On November 3, 2022 Schrödinger, Inc. (Nasdaq: SDGR), whose physics-based computational platform is transforming the way therapeutics and materials are discovered, reported financial results for the third quarter of 2022 (Press release, Schrodinger, NOV 3, 2022, View Source [SID1234622960]).

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"We delivered a strong quarter, with third quarter software revenue in line with our expectations and strong drug discovery revenue, reflecting progress across our portfolio of collaborative and proprietary programs," stated Ramy Farid, Ph.D., chief executive officer at Schrödinger. "As we progress through the remainder of the year, we are focused on continuing to drive software adoption and advancing our pipeline. Today we announced that we’ve initiated our Phase 1 study for our MALT1 program and we are looking forward to presenting new preclinical data from our CDC7 program at the upcoming ASH (Free ASH Whitepaper) meeting. We are very positive about the long-term potential of our underlying business – this quarter’s results highlight the benefits of our balanced model encompassing software licensing, collaborations and proprietary programs."

At September 30, 2022, Schrödinger had cash, cash equivalents, restricted cash and marketable securities of approximately $479 million, compared to approximately $513 million at June 30, 2022.

Recent Company Highlights

In October, Schrödinger hosted Platform Day during which the company provided a detailed review of its technology platform and demonstrated the impact of this platform across a growing portfolio that includes 9 collaborative programs in the clinic, 12 active collaborative projects and 18 proprietary programs. During the event, Schrödinger highlighted areas for future innovation and discussed the opportunities for value creation. The company also described six drug discovery case studies, including collaborative programs with Nimbus Therapeutics and Morphic Therapeutic as well as case studies from Schrödinger’s proprietary MALT1, CDC7 and Wee1 programs. Additionally, the company reviewed near- and longer-term opportunities for continued innovation of its physics-based computational platform, including increasing the number and type of discovery targets the platform can advance through hit identification, improving the effectiveness and efficiency with which the platform can advance targets through lead optimization, and expanding the applicability of the platform to new high-value areas.
In October, Schrödinger announced that it entered into a collaboration with Eli Lilly and Company. Under the terms of the agreement, Schrödinger is responsible for the discovery and optimization of small molecule compounds addressing an undisclosed target. Lilly is responsible for preclinical development, clinical development and commercialization. Schrödinger received an upfront payment and is eligible to receive up to $425 million in discovery, development and commercial milestone payments. Schrödinger is also eligible to receive low single- to low double-digit royalties on net sales of any products emerging from the collaboration in all markets.
Schrödinger reported that its Phase 1 clinical trial of its MALT1 inhibitor, SGR-1505, is open to patient enrollment. This dose-escalation study is designed to evaluate the safety, pharmacokinetics, pharmacodynamics, and early signals of clinical activity of SGR-1505 as a monotherapy in patients with relapsed or refractory B-cell malignancies. Once the recommended dose is determined, an expansion cohort is planned to evaluate SGR-1505 in combination with other anti-cancer agents, such as BTK and BCL-2 inhibitors, in patients with specific B-cell malignancies.
Earlier today, Schrödinger announced that new preclinical data for SGR-2921, a CDC7 inhibitor, will be presented during a poster session at the American Society of Hematology (ASH) (Free ASH Whitepaper) 64th Annual Meeting in December 2022. The data demonstrate the strong anti-tumor activity of SGR-2921 in preclinical models of acute myeloid leukemia (AML) both alone and in combination with standard of care therapies for the treatment of AML. SGR-2921 is advancing through IND-enabling studies to support a planned IND submission in the first half of 2023.
Schrödinger has identified multiple novel Wee1 inhibitors, and preclinical studies are ongoing. Schrödinger’s goal is to select a differentiated Wee1 inhibitor that demonstrates strong anti-tumor activity with limited off-target effects. The company now expects to select a Wee1 development candidate in the first half of 2023 and submit an IND in the first half of 2024. Wee1 is emerging as a potentially important therapeutic target for a range of solid tumors, including ovarian and uterine cancer.
In October, Schrödinger’s collaborator Morphic Therapeutic presented Phase 1 data from MORF-057 at the United European Gastroenterology Week 2022. These data reinforce previously reported safety and pharmacodynamic data from the MORF-057-101 study. MORF-057 is being developed as an oral α4β7 inhibitor candidate for the treatment of inflammatory bowel disease, with an initial focus in ulcerative colitis.
In August, Schrödinger’s collaborator Nimbus Therapeutics presented data at the American Chemical Society Fall 2022 meeting describing how structural biology and computational chemistry insights were leveraged to produce NDI-034858, its novel TYK2 inhibitor. Phase 2 clinical studies are ongoing to evaluate NDI-034858 in moderate-to-severe plaque psoriasis and psoriatic arthritis.
Schrödinger was recently ranked Number 21 on Newsweek’s List of "America’s 100 Most Loved Workplaces."
2022 Financial Outlook
As of November 3, 2022, Schrödinger outlined the following expectations for the fiscal year ending December 31, 2022:

