On May 4, 2022 IVERIC bio, Inc. (Nasdaq: ISEE) reported financial and operating results for the first quarter ended March 31, 2022 and provided a general business update (Press release, Ophthotech, MAY 4, 2022, View Source [SID1234613593]).

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"During the first quarter, we continued the momentum of 2021 for GATHER2, our second Phase 3 clinical trial for Zimura (avacincaptad pegol), a novel complement inhibitor, for the treatment of geographic atrophy (GA)," stated Glenn P. Sblendorio, Chief Executive Officer of Iveric Bio. "We look forward to the exciting opportunities that lie ahead in 2022, including reporting topline data from GATHER2 and being closer to reaching our goal of providing patients and physicians with a treatment for GA for which there are currently no treatments options available."

•The Company expects topline GATHER2 data to be available in the third quarter of this year, approximately one year after the enrollment of the last patient plus the time needed for database lock and analysis. If the results from GATHER2 are positive, the Company plans to submit a new drug application (NDA) with the U.S. Food and Drug Administration (FDA) and a marketing authorization application (MAA) with the European Medicines Agency.

•Patient retention for the GATHER2 clinical trial, as measured by the injection fidelity rate, continues to exceed the Company’s expectations. The Company is targeting an injection fidelity rate for GATHER2, as measured through month 12, of greater than 90%. Injection fidelity is calculated by dividing the total number of actual injections (drug and sham) for all patients by the total number of expected injections (drug and sham) based on the total number of patients enrolled in the trial. The Company considers injection fidelity to be the most important and stringent measure of patient retention because it reflects the timely administration of the drug or sham into the patient’s eye.

•The Company is currently more than 94% complete with year one of the GATHER2 clinical trial, based on the number of scheduled patient visits.

"We are pleased with the strength of our current cash position and with the progress achieved during this first quarter," stated Pravin U. Dugel, MD, President of Iveric Bio. "As we get closer to reporting the GATHER2 topline data, we continue to prepare for a potential submission of an NDA in the U.S. for Zimura for the treatment of GA as efficiently as possible. We are well-positioned with an established medical affairs team in place, and we continue to build out our commercial infrastructure with a team that has extensive experience in launching drugs to treat retinal diseases with large market potential. Additionally, during this year we continue to provide additional exploratory analyses from GATHER1, our first pivotal clinical trial for Zimura in GA, which analyses we believe further support the consistency of the positive data previously reported for GATHER1 and inform future potential development opportunities for Zimura in other indications."

Zimura (avacincaptad pegol): Complement C5 Inhibitor

•Today, the Company provided results from a post-hoc analysis of GATHER1 evaluating the reduction in GA lesion growth observed for patients receiving Zimura as compared to patients receiving sham in a subset of patients based on the distance of a patient’s GA lesion to the foveal center at baseline. See the press release issued earlier today. The Company believes the results of this post-hoc analysis are consistent with the other results previously reported for GATHER1.

•In March 2022, the U.S. Patent and Trademark Office (USPTO) granted the Company a patent with claims covering methods of using Zimura for the treatment of GA. Subject to any patent term adjustments or extensions the Company may obtain, the issued patent is expected to expire in 2034.

•In April 2022, the Company provided results from a post-hoc analysis of the 8 cases of choroidal neovascularization (CNV) reported for the Zimura 2 mg group (n=67 patients) in the GATHER1 trial. An independent and masked reading center reviewed the optical coherence tomography (OCT) images of those patients at the 12-month and 18-month timepoints and classified the cases as non-exudative macular neovascularization (MNV) (2 cases at 12 months and 18 months) and exudative MNV (4 cases at 12 months and 6 cases at 18 months). The reading center also found that among the 6 patients who developed exudative MNV at 18 months, 5 of those patients had a double layer sign at baseline. See the Company’s Form 8-K filed on April 4, 2022, for full results from this analysis. Based on scientific literature and clinical understanding among the retinal community, the Company believes that the presence of a double-layer sign on OCT may be a useful biomarker to predict the future onset of cases of exudative MNV.

•In February 2022, results from a post-hoc analysis that evaluated various GA growth parameters to explore the rate of disease progression within various regions in the fovea among a subset of patients from GATHER1 were presented at the Angiogenesis, Exudation and Degeneration conference. Consistent with the overall results of GATHER1, in the post-hoc analysis a reduction in lesion growth in five standardized regions surrounding and including the central foveal area was observed for patients receiving Zimura 2 mg as compared to patients receiving sham over a period of 18 months. The Company believes preserving the central fovea region may be associated with clinical outcomes important to GA patients.

•The Company plans to initiate a clinical trial studying Zimura in patients with intermediate AMD in the fourth quarter of 2022, following planned interactions with the FDA and other regulatory authorities. The Company’s development strategy in this indication is subject to regulatory feedback.

•Patient enrollment in STAR, the Company’s Phase 2b screening clinical trial of Zimura for the treatment of autosomal recessive Stargardt disease (STGD1), is ongoing. The results of this clinical trial are expected after the topline results of GATHER2.

IC-500: HtrA1 (high temperature requirement A serine peptidase 1 protein) Inhibitor
•The Company is planning for IND-enabling toxicology studies for IC-500. The Company expects to submit an investigational new drug application (IND) to the FDA for IC-500 during mid-2023.

Gene Therapy Programs in Orphan Inherited Retinal Diseases (IRDs)
•As the Company focuses its efforts and resources on the development and potential commercialization of Zimura, the Company is exploring potential collaborations for the future development and potential commercialization of IC-100, the Company’s product candidate for Rhodopsin-Mediated Autosomal Dominant Retinitis Pigmentosa (RHO-adRP) and IC-200, the Company’s product candidate for BEST1-Related IRDs.
•The Company is continuing its minigene programs for Leber’s Congenital Amaurosis type 10 (CEP290), autosomal recessive Stargardt Disease (ABCA4) and Usher’s syndrome (USH2A).

Corporate Updates
The Company expanded its Board of Directors by adding Christine Ann Miller, a pharmaceutical veteran, to the Company’s board of directors in January 2022.

First Quarter 2022 Financial Update and 2022 Cash Guidance

•As of March 31, 2022, the Company had approximately $345.7 million in cash, cash equivalents and available-for-sale securities.

•The Company estimates its year-end 2022 cash, cash equivalents and available-for-sale securities to range between $215 and $225 million. The Company also estimates that its cash, cash equivalents and available-for-sale securities will be sufficient to fund its planned capital expenditure requirements and operating expenses through at least mid-2024. These estimates are based on the Company’s current business plan, including the continuation of its ongoing clinical development programs for Zimura in GA and STGD1 and the initiation of an intermediate AMD clinical trial, preparation and potential filing of an NDA and MAA for Zimura in GA, continuing preparations for potential commercial launch of Zimura in GA, investing in sustained release delivery technologies for Zimura, and the advancement of its IC-500 development program. Excluded from these estimates are any potential approval or sales milestones payable to Archemix Corp. or any potential expenses for actual commercial launch of Zimura, such as associated sales force expenses, any additional expenditures related to potentially studying Zimura in indications outside of GA, STGD1 and intermediate AMD, or resulting from the potential in-licensing or acquisition of additional product candidates or technologies, or any associated development the Company may pursue.

2022 Q1 Financial Highlights

•R&D Expenses: Research and development expenses were $22.6 million for the quarter ended March 31, 2022, compared to $18.5 million for the same period in 2021. Research and development expenses increased primarily due to the continued progress and patient recruitment activities of our GATHER2 clinical trial, increased manufacturing activities for Zimura, and increases in personnel costs, including share-based compensation associated with additional research and development staffing.

•G&A Expenses: General and administrative expenses were $12.1 million for the quarter ended March 31, 2022, compared to $8.3 million for the same period in 2021. General and administrative expenses increased primarily due increases in personnel costs, including share-based compensation associated with preparations for potential commercial launch of Zimura in GA.

•Net Loss: The Company reported a net loss for the quarter ended March 31, 2022 of $34.5 million, or ($0.29) per diluted share, compared to a net loss of $26.8 million, or $(0.29) per diluted share, for the same period in 2021.

Conference Call/Web Cast Information
Iveric Bio will host a conference call/webcast to discuss the Company’s financial and operating results and provide a business update. The call is scheduled for May 4, 2022, at 8:00 a.m. Eastern Time. To participate in this conference call, dial 1-888-317-6003 (USA) or 1-412-317-6061 (International), passcode 1313914. A live, listen-only audio webcast of the conference call can be accessed on the Investors section of the Iveric Bio website at www.ivericbio.com. A replay will be available approximately two hours following the live call for two weeks. The replay number is 1-877-344-7529 (USA Toll Free), passcode 9999784.

On May 4, 2022 Northwest Biotherapeutics (OTCQB: NWBO) ("NW Bio"), a biotechnology company developing DCVax personalized immune therapies for solid tumor cancers, reported that a presentation entitled "Autologous Tumor Lysate-Loaded Dendritic Cell Vaccination for Glioblastoma" will be made on May 10, 2022 at 11:10 a.m., by Dr. Linda Liau at the Frontiers of Cancer Immunotherapy Conference (CIMT) (Free CIMT Whitepaper) of the New York Academy of Sciences (Press release, Northwest Biotherapeutics, MAY 4, 2022, View Source [SID1234613592]).

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This presentation can be viewed virtually by registering online at the Academy’s website at View Source

On May 4, 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 first quarter ended March 31, 2022 (Press release, Fate Therapeutics, MAY 4, 2022, View Source [SID1234613590]).

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"We have made significant progress across our disease areas, operations, and collaborations in early 2022, including preparing for submission to the FDA of our multi-disciplinary RMAT briefing package to inform pivotal study readiness in relapsed / refractory aggressive lymphoma, as well as our FT596 plus R-CHOP clinical protocol to initiate investigation in first-line patients," said Scott Wolchko, President and Chief Executive Officer of Fate Therapeutics. "We are also poised to treat the first solid tumor patient with FT536, our multi-antigen targeted CAR MICA/B NK cell product candidate, and have initiated IND-enabling activities for two CAR NK cell product candidates under our collaboration with Janssen. We look forward to providing clinical updates for our multiplexed-engineered, iPSC-derived NK and T-cell product candidates across our disease franchises in the second half of 2022."

B-cell Malignancy Disease Franchise

FT596+R Enrollment Ongoing in Single- and Multi-dose, Multi-cycle Cohorts for R/R BCL. The Company’s multi-center Phase 1 study of FT596 in combination with rituximab (FT596+R) for relapsed / refractory (r/r) B-cell lymphoma (BCL) is currently enrolling patients in the following cohorts to further assess dose and treatment schedule: multi-dose at 900 million cells per dose with FT596 being administered on Day 1 and Day 15; single-dose at 1.8 billion cells; and single-dose at 900 million cells. The Company plans to open a multi-dose cohort at 1.8 billion cells per dose, with FT596 being administered on Day 1 and Day 15, upon clearance of dose-limiting toxicities (DLTs). Each cohort permits eligible patients to receive multiple treatment cycles.
FT596+R-CHOP Clinical Protocol to be Submitted to FDA in 2Q22. In the second quarter of 2022, the Company plans to submit a new clinical protocol to the FT596 Investigational New Drug (IND) application to assess the safety and activity of adding FT596 to R-CHOP, the standard first-line immunochemotherapy for patients with aggressive lymphomas. The proposed treatment schema includes administering up to six doses of FT596, without conditioning chemotherapy, with one dose being administered with each of six standard cycles of R-CHOP. The objective of the Phase 1 study is to inform the feasibility of development of FT596 in first-line aggressive lymphoma patients treated outpatient in the community setting.
FT516 Multi-disciplinary RMAT Meeting Planned for mid-2022. In December, the Company announced that the U.S. Food and Drug Administration (FDA) granted Regenerative Medicine Advanced Therapy (RMAT) designation to FT516 for the treatment of r/r diffuse large B-cell lymphoma (DLBCL). The Company plans to hold a multi-disciplinary meeting with the FDA in mid-2022 to discuss key CMC topics and pivotal study design in patients who have progressed or relapsed following prior treatment with FDA‑approved CD19‑directed chimeric antigen receptor (CAR) T-cell therapy. No standard therapies are available for these patients, and recent retrospective analyses of real-world data presented at the 2021 Annual Meeting of the American Society of Hematology (ASH) (Free ASH Whitepaper) demonstrate extremely poor treatment outcomes with complete response rates of administered therapies ranging from 5% to 25% and overall survival ranging from 5.2 months to 7.5 months.
FT516+R Enrollment Ongoing in Multiple, Multi-dose, Multi-cycle, Disease-specific Expansion Cohorts for R/R BCL. The Company’s multi-center 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, multi-cycle expansion cohorts at 900 million cells per dose, including patients with r/r aggressive lymphomas who have previously been treated with CD19-targeted CAR T-cell therapy.
FT819 Enrollment Ongoing in Second Single-dose and First Multi-dose Escalation Cohorts. The Company is conducting a landmark Phase 1 study of FT819, the first-ever T-cell therapy manufactured from a clonal master induced pluripotent stem cell (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, ensuring complete bi-allelic disruption of T-cell receptor expression and promoting uniform CAR expression. Dose escalation is ongoing in the second single-dose cohort of 180 million cells and in the first multi-dose cohort of 30 million cells per dose for r/r BCL. In the first FT819 single-dose escalation cohort (90 million cells) for r/r BCL, there were no DLTs and no FT819-related Grade ≥3 adverse events.
Proof-of-concept Data of ADR-armed CAR NK Cells for Conditioning-free Therapy Presented at AACR (Free AACR Whitepaper). At the American Association for Cancer Research (AACR) (Free AACR Whitepaper) Annual Meeting 2022 held in April, the Company highlighted its novel synthetic alloimmune defense receptor (ADR), which targets 4-1BB expressed on allo-reactive host T and NK cells. In a mixed lymphocyte reaction assay, ADR-armed iPSC-derived CAR NK cells inhibited the expansion of allo-reactive T and NK cells and exhibited enhanced functional persistence in whole peripheral blood mononuclear cell milieu. Furthermore, in a preclinical model designed to induce rejection, ADR-armed iPSC-derived CAR NK cells exhibited robust tumor control in vivo in the presence of host allo-reactive T-cell system. These preclinical data provide proof-of-concept that ADR-armed iPSC-derived CAR NK cell therapies have the potential to maintain potent anti-tumor activity without requiring chemotherapy conditioning.
AML Disease Franchise

FT538 Enrollment Ongoing in Multi-dose Escalation Cohort of 1 Billion Cells per Dose. The Company’s Phase 1 study is designed to assess three once-weekly doses of FT538 as monotherapy, and is currently enrolling patients in the third multi-dose escalation cohort (1 billion cells per dose) for r/r acute myeloid leukemia (AML). 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 third multi-dose escalation cohort at 1 billion cells per dose.
Multiple Myeloma Franchise

First Patients Treated with FT576+D in Phase 1 Study. The multi-center Phase 1 clinical trial is designed to assess single-dose and multi-dose treatment schedules of FT576 as monotherapy and in combination with daratumumab (FT576+D) for the treatment of r/r multiple myeloma (MM). There were no DLTs observed in the first single-dose escalation cohort (100 million cells) as monotherapy. In addition, the first patient has been treated in the first single-dose escalation cohort (100 million cells) of FT576+D. The Company plans to enroll the multi-dose treatment schedule, with FT576 administered at 100 million cells per dose on Days 1 and 15, upon clearance of the first single-dose escalation cohort of FT576+D.
Initial Preclinical Data of Dual CAR NK Cells Presented at AACR (Free AACR Whitepaper). The Company unveiled a dual CAR approach targeting two tumor-associated antigens to overcome mechanisms of resistance for r/r MM. Using the multiplexed-engineered master iPSC line of FT576 as starting material, the Company engineered into the master iPSC line a second CAR targeting the major histocompatibility complex (MHC) class I chain-related proteins A (MICA) and B (MICB), which proteins are highly expressed on malignant plasma cells and precursors in the bone marrow of MM. The Company showed that, in an aggressive xenograft model of heterogeneously-mixed cancer cells, iPSC-derived dual CAR NK cells targeting BCMA and MICA/B demonstrate superior tumor control in vivo compared to iPSC-derived single CAR NK cells.
Solid Tumor Franchise

On-track for First Patient Treatment with FT536 CAR MICA/B-targeted NK Cell Product Candidate. The Company is preparing to initiate a multi-center Phase 1 clinical trial to assess a multi-dose, multi-cycle treatment schedule of FT536 as monotherapy and in combination with monoclonal antibody therapy for advanced solid tumors. The off-the-shelf, multiplexed-engineered, iPSC-derived NK cell product candidate incorporates both a novel CAR targeting MICA/B, high expression of which has been reported on many solid tumors, as well as the Company’s proprietary high-affinity, non-cleavable CD16 (hnCD16) Fc receptor to promote dual-antigen targeting of solid tumors. The Company has successfully completed manufacture and is conducting final release testing, and is working with the study’s first clinical site to initiate enrollment in the second quarter of 2022.
Novel CAR Targeting pan-Cancer Antigen B7-H3 Featured at AACR (Free AACR Whitepaper). The Company presented preclinical data in collaboration with investigators from the University of Minnesota demonstrating the specificity and function of a novel camelid nanobody CAR targeting B7-H3 (camB7-H3), a member of the B7 family of immunoregulatory proteins that is overexpressed in cancer and promotes tumor growth, metastasis, and drug resistance. The Company showed that camB7-H3 CAR T cells exhibit target-specific binding and activity in vitro against several solid tumor cell lines and promote durable disease control in vivo in an aggressive disseminated xenograft model of B7-H3-expressing tumor cells. The Company is currently assessing several multiplexed-engineered, iPSC-derived camB7-H3 CAR NK cell and CAR T-cell product candidates for IND candidate selection.
Other Corporate Highlights

Preclinical Milestone Reached for Third Product Candidate under Janssen Collaboration. In April 2022, Janssen nominated a third iPSC-derived, CAR-targeted cell product candidate incorporating a Janssen proprietary antigen binding domain, triggering the payment of a milestone fee to the Company under the collaboration.
Second GMP Manufