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).

On November 3, 2022 Amgen (NASDAQ:AMGN) reported financial results for the third quarter of 2022 (Press release, Amgen, NOV 3, 2022, View Source [SID1234622955]). Key results include:

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Total revenues decreased 1% to $6.7 billion in comparison to the third quarter of 2021, resulting from a 1% decline in global product sales, which reflected 8% volume growth offset primarily by 5% lower net selling price and 2% negative impact from foreign exchange. Excluding the 2% negative impact of foreign exchange on product sales, total revenues increased 2%.
Volumes grew double-digits for a number of products including LUMAKRAS/LUMYKRAS (sotorasib), Repatha (evolocumab), EVENITY (romosozumab-aqqg), Parsabiv (etelcalcetide), and Vectibix (panitumumab).
GAAP earnings per share (EPS) increased from $3.31 to $3.98 driven by a decrease in operating expenses due to a $0.4 billion licensing-related upfront payment to Kyowa Kirin Co., Ltd. (KKC) in Q3 2021 and lower weighted-average shares outstanding in Q3 2022.
GAAP operating income increased from $2.4 billion to $2.7 billion, and GAAP operating margin increased 5.0 percentage points to 42.6%.
Non-GAAP EPS increased from $4.08 to $4.70 driven by a decrease in operating expenses due to a $0.4 billion licensing-related upfront payment to KKC in Q3 2021 and lower weighted-average shares outstanding in Q3 2022.
Non-GAAP operating income increased from $3.1 billion to $3.3 billion, and non-GAAP operating margin increased 4.2 percentage points to 52.5%.
The Company generated $2.8 billion of free cash flow for the third quarter versus $2.2 billion in the third quarter of 2021.
2022 total revenues guidance revised to $26.0-$26.3 billion; EPS guidance revised to $11.46-$12.17 on a GAAP basis, and $17.25-$17.85 on a non-GAAP basis.
"Our medicines generated 8% volume growth in the quarter globally, with 11 products achieving record quarterly sales," said Robert A. Bradway, chairman and chief executive officer. "This growth reflects the strong underlying demand for our medicines and the value they bring to patients."

Non-GAAP EPS has been recast due to an update to our non-GAAP policy effective January 1, 2022, resulting in a $0.59 reduction of previously-reported non-GAAP EPS for the third quarter of 2021. Refer to Non-GAAP Financial Measures below for further discussion.

Product Sales Performance

Total product sales decreased 1% for the third quarter of 2022 versus the third quarter of 2021. Unit volumes grew 8% but were more than offset by 5% lower net selling price, 2% negative impact from foreign exchange, 1% lower inventory levels and 1% unfavorable changes to estimated sales deductions.

General Medicine

Prolia sales increased 7% year-over-year for the third quarter, driven by 8% volume growth.
EVENITY sales increased 35% year-over-year to a record $201 million for the third quarter, driven by strong volume growth across our markets. U.S. volumes grew 45% year-over-year and volumes outside the U.S. grew 30%.
Repatha sales increased 14% year-over-year for the third quarter, driven by 52% volume growth, partially offset by lower net selling price. In the U.S., sales grew 2%, driven by 32% volume growth, offset by lower net selling price resulting from higher rebates to support and expand access for patients. Outside the U.S., sales grew 26%, driven by 73% volume growth partially offset by lower net selling price; this volume growth and lower net selling price were both impacted by the inclusion of Repatha on China’s National Reimbursement Drug List as of January 1, 2022. Repatha remains the global proprotein convertase subtilisin/kexin type 9 (PCSK9) segment leader, with over 1.2 million patients treated since launch.
Aimovig (erenumab-aooe) sales increased 35% year-over-year for the third quarter, driven by favorable changes to estimated sales deductions and higher net selling price, partially offset by a 7% decline in volume.
Inflammation

TEZSPIRE (tezepelumab-ekko) generated $55 million of sales in the third quarter, driven by continued strong adoption in the U.S. by both allergists and pulmonologists across patients with all types of severe asthma. Healthcare providers acknowledge TEZSPIRE’s unique, differentiated profile and its broad potential to treat the 2.5 million patients worldwide with severe asthma who are uncontrolled, without any phenotypic and biomarker limitation.
Otezla (apremilast) sales increased 3% year-over-year for the third quarter, driven by 9% volume growth, partially offset by lower inventory levels and unfavorable foreign exchange impact. We expect continued volume growth given Otezla’s unique, broad indication to treat patients suffering from mild, moderate or severe psoriasis.
Enbrel (etanercept) sales decreased 14% year-over-year for the third quarter, driven by lower net selling price, a 5% decline from unfavorable changes to estimated sales deductions, and a 3% decline in volume. The 5% unfavorable impact of changes to estimated sales deductions results from a $114 million favorable adjustment in the third quarter of 2021, more than offsetting a $47 million favorable adjustment in this quarter. Going forward, we expect net selling price to continue to decline year-over-year, driven by increased competition.
AMGEVITA (adalimumab) sales increased 5% year-over-year for the third quarter, driven by 27% volume growth, partially offset by foreign exchange impact and lower net selling price resulting from increased competition. AMGEVITA continued to be the most prescribed adalimumab biosimilar in Europe.
Hematology-Oncology

