On August 4, 2021 Xencor, Inc. (NASDAQ:XNCR), a clinical-stage biopharmaceutical company developing engineered monoclonal antibodies and cytokines for the treatment of cancer and autoimmune diseases, reported financial results for the second quarter ended June 30, 2021 and provided a review of recent business and portfolio highlights (Press release, Xencor, AUG 4, 2021, View Source [SID1234585711]).

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"Xencor is applying its leading protein engineering tools and XmAb technology to overcome historical challenges in creating therapeutic molecules from bispecific antibodies or cytokines. For our most advanced clinical programs, we recently initiated a Phase 2 clinical study for XmAb717, our PD-1 x CTLA-4 bispecific antibody, in metastatic prostate cancer, and we plan to initiate a Phase 2 study of plamotamab in lymphoma. Our cytokine portfolio is rapidly advancing with XmAb306, our long-acting IL-15 for oncology, and XmAb564, our IL-2 for autoimmune disease, both of which are in Phase 1 studies," said Bassil Dahiyat, Ph.D., president and chief executive officer at Xencor. "We are also at the forefront of efforts to engage CD28 to selectively activate T cells, and we plan to initiate clinical studies in 2022 for XmAb808, our B7-H3 x CD28 bispecific antibody, as well as our third clinical cytokine program, an IL-12-Fc candidate."

"Additionally, Vir Biotechnology and GSK’s sotrovimab was recently authorized for the treatment of mild-to-moderate COVID-19, becoming the third antibody incorporating XmAb technology to be made commercially available for patients. The licensing of our XmAb technologies expands their application to areas of medicine outside our internal focus and provides us with important sources of non-dilutive capital, which we use to advance and expand our broad internal portfolio of novel bispecific antibodies and cytokine drug candidates."

Recent Portfolio Highlights and Upcoming Data Presentations

XmAb717 (PD-1 x CTLA-4): A Phase 2 study was initiated for patients with metastatic castration-resistant prostate cancer. The study is evaluating XmAb717 as a monotherapy or in combination with other agents, depending on the tumor’s molecular subtype. Later this year, the Company anticipates initiating new studies of XmAb717 in additional tumor types and plans to announce additional data from the Phase 1 expansion cohorts for prostate cancer and renal cell carcinoma, as well as a cohort with multiple tumor types.
Plamotamab (CD20 x CD3): The Company plans to initiate a clinical study to investigate the chemotherapy-free triple combination of plamotamab, tafasitamab and lenalidomide in patients with relapsed or refractory diffuse large B cell lymphoma, an aggressive form of non-Hodgkin lymphoma, in late 2021 or early 2022. Plamotamab, which redirects T cells to tumors, and tafasitamab, a CD19-directed antibody, combine distinct immune pathways to generate a powerful anti-tumor effect and is a differentiated approach to treating patients with lymphomas. The Company plans to announce data from the ongoing Phase 1 study later this year.
Tidutamab (SSTR2 x CD3): A Phase 2 study was initiated for patients with Merkel cell carcinoma and small cell lung cancer, which are SSTR2-expressing tumor types known to be responsive to immunotherapy and are cancers with high unmet medical need. Later this year, the Company plans to announce updated data from the Phase 1 expansion cohort in patients with neuroendocrine tumor patients, including longer clinical follow-up and updated biomarker data.
XmAb564 (regulatory T cell selective IL-2-Fc): XmAb564 is a potency-reduced IL-2 cytokine engineered to selectively activate regulatory T cells for the treatment of autoimmune disease and is fused to an XmAb Fc domain for extended half-life. A Phase 1 single-ascending dose clinical trial was started in May to evaluate the safety, pharmacokinetics and biomarkers activity of a subcutaneous dose in healthy volunteers.
XmAb819 (ENPP3 x CD3): XmAb819 is engineered with reduced-potency CD3 binding as well as a multivalent 2+1 bispecific antibody format to enable greater tumor selectivity. XmAb819 is in development for patients with renal cell carcinoma, and the Company plans to submit an investigational new drug (IND) application in 2021 and initiate a Phase 1 study in early 2022.
Partnership Updates

Vir Biotechnology, Inc.: Sotrovimab (VIR-7831), an antibody that targets the SARS-CoV-2 virus, received emergency use authorization from the U.S. Food and Drug Administration for the treatment of mild-to-moderate COVID-19 in high-risk adults and pediatric patients, and is made available by Vir and its partner GlaxoSmithKline plc. Sotrovimab incorporates Xencor’s Xtend Fc technology for longer duration of action. VIR-7832, a second antibody licensed to Vir, which targets the SARS-CoV-2 virus in addition to incorporating Xtend technology and other XmAb Fc technologies, is currently enrolling patients to a Phase 1b/2a study.
Additional Partnering News: Xencor granted a license to Bristol Myers Squibb for its Xtend Fc technology to extend the half-life of a novel antibody combination therapy for SARS-CoV-2 infection, and the combination is currently in the NIH ACTIV-2 Phase 2/3 trial for infected patients. In addition, the Company received a development milestone from Novartis under the 2016 collaboration and license agreement related to IND-enabling activities for an undisclosed program using XmAb Fc technologies.
Second Quarter Ended June 30, 2021 Financial Results

Cash, cash equivalents and marketable investment securities totaled $603.7 million at June 30, 2021, compared to $604.0 million at December 31, 2020. Total proceeds from royalties, milestones, sale of an investment equity security, and a net increase in the value of marketable equity securities offset net spending of $90.5 million on operations for the first six months of 2021.

