On November 5, 2020 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies for the treatment of cancer and autoimmune diseases, reported financial results for the third quarter ended September 30, 2020 and provided a review of recent business and clinical highlights (Press release, Xencor, NOV 5, 2020, View Source [SID1234570048]).

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"In 2020, we have reported advances for multiple programs in our clinical pipeline. Monjuvi became the second drug with XmAb Fc technology to receive marketing approval in the United States, and we reported initial clinical results from multiple programs across our portfolio of XmAb bispecific antibodies in oncology. In the coming weeks, we will present additional clinical data from some of these programs, including updated results from the Phase 1 studies of XmAb20717 at SITC (Free SITC Whitepaper), and vibecotamab at ASH (Free ASH Whitepaper)," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "We also continue to leverage our protein engineering expertise to rapidly generate drug candidates with our XmAb bispecific Fc domains, in order to advance a range of innovative technologies and molecules, and at SITC (Free SITC Whitepaper) next week, we will be presenting new preclinical data from our B7-H3 x CD28 and PD-1 x TGFβR2 bispecific antibody programs, as well as our IL-12-Fc program."

Dr. Dahiyat continued, "Looking ahead to next year, we are on track to initiate a Phase 1 study of XmAb27564, our IL-2 cytokine for autoimmune disease, in healthy volunteers in early 2021. Subject to potential COVID-19 impacts, we also plan to advance clinical studies across all our CD3 programs including vibecotamab, plamotamab, tidutamab and XmAb30819, which is our first XmAb 2+1 bispecific antibody and targets the underexplored tumor target ENPP3."

COVID-19 Business Update

Clinical Studies: The pandemic did not significantly disrupt patient enrollment to Xencor’s six ongoing clinical studies during the third quarter of 2020. Manufacturers that provide the Company’s drug supply are currently experiencing critical shortages of material used in their manufacturing processes. Xencor has sufficient supplies of drug material to continue conducting ongoing studies without interruption; however, delays are expected in the development timelines for the preclinical XmAb30819 program. Timelines for additional early-stage programs and ongoing clinical programs could be affected if the supply interruption extends longer than current estimates.

Workforce and Research Operations: During the third quarter, Xencor continued to require non-laboratory employees to work remotely.

Licensing and Partnerships: Xencor is monitoring potential impacts to partnership revenues, which are primarily milestone payments and royalties. There was no impact during the third quarter as the Company earned revenue from its partners and collaborators including Alexion, MorphoSys and Omeros. If the pandemic affects the sales or clinical and regulatory progress of partnered programs, Xencor’s revenue could be adversely affected in the future.

Recent Business and Clinical Highlights

Tidutamab (SSTR2 x CD3): In October, the Company presented initial dose-escalation data from the ongoing Phase 1 study in patients with neuroendocrine tumors (NET). Tidutamab was generally well tolerated at the recommended dose identified for the expansion portion of the study, a 0.3 mcg/kg priming dose and subsequent 1.0 mcg/kg repeated doses. Peripheral blood biomarkers indicated tidutamab induced acute and sustained T-cell activation at this dose, and a dose-dependent increase in proliferation and activation markers of CD8+ T cells was observed, which is consistent with tidutamab’s mechanism of action. The best overall response was stable disease in the analysis to describe clinical activity (n=14), and the median duration of treatment was approximately seven months. Completion of enrollment and longer follow-up are required to evaluate progression-free survival and the clinical utility of tidutamab for patients with NET. Xencor plans to initiate an additional clinical study in patients with Merkel cell carcinoma and small cell lung cancer, SSTR2-expressing tumor types known to be responsive to immunotherapy, in early 2021.

New Clinical Collaboration: In September, Xencor and MD Anderson entered a strategic collaboration to design and execute new investigator-sponsored clinical studies with Xencor’s portfolio of XmAb drug candidates, including novel bispecific antibodies and engineered cytokines. Xencor is committing $10 million in funding and supporting these studies over an initial five-year term.

Select Internal Programs: Xencor will present updated data from the vibecotamab and XmAb20717 programs, as well as data from several preclinical-stage programs, at upcoming scientific and medical meetings.