LUMAKRAS/LUMYKRAS (sotorasib) generated $75 million of sales for the third quarter, driven by volume growth. Quarter-over-quarter sales declined 3% driven by lower net selling price due to an unfavorable price adjustment resulting from a reimbursement approval in Germany, partially offset by 15% volume growth. In the U.S., LUMAKRAS has been prescribed to over 3,700 patients by over 2,200 physicians in both academic and community settings. Outside the U.S., LUMYKRAS has now been approved in over 45 countries around the world. We are actively launching in 30 markets and pursuing reimbursement in the remaining countries.
KYPROLIS (carfilzomib) sales increased 9% year-over-year for the third quarter, driven by 11% volume growth.
XGEVA (denosumab) sales decreased 4% year-over-year for the third quarter, driven by a 3% decline in volume, lower inventory levels, and unfavorable foreign exchange impact, partially offset by higher net selling price.
Vectibix (panitumumab) sales increased 24% year-over-year for the third quarter, driven by volume growth. In the third quarter, volume growth benefited from the timing of shipments to Takeda, our partner in Japan.
Nplate (romiplostim) sales increased 5% year-over-year for the third quarter, primarily driven by 12% volume growth, partially offset by unfavorable changes to estimated sales deductions. In the third quarter, volume growth benefited from increased shipments to KKC, our partner in Japan.
BLINCYTO (blinatumomab) sales increased 14% year-over-year for the third quarter, driven by volume growth.
MVASI sales decreased 24% year-over-year for the third quarter, primarily driven by lower net selling price. The most recently published Average Selling Price (ASP) for MVASI in the U.S. declined 37% year-over-year and 12% quarter-over-quarter. Looking forward, we expect continued net selling price erosion and declining volume driven by increased competition and continued ASP erosion.
KANJINTI (trastuzumab-anns) sales decreased 38% year-over-year for the third quarter, primarily driven by lower net selling price and decline in volume, partially offset by favorable changes to estimated sales deductions. The most recently published ASP for KANJINTI in the U.S. declined 38% year-over-year and 11% quarter-over-quarter. Going forward, we expect continued net selling price deterioration and volume declines driven by increased competition and continued ASP erosion.
Established Products

Total sales of our established products, which include Neulasta (pegfilgrastim), NEUPOGEN (filgrastim), EPOGEN (epoetin alfa), Aranesp (darbepotein alfa), Parsabiv (etelcalcetide), and Sensipar/Mimpara (cinacalcet), decreased 17% year-over-year for the third quarter, primarily driven by lower net selling price and lower inventory levels. In the third quarter, the published ASP for Neulasta in the U.S. declined 24% year-over-year and 7% quarter-over-quarter. In the aggregate, we expect the year-over-year net selling price and volume erosion for this portfolio of products to continue.
Operating Expense, Operating Margin and Tax Rate Analysis

On a GAAP basis:

Total Operating Expenses decreased 8%. Cost of Sales margin remained flat. Research & Development (R&D) expenses decreased 22% primarily due to a $400 million licensing-related upfront payment to KKC in 2021. Selling, General & Administrative (SG&A) expenses decreased 1%.
Operating Margin as a percentage of product sales increased 5.0 percentage points to 42.6%.
Tax Rate decreased 2.2 percentage points primarily due to the prior year nondeductible Acquired In-Process Research & Development (Acquired IPR&D) expense arising from the acquisition of Five Prime Therapeutics and net favorable items, partially offset by a nondeductible loss from a nonstrategic divestiture.
On a non-GAAP basis:

Total Operating Expenses decreased 8%. Cost of Sales margin increased 0.3 percentage points driven by changes in product mix, partially offset by lower manufacturing cost and lower costs associated with COVID-19 antibody shipments. R&D expenses decreased 22% primarily due to a $400 million licensing-related upfront payment to KKC in 2021. Without the one-time KKC upfront payment, R&D expenses increased 10% primarily due to higher late-stage program support and research and early pipeline spend, partially offset by lower marketed product support. SG&A expenses increased 1%.
Operating Margin as a percentage of product sales increased 4.2 percentage points to 52.5%.
Tax Rate decreased 0.4 percentage points primarily due to net favorable items during the quarter as compared to the prior year.
Cash Flow and Balance Sheet

The Company generated $2.8 billion of free cash flow in the third quarter of 2022 versus $2.2 billion in the third quarter of 2021 primarily driven by favorable changes in working capital.
The Company’s third quarter 2022 dividend of $1.94 per share was declared on August 3, 2022, and was paid on September 8, 2022, to all stockholders of record as of August 18, 2022, representing a 10% increase from 2021.
During the third quarter, 1.5 million shares of common stock were retired in connection with the final settlement of accelerated share repurchase agreements that the Company entered into in February 2022.
Cash and investments totaled $11.5 billion and debt outstanding totaled $38.7 billion as of September 30, 2022.
2022 Guidance

For the full year 2022, the Company now expects:

Total revenues in the range of $26.0 billion to $26.3 billion.
On a GAAP basis, EPS in the range of $11.46 to $12.17, and a tax rate in the range of 11.0% to 12.5%.
On a non-GAAP basis, EPS in the range of $17.25 to $17.85, and a tax rate in the range of 13.5% to 14.5%.
Capital expenditures to be approximately $950 million, unchanged from previous guidance.
Share repurchases in the range of $6.0 billion to $7.0 billion, unchanged from previous guidance.
Third Quarter Product and Pipeline Update

The Company provided the following updates on selected product and pipeline programs:

General Medicine

Repatha

An abstract based on data from the Repatha FOURIER and FOURIER-open label extension studies highlighting the association between the significant and sustained achievement of low and very low, low-density lipoprotein cholesterol (LDL-C) levels and lower rates of major cardiovascular events has been accepted as a late-breaking abstract at the American Heart Association Scientific Sessions (AHA) in November.
Olpasiran (AMG 890)

An abstract based on the end-of-treatment analysis data from a Phase 2 study of olpasiran, a small interfering RNA molecule that reduces Lipoprotein(a) (Lp(a)) synthesis in the liver in subjects with elevated Lp(a) has been accepted as a late-breaking clinical trial presentation at AHA in November.
AMG 133

A Phase 1 study of AMG 133, a multispecific that inhibits the gastric inhibitory polypeptide receptor (GIPR) and activates the glucagon-like peptide 1 (GLP-1) receptor, has completed enrollment.
Data from the single- and multiple-dose cohorts of this Phase 1 study will be presented at the 20th World Congress on Insulin Resistance, Diabetes, and Cardiovascular Disease (WCIRDC) Hybrid Conference in December.
Webcast call Monday, November. 7, 2022

David M. Reese, M.D., executive vice president of Research and Development at Amgen, along with members of Amgen’s R&D team and a clinical investigator, will discuss the Phase 2 data on olpasiran, data from the Repatha FOURIER and FOURIER-open label extension studies and will provide an update on a Phase 1 study of AMG 133 during the call. The webcast will be broadcast over the internet simultaneously and will be available to members of the news media, investors and the general public.
Inflammation

Otezla

In September, results were presented from:
The Phase 3 SPROUT study, evaluating Otezla in pediatric patients (ages 6 through 17) with moderate to severe plaque psoriasis. Otezla treatment resulted in significant improvements in measures of disease severity at week 16 compared with placebo.
The Phase 3 DISCREET study, evaluating Otezla in adult patients with moderate to severe genital psoriasis. Otezla treatment showed a clinically meaningful and statistically significant improvement in genital psoriasis, including improvements in skin clearance, itch, and quality of life at week 16 compared with placebo.
In both studies, safety findings were consistent with the known profile of Otezla; no new signals were identified.
Based on these results, discussions with the FDA are ongoing for DISCREET to add clinical data to Otezla U.S. prescribing information. Discussions with regulatory authorities globally for SPROUT are forthcoming.
TEZSPIRE

In September, TEZSPIRE was approved
in the European Union as an add-on maintenance treatment in adults and adolescents 12 years and older with severe asthma who are inadequately controlled despite high-dose inhaled corticosteroids plus another medicinal product for maintenance treatment.
by the Japanese Ministry of Health, Labour, and Welfare for the treatment of bronchial asthma in patients with severe or refractory disease in whom asthma symptoms cannot be controlled with mid- or high-dose inhaled corticosteroids and other long-term maintenance therapies.
Regulatory reviews continue in other jurisdictions.
In severe asthma, the PASSAGE Phase 4 real-world effectiveness study, the WAYFINDER Phase 3b study, and the SUNRISE Phase 3 study are enrolling patients.
A Phase 3 study continues to enroll patients with chronic rhinosinusitis with nasal polyps.
Planning is underway for a Phase 3 study in patients with eosinophilic esophagitis.
A Phase 2b study in patients with chronic spontaneous urticaria is fully enrolled, with data readout anticipated in H1-2023.
A Phase 2 study continues to enroll patients with chronic obstructive pulmonary disease.
Rocatinlimab (AMG 451 / KHK4083)