Total revenue is now expected to range from $167 million to $175 million, compared to the prior expectation of $161 million to $181 million. The updated range represents growth of 21 percent to 27 percent over 2021.
Total software revenue is now expected to range from $122 million to $127 million, compared to the prior expectation of $126 million to $136 million. The updated range represents eight percent to 12 percent growth over 2021. The full year 2022 software revenue expectation implies fourth quarter 2022 software revenue to range from $34 million to $39 million.
Total drug discovery revenue is now expected to range from $45 million to $48 million, compared to the prior expectation of $35 million to $45 million. This higher range represents 82 percent to 94 percent growth over 2021.
Operating expense growth is now expected to be approximately 40 percent for 2022 compared to the prior expectation of slightly lower than 42 percent.
Software gross margin percentage is still expected to be in the mid-70s.
"Despite the challenging macroeconomic and industry environment, our tightened total revenue guidance for 2022 remains within our original range," stated Geoff Porges, MBBS, chief financial officer at Schrödinger. "We consider our balanced business model to be one of our greatest strengths, and this quarter’s results reflect the growing contribution of our drug discovery portfolio to our operating results and overall value."

Webcast and Conference Call Information
Schrödinger will host a conference call to discuss its third quarter 2022 financial results on Thursday, November 3, 2022, at 4:30 p.m. ET. The live webcast can be accessed under "News & Events" in the investors section of Schrödinger’s website, View Source To participate in the live call, please register for the call here. It is recommended that participants register at least 15 minutes in advance of the call. Once registered, participants will receive the dial-in information. The archived webcast will be available on Schrödinger’s website for approximately 90 days following the event.

On November 3, 2022 Oncternal Therapeutics, Inc. (Nasdaq: ONCT), a clinical-stage biopharmaceutical company focused on the development of novel oncology therapies, reported financial results for the third quarter of 2022 (Press release, Oncternal Therapeutics, NOV 3, 2022, View Source [SID1234622959]).

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"This past quarter was a pivotal one for Oncternal’s leading ROR1 programs, highlighted by initiation of the Company’s first global registrational clinical study for zilovertamab in MCL and the FDA clearance of the IND for ONCT-808, our ROR1 targeting CAR T product candidate, for the treatment of patients with advanced aggressive B-cell lymphoma," said James Breitmeyer, M.D., Ph.D., Oncternal’s President and CEO. "These exciting developments are backed by a strong clinical data foundation, as highlighted by acceptance of our zilovertamab Phase 1/2 data update in MCL and CLL for an oral presentation at the upcoming American Society of Hematology (ASH) (Free ASH Whitepaper) annual meeting in December. We are now looking forward to ramping up site enrollment for our Phase 3 clinical study globally, to the initiation of our first CAR T Phase 1/2 study from which we expect an initial clinical data readout next year, and to the further advancement towards the clinic of ONCT-534, our DAARI product candidate that may address key resistance mechanisms in metastatic prostate cancer. We continue to exercise prudent cash management and expect our existing cash and cash equivalents will last into the first half of 2024."

Recent Highlights

Initiated the Phase 3 global registrational study of zilovertamab, Study ZILO-301 (NCT05431179), for the treatment of patients with relapsed/refractory mantle cell lymphoma (MCL)
Received a ‘Study May Proceed’ letter from the U.S. Food and Drug Administration (FDA), 30 days after submitting our Investigational New Drug (IND) application for our Phase 1/2 study of ONCT-808, an autologous chimeric antigen receptor (CAR) T therapy targeting ROR1, in patients with aggressive B-cell lymphoma, including those who have failed previous CD19 CAR T treatment
Expected Upcoming Milestones

Zilovertamab, our ROR1 antibody program
Opening of sites outside of the U.S. for global clinical registrational Phase 3 Study ZILO-301, in the first quarter of 2023
Interim clinical data update for patients with MCL and CLL treated with zilovertamab plus ibrutinib in ongoing Phase 1/2 Study CIRM-0001, as oral presentation at the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in December 2022
ONCT-808, lead candidate in our autologous ROR1-targeted CAR T cell therapy program
Initiation of Phase 1/2 Study in patients with aggressive B-cell lymphoma in the first quarter of 2023
Initial clinical data update in 2023
ONCT-534, lead candidate in our DAARI program
U.S. FDA pre-IND feedback in December 2022
Third Quarter 2022 Financial Results
Our grant revenue was $0.4 million for the third quarter ended September 30, 2022. Our grant revenue is derived from two research and development grant awards from the National Institutes of Health (NIH).

Our total operating expenses for the third quarter ended September 30, 2022 were $11.7 million, including $2.0 million in non-cash stock-based compensation expense. Research and development expenses for the quarter totaled $8.4 million, and general and administrative expenses for the quarter totaled $3.3 million. Net loss for the third quarter was $11.1 million, or a loss of $0.21 per share, basic and diluted.

As of September 30, 2022, we had approximately 55.5 million shares of common stock outstanding, $70.6 million in cash and cash equivalents and no debt. Based on our current operating plan, we believe these funds will be sufficient to fund our operations into the first half of 2024. Our cash guidance is subject to a number of assumptions, including those related to the pace of our research and clinical development programs, among other aspects of our business and the geopolitical environment.