Total revenue for the second quarter ended June 30, 2021 was $67.4 million, compared to $13.1 million for the same period in 2020. Revenues in the second quarter were primarily related to revenue earned under the Company’s Janssen, Genentech and Novartis collaborations, and royalties from Alexion, Vir and MorphoSys, compared to revenues from the same period in 2020, which were primarily licensing revenue from Gilead and royalty revenue from Alexion. Total revenue for the six months ended June 30, 2021 was $101.4 million, compared to $45.5 million for the same period in 2020. Revenues for the six-month period in 2021 were primarily revenue earned from research collaborations with Janssen, Genentech and Novartis, milestone revenue from MorphoSys, and royalty revenue from Alexion, Vir and MorphoSys, compared to the same period in 2020, which were primarily licensing revenue from Gilead and Aimmune, milestone revenue from MorphoSys, and royalty revenue from Alexion.

Research and development (R&D) expenses for the second quarter ended June 30, 2021 were $49.5 million, compared to $43.5 million for the same period in 2020. Total R&D expenses for the six months ended June 30, 2021 were $90.9 million, compared to $77.4 million for the same period in 2020. Increased R&D expenses for the second quarter and first six months of 2021 over amounts for the same periods in 2020 were primarily due to additional spending on XmAb104 (PD-1 x ICOS) and XmAb819 development programs and other early-stage programs. Additional spending on XmAb306 also contributed to increased R&D expenses during the first six months of 2021.

General and administrative (G&A) expenses for the second quarter ended June 30, 2021 were $8.9 million, compared to $7.2 million for the same period in 2020. Total G&A expenses for the six months ended June 30, 2021 were $17.1 million, compared to $14.4 million for the same period in 2020. Increased G&A expenses for the second quarter and first six months of 2021 over amounts for the same periods in 2020 were primarily due to increased G&A staffing and spending on professional services.

Other income for the second quarter ended June 30, 2021 was $43.2 million, compared to $2.6 million in the same period in 2020. Other income for the six months ended June 30, 2021 was $56.3 million, compared to $3.3 million in the same period in 2020. Other income for the second quarter and first six months of 2021 includes realized gains on the sale of an investment equity security and an increase in unrealized gains on the Company’s marketable equity investments.

Non-cash, stock-based compensation expense for the six months ended June 30, 2021 was $17.6 million, compared to $14.7 million for same period in 2020.

Net income for the second quarter ended June 30, 2021 was $52.2 million, or $0.87 on a fully diluted per share basis, compared to net loss of $35.0 million, or $(0.61) on a fully diluted per share basis, for the same period in 2020. For the six months ended June 30, 2021, net income was $49.8 million, or $0.82 on a fully diluted per share basis, compared to net loss of $43.1 million, or $(0.76) on a fully diluted per share basis, for the same period in 2020. Net income reported for the second quarter ended June 30, 2021 and first six months of 2021, compared to the net loss reported for the same periods in 2020, were primarily due to higher collaboration, milestone and royalty revenues and other income in 2021 compared to 2020.

The total shares outstanding were 58,315,485 as of June 30, 2021, compared to 57,214,253 as of June 30, 2020.

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 2021 with between $475 million and $500 million in cash, cash equivalents and marketable securities.

Conference Call and Webcast

Xencor will host a conference call today at 4:30 p.m. ET (1:30 p.m. PT) to discuss these second quarter 2021 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 1389708. A live webcast of the conference call will be available online from the Investors section of Xencor’s website at View Source The webcast will be archived on Xencor’s website for 30 days.

On August 4, 2021 Horizon Therapeutics plc (Nasdaq: HZNP) reported record second-quarter 2021 financial results and increased both its full-year 2021 net sales and adjusted EBITDA guidance (Press release, Horizon Pharma, AUG 4, 2021, View Source [SID1234585727]).

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"Driving our record second-quarter performance was our highly successful TEPEZZA relaunch, which allowed Thyroid Eye Disease patients to rapidly access therapy and resulted in an increase in our full-year expectations," said Tim Walbert, chairman, president and chief executive officer, Horizon. "Our increased full-year net sales and adjusted EBITDA guidance represents strong double-digit year-over-year growth driven by TEPEZZA, KRYSTEXXA and our other rare disease medicines, where we are seeing continued strong underlying demand given the significant benefits our medicines provide to patients. We also initiated three clinical trials and acquired a biologics drug product manufacturing facility to support our strategy to maximize our key growth drivers, expand our pipeline and build a global presence. Horizon remains one of the fastest-growing biotechnology companies, underscoring our commitment to generate value for patients and our shareholders."