In September, data were presented
from a Phase 2 study of rocatinlimab, an anti-OX40 monoclonal antibody, which demonstrated improvement in head and neck atopic dermatitis in patients with moderate to severe disease.
demonstrating that rocatinlimab provides durable normalization of atopic dermatitis inflammation-related gene expression in skin biopsies from atopic dermatitis patients.
The ROCKET Phase 3 program evaluating rocatinlimab in patients with moderate to severe atopic dermatitis was initiated in June. Following additional discussions with regulators and our partner, we are amending the studies to further improve patient convenience and investigate a range of doses. Amendments are not related to safety or efficacy issues.
Rozibafusp alfa (AMG 570)

A Phase 2b study of rozibafusp alfa, an antibody-peptide conjugate that simultaneously blocks inducible T-cell costimulatory ligand (ICOSL) and B-cell activating factor (BAFF) activity, continues to enroll patients with systemic lupus erythematosus (SLE).
Efavaleukin alfa (AMG 592)

A Phase 2b study of efavaleukin alfa, an interleukin-2 (IL-2) mutein Fc fusion protein, continues to enroll patients with SLE while a Phase 2b study continues to enroll patients with ulcerative colitis.
Ordesekimab (AMG 714 / PRV-015)

A Phase 2b study of AMG 714, a monoclonal antibody that binds interleukin-15, continues to enroll patients with nonresponsive celiac disease.
Oncology

LUMAKRAS/LUMYKRAS

In August, data were presented demonstrating that
in a mostly pretreated advanced non-small cell lung cancer (NSCLC) population, lead-in cohorts treated with LUMAKRAS followed by a combination of LUMAKRAS and immunotherapy demonstrated durable clinical activity with lower rates of grade 3-4 Treatment-Related Adverse Events (TRAEs) compared to concurrently treated cohorts. Dose expansion is ongoing in treatment-naïve patients using lower-dose LUMAKRAS lead-in followed by combination of LUMAKRAS with pembrolizumab.
LUMAKRAS given in combination with Src homology region 2-containing protein tyrosine phosphatase 2 (SHP2) inhibitor RMC-4630 demonstrated promising clinical activity in patients with KRAS G12C-mutated NSCLC, most notably in KRAS G12C inhibitor-naïve patients.
In September, data were presented demonstrating that
in the global Phase 3 CodeBreaK 200 trial, LUMAKRAS treatment led to increased progression-free survival (PFS) (primary endpoint) and a significantly higher objective response rate (ORR) (key secondary endpoint) in patients with KRAS G12C-mutated NSCLC compared with intravenous chemotherapy docetaxel. Patient-reported outcomes (a key secondary endpoint) also favored LUMAKRAS versus docetaxel.
in the Phase 1b CodeBreaK 101 study, LUMAKRAS combined with Vectibix demonstrated encouraging efficacy and safety in patients with chemo-refractory metastatic colorectal cancer (CRC). This combination delivered a 30% ORR with a median PFS of 5.7 months. With a median follow up of 8.8 months, median overall survival (OS) was not yet reached. A Phase 3 trial continues to enroll using this combination.
The Company is planning to initiate a Phase 3 study of LUMAKRAS plus chemotherapy in first-line KRAS G12C mutant and PD-L1 negative advanced/metastatic NSCLC.
BLINCYTO

Eastern Cooperative Oncology Group and the American College of Radiology Imaging Network (ECOG-ACRIN) Cancer Research Group announced that a National Cancer Institute sponsored, registration enabling BLINCYTO randomized controlled trial (E1910) in adults with newly diagnosed Philadelphia chromosome negative B-cell acute lymphoblastic leukemia, met the primary endpoint of statistically significant improvement in OS at a predefined interim analysis. This study investigated the addition of BLINCYTO to standard of care chemotherapy. Data were submitted to a medical congress taking place later this year and will be submitted to regulatory authorities in due course.
Vectibix

American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) guidelines in the U.S. and European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) guidelines in Europe were updated to indicate anti-EGFR monoclonal antibodies are preferred treatment over bevacizumab in patients with RAS wild type (RAS/BRAF wild type by ESMO (Free ESMO Whitepaper)) metastatic CRC and left-sided tumors. These updates were based on the Vectibix PARADIGM study that was presented at ASCO (Free ASCO Whitepaper), where data demonstrated that the mFOLFOX6 + Vectibix combination provides a statistically significant improvement in OS over the mFOLFOX6 + bevacizumab combination as first-line treatment for metastatic CRC patients with a left-sided primary tumor and in the overall population.
Bemarituzumab