On November 3, 2022 MacroGenics, Inc. (NASDAQ: MGNX), a biopharmaceutical company focused on developing and commercializing innovative antibody-based therapeutics for the treatment of cancer, reported financial results for the quarter ended September 30, 2022 (Press release, MacroGenics, NOV 3, 2022, View Source [SID1234622958]).

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"Over the past few months, we have strengthened our financial position by generating non-dilutive capital through our partnering efforts. We have achieved this through the receipt of $30 million in milestone payments from Incyte during the quarter and the subsequent receipt of a $60 million upfront payment from Gilead for our recently announced MGD024 collaboration. In addition, over the next few weeks, we await the U.S. Food and Drug Administration (FDA) decision regarding Provention Bio’s teplizumab biologics license application (BLA), which would generate an additional $60 million milestone payment obligation to MacroGenics, if approved," said Scott Koenig, M.D., Ph.D., President and CEO of MacroGenics. "Moreover, we are focused on advancing our pipeline of clinical and preclinical product candidates. We look forward to initiating the MGC018 TAMARACK study later this year, continuing to enroll the MGC018 combination study with lorigerlimab and the MGD024 dose-escalation study, as well as reporting data from the lorigerlimab monotherapy expansion cohorts in early 2023."

Updates on Proprietary Investigational Programs

Recent progress and anticipated events related to MacroGenics’ investigational product candidates in clinical development are highlighted below.

MGC018, now also known as vobramitamab duocarmazine, is an antibody-drug conjugate (ADC) that targets B7-H3, an antigen with broad expression across multiple solid tumor types and a member of the B7 family of molecules involved in immune regulation.
MacroGenics continues to expect to start the Phase 2 portion of the TAMARACK study of vobramitamab duocarmazine in patients with metastatic castration-resistant prostate cancer (mCRPC) by year-end 2022. The Company believes that this should enable interim data from the Phase 2 portion of the study in 2024.
Patient recruitment continues in a Phase 1/2 dose escalation study of vobramitamab duocarmazine in combination with lorigerlimab in patients with various advanced solid tumors.
Lorigerlimab is a bispecific, tetravalent PD-1 × CTLA-4 DART molecule. MacroGenics enrolled a Phase 1/2 dose expansion study with lorigerlimab as monotherapy in cohorts of patients with microsatellite stable colorectal cancer, mCRPC, melanoma and checkpoint-naïve non-small cell lung cancer (NSCLC) and expects to provide a data update from this study in the first quarter of 2023.
MGD024 is a next-generation, humanized CD123 × CD3 DART molecule designed to minimize cytokine-release syndrome, while maintaining anti-tumor cytolytic activity, and permitting intermittent dosing through a longer half-life. MacroGenics continues to enroll patients in a Phase 1 dose-escalation study of MGD024 in patients with CD123-positive neoplasms, including acute myeloid leukemia and myelodysplastic syndromes.
Other Program Updates:

Teplizumab is an investigational, anti-CD3 mAb acquired from MacroGenics by Provention Bio, Inc. under an asset purchase agreement in 2018. Provention Bio is developing teplizumab for the prevention and treatment of type 1 diabetes (T1D). The Prescription Drug User Fee Act (PDUFA) target date for action on the BLA for teplizumab for the prevention of T1D is November 17, 2022. MacroGenics is eligible to receive royalties on net sales of teplizumab, if approved, in addition to milestone payments, including $60 million upon approval of a BLA in the United States.
Retifanlimab is an investigational anti-PD-1 mAb that has been exclusively licensed to Incyte Corporation. MacroGenics is eligible to receive royalties on net sales of retifanlimab, if approved, in addition to milestone payments. In July 2022, MacroGenics received $30 million in milestone payments from Incyte as part of its collaboration agreement. Retifanlimab is currently being studied as monotherapy or in combination with other agents across multiple studies.
Gilead Collaboration

On October 14, 2022, MacroGenics and Gilead Sciences, Inc. entered into an exclusive option and collaboration agreement to develop MGD024 and up to two additional bispecific research programs. The agreement grants Gilead the option to license MGD024. As part of the agreement, Gilead paid MacroGenics an upfront payment of $60 million and MacroGenics will be eligible to receive up to $1.7 billion in target nomination, option fees, and development, regulatory and commercial milestones. MacroGenics will also be eligible to receive tiered, low double-digit royalties on worldwide net sales of MGD024 and a flat royalty on worldwide net sales of products resulting from the two additional research programs.

MacroGenics will be responsible for the ongoing Phase 1 study of MGD024 during which Gilead may elect to exercise its option to license the program at predefined decision points. The Phase 1 study includes a dose escalation segment and an expansion segment that is intended to evaluate MGD024 as monotherapy and in combination with other therapies across multiple indications.