Second Quarter and Recent Company Highlights

Strong TEPEZZA Relaunch Exceeded Expectations: In April, the Company resumed supplying the market with TEPEZZA following a supply disruption that began in December 2020 due to U.S.-government-mandated COVID-19 vaccine orders. Second-quarter net sales of $453.3 million exceeded expectations, and today, the Company increased its TEPEZZA full-year 2021 net sales guidance to greater than $1.550 billion from greater than $1.275 billion on continued strong new patient demand. In May, the Company resumed its unbranded television campaign and launched its first branded TEPEZZA television campaign, which is expected to drive broader reach and awareness of Thyroid Eye Disease (TED) and TEPEZZA, motivating patients to seek treatment more quickly.

Entered into Agreement with Arrowhead to Develop Next-Generation Gout Medicine: In June, the Company entered into an agreement with Arrowhead Pharmaceuticals Inc., for a discovery-stage investigational RNA interference (RNAi) therapeutic targeting xanthine dehydrogenase (XDH) as a potential treatment for people with uncontrolled gout. Gout is a serious and painful form of arthritis that is caused by excess serum uric acid in the blood and XDH represents a clinically validated target that is the primary source of serum uric acid. There are more than nine million gout patients in the United States, and a meaningful portion of the patients treated do not respond sufficiently to conventional therapies.

Acquired Biologics Manufacturing Facility in Waterford, Ireland: In July, the Company completed the acquisition of a biologics drug product manufacturing facility from EirGen Pharma in Waterford, Ireland. The Company intends to use the manufacturing facility to support the growth of the Company’s on-market medicines, including TEPEZZA, KRYSTEXXA and UPLIZNA (inebilizumab-cdon), as well as development-stage biologics.

New Chronic TED Data Published: Data published from two recent independent physician case studies of 40 chronic TED patients who showed benefit after treatment with TEPEZZA were published in Eye, the official journal for the Royal College of Ophthalmologists, and Orbit, the International Journal on Orbital Disorders, Oculoplastic and Lacrimal Surgery. These case studies add to the growing body of evidence supporting the use of TEPEZZA in chronic TED patients.

Initiated Enrollment in Three Clinical Trials:
In May, the first patient was enrolled in an open-label trial to evaluate KRYSTEXXA plus methotrexate in patients who were not complete responders to treatment with KRYSTEXXA monotherapy. Patients who were not complete responders to KRYSTEXXA monotherapy have limited options available to address their uncontrolled gout, which is gout refractory to conventional therapies.

In June, the first patient was enrolled in a Phase 2 randomized, placebo-controlled trial to evaluate HZN-7734 in patients with moderate to severe active systemic lupus erythematosus (SLE), a disease in which the body’s immune system attacks its own tissues and organs.

In July, the first patient was enrolled in a Phase 1 trial to evaluate HZN-1116 in patients with autoimmune diseases.

Hosting Virtual R&D Day in September for Investors and Analysts: The Company will host a virtual R&D Day on Sept. 29, featuring presentations from the Company’s R&D leadership team and key opinion leaders with a focus on the Company’s expanded pipeline.

Presented New UPLIZNA Data at Medical Meetings: The Company participated in several key medical meetings in the quarter, highlighting new UPLIZNA data. In April, new end-of-study data from the open-label extension period of the pivotal Phase 3 trial in patients with neuromyelitis optica spectrum disorder (NMOSD) were presented at the American Academy of Neurology’s 73rd Annual Meeting. The data demonstrated that UPLIZNA was generally well-tolerated for at least four years, and that long-term UPLIZNA treatment provided a sustained reduction in NMOSD attack risk from baseline, regardless of the time of treatment initiation. The Company also presented three oral sessions on UPLIZNA at the 7th Congress of the European Academy of Neurology (EAN) in June. Additionally, a new analysis of the pivotal Phase 3 trial demonstrating that the medicine consistently reduced the risk of worsening disability in people living with NMOSD was published in the May issue of Neurology Neuroimmunology & Neuroinflammation.

Received Multiple Best Workplace Awards: During the second quarter, the Company received four workplace recognitions reflecting the high engagement of its employees. In April, the Company was named one of Fortune’s "100 Best Companies to Work For" in the United States for the first time and was placed on Crain’s Chicago Business’ 2021 "Best Places to Work in Chicago" list for the sixth consecutive year. In May, Great Place to Work named the Company to the "Best Workplaces in Chicago" list for the fifth consecutive year. In July, Fortune and Great Place to Work named the Company to the "Best Workplaces for Millennials" list for the second consecutive year and the Company was the highest ranked biotechnology company on the list.
Key Clinical Development Programs

TEPEZZA, an insulin-like growth factor type 1 receptor (IGF-1R) antagonist monoclonal antibody.
Chronic TED Trial: Phase 4 randomized, placebo-controlled trial to evaluate TEPEZZA in chronic TED expected to initiate in the coming weeks.