FORTITUDE-101, a Phase 3 study of bemarituzumab a fibroblast growth factor receptor 2b (FGFR2b) targeting monoclonal antibody, plus chemotherapy, versus placebo plus chemotherapy in first-line gastric cancer with FGFR2b overexpression continues to enroll patients.
FORTITUDE-102, a Phase 1b/3 study of bemarituzumab plus chemotherapy and nivolumab versus chemotherapy and nivolumab in first-line gastric cancer with FGFR2b overexpression is enrolling patients in the Phase 3 portion of the study.
FORTITUDE-103, a Phase 1b study of bemarituzumab plus oral chemotherapy regimens in first-line gastric cancer is enrolling patients.
FORTITUDE-201, a Phase 1b study of bemarituzumab monotherapy and in combination with standard of care therapy continues to enroll patients with squamous NSCLC with FGFR2b overexpression.
FORTITUDE-301, a Phase 1b/2 basket study evaluating the safety and efficacy of bemarituzumab monotherapy in solid tumors with FGFR2b overexpression is enrolling patients.
Tarlatamab (AMG 757)

In August, Phase 1 data from DeLLphi-300 were presented demonstrating that in heavily pretreated patients with small-cell lung cancer (SCLC), tarlatamab, a half-life extended (HLE) bispecific T-cell engager (BiTE) molecule targeting delta-like ligand 3 (DLL3), delivered a confirmed ORR of 23%, a median duration of response of 13.0 months and a median OS of 13.2 months. DeLLphi-301, a potentially registrational Phase 2 study of tarlatamab continues to enroll patients in this setting.
DeLLphi-300, a Phase 1 study of tarlatamab, continues to enroll patients with relapsed/refractory SCLC.
DeLLphi-302, a Phase 1b study of tarlatamab in combination with AMG 404, an anti-programmed cell death-1 monoclonal antibody, continues to enroll patients with second-line or later SCLC.
DeLLphi-303, a Phase 1b study of tarlatamab in combination with standard of care in first-line SCLC, is enrolling patients.
DeLLpro-300, a Phase 1b study of tarlatamab, continues to enroll patients with de novo or treatment-emergent neuroendocrine prostate cancer.
AMG 509

A Phase 1 dose-escalation study of AMG 509, a bispecific molecule targeting six-transmembrane epithelial antigen of prostate 1 (STEAP1) continues to enroll patients with metastatic castrate-resistant prostate cancer (mCRPC).
AMG 340

A Phase 1 dose-escalation study of AMG 340, a lower T-cell affinity BiTE molecule targeting prostate-specific membrane antigen (PSMA), continues to enroll patients with mCRPC.
AMG 193

A Phase 1/1b/2 study of AMG 193, a novel small molecule methylthioadenosine (MTA) cooperative protein arginine methyltransferase 5 (PRMT5) molecular glue, continues to enroll patients with advanced methylthioadenosine phosphorylase (MTAP)-null solid tumors.
Biosimilars

In August, the Company announced positive top-line results from the DAHLIA study, a randomized, double-blind, active-controlled, two-period crossover Phase 3 study evaluating the efficacy and safety of ABP 959, a biosimilar candidate to SOLIRIS (eculizumab), compared with SOLIRIS in adult patients with paroxysmal nocturnal hemoglobinuria (PNH).
The primary analysis of a randomized, double-blind, active controlled, Phase 3 study evaluating the efficacy and safety of ABP 938, an investigational biosimilar to EYLEA (aflibercept) compared with EYLEA met its primary endpoint in subjects with neovascular age-related macular degeneration; final analysis is expected in 2023.
A Phase 3 study evaluating the efficacy and safety of ABP 654 compared to STELARA (ustekinumab) in adult patients with moderate to severe plaque psoriasis has completed, and these data were submitted to the FDA to support U.S. approval.
A Phase 3 study to support an interchangeability designation in the U.S. for ABP 654 is ongoing.
A Phase 3 study to support an interchangeability designation in the U.S. for AMJEVITA (adalimumab-atto) is ongoing.
TEZSPIRE is being developed in collaboration with AstraZeneca.
Rocatinlimab, formerly AMG 451 / KHK4083 is being developed in collaboration with KKC.
Ordesekimab formerly AMG 714 and also known as PRV-015 is being developed in collaboration with Provention Bio.
AMG 509 is being developed in collaboration with Xencor.
STELARA is a registered trademark of Janssen Pharmaceutica NV.
EYLEA is a registered trademark of Regeneron Pharmaceuticals, Inc.
SOLIRIS is a registered trademark of Alexion Pharmaceuticals, Inc.