● Vibecotamab (CD123 x CD3): Updated results from the ongoing Phase 1 study in patients with acute myeloid leukemia will be presented at the 62nd American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting in December 2020. Patient enrollment continues in this study, and Xencor plans to initiate additional clinical studies evaluating vibecotamab in 2021.

● Plamotamab (CD20 x CD3): Patient enrollment continues in the Phase 1 study in non-Hodgkin lymphoma and chronic lymphocytic leukemia, with planned expansion cohorts expected to open in 2021. In addition, operational preparation for a Phase 2 monotherapy trial in diffuse large B-cell lymphoma (DLBCL) is underway, as well as for a Phase 2 combination therapy study.

● XmAb20717 (PD-1 x CTLA-4): Updated results from the ongoing Phase 1 study in patients with advanced solid tumors will be presented at the 35th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in November 2020. The study is currently enrolling patients with renal cell carcinoma to an expansion cohort and continues to enroll patients in additional dose-escalation cohorts. Expansion cohorts for patients with melanoma, advanced non-small cell lung cancer, prostate cancer, and other cancers without approved checkpoint therapies are fully enrolled.

● New data from three preclinical-stage programs, including the IL-12-Fc cytokine program, the CD28 bispecific antibody platform, and the PD-1 x TGFβR2 bispecific antibody program, will also be presented at the SITC (Free SITC Whitepaper) Annual Meeting in November 2020.

Select Partnered Programs: Xencor’s partners expand the use of XmAb technology by providing late-stage development capabilities, successful track records of developing or commercializing programs or have programs for potential combination with Xencor’s bispecific antibody or cytokine drug candidates. Additionally, the plug-and-play nature of XmAb technologies enables selective access for licensees with limited effort or resources by Xencor.

● Monjuvi (MorphoSys): Monjuvi is a CD19-directed cytolytic antibody indicated in combination with lenalidomide as a second-line treatment option for the treatment of adult patients with relapsed or refractory diffuse large B-cell lymphoma (DLBCL). Tafasitamab, which was engineered with an XmAb Cytotoxic Fc Domain, was created at Xencor and is the second product with Xencor’s XmAb technology to be approved by the FDA. Upon Monjuvi’s approval in July, Xencor earned a $25 million milestone payment from MorphoSys under the license agreement between the companies and is eligible to receive royalties on worldwide net sales in the high-single to low-double digit percent range, as well as additional development, regulatory and sales milestone payments. The European Marketing Authorization Application for tafasitamab is currently under review, and MorphoSys expects a decision in the second half of 2021.

● Ultomiris (Alexion): Alexion’s Ultomiris uses Xtend technology for longer half-life. In September, Japan’s Ministry of Health, Labour and Welfare approved Ultomiris for adults and children with atypical hemolytic uremic syndrome (aHUS). Ultomiris previously has received marketing authorizations from regulatory agencies in the U.S., Europe and Japan for the treatment of adult patients with paroxysmal nocturnal hemoglobinuria (PNH) and in the U.S. and Europe for aHUS. In addition to evaluating Ultomiris in a broad late-stage development program, Alexion is conducting a randomized, controlled Phase 3 study in adults with COVID-19 who are hospitalized with severe pneumonia or acute respiratory distress syndrome. Xencor is eligible to receive additional sales-based milestone payments and a low single-digit royalty on net sales of Ultomiris.

● VIR-7831 and VIR-7832 (Vir Biotechnology): Vir has non-exclusive access to Xencor’s Xtend Fc technology to extend the half-life of VIR-7831 and VIR-7832, novel antibodies that Vir is investigating as potential treatments for patients with COVID-19, as well as prophylactic use against infection from the virus. Vir has commenced a Phase 3 clinical study of VIR-7831 for the early treatment of COVID-19 patients who are at high risk of hospitalization; Vir plans to initiate a clinical study of VIR-7832 in the near future. Xencor is eligible to receive royalties on the net sales of approved products in the mid-single digit percent range.