Subcutaneous (SC) Administration: Phase 1 pharmacokinetic trial underway to explore SC administration of TEPEZZA.

Diffuse Cutaneous Systemic Sclerosis Exploratory Trial: Phase 1 exploratory trial to evaluate TEPEZZA in dcSSc expected to initiate in the third quarter of 2021.

KRYSTEXXA, a recombinant uricase enzyme that converts urate into a water-soluble liquid, allantoin, that can be easily excreted from the body.

MIRROR Randomized Controlled Trial: Phase 4 randomized, placebo-controlled trial underway to evaluate KRYSTEXXA plus methotrexate to increase the complete response rate in patients with uncontrolled gout.

PROTECT Trial: Phase 4 open-label trial underway to evaluate KRYSTEXXA to improve management of uncontrolled gout in kidney transplant patients.

Shorter Infusion Duration Trial: Phase 4 open-label trial underway to evaluate the impact of administering KRYSTEXXA plus methotrexate over a shorter infusion duration in patients with uncontrolled gout.

Monthly Dosing Trial: Phase 4 open-label trial underway to evaluate monthly dosing of KRYSTEXXA plus methotrexate in patients with uncontrolled gout.

Retreatment Trial: Phase 4 open-label trial initiated in May 2021 to evaluate KRYSTEXXA plus methotrexate in patients who were not complete responders to KRYSTEXXA monotherapy.

UPLIZNA, an anti-CD19 humanized monoclonal antibody that depletes B cells, including the pathogenic cells that produce autoantibodies.

Myasthenia Gravis Trial: Phase 3 randomized, placebo-controlled trial underway to evaluate UPLIZNA in patients with myasthenia gravis, a chronic, rare, autoimmune neuromuscular disease that affects voluntary muscles, especially those that control the eyes, mouth, throat and limbs.

IgG4-Related Disease Trial: Phase 3 randomized, placebo-controlled trial underway to evaluate UPLIZNA in patients with IgG4-related disease, which is a group of disorders marked by tumor-like swelling and fibrosis of affected organs, such as the pancreas, salivary glands and kidneys.

Kidney Transplant Desensitization Trial: Phase 2 open-label trial underway to evaluate UPLIZNA, HZN-4920 or both in highly-sensitized patients waiting for a kidney transplant.

HZN-825, an oral lysophosphatidic acid receptor 1 (LPAR1) antagonist that prevents gene activation.

Diffuse Cutaneous Systemic Sclerosis Trial: Pivotal Phase 2b trial to evaluate HZN-825 in diffuse cutaneous systemic sclerosis expected to initiate in the third quarter of 2021.

Interstitial Lung Disease Trial: Pivotal Phase 2b trial to evaluate HZN-825 in idiopathic pulmonary fibrosis, the most common form of interstitial lung disease, expected to initiate in the third quarter of 2021.

HZN-4920, a CD40 ligand antagonist that blocks T cell interaction with the CD40-expressing B cells, disrupting the overactivation of the CD40 ligand co-stimulatory pathway. Several autoimmune diseases are associated with the overactivation of this pathway.

Sjögren’s Syndrome Trial: Phase 2b randomized, placebo-controlled trial underway to evaluate HZN-4920 in patients with Sjögren’s syndrome, a chronic, systemic autoimmune condition that impacts exocrine glands, including the salivary and tear glands.

Rheumatoid Arthritis Trial: Phase 2 randomized, placebo-controlled trial underway to evaluate HZN-4920 in patients with rheumatoid arthritis.

Kidney Transplant Rejection Trial: Phase 2 open-label trial underway to evaluate HZN-4920 in kidney transplant rejection patients.
HZN-7734, an anti-ILT7 human monoclonal antibody that depletes certain dendritic cells. Depleting these cells may interrupt the cycle of inflammation that causes tissue damage in diseases such as lupus, and a variety of other autoimmune conditions.

SLE Trial: Phase 2 randomized, placebo-controlled trial initiated in June 2021 to evaluate HZN-7734 in patients with SLE, a disease in which the body’s immune system attacks its own tissues and organs.

HZN-1116 Autoimmune Disease Trial: Phase 1 trial initiated in July 2021 to evaluate HZN-1116, a monoclonal antibody, in patients with autoimmune diseases.
Second-Quarter Financial Results

Note: For additional detail and reconciliation of non-GAAP financial measures to the most directly comparable GAAP financial measures, please refer to the tables at the end of this release.