Non-GAAP Financial Measures

In this news release, management has presented its operating results for the third quarters of 2022 and 2021, in accordance with U.S. Generally Accepted Accounting Principles (GAAP) and on a non-GAAP basis. In addition, management has presented its full year 2022 EPS and tax guidance in accordance with GAAP and on a non-GAAP basis. These non-GAAP financial measures are computed by excluding certain items related to acquisitions, divestitures, restructuring and certain other items from the related GAAP financial measures. Beginning January 1, 2022, following industry guidance from the U.S. Securities and Exchange Commission, the Company no longer excludes adjustments for upfront license fees, development milestones and IPR&D expenses of pre-approval programs related to licensing, collaboration and asset acquisition transactions from its non-GAAP financial measures. For purposes of comparability, the non-GAAP financial results for the third quarter of 2021 have been updated to reflect this change. Reconciliations for these non-GAAP financial measures to the most directly comparable GAAP financial measures are included in the news release. Management has presented Free Cash Flow (FCF), which is a non-GAAP financial measure, for the third quarters of 2022 and 2021. FCF is computed by subtracting capital expenditures from operating cash flow, each as determined in accordance with GAAP. Management has also presented Total Revenues Adjusted for Foreign Currency Impact, which is a non-GAAP financial measure, for the third quarter of 2022. Total Revenues Adjusted for Foreign Currency Impact is computed by converting our current period local currency product sales using the prior period foreign currency exchange rates and comparing that to our current period product sales.

The Company believes that its presentation of non-GAAP financial measures provides useful supplementary information to and facilitates additional analysis by investors. The Company uses certain non-GAAP financial measures to enhance an investor’s overall understanding of the financial performance and prospects for the future of the Company’s ongoing business activities by facilitating comparisons of results of ongoing business operations among current, past and future periods. The Company believes that FCF provides a further measure of the Company’s liquidity. Further, the Company believes Total Revenues Adjusted for Foreign Currency Impact provides supplementary information on the Company’s product sales performance by excluding changes in foreign currency exchange rates between comparative periods.

The Company uses the non-GAAP financial measures set forth in the news release in connection with its own budgeting and financial planning internally to evaluate the performance of the business, including to allocate resources and to evaluate results relative to incentive compensation targets. The non-GAAP financial measures are in addition to, not a substitute for, or superior to, measures of financial performance prepared in accordance with GAAP.

On November 3, 2022 Iovance Biotherapeutics, Inc. (NASDAQ: IOVA), a late-stage biotechnology company developing novel T cell-based cancer immunotherapies (tumor infiltrating lymphocyte, TIL, and peripheral-blood lymphocyte, PBL), reported third quarter and year-to-date 2022 financial results and corporate updates (Press release, Iovance Biotherapeutics, NOV 3, 2022, View Source [SID1234622954]).

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Frederick Vogt, Ph.D., J.D., Interim President and Chief Executive Officer of Iovance, stated, "Iovance has made tremendous progress year-to-date. With our rolling BLA submission for lifileucel and six active clinical trials of TIL therapy underway, we are executing our mission to innovate, develop and deliver TIL therapy for patients with cancer. We are on track to complete our BLA submission in the fourth quarter. As we prepare for our first potential FDA approval and commercial launch and advance our pipeline and technology platforms, we believe we have multiple opportunities to create significant value for patients with cancer as well as for our shareholders."

Third Quarter 2022 Highlights and Recent Corporate Updates

Regulatory and Clinical Updates for Iovance TIL Therapy (Lifileucel) in Advanced Melanoma

BLA Submission: A rolling BLA submission for lifileucel in advanced melanoma (post-anti-PD-1 therapy) commenced in August 2022 and is anticipated to complete in the fourth quarter of 2022.

C-144-01 Trial Presentation and Poster at Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper): Iovance reported positive topline clinical data from Cohorts 2 and 4 of the C-144-01 clinical trial in advanced melanoma in the second quarter of 2022. A pooled analysis and additional results for Cohorts 2 and 4 will be presented during SITC (Free SITC Whitepaper)’s 37th Annual Meeting as well as a Webcast on November 10, 2022.

Phase 3 trial in frontline advanced melanoma: Iovance remains on track to begin the Phase 3 trial of lifileucel in combination with pembrolizumab in frontline advanced melanoma in late 2022. The Phase 3 trial is intended to expand the opportunity for lifileucel as an earlier treatment and serve as a confirmatory study.

Poster at European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2022: A poster at ESMO (Free ESMO Whitepaper) highlighted the potential for lifileucel in advanced melanoma patients who progress after anti-LAG-3 and anti-PD-1 combination therapy. Lifileucel response rates were consistent between the overall C-144-01 study population and a C-144-01 subgroup analysis of patients treated with prior anti-LAG-3 containing therapy.
Manufacturing and Commercial Preparations

The Iovance Cell Therapy Center (iCTC) is currently operating flex suites for clinical manufacturing and core suites for activities to support BLA submission and review, including pre-approval inspections, in preparation for commercial supply.