Third Quarter 2022 Financial Results

Cash Position: Cash, cash equivalents and marketable securities as of September 30, 2022, were $123.6 million, compared to $243.6 million as of December 31, 2021. The September 30, 2022 balance did not include $60 million subsequently received from Gilead in October 2022.
Revenue: Total revenue, consisting primarily of revenue from collaborative agreements, was $41.7 million for the quarter ended September 30, 2022, compared to total revenue of $15.7 million for the quarter ended September 30, 2021. Revenue for the quarter ended September 30, 2022 included MARGENZA net sales of $4.4 million, compared to $3.6 million for the quarter ended September 30, 2021.
R&D Expenses: Research and development expenses were $48.2 million for the quarter ended September 30, 2022, compared to $49.8 million for the quarter ended September 30, 2021. The decrease was primarily related to decreased retifanlimab manufacturing costs for Incyte, and decreased costs related to discontinued studies. These decreases were partially offset by increased development, manufacturing and clinical trial costs related to vobramitamab duocarmazine, increased expenses related to discovery projects and preclinical molecules, and increased clinical expenses related to lorigerlimab and MGD024.
SG&A Expenses: Selling, general and administrative expenses were $15.4 million for the quarter ended September 30, 2022, compared to $17.2 million for the quarter ended September 30, 2021. The decrease was primarily related to decreased selling costs for MARGENZA as well as decreased consulting expenses.
Net Loss: Net loss was $24.8 million for the quarter ended September 30, 2022, compared to net loss of $52.9 million for the quarter ended September 30, 2021.
Shares Outstanding: Shares of common stock outstanding as of September 30, 2022 were 61,462,189.
Cash Runway Guidance: MacroGenics anticipates that its cash, cash equivalents and marketable securities balance of $123.6 million as of September 30, 2022, $60 million subsequently received from Gilead, projected and anticipated future payments from partners and product revenues should extend its cash runway into mid-2024. This cash runway guidance reflects anticipated expenditures related to the planned Phase 2 portion of the TAMARACK study as well as MacroGenics’ other ongoing studies.
Conference Call Information

To participate via telephone, please register in advance at this link. Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call.

The listen-only webcast of the conference call can be accessed under "Events & Presentations" in the Investor Relations section of MacroGenics’ website at View Source A recorded replay of the webcast will be available shortly after the conclusion of the call and archived on MacroGenics’ website for 30 days following the call.

On November 3, 2022 Rigel Pharmaceuticals, Inc. (Nasdaq: RIGL) reported financial results for the third quarter ended September 30, 2022, 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 3, 2022, View Source [SID1234622957]).

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"We are excited to have several poster presentations at ASH (Free ASH Whitepaper) that showcase our hematology-oncology portfolio. In particular, updated data from the Phase 2 registrational study of olutasidenib in patients with mIDH1 relapsed or refractory acute myeloid leukemia demonstrate durable remissions, which we believe truly differentiates olutasidenib as a potential market leading therapy," said Raul Rodriguez, Rigel’s president and CEO. "In addition, during the third quarter of 2022, we made meaningful progress to position the company for the potential launch of olutasidenib and to drive growth in TAVALISSE ITP sales."

Business Update

In the third quarter of 2022, TAVALISSE net product sales were $19.2 million, an increase of 20% compared to the same period of 2021.
In August, Rigel announced an exclusive license agreement with Forma Therapeutics, Inc. (Forma) to develop, manufacture and commercialize olutasidenib, an investigational, oral, small molecule inhibitor of mutant isocitrate dehydrogenase-1 (mIDH1) for the treatment of relapsed/refractory acute myeloid leukemia (R/R AML) and other malignancies. Forma’s New Drug Application (NDA) for olutasidenib is under review by the U.S. Food and Drug Administration (FDA) with a Prescription Drug User Fee Act (PDUFA) target action date of February 15, 2023.
Today, Rigel announced five poster presentations at the 64th ASH (Free ASH Whitepaper) Annual Meeting, including updated data from the interim analysis of 147 efficacy evaluable patients with mIDH1 R/R AML who received olutasidenib monotherapy 150 mg twice daily. Results from the interim analysis of patients with mIDH1 R/R AML demonstrated a 35% CR+CRh* rate with a median duration of 25.9 months. The abstract concluded that the observed activity is clinically meaningful and represents a potential therapeutic advance in the treatment of this patient population.
This week, Rigel announced top-line results from the FOCUS Phase 3 clinical trial of fostamatinib in high-risk hospitalized COVID-19 patients. While the trial approached but did not meet statistical significance (p=0.0603) in the primary efficacy endpoint of the number of days on oxygen through Day 29, all prespecified secondary endpoints in the study numerically favored fostamatinib over placebo, including mortality, time to sustained recovery, change in ordinal scale assessment, and number of days in the ICU. The Company is evaluating the opportunity and next steps in collaboration with its partner, the U.S. Department of Defense.
In October, Rigel announced that it does not expect to file a supplemental NDA for fostamatinib for the treatment of patients with warm autoimmune hemolytic anemia (wAIHA) based on guidance from the FDA’s review of the Company’s re-analysis of data from the FORWARD Phase 3 trial. Rigel will continue to explore its options for the wAIHA program in relation to its complete portfolio of development opportunities.
In October, Rigel also announced a 16% reduction in its workforce, resulting in the elimination of 30 positions primarily in development and administration.
*CR+CRh: Complete remission (CR) plus a complete remission with partial hematological recovery (CRh)

Financial Update
For the third quarter of 2022, Rigel reported a net loss of $19.0 million, or $0.11 per basic and diluted share, compared to a net loss of $21.0 million, or $0.12 per basic and diluted share, for the same period of 2021.