Net Sales: Second-quarter 2021 net sales were $832.5 million, an increase of 80 percent compared to the second quarter of 2020.
Gross Profit: Under U.S. GAAP, the second-quarter 2021 gross profit ratio was 75.9 percent compared to 73.7 percent in the second quarter of 2020. The non-GAAP gross profit ratio in the second quarter of 2021 was 87.7 percent compared to 88.4 percent in the second quarter of 2020.
Operating Expenses: Research and development (R&D) expenses were 16.8 percent of net sales and selling, general and administrative (SG&A) expenses were 42.7 percent of net sales. Non-GAAP R&D expenses were 9.7 percent of net sales, and non-GAAP SG&A expenses were 33.8 percent of net sales.
Income Tax Benefit: In the second quarter of 2021, income tax benefit on a GAAP and non-GAAP basis was $42.5 million and $35.6 million, respectively.
Net Income: On a GAAP basis in the second-quarter of 2021, net income was $158.1 million. Second-quarter 2021 non-GAAP net income was $381.4 million.
Adjusted EBITDA: Second-quarter 2021 adjusted EBITDA was $366.9 million.
Earnings (Loss) per Share: On a GAAP basis, diluted earnings per share in the second quarter of 2021 was $0.67. GAAP loss per share in the second quarter of 2020 was $0.42. Non-GAAP diluted earnings per share in the second quarter of 2021 and 2020 were $1.62 and $0.40, respectively. Weighted average shares outstanding used for calculating GAAP and non-GAAP diluted earnings per share in the second quarter of 2021 were 235.2 million.
Second-Quarter Segment Results

Management uses net sales and segment operating income to evaluate the performance of the Company’s two segments, the orphan segment and the inflammation segment. While segment operating income contains certain adjustments to the directly comparable GAAP figures in the Company’s consolidated financial results, it is considered to be prepared in accordance with GAAP for purposes of presenting the Company’s segment operating results.

Second-quarter 2021 net sales of the orphan segment, the Company’s strategic growth segment, were $746.5 million, an increase of 97 percent over the prior year’s quarter, driven by the strong relaunch execution of TEPEZZA, as well as strong year-over-year growth of KRYSTEXXA, RAVICTI and PROCYSBI. The orphan segment represented 90 percent of total second-quarter net sales.
KRYSTEXXA second-quarter 2021 net sales increased 73 percent year-over-year driven by increased adoption of KRYSTEXXA plus immunomodulation, which now exceeds 40 percent. In addition, the Company continues to see strong uptake of KRYSTEXXA from both rheumatologists and nephrologists.
Second-quarter 2021 orphan segment operating income was $321.2 million, which includes additional investment associated with TEPEZZA, UPLIZNA and the Company’s pipeline programs.
Second-quarter 2021 net sales of the inflammation segment were $86.0 million, and segment operating income was $46.8 million.
Cash Flow Statement and Balance Sheet Highlights

On a GAAP basis, operating cash flow in the second quarter of 2021 was $89.4 million. Non-GAAP operating cash flow was $146.7 million.
As of June 30, 2021, the Company had cash and cash equivalents of $812.3 million.
As of June 30, 2021, the total principal amount of debt outstanding was $2.614 billion, and the gross-debt-to-last-12-months adjusted EBITDA leverage ratio was 2.3 times.

2021 Guidance

The Company now expects full-year 2021 net sales to range between $3.025 billion and $3.125 billion, representing 40 percent growth at the midpoint and an increase from the previous range of $2.75 billion and $2.85 billion. The company now expects TEPEZZA full-year 2021 net sales of greater than $1.550 billion with year-over-year growth of more than 50 percent in the fourth quarter, compared to the previous guidance of greater than $1.275 billion. The Company continues to expect KRYSTEXXA full-year 2021 net sales of greater than $500 million. Full-year 2021 adjusted EBITDA is now expected to range between $1.26 billion and $1.30 billion, representing 28 percent growth at the midpoint and an increase from the previous guidance range of $1.02 billion and $1.06 billion.

Webcast

At 8 a.m. EST / 1 p.m. IST today, the Company will host a live webcast to review its financial and operating results and provide a general business update. The live webcast and a replay may be accessed at View Source Please connect to the Company’s website at least 15 minutes prior to the live webcast to ensure adequate time for any software download that may be needed to access the webcast. A replay of the webcast will be available approximately two hours after the live webcast.

On August 4, 2021 Schrödinger, Inc. (Nasdaq: SDGR), whose physics-based software platform is transforming the way therapeutics and materials are discovered, and Zai Lab Limited (Nasdaq: ZLAB; HKEX: 9688), an innovative commercial-stage biopharmaceutical company, reported a global discovery, development and commercialization collaboration focused on a novel program in oncology targeting DNA damage response (Press release, Schrodinger, AUG 4, 2021, View Source [SID1234585743]).