The iCTC facility as currently built has annual capacity to supply TIL therapies for 2,000+ patients, with flexibility to build out existing shell space to supply 5,000+ patients.

Contract manufacturers provide additional flexibility and capacity for Iovance to meet potential commercial and clinical demand, including a new agreement for two cGMP manufacturing suites for commercial manufacturing and supply.

Iovance is executing several initiatives ahead of potential commercialization in 2023, including on-boarding and personnel training at authorized treatment centers (ATCs), education and awareness, and other launch readiness activities.
Clinical Pipeline

Iovance TIL therapy (LN-145) in mNSCLC: Enrollment is ongoing at more than 40 active clinical sites in the U.S., Canada and Europe for the IOV-LUN-202 trial of LN-145 in patients with mNSCLC. Iovance is engaged in discussions with the FDA about the potential for IOV-LUN-202 to serve as a registrational trial for LN-145 in mNSCLC and intends to execute an updated regulatory strategy based on this dialogue and feedback.

Iovance PD-1 inactivated TIL therapy (IOV-4001) in previously treated advanced melanoma or mNSCLC: the first patient was dosed, and completed the safety observation period, in the IOV-GM1-201 trial of IOV-4001, Iovance’s first genetically modified TIL therapy. To inactivate the gene coding for the PD-1 protein, IOV-4001 utilizes the gene editing TALEN technology licensed from Cellectis.

Lifileucel in advanced cervical cancer: Iovance expanded Cohort 2 of the ongoing C-145-04 trial to enroll additional patients. Following FDA discussions and feedback, Cohort 2 is intended to support a BLA in cervical cancer following progression on chemotherapy and pembrolizumab.
Research Programs for Next-Generation TIL Therapies and Related Technologies

Additional research and preclinical studies focused on optimizing TIL therapy consist of several targets for genetic modification using the gene-editing TALEN technology, including double genetic knock-out programs, as well as approaches to increase TIL potency using CD39/69 double negative TILs and gene knock-in targets that incorporate enhancements such as tethered cytokines.

A novel interleukin-2 (IL-2) analog (IOV-3001) is in IND-enabling studies supporting its use as part of the TIL treatment regimen following TIL infusion.
Corporate

Cash position of $366.6 million at September 30, 2022 is expected to be sufficient into 2024.

Iovance currently owns at least 60 granted or allowed U.S. and international patents for TIL compositions and methods of treatment and manufacturing in a broad range of cancers, with Gen 2 patent rights expected to provide exclusivity into 2038. More information on Iovance’s patent portfolio can be found on the Intellectual Property page on www.iovance.com.
Third Quarter and Year-to-Date 2022 Financial Results

Iovance had $366.6 million in cash, cash equivalents, investments and restricted cash at September 30, 2022, compared to $602.1 million at December 31, 2021. The cash position is expected to be sufficient to fund current and planned operations into 2024.

Jean-Marc Bellemin, Chief Financial Officer of Iovance, said, "As a late-stage oncology company approaching potential commercialization, our cash position continues to support our prudent investments in commercial launch preparations, internal manufacturing and pipeline expansion into several milestones to create value for patients and shareholders."

Net loss for the third quarter ended September 30, 2022, was $99.6 million, or $0.63 per share, compared to a net loss of $86.1 million, or $0.55 per share, for the third quarter ended September 30, 2021. Net loss for the nine months ended September 30, 2022, was $290.6 million, or $1.85 per share, compared to a net loss of $242.9 million, or $1.60 per share, for the same period ended September 30, 2021.

Research and development expenses were $72.5 million for the third quarter ended September 30, 2022, an increase of $7.1 million compared to $65.4 million for the same period ended September 30, 2021. Research and development expenses were $214.2 million for the nine months ended September 30, 2022, an increase of $30.8 million compared to $183.4 million for the same period ended September 30, 2021.

The increases in research and development expenses in the third quarter and year-to-date 2022 over the prior year periods were primarily attributable to growth of the internal research and development team, including stock-based compensation expense, as well as facility-related and internal research program costs, which were partially offset by lower clinical and manufacturing costs driven by completion of enrollment of pivotal clinical trials.

General and administrative expenses were $27.9 million for the third quarter ended September 30, 2022, an increase of $7.0 million compared to $20.9 million for the same period ended September 30, 2021. General and administrative expenses were $77.6 million for the nine months ended September 30, 2022, an increase of $17.8 million compared to $59.8 million for the same period ended September 30, 2021.

The increase in general and administrative expenses in the third quarter and year-to-date 2022 compared to the prior year periods were primarily attributable to growth of the internal general and administrative and commercial teams, including stock-based compensation expense, and facility-related costs associated with the build-out of the new corporate headquarters, as well as costs associated with pre-commercial activities.