For the third quarter of 2022, total revenues were $22.4 million, consisting of $19.2 million in TAVALISSE net product sales, $0.7 million in contract revenues from collaborations and $2.5 million in government contract revenue. TAVALISSE net product sales of $19.2 million increased by 20%, compared to $16.0 million in the third quarter of 2021. Contract revenues from collaborations during the third quarter of 2022 consisted primarily of revenue from Grifols related to the delivery of fostamatinib supply, performance of certain research and development services pursuant to the collaboration agreement and royalty revenue. Government contract revenue for the third quarter of 2022 was related to the income recognized pursuant to the agreement with the U.S. Department of Defense (DOD) to support Rigel’s ongoing Phase 3 clinical trial of fostamatinib in hospitalized patients with COVID-19.

For the third quarter of 2022, total costs and expenses were $40.8 million, compared to $41.3 million for the same period of 2021. The decrease in costs and expenses was primarily due to a decrease in research and development costs related to the Phase 3 clinical trial for wAIHA, the Phase 3 clinical trial in high-risk hospitalized patients with COVID-19 and the IRAK 1/4 inhibitor program. These decreases were partially offset by increased personnel related costs and commercial activities.

For the nine months ended September 30, 2022, Rigel reported a net loss of $60.0 million, or $0.35 per basic and diluted share, compared to a net income of $4.7 million, or $0.03 per basic and diluted share, for the same period of 2021.

For the nine months ended September 30, 2022, total revenues were $69.0 million, consisting of $53.9 million in TAVALISSE net product sales, $12.5 million in contract revenues from collaborations and $2.5 million in government contract revenue. TAVALISSE net product sales of $53.9 million increased by 19% compared to $45.4 million in the same period of 2021. Contract revenues from collaborations for the nine months ended September 30, 2022, consisted of $7.6 million in revenue from Kissei primarily related to a milestone payment and delivery of fostamatinib supply, $2.0 million in revenue related to the license agreement with Knight, $2.4 million in revenue from Grifols related to the delivery of fostamatinib supply, performance of certain research and development services pursuant to the collaboration agreement and royalty revenue, and $0.5 million in revenue related to the license agreement with Eli Lilly. Government contract revenue for the nine months ended September 30, 2022, was related to the income recognized pursuant to the agreement with the DOD as mentioned above.

For the nine months ended September 30, 2022, total costs and expenses were $126.6 million, compared to $119.9 million for the same period of 2021. The increase in costs and expenses was primarily due to increased personnel costs from the sales force expansion, increased commercial-related activities, and increased research and development costs for the IRAK1/4 inhibitor program. These increases were partially offset by decreased research and development costs related to the Phase 3 clinical trial for wAIHA and the ongoing Phase 3 clinical trial in high-risk hospitalized patients with COVID-19.

As of September 30, 2022, Rigel had cash, cash equivalents and short-term investments of $81.6 million, compared to $125.0 million as of December 31, 2021.

Conference Call and Webcast with Slides Today at 4:30pm Eastern Time
Rigel will host a live conference call and webcast today at 4:30 p.m. Eastern Time (1:30 p.m. Pacific Time) to discuss financial results and provide an update on the business.

Participants can access the live conference call by dialing (877) 407-3088 (domestic) or (201) 389-0927 (international). The conference call 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 are 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. 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 AML
Acute myeloid leukemia (AML) is a cancer that starts in a person’s bone marrow but often quickly moves into the blood. AML develops from immature blood cells, known as myeloid cells, that are supposed to mature into white blood cells. However, the diseased myeloid cells do not function properly. They instead multiply rapidly, which causes normal blood cell production to fail. AML occurs primarily in adults and accounts for about 1 percent of all adult cancers. The American Cancer Society estimates that in the United States alone, there will be about 20,050 new cases, most in adults, in 2022.1

Relapsed AML affects about half of all patients who, following treatment and remission, experience a return of leukemia cells in the bone marrow.2 Refractory AML, which affects between 10 and 40 percent of newly diagnosed patients, occurs when a patient fails to achieve remission even after intensive treatment.3

About AIHA
Autoimmune hemolytic anemia (AIHA) is a rare, serious blood disorder in which the immune system produces antibodies that lead to the destruction of the body’s own red blood cells. Warm antibody AIHA (wAIHA), which is the most common form of AIHA, is characterized by the presence of antibodies that react with the red blood cell surface at body temperature. wAIHA affects approximately 36,000 adult patients in the U.S.4 and can be a severe, debilitating disease. To date, there are no disease-targeted therapies approved for wAIHA, despite the unmet medical need that exists for these patients.

