 million, compared to $40.4 million for the same period in 2019. The increase was primarily due to personnel costs, preclinical costs, and clinical trial costs related to DCC-3014, rebastinib, and the Phase 3 INTRIGUE trial in second-line GIST. The increase was partially offset by a decrease in clinical trial expenses related to the Phase 3 INVICTUS trial in fourth-line and fourth-line plus GIST. Non-cash, stock-based compensation was $4.5 million and $2.0 million for the third quarters of 2020 and 2019, respectively.
SG&A Expenses: Selling, general and administrative expenses for the third quarter of 2020 were $30.1 million, compared to $18.0 million for the same period in 2019. The increase was primarily a result of personnel costs as well as external spend associated with commercial preparedness and launch of QINLOCK, increased expenses incurred in connection with Deciphera’s new headquarters that commenced in October 2019, and technology-related costs to support the growth of the business. Non-cash, stock-based compensation was $5.3 million and $2.7 million for the third quarters of 2020 and 2019, respectively.
Net Loss: For the third quarter of 2020, Deciphera reported a net loss of $63.7 million, or $1.13 per share, compared with a net loss of $56.2 million, or $1.28 per share, for the same period in 2019. The increase in net loss was primarily related to increases in R&D and SG&A expenses, partially offset by the recognition of revenues in the third quarter of 2020, as discussed above.
Cash Position: As of September 30, 2020, cash, cash equivalents and marketable securities were $584.3 million, compared to $579.6 million as of December 31, 2019. The increase was primarily due to the Company’s follow-on public offering in February 2020 that provided net proceeds of $188.4 million, partially offset by cash used in operations. Based on its current operating plans, Deciphera expects its current cash, cash equivalents, and marketable securities together with anticipated product revenues, but excluding any potential future milestone payments or other payments under its collaboration or license agreements, will enable the Company to fund its operating and capital expenditures into the second half of 2022.
Conference Call and Webcast

Deciphera will host a conference call and webcast to discuss this announcement today, November 5, 2020 at 4:30 PM ET. To access the live call by phone please dial (866) 930-5479 (domestic) or (409) 216-0603 (international); the conference ID is 6048987. A live audio webcast of the event may also be accessed through the "Investors" section of Deciphera’s website at www.deciphera.com. A replay of the webcast will be available for 30 days following the event.

DCprime to Present Interim Clinical Data of ADVANCE II Trial in Oral Presentation at ASH 2020 Meeting

On November 5, 2020 DCprime, the front-runner in the field of relapse vaccines, reported the upcoming oral presentation of interim results from its ongoing Phase II clinical trial (ADVANCE II, Clintrials.gov: NCT03697707) at the virtual 62nd ASH (Free ASH Whitepaper) Annual Meeting and Exposition on December 5, 2020 (Press release, DCPrime, NOV 5, 2020, View Source [SID1234570041]). The Interim data on both primary and secondary endpoints of the trial highlight the potential of the company’s lead vaccine candidate, DCP-001, to improve the treatment options for patients with Acute Myeloid Leukemia (AML) in the post-remission setting. The study continues to enroll patients at the higher of two vaccine doses tested and updated data will be shown at ASH (Free ASH Whitepaper).

The oral presentation entitled "Conversion from MRD positive to negative status in AML patients in CR1 after treatment with an Allogeneic Leukemia-derived Dendritic Cell Vaccine" will be presented by Prof. Dr. Arjan van de Loosdrecht from the Department of Hematology at Amsterdam UMC, Amsterdam, The Netherlands, and Principal Investigator for the study.

The accepted abstract is listed below and is now available online on the ASH (Free ASH Whitepaper) website: View Source

ORAL PRESENTATION DETAILS:
Presentation Title: #168: Conversion from MRD positive to negative status in AML patients in CR1 after treatment with an Allogeneic Leukemia-derived Dendritic Cell Vaccine

Session Title: Acute Myeloid Leukemia: Novel therapy, excluding transplantation: Advances in immunotherapeutics for management of AML

Session Date: Saturday, December 5, 2020

Presentation Time: 12:45 PM EST

Presenter: Prof. Dr. Arjan van de Loosdrecht – Department of Hematology, VUmc