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"With an established track record of developing and commercializing therapeutics in oncology, Zai Lab is an ideal partner for Schrödinger on this project," said Karen Akinsanya, Ph.D., executive vice president, chief biomedical scientist and head of discovery R&D at Schrödinger. "Together, we will aim to accelerate and expand our focus on targeted DNA damage response inhibition, which is emerging as an important therapeutic strategy for a broad range of cancers. Additionally, the structure of this collaboration provides us with the opportunity to gain development and commercial expertise and the potential to participate more significantly in the downstream value of the program."

"We are pleased to be collaborating with Schrödinger, a recognized leader in physics-based computational drug discovery," said Alan Sandler, M.D., president and head of global development, oncology, at Zai Lab. "This program will complement our existing discovery efforts in the DNA damage response pathway in addition to potential combinatorial approaches within our pipeline, such as with the PARP inhibitor Zejula."

The research program will be conducted jointly by the Schrödinger and Zai Lab scientific teams. The companies will be responsible for their own research program expenses, and under the terms of the collaboration agreement, Zai Lab will make an upfront payment to Schrödinger to help fund Schrödinger’s share of research costs. Following the selection of a development candidate, Zai Lab will assume primary responsibility for global development, manufacturing and commercialization. The agreement provides Schrödinger co-development and co-commercialization rights in the U.S. If Schrödinger elects to co-fund clinical development of a product candidate under the collaboration, it will be entitled to 50 percent of the profits, if any, from the commercialization of such product candidate in the United States. Schrödinger will also be eligible to receive up to approximately $338 million in preclinical, clinical, regulatory and sales-based milestone payments. Additionally, Schrödinger is entitled to receive royalties on net sales outside the U.S.

On August 4, 2021 argenx (Euronext & Nasdaq: ARGX), a global immunology company committed to improving the lives of people suffering from severe autoimmune diseases and cancer, reported that members of management will participate in a fireside chat at the 2021 Wedbush PacGrow Virtual Healthcare Conference on Wednesday, August 11, 2021 at 11:30 a.m. ET (Press release, argenx, AUG 4, 2021, View Source [SID1234585765]).

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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

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A live webcast of the presentation may be accessed on the Investors section of the argenx website at argenx.com/investors. A replay of the webcast will be available on the argenx website for approximately 90 days following the call.

On August 4, 2021 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to the development of programmed cellular immunotherapies for patients with cancer, reported business highlights and financial results for the second quarter ended June 30, 2021 (Press release, Fate Therapeutics, AUG 4, 2021, View Source [SID1234585801]).

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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

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"We are very pleased with the early clinical safety and activity we have observed with our off-the-shelf, iPSC-derived NK cell programs in relapsed / refractory lymphoma and acute myeloid leukemia, where interim Phase 1 data indicate FT516 and FT538 are well tolerated and can deliver complete responses for patients. We look forward to sharing additional clinical data from our FT516 and FT596 programs in B-cell lymphoma at our upcoming investor event," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "Additionally, treatment of the first patient with FT819, the first-ever iPSC-derived T-cell therapy to undergo clinical investigation, is a landmark achievement and further demonstrates the Company’s leadership in off-the-shelf, iPSC-derived cell therapy and the versatility of its proprietary iPSC Product Platform."

B-cell Malignancy Disease Franchise

Positive Interim Phase 1 Clinical Data of FT516 Presented at ASCO (Free ASCO Whitepaper). At the 2021 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting (ASCO) (Free ASCO Whitepaper) held in June, the Company highlighted interim clinical data from its dose-escalating Phase 1 study of FT516 in combination with rituximab for the treatment of relapsed / refractory B-cell lymphoma (BCL). As of the data cutoff date of March 11, 2021, eight of eleven patients (73%) in Dose Cohorts 2 and 3 (n=4 at 90 million cells / dose and n=7 at 300 million cells / dose, respectively) achieved an objective response, including six patients (55%) who achieved a complete response. Notably, two of four patients previously treated with autologous CD19 CAR-T cell therapy achieved a complete response. The FT516 treatment regimen was well tolerated, and no treatment-emergent adverse events of any grade of cytokine release syndrome (CRS), immune effector cell-associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GVHD) were reported. Dose escalation is ongoing with enrollment in Dose Cohort 4 (900 million cells / dose).
FT596 Phase 1 Clinical Trial Enrolling in Dose Cohort 4. The dose-escalating Phase 1 study of FT596 for patients with relapsed / refractory BCL has successfully cleared dose-limiting toxicity in Dose Cohort 3 (single dose of 300 million cells) as monotherapy and in combination with rituximab. Dose escalation of the single-dose treatment schedule is ongoing in both regimens with enrollment in Dose Cohort 4 (900 million cells). The Company is also preparing to initiate enrollment of a multi-dose treatment schedule in both regimens, with FT596 administered on Day 1 and Day 15 at 300 million cells / dose with the potential to dose escalate to 900 million cells / dose.
First Patient Treated in Landmark Phase 1 Study of iPSC-derived T-cell Therapy. In July, the first patient was treated in the Company’s landmark Phase 1 clinical trial of FT819, the first-ever T-cell therapy derived from a clonal master induced pluripotent stem cell (iPSC) line to undergo clinical investigation. FT819 is an off-the-shelf, allogeneic CAR T-cell therapy targeting CD19, and 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 (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 GVHD. The first patient received a single FT819 dose of 90 million cells for the treatment of relapsed / refractory acute lymphoblastic leukemia (ALL).
AML Disease Franchise

Interim Phase 1 Clinical Data of FT516 Demonstrate Anti-leukemic Activity. At a virtual investor event in May, the Company highlighted interim clinical data from its dose-escalating Phase 1 study of FT516 as monotherapy for the treatment of relapsed / refractory acute myeloid leukemia (AML). As of the data cutoff date of April 16, 2021, of the nine patients treated in Dose Cohorts 1 and 2 (n=3 at 90 million cells / dose and n=6 at 300 million cells / dose, respectively), six patients showed anti-leukemic activity as evidenced by on-treatment reduction in bone marrow blasts, with four patients (44%) achieving an objective response with complete clearance of leukemic blasts in the bone marrow. Three of these four responders achieved a best overall response of complete remission with incomplete hematopoietic recovery (CRi) based on 2017 ELN response criteria, including two patients in Dose Cohort 2 with ongoing remission without further therapeutic intervention at six months’ follow-up. The FT516 treatment regimen was well tolerated, and no treatment-emergent adverse events of any grade of CRS, ICANS, or GVHD were reported. Dose escalation is ongoing with enrollment in Dose Cohort 3 (900 million cells / dose).
Anti-leukemic Activity Observed in Dose Cohort 1 of FT538 Phase 1 Study. The Company also highlighted initial clinical data from its dose-escalating Phase 1 Study of FT538 as monotherapy for the treatment of relapsed / refractory AML. As of the data cutoff date of May 6, 2021, two patients in Dose Cohort 1 (100 million cells / dose) were evaluable for safety and anti-leukemic activity, both of whom showed anti-leukemic activity as evidenced by on-treatment reduction in bone marrow blasts. One patient, who was refractory to their two most recent prior therapies, achieved a CRi based on 2017 ELN response criteria at the end of the first treatment cycle. The FT538 treatment regimen was well tolerated, and no treatment-emergent adverse events of any grade of CRS, ICANS, or GVHD were reported. No dose-limiting toxicities have been observed, and dose escalation is ongoing with enrollment in Dose Cohort 1. Upon clearance of Dose Cohort 1, enrollment is set to commence in an investigator-initiated Phase 1 clinical trial of FT538 in combination with the CD38-targeted monoclonal antibody daratumumab in patients with relapsed / refractory AML, a therapeutic strategy designed to exploit the product candidate’s proprietary high-affinity, non-cleavable (hnCD16) receptor and CD38 knock-out (CD38KO) to target and eliminate CD38+ leukemic blasts.
Adaptive Phenotype and Functionality of FT538 Featured at ASGCT (Free ASGCT Whitepaper) Symposium. At the 24th Annual American Society of Gene & Cell Therapy Meeting (ASGCT) (Free ASGCT Whitepaper) held virtually in May, Dr. Jeffrey S. Miller, Professor of Medicine, University of Minnesota and Deputy Director of the Masonic Cancer Center, presented preclinical data demonstrating that the metabolic, transcriptional and functional properties of FT538 are substantially similar to those of adaptive NK cells, a discrete subset of memory-like NK cells with superior effector function. The deletion of the CD38 gene (CD38KO) was shown to enhance metabolic fitness, resistance to oxidative stress, serial innate cytotoxicity, and antibody-dependent cellular cytotoxicity compared to peripheral blood NK cells.
Multiple Myeloma Franchise

Multiple Clinical Sites Activated for Phase 1 Study of FT538 in Combination with Daratumumab. The Phase 1 clinical trial is designed to assess three once-weekly doses of FT538 in combination with the CD38-targeted monoclonal antibody, daratumumab, for patients with relapsed / refractory multiple myeloma (NCT04614636). Multiple clinical sites have now been activated for study conduct, and the Company will initiate enrollment at 100 million cells per dose upon clearance of the first dose cohort in its Phase 1 study of FT538 in relapsed / refractory AML.
Initiated GMP Production of FT576 for Phase 1 Study. FT576 is derived from a clonal master iPSC line engineered with four functional components (CAR-BCMA + hnCD16 + IL-15RF + CD38KO) designed to enable multi-antigen targeting of myeloma cells, augment antibody-dependent cellular cytotoxicity (ADCC), promote NK cell activation without exogenous cytokine support, enhance NK cell persistence and prevent anti-CD38 monoclonal antibody-induced fratricide. GMP manufacture of FT576 is ongoing, and the Company is preparing to initiate a multi-center Phase 1 clinical trial to assess single-dose and multi-dose treatment regimens of FT576 as monotherapy and in combination with CD38-targeted monoclonal antibody therapy for the treatment of relapsed / refractory multiple myeloma.
Solid Tumor Franchise