About COVID-19 & SYK Inhibition
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.5 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.6

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 pro-inflammatory cytokine release by monocytes and macrophages, production of neutrophil extracellular traps (NETs) by neutrophils, and platelet aggregation.7,8,9,10 Furthermore, SYK inhibition in neutrophils and platelets may lead to decreased thrombo-inflammation, 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 3, 2022 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 third quarter ended September 30, 2022 (Press release, Fate Therapeutics, NOV 3, 2022, View Source [SID1234622956]).

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"We are very pleased with the positive feedback from the FDA under our FT516 RMAT designation in support of our iPSC product platform and potential registrational pathways for the treatment of relapsed / refractory aggressive lymphomas, including for patients who have previously failed CD19-targeted CAR T-cell therapy, and we look forward to engaging the FDA in the fourth quarter to discuss CMC topics in support of pivotal trial readiness," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "We are also excited to present interim Phase 1 clinical data at the upcoming SITC (Free SITC Whitepaper) and ASH (Free ASH Whitepaper) conferences, including for our iPSC-derived CAR NK cell programs FT576 in multiple myeloma and FT536 in solid tumors as well as for the first-ever iPSC-derived CAR T-cell program FT819 in B-cell lymphoma. Finally, under our collaboration with Janssen, we are pleased to announce our first IND candidate FT555, a multiplexed-engineered, iPSC-derived CAR NK cell targeting GPRC5D for multiple myeloma, and that Janssen has also exercised its commercial option to an additional product candidate targeting an undisclosed hematologic malignancy antigen."

B-cell Malignancy Disease Franchise

FT596+R Dose and Dose Schedule Optimization Ongoing for R/R BCL. The Company’s multicenter Phase 1 study is designed to assess single-dose and multi-dose treatment schedules of FT596, its off-the-shelf, multiplexed-engineered, induced pluripotent stem cell (iPSC)-derived chimeric antigen receptor (CAR) natural killer (NK) cell product candidate targeting CD19, in combination with rituximab (FT596+R) for the treatment of relapsed / refractory (r/r) B-cell lymphoma (BCL). Enrollment of a three-dose escalation cohort at 1.8 billion cells per dose, and of two-dose cohorts at 900 million cells per dose and at 1.8 billion cells per dose, is currently ongoing. The clinical protocol permits eligible patients to receive multiple treatment cycles.
Community Site Activation Ongoing for FT596+R-CHOP in First-line Aggressive BCL. The Company is engaged with multiple community sites to initiate enrollment of its Phase 1b study of FT596 combined with R-CHOP, the standard immunochemotherapy regimen for patients with newly-diagnosed aggressive lymphomas. The study’s objective is to assess the safety and activity and to inform the feasibility of developing FT596 without conditioning chemotherapy in the outpatient setting. The treatment schema includes administering up to six doses of FT596, with each dose being administered with each of six standard cycles of R-CHOP.
Positive Feedback Received from FDA under FT516 RMAT Designation. Under the Regenerative Medicine Advanced Therapy (RMAT) designation granted to the Company’s FT516 program, the Company engaged the U.S. Food and Drug Administration (FDA) and received positive feedback regarding its production, characterization, and release of its clonal master iPSC bank for use in the routine manufacture of drug product as well as potential registrational pathways for the treatment of patients with r/r aggressive lymphomas, including for patients who have relapsed or are refractory to FDA-approved CD19-directed CAR T-cell therapy. In addition, the Company was granted a follow-up meeting, scheduled for December, to review Chemistry, Manufacturing, and Controls (CMC) components of its iPSC product platform, including its drug product release specification. The Company’s multicenter Phase 1 study of FT516 in combination with rituximab (FT516+R) for r/r BCL is currently enrolling patients in multiple disease-specific, multi-dose expansion cohorts at 900 million cells per dose.
FT819 Enrollment Ongoing in Single-dose and Multi-dose Escalation Cohorts. At the 64th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition scheduled to take place December 10-13, 2022 in New Orleans, Louisiana, the Company plans to present interim Phase 1 dose-escalation data from its landmark study of FT819, the first-ever T-cell product candidate manufactured from a clonal master iPSC line to undergo clinical investigation. The product candidate’s clonal master iPSC line is created from a single iPSC that has a novel CD19-targeted 1XX CAR construct (1XX-CAR19) integrated into the T-cell receptor alpha constant (TRAC) locus, designed to ensure complete bi-allelic disruption of T-cell receptor expression and promote uniform CAR expression. Dose escalation is ongoing in the third single-dose escalation cohort at 360 million cells and in the second three-dose escalation cohort at 60 million cells per dose for r/r BCL.
Multiple Myeloma Franchise