For additional information, please see the Company’s Selected Condensed Consolidated Balance Sheet and Statement of Operations below.

Webcast and Conference Call

To participate in the conference call, please register at https://register.vevent.com/register/BI4721983fb77a4615b46f4ab97c051712. The live and archived webcast can be accessed in the Investors section of the Company’s website, IR.Iovance.com. The archived webcast will also be available for one year.

On November 3, 2022 Gossamer Bio, Inc. (Nasdaq: GOSS), a clinical-stage biopharmaceutical company focused on discovering, acquiring, developing and commercializing therapeutics in the disease areas of immunology, inflammation and oncology, reported its financial results for the third quarter ended September 30, 2022 and provided a business update (Press release, Gossamer Bio, NOV 3, 2022, View Source [SID1234622953]).

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"It has been a productive quarter as we eagerly await topline results from the Phase 2 TORREY Study," said Faheem Hasnain, Chairman, Co-Founder and CEO of Gossamer Bio. "Additionally, our team continues to enroll the dose escalation portion of the STAR CNS Study of GB5121, our CNS-penetrant BTK inhibitor for the treatment of CNS lymphomas."

Product Candidate Updates

Seralutinib (GB002): Inhaled PDGFR, CSF1R and c-KIT Inhibitor for Pulmonary Arterial Hypertension (PAH)

Ongoing TORREY Study is a Phase 2 clinical trial in patients with PAH whose disease has progressed despite standard-of-care therapy. The primary endpoint is change in pulmonary vascular resistance from baseline at week 24.
Topline data from the Phase 2 TORREY Study are expected in the second half of November or first half of December.
Ahead of these data, Gossamer has commenced investment in operational activities to enable the commencement of a registrational PAH Phase 3 clinical program in the third quarter of 2023.
GB5121: Oral, CNS-Penetrant BTK Inhibitor for Primary CNS Lymphoma (PCNSL) and other Rare CNS Malignancies

Enrollment ongoing in Phase 1b/2 STAR CNS Study in relapsed / refractory PCNSL and other rare CNS malignancies.
Results from the STAR CNS study to be presented at relevant medical conferences, as data become available.
GB7208: Oral, CNS-Penetrant BTK Inhibitor for Multiple Sclerosis

Program highlighted in two poster presentations at the 38th Congress of the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS; October 2022):
P556: GB7208 is a CNS-Penetrant BTK Inhibitor Demonstrating Potent Activity on Pathogenic Pathways Implicated in Multiple Sclerosis
P690: GB7208 is a Novel, Highly Potent and Selective CNS-Penetrant BTK Inhibitor for Neuroinflammatory and Neurodegenerative Diseases
Posters are available online at: View Source
Preclinical Pipeline Updates

Data generated for two internally developed preclinical programs presented at recent medical conferences:
10th Annual Meeting of the International Cytokine & Interferon Society (September 2022):
P109: Identification of Novel Inhibitor(s) Targeting NLRP3 Inflammasome Activation
34th EORTC-NCI-AACR (Free EORTC-NCI-AACR Whitepaper) Symposium (October 2022):
P350: An Orally Bioavailable ENPP1-Selective Inhibitor Demonstrates Superior Immune Preservation Effects over STING Agonists and Confers Anti-Tumor Efficacy in Combination with Other Therapies in Syngeneic Tumor Models
Poster highlighting a third internally developed program to be presented at the upcoming 37th Annual Meeting of the Society for Immunotherapy of Cancer (SITC) (Free SITC Whitepaper), or SITC (Free SITC Whitepaper), in Boston from November 8-12, 2022:
P855: Diacylglycerol Kinase Alpha and Zeta Dual Inhibitors Enhance T Cell Responses and Promote Robust and Durable Anti-Tumor T Cell Immunity
Posters are available, or will be available, online at: View Source
Financial Results for Quarter Ended September 30, 2022

Cash, Cash Equivalents and Marketable Securities: Cash, cash equivalents and marketable securities as of September 30, 2022, were $304.4 million. The Company expects the combination of current cash, cash equivalents and marketable securities, and access to its debt facility, will be sufficient to fund its operating and capital expenditures into the second quarter of 2024.
Research and Development (R&D) Expenses: For the quarter ended September 30, 2022, R&D expenses were $44.5 million, compared to $43.2 million for the same period in 2021.
General and Administrative (G&A) Expenses: For the quarter ended September 30, 2022, G&A expenses were $11.5 million, compared to $12.5 million for the same period in 2021.
Net Loss: Net loss for the quarter ended September 30, 2022, was $59.4 million, or $0.65 per share, compared to a net loss of $60.2 million, or $0.80 per share, for the same period in 2021.