● Omeros Corporation: In August, Xencor entered into a technology license agreement providing Omeros a non-exclusive license to its Xtend Fc technology, an exclusive license to apply Xtend technology to an identified antibody and options to apply Xtend technology to three additional antibodies. Omeros is responsible for all development and commercialization activities for all target candidates. Pursuant to these licenses, the Company received an upfront payment of $5.0 million and is eligible to receive development, regulatory and sales milestone payments for each product incorporating the selected antibodies. In addition, the Company is eligible to receive a royalty in the mid-single digit percent range on net sales of commercialized products.

Monjuvi is a registered trademark of MorphoSys AG. Ultomiris is a registered trademark of Alexion Pharmaceuticals, Inc.

Third Quarter Ended September 30, 2020 Financial Results

Cash, cash equivalents and marketable and equity securities totaled $582.9 million at September 30, 2020, compared to $601.3 million at December 31, 2019. The decrease reflects cash used to fund operating activities in the first nine months of 2020, offset by total proceeds of $89.1 million received in upfront payments, milestone payments and royalties from licensing agreements.

Total revenue for the third quarter ended September 30, 2020 was $35.4 million, compared to $21.8 million for the same period in 2019. Revenues in the third quarter included milestone revenue from MorphoSys, licensing revenue from Omeros and royalty revenue from Alexion, compared to revenues from the same period in 2019, which primarily reflects milestone revenue from the Alexion, Amgen and Novartis collaborations. Total revenue for the nine months ended September 30, 2020 was $80.8 million, compared to $153.2 million for the same period in 2019. Revenues for the nine-month period in 2020 include royalty revenue from Alexion, milestone revenue from MorphoSys, and licensing revenue from Gilead, Aimmune and Omeros, compared to licensing and collaboration revenue from Genentech and Astellas and milestone revenue from the Alexion, Amgen and Novartis collaborations in 2019.

Research and development expenditures for the third quarter ended September 30, 2020 were $44.5 million, compared to $29.8 million for the same period in 2019. Total research and development expenses for the nine months ended September 30, 2020 were $121.9 million, compared to $91.3 million for the same period in 2019. Additional spending on research and development expenses for the third quarter and first nine months of 2020 over amounts for the same periods in 2019 is primarily due to increased spending on clinical programs, including plamotamab and XmAb20717, and the IL-2-Fc cytokine development program, XmAb27564.

General and administrative expenses for the third quarter ended September 30, 2020 were $7.6 million, compared to $6.3 million in the same period in 2019. Total general and administrative expenses for the nine months ended September 30, 2020 were $22.1 million, compared to $17.5 million for the same period in 2019. Additional spending on general and administrative expenses for the third quarter and first nine months of 2020 over amounts for the same periods in 2019 is primarily due to increased compensation costs related to additional general and administrative staffing and spending on intellectual property, including patents and licensing costs.

Non-cash, stock-based compensation expense for the nine months ended September 30, 2020 was $23.1 million, compared to $ 24.7 million for same period in 2019.

Net loss for the third quarter ended September 30, 2020 was $12.6 million, or $(0.22) on a fully diluted per share basis, compared to net loss of $10.2 million, or $(0.18) on a fully diluted per share basis, for the same period in 2019. The higher net loss reported for third quarter of 2020 compared to the same period in 2019 is primarily due to increased research and development spending over increased revenue earned during the period. For the nine months ended September 30, 2020, net loss was $55.6 million, or $(0.97) on a fully diluted per share basis, compared to net income of $53.8 million, or $0.92 on a fully diluted per share basis, for the same period in 2019. The net loss reported for the nine months ended September 30, 2020 compared to net income reported for the same period in 2019 is primarily due to higher

collaboration and licensing revenue reported in 2019 compared to 2020 and increased spending on research and development programs in 2020 over 2019 amounts.

The total shares outstanding were 57,374,937 as of September 30, 2020, compared to 56,714,788 as of September 30, 2019.

Financial Guidance

Based on current operating plans, Xencor expects to have cash to fund research and development programs and operations into 2024. Xencor expects to end 2020 with between $525 million and $575 million in cash, cash equivalents and marketable and equity securities.

Conference Call and Webcast

Xencor will host a conference call today at 4:30 p.m. EST (1:30 p.m. PST) to discuss these third quarter 2020 financial results and provide a corporate update.

The live call may be accessed by dialing (877) 359-9508 for domestic callers or +1 (224) 357-2393 for international callers and referencing conference ID number 7307079. A live webcast of the conference call will be available online from the Investors section of Xencor’s website at www.xencor.com. The webcast will be archived on Xencor’s website for 30 days.

On November 5, 2020 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) today reported financial results for the third quarter ended September 30, 2020, including sales of TAVALISSE (fostamatinib disodium hexahydrate) tablets, for the treatment of adults with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment (Press release, Rigel, NOV 5, 2020, View Source [SID1234570047]).

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"Our team has done an excellent job advancing our key value drivers while adapting to the widespread changes in the current global environment," said Raul Rodriguez, Rigel’s president and CEO. "We have continued to grow our TAVALISSE franchise with third quarter sales increasing 39% year-over-year and our global Phase 3 clinical trial for warm AIHA having enrolled over 60% of our patient goal. Additionally, exploration of fostamatinib’s potential in COVID-19 is rapidly expanding with our Phase 3 clinical trial launching this quarter and enrollment ongoing in the Phase 2 trials sponsored by the NIH/NHLBI and Imperial College London."

Business Update

Rigel’s FORWARD study, a Phase 3 pivotal trial of TAVALISSE in warm autoimmune hemolytic anemia (AIHA), has enrolled 57 of the 90 patients targeted for enrollment. The trial currently has over 90 clinical trial sites established across 22 countries.

Rigel plans to launch a Phase 3 clinical trial to evaluate the safety and efficacy of fostamatinib in hospitalized COVID-19 patients without respiratory failure that have certain high-risk prognostic factors. This multi-center, double-blind, placebo-controlled, adaptive design study is expected to enroll over 300 evaluable patients that will be randomly assigned to either fostamatinib plus standard of care (SOC) or matched placebo plus SOC (1:1). Treatment will be administered orally twice daily for 14 days. There will be a follow-up period to day 60. The primary endpoint of this study is the proportion of subjects who progress to severe/critical disease within 29 days.

The Phase 2 clinical trial sponsored by the NIH/NHLBI, in collaboration with Inova Health System, to evaluate the safety of fostamatinib for the treatment of hospitalized COVID-19 patients has enrolled 9 patients. This multi-center, double-blind, placebo-controlled study will randomly assign fostamatinib plus SOC or matched placebo plus SOC (1:1) to approximately 60 evaluable patients. Treatment will be administered orally twice daily for 14 days. There will be a follow-up period to day 60. The primary endpoint of this study is cumulative incidence of serious adverse events (SAE) through day 29. The trial also includes multiple secondary endpoints designed to assess the early efficacy and clinically relevant endpoints of disease course.

The Imperial College London-sponsored Phase 2 clinical trial to evaluate the efficacy of fostamatinib for the treatment of COVID-19 pneumonia has begun enrolling patients. The study is a two-stage, open label, controlled clinical trial with patients randomized (1:1:1) to fostamatinib plus SOC, ruxolitinib plus SOC, or SOC. Treatment will be administered twice daily for 14 days and patients will receive a follow-up assessment at day 14 and day 28 after the first dose. The primary endpoint of this study is progression from mild to severe COVID-19 pneumonia within 14 days in hospitalized patients.

Rigel recently launched FORTE, an observational study to further evaluate TAVALISSE as a second-line treatment for adult chronic ITP. The study goal is to generate additional data on patient quality of life and financial expenditures relative to the healthcare of ITP patients. Along with the post-hoc data analysis of its Phase 3 clinical program, Rigel plans to use this study to further increase and enhance its database of TAVALISSE in early line treatment of adult chronic ITP patients.

Financial Update

For the third quarter of 2020, Rigel reported a net loss of $14.2 million, or $0.08 per share, compared to a net loss of $11.5 million, $0.07 per share, in the same period of 2019.

In the third quarter of 2020, total revenues were $18.4 million, consisting of $16.3 million in net product sales and $2.1 million in contract revenues from collaborations for the achievement of a milestone in accordance with the amended license and collaboration agreement with Daiichi-Sankyo. Net product sales increased by 39% from $11.7 million in the third quarter of 2019. The decrease in contract revenues from collaborations in the third quarter of 2020 from $9.1 million in the same period of 2019 was due to developmental and commercial milestones from our various collaborative partners in 2019, partially offset by the milestone in the third quarter of 2020 from Daiichi-Sankyo as noted above.

Rigel reported total costs and expenses of $32.2 million in the third quarter of 2020, compared to $32.9 million in the same period of 2019. The decrease in total costs and expenses was primarily due to decreases to the timing of certain commercial-related activities due to the COVID-19 pandemic, partially offset by the increases in personnel-related costs and increased use of consultants.

For the nine months ended September 30, 2020, Rigel reported a net loss of $10.5 million, or $0.06 per share, compared to a net loss of $49.7 million, or $0.30 per share, in the same period of 2019.

Rigel reported total revenues of $90.2 million for the nine months ended September 30, 2020, compared to $43.9 million in the same period of 2019. Total revenues for the nine months ended September 30, 2020 consisted of $43.9 million in net product sales and $46.2 million in contract revenues from collaborations. The increase in contract revenues from collaborations related to revenue from the upfront fee previously received in 2019, as well as the milestone payment received from Grifols in the first quarter of 2020 upon EC approval of the MAA for fostamatinib in Europe and the $2.1 million in contract revenues for achievement of a milestone in accordance with the amended license and collaboration agreement with Daiichi-Sankyo, partially offset by the developmental and commercial milestones from our various collaborative partners in 2019.

Total costs and expenses for the nine months ended September 30, 2020 were $100.3 million, compared to $95.6 million in the same period of 2019. The increase in total costs and expenses was primarily related to increases in research and development cost for the on-going Phase 3 trial in warm AIHA, Phase 1 trial in RIP 1 inhibitor program and Phase 1 trial in IRAK 1/4 inhibitor program, partially offset by decreases in stock-based compensation expense and various third-party costs.

As of September 30, 2020, Rigel had cash, cash equivalents and short-term investments of $72.8 million, compared to $98.1 million as of December 31, 2019.

Conference Call and Webcast with Slides Today at 4:30pm Eastern Time

Rigel will hold a live conference call and webcast today at 4:30pm Eastern Time (1:30pm Pacific Time).

Participants can access the live conference call by dialing 1-800-954-0603 (domestic) or 1-415-226-5355 (international). The conference call and accompanying slides will also be webcast live and can be accessed from the Investor Relations section of the company’s website at www.rigel.com. The webcast will be archived and available for replay after the call via the Rigel website.

About ITP

In patients with ITP (immune thrombocytopenia), the immune system attacks and destroys the body’s own blood platelets, which play an active role in blood clotting and healing. Common symptoms of ITP include fatigue, excessive bruising and bleeding. People suffering with chronic ITP may live with an increased risk of severe bleeding events that can result in serious medical complications or even death. In addition to fostamatinib, current therapies for ITP include steroids, blood platelet production boosters (TPO-RAs) and splenectomy. However, not all patients respond to existing therapies. As a result, there remains a significant medical need for additional treatment options for patients with ITP.

About AIHA

Autoimmune hemolytic anemia (AIHA) is a rare, serious blood disorder in which the immune system produces antibodies that result in the destruction of the body’s own red blood cells. AIHA affects approximately 45,000 adult patients in the U.S. and can be a severe, debilitating disease. Warm AIHA (wAIHA), the most common form of AIHA, is characterized by the presence of antibodies that react with the red blood cell surface at body temperature. To date, there are no disease-targeted therapies approved for AIHA, despite the unmet medical need that exists for these patients.

About Coronavirus Disease 2019 (COVID-19) & SYK-Signaling

COVID-19 is the infectious disease caused by Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2). SARS-CoV-2 primarily infects the upper and lower respiratory tract and can lead to acute respiratory distress syndrome (ARDS). Additionally, some patients develop other organ dysfunction including myocardial injury, acute kidney injury, shock resulting in endothelial dysfunction and subsequently micro and macrovascular thrombosis.1 Much of the underlying pathology of SARS-CoV-2 is thought to be secondary to a hyperinflammatory immune response associated with increased risk of thrombosis.2

Spleen tyrosine kinase (SYK) is involved in the intracellular signaling pathways of many different immune cells. Therefore, SYK inhibition may improve outcomes in patients with COVID-19 via inhibition of key Fc gamma receptor (FcγR) and c-type lectin receptor (CLR) mediated drivers of pathology, such as inflammatory cytokine release by monocytes and macrophages, production of neutrophil extracellular traps (NETs) by neutrophils, and platelet aggregation.3,4,5 Furthermore, SYK inhibition in neutrophils and platelets may lead to decreased thromboinflammation, alleviating organ dysfunction in critically ill patients with COVID-19.

About TAVALISSE

Indication

TAVALISSE (fostamatinib disodium hexahydrate) tablets is indicated for the treatment of thrombocytopenia in adult patients with chronic immune thrombocytopenia (ITP) who have had an insufficient response to a previous treatment.

Important Safety Information

Warnings and Precautions

·Hypertension can occur with TAVALISSE treatment. Patients with pre-existing hypertension may be more susceptible to the hypertensive effects. Monitor blood pressure every 2 weeks until stable, then monthly, and adjust or initiate antihypertensive therapy for blood pressure control maintenance during therapy. If increased blood pressure persists, TAVALISSE interruption, reduction, or discontinuation may be required.

·Elevated liver function tests (LFTs), mainly ALT and AST, can occur with TAVALISSE. Monitor LFTs monthly during treatment. If ALT or AST increase to >3 x upper limit of normal, manage hepatotoxicity using TAVALISSE interruption, reduction, or discontinuation.

·Diarrhea occurred in 31% of patients and severe diarrhea occurred in 1% of patients treated with TAVALISSE. Monitor patients for the development of diarrhea and manage using supportive care measures early after the onset of symptoms. If diarrhea becomes severe (≥Grade 3), interrupt, reduce dose or discontinue TAVALISSE.

·Neutropenia occurred in 6% of patients treated with TAVALISSE; febrile neutropenia occurred in 1% of patients. Monitor the ANC monthly and for infection during treatment. Manage toxicity with TAVALISSE interruption, reduction, or discontinuation.

·TAVALISSE can cause fetal harm when administered to pregnant women. Advise pregnant women the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment and for at least 1 month after the last dose. Verify pregnancy status prior to initiating TAVALISSE. It is unknown if TAVALISSE or its metabolite is present in human milk. Because of the potential for serious adverse reactions in a breastfed child, advise a lactating woman not to breastfeed during TAVALISSE treatment and for at least 1 month after the last dose.

Drug Interactions

·Concomitant use of TAVALISSE with strong CYP3A4 inhibitors increases exposure to the major active metabolite of TAVALISSE (R406), which may increase the risk of adverse reactions. Monitor for toxicities that may require a reduction in TAVALISSE dose.

·It is not recommended to use TAVALISSE with strong CYP3A4 inducers, as concomitant use reduces exposure to R406.

·Concomitant use of TAVALISSE may increase concentrations of some CYP3A4 substrate drugs and may require a dose reduction of the CYP3A4 substrate drug.

·Concomitant use of TAVALISSE may increase concentrations of BCRP substrate drugs (eg, rosuvastatin) and P-Glycoprotein (P-gp) substrate drugs (eg, digoxin), which may require a dose reduction of the BCRP and P-gp substrate drug.

Adverse Reactions

·Serious adverse drug reactions in the ITP double-blind studies were febrile neutropenia, diarrhea, pneumonia, and hypertensive crisis, which occurred in 1% of TAVALISSE patients. In addition, severe adverse reactions occurred including dyspnea and hypertension (both 2%), neutropenia, arthralgia, chest pain, diarrhea, dizziness, nephrolithiasis, pain in extremity, toothache, syncope, and hypoxia (all 1%).

·Common adverse reactions (≥5% and more common than placebo) from FIT-1 and FIT-2 included: diarrhea, hypertension, nausea, dizziness, ALT and AST increased, respiratory infection, rash, abdominal pain, fatigue, chest pain, and neutropenia.

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]).

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"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.

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]).

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!

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.

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]).

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!

"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).