FT576 Enrollment Ongoing in Multi-dose Escalation Cohorts. The multicenter Phase 1 study is designed to assess single-dose and multi-dose treatment schedules of FT576, the Company’s multiplexed-engineered, iPSC-derived CAR NK cell product candidate targeting B-cell maturation antigen (BCMA), as monotherapy and in combination with daratumumab for the treatment of r/r multiple myeloma (MM). The Company has initiated enrollment in the two-dose escalation cohorts at 300 million cells per dose. At ASH (Free ASH Whitepaper), the Company will present interim Phase 1 data from the first and second single-dose escalation cohorts as monotherapy (100 million cells and 300 million cells, respectively) and from the first single-dose escalation cohort (100 million cells) in combination with daratumumab.
FT538 Enrollment Ongoing in Third Multi-dose Escalation Cohort. The Company’s Phase 1 study is designed to assess three once-weekly doses of FT538 in combination with daratumumab for the treatment of r/r MM, and is currently enrolling patients in the third multi-dose escalation cohort (1 billion cells per dose). At ASH (Free ASH Whitepaper), the Company will present interim Phase 1 data from the first and second multi-dose escalation cohorts (100 million cells per dose and 300 million cells per dose, respectively).
AML Disease Franchise

FT538 Enrollment Ongoing in Fourth Multi-dose Escalation Cohort. The Company’s Phase 1 study is designed to assess three once-weekly doses of FT538 as monotherapy for the treatment of r/r acute myeloid leukemia (AML), and is currently enrolling patients in the fourth multi-dose escalation cohort (1.5 billion cells per dose). In addition, an investigator-initiated study of FT538 in combination with the CD38-targeted monoclonal antibody daratumumab, which is designed to assess the therapeutic potential of targeting CD38+ leukemic blasts, is enrolling patients in the fourth multi-dose escalation cohort (1.5 billion cells per dose).
Solid Tumor Franchise

FT536 Clears First Multi-dose Escalation Cohort as Monotherapy. At the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) 37th Annual Meeting being held in Boston, MA, and virtually, November 8-12, 2022, the Company plans to present interim Phase 1 dose-escalation data for FT536, the Company’s first CAR NK cell product candidate for the treatment of advanced solid tumors which uniquely targets the alpha-3 domains of the major histocompatibility complex (MHC) class I related proteins A (MICA) and B (MICB). The Company is currently conducting a multicenter Phase 1 study designed to assess a multi-dose, multi-cycle treatment schedule of FT536 as monotherapy and in combination with monoclonal antibody therapy. In the monotherapy regimen, no dose-limiting toxicities (DLTs) were observed in the first three-dose escalation cohort (100 million cells per dose), and enrollment is ongoing in the second three-dose escalation cohort (300 million cells per dose). In addition, the Company has now initiated enrollment of the combination regimen, which allows for administration of FT536 in combination with each of five monoclonal antibodies to promote multi-antigen targeting (EGFR- and MET-targeted amivantamab; EGFR-targeted cetuximab; HER2-targeted trastuzumab; PD1-targeted pembrolizumab; and PDL1-targeted avelumab).
Initial FT538 Clinical Data in Combination with Monoclonal Antibody Therapy to be Presented at SITC (Free SITC Whitepaper). The Company is currently conducting a multicenter Phase 1 study designed to assess a multi-dose, multi-cycle treatment schedule of FT538 in combination with anti-PD1/L1 or antibody-dependent cellular cytotoxicity (ADCC)-competent monoclonal antibody therapy in patients with advanced solid tumors. At SITC (Free SITC Whitepaper), the Company will present initial clinical data from the first eight patients treated in the first three-dose escalation cohort (100 million cells per dose) of FT538 in combination with cetuximab (n=3), trastuzumab (n=2), and avelumab (n=3). All eight patients completed at least one cycle of treatment with FT538, and no DLTs were observed.
New Preclinical Candidate FT873 CAR T-cell Targeting pan-Cancer Antigen B7-H3 Unveiled. At SITC (Free SITC Whitepaper), the Company will present preclinical data of FT873, a multiplexed-engineered, iPSC-derived CAR T-cell targeting B7 homolog 3 protein (B7-H3), a member of the B7 family of immunoregulatory proteins that is overexpressed in cancer and promotes tumor growth, metastasis, and drug resistance. The newly-disclosed product candidate for the treatment of solid tumors incorporates three functional elements into the T-cell receptor alpha constant (TRAC) locus: a novel camelid nanobody CAR targeting B7-H3, an IL7 receptor fusion protein, and a high-affinity, non-cleavable CD16 (hnCD16) Fc receptor. In addition to CAR targeting, the synthetic T-cell receptors are designed to improve fitness and to enable T cells to engage monoclonal antibodies and mediate a potent ADCC response.
Janssen Collaboration Highlights