Completed Qualification of FT536 Clonal Master Engineered iPSC Bank. The master cell bank, which was created from a single iPSC clone engineered with four functional elements including a novel CAR targeting the alpha-3 domain of the pan-tumor associated stress antigens MICA and MICB, has successfully been released for initiation of FT536 GMP manufacture. Pilot manufacturing runs in support of the Investigational New Drug (IND) application for FT536 are ongoing. The Company plans to submit an IND application to the U.S. Food and Drug Administration (FDA) in the second half of 2021 to initiate a Phase 1 clinical trial of FT536 for the treatment of solid tumors. In preclinical studies, FT536 has demonstrated superior recognition and killing against a broad array of cancer cell lines compared to expanded primary NK cells as well as anti-NKG2D CAR T cells.
Preclinical Milestone Reached for First Product Candidate under Janssen Collaboration. In June, the Company and Janssen elected to initiate IND-enabling activities for an iPSC-derived CAR NK cell product candidate incorporating a Janssen proprietary antigen binding domain that targets an antigen expressed on certain solid tumors, triggering the payment of a milestone fee to the Company from Janssen under the collaboration. Janssen maintains an option to develop and commercialize the iPSC-derived CAR NK cell product candidate in all territories of the world, with the Company retaining the option to co-commercialize the product candidate in the United States.
Other Corporate Highlights

Appointed Dr. Mark Plavsic as Chief Technical Officer. Dr. Plavsic brings to the Company over 20 years of broad technical excellence in global biopharmaceutical operations, having led teams in the commercial-scale cGMP manufacture and distribution, as well as the clinical-stage process, assay, and formulation development, of complex biologics. Mark will oversee the Company’s manufacturing, technical, and supply chain operations.
Appointed Dr. Yuan Xu to its Board of Directors. Dr. Xu has over 25 years of discovery, development, manufacturing, and commercial experience in the global biopharmaceuticals business, most recently serving as the Chief Executive Officer and Board Member of Legend Biotech Corporation, where she led the company’s efforts in advancing ciltacabtagene autoleucel (cilta-cel) from proof-of-concept in 2018 to BLA preparation in 2020.
Second Quarter 2021 Financial Results

Cash & Investment Position: Cash, cash equivalents and investments as of June 30, 2021 were $845.1 million.
Total Revenue: Revenue was $13.4 million for the second quarter of 2021, which was derived from the Company’s collaborations with Janssen and Ono Pharmaceutical.
R&D Expenses: Research and development expenses were $48.0 million for the second quarter of 2021, which includes $8.6 million of non-cash stock-based compensation expense.
G&A Expenses: General and administrative expenses were $12.2 million for the second quarter of 2021, which includes $4.6 million of non-cash stock-based compensation expense.
Shares Outstanding: Common shares outstanding were 94.3 million, and preferred shares outstanding were 2.8 million, as of June 30, 2021. Each preferred share is convertible into five common shares.
Today’s Conference Call and Webcast
The Company will conduct a conference call today, Wednesday, August 4, 2021 at 5:00 p.m. ET to review financial and operating results for the quarter ended June 30, 2021. In order to participate in the conference call, please dial please dial 800-773-2954 (toll free) or 847-413-3731 (toll) and refer to conference ID 50196101. The live webcast can be accessed under "Events & Presentations" in the Investors 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 350 issued patents and 150 pending patent applications.

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 a 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 a 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 a 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 (CD38KO), 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 a 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).

About FT819
FT819 is an investigational, universal, off-the-shelf, T-cell receptor (TCR)-less CD19 chimeric antigen receptor (CAR) T-cell cancer immunotherapy derived from a clonal master induced pluripotent stem cell (iPSC) line, which is engineered with the following features designed to improve the safety and efficacy of CAR19 T-cell therapy: a novel 1XX CAR signaling domain, which has been shown to extend T-cell effector function without eliciting exhaustion; integration of the CAR19 transgene directly into the T-cell receptor alpha constant (TRAC) locus, which has been shown to promote uniform CAR19 expression and enhanced T-cell potency; and complete bi-allelic disruption of TCR expression for the prevention of graft-versus-host disease (GvHD). FT819 demonstrated antigen-specific cytolytic activity in vitro against CD19-expressing leukemia and lymphoma cell lines comparable to that of primary CAR T cells, and persisted and maintained tumor clearance in the bone marrow in an in vivo disseminated xenograft model of lymphoblastic leukemia (Valamehr et al. 2020). FT819 is being investigated in a multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell malignancies, including B-cell lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia (NCT04629729).