FT555 IND Candidate from GPRC5D Antigen Program for MM to be Presented at ASH (Free ASH Whitepaper). In May, Janssen exercised its commercial option to FT555, a multiplexed-engineered, iPSC-derived CAR NK cell product candidate targeting GPRC5D, a tumor-associated orphan G-protein-coupled receptor found to be highly expressed on myeloma cells. The companies will jointly present preclinical data at ASH (Free ASH Whitepaper) demonstrating that administration of FT555 resulted in robust tumor growth inhibition in vivo in a disseminated xenograft mouse model comprised of engrafted MM.1S cells, and that the durability of tumor growth inhibition as well as survival were further enhanced in combination with daratumumab to simultaneously co-target GPRC5D and CD38 antigens.
Commercial Option Exercised for Second Hematologic Malignancy Product Candidate. In September, Janssen exercised its commercial option, subject to Hart-Scott-Rodino regulatory clearance, to a second multiplexed-engineered, iPSC-derived CAR NK cell product candidate, which targets an undisclosed antigen expressed on certain blood cancers. The Company expects to submit an IND application for the product candidate under the collaboration during the fourth quarter of 2022.
Preclinical Development Ongoing for Two Solid Tumor Antigen Programs. The companies will jointly present preclinical data at SITC (Free SITC Whitepaper) of an iPSC-derived CAR T-cell program targeting human kallikrein-related peptidase 2 (KLK2), an antigen with prostate-restricted expression that is maintained during prostate cancer progression. Preclinical data demonstrate that iPSC-derived CAR T cells targeting KLK2 have the potential to infiltrate the tumor mass and eliminate tumor cells in a highly-selective manner and to prolong survival in xenograft models of prostate cancer. In addition, during the third quarter, Janssen selected an undisclosed solid tumor-associated antigen as its fourth and final antigen program for initiation of product candidate development.
Third Quarter 2022 Financial Results

Cash & Investment Position: Cash, cash equivalents and investments as of September 30, 2022 were $519.1 million.
Total Revenue: Revenue was $15.0 million for the third quarter of 2022, which was derived from the Company’s collaborations with Janssen and ONO.
R&D Expenses: Research and development expenses were $79.8 million for the third quarter of 2022, which includes $12.5 million of non-cash stock-based compensation expense.
G&A Expenses: General and administrative expenses were $21.6 million for the third quarter of 2022, which includes $7.0 million of non-cash stock-based compensation expense.
Shares Outstanding: Common shares outstanding were 97.1 million, and preferred shares outstanding were 2.8 million, as of September 30, 2022. 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 3, 2022 at 5:00 p.m. ET to review financial and operating results for the quarter ended September 30, 2022. In order to participate in the conference call, please register using the conference link here. 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 are designed to 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 designed to overcome 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 therapeutic 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 relapsed / refractory acute myeloid leukemia and in combination with CD20-targeted monoclonal antibodies for the treatment of relapsed / refractory B-cell lymphoma (NCT04023071).

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 and prevents antigen escape, 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 multicenter 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 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. 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. FT819 is being investigated in a multicenter 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).

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). FT538 is also being investigated in a multi-dose Phase 1 clinical trial in combination with one of an array of tumor-targeting monoclonal antibodies for the treatment of advanced solid tumors (NCT05069935).

About FT576
FT576 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 four functional components: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology that targets B-cell maturation antigen (BCMA); 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. In preclinical studies, FT576 has demonstrated that the high-avidity binding of the BCMA-targeted CAR construct enables sustained tumor control against various multiple myeloma cell lines, including in long-term in vivo xenograft mouse models. Additionally, in combination with daratumumab, FT576 has shown complete tumor clearance and improved survival compared to primary BCMA-targeted CAR T cells in a disseminated xenograft model of multiple myeloma. FT576 is being investigated in a multicenter Phase 1 clinical trial for the treatment of relapsed / refractory multiple myeloma as a monotherapy and in combination with daratumumab (NCT05182073).

About FT536
FT536 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 four functional components: a proprietary chimeric antigen receptor (CAR) optimized for NK cell biology that uniquely targets the alpha-3 domains of the major histocompatibility complex (MHC) class I related proteins A (MICA) and B (MICB); 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. High expression of MICA and MICB proteins (MICA/B), which is induced by cellular stress, damage or transformation, has been reported on many solid tumors, and while cytotoxic lymphocytes, such as NK cells and CD8+ T cells, can recognize and bind the membrane-distal alpha-1 and alpha-2 domains of MICA/B, cancer cells frequently evade immune cell recognition by proteolytic shedding of the alpha-1 and alpha-2 domains of MICA/B. Recent publications have demonstrated that antibody targeting of the MICA/B alpha-3 domains specifically prevents MICA/B shedding and restores NK cell-mediated immunity (DOI:10.1126/science.aao0505), and that cancers with B2M and JAK1 inactivating mutations resulting in loss of MHC Class I expression can be effectively targeted with MICA/B alpha-3 domain-specific antibodies to restore NK cell-mediated immunity against solid tumors resistant to cytotoxic T cells (DOI: 10.1158/2326-6066.CIR-19-0483). In preclinical studies, FT536 has been shown to elicit innate cytotoxicity, MICA/B-specific activity against multiple solid tumor targets, and antibody cellular cytotoxicity (ADCC) in combination with tumor-targeting antibodies. FT536 is being investigated in a multi-dose Phase 1 clinical trial in combination with one of an array of tumor-targeting monoclonal antibodies for the treatment of advanced solid tumors (NCT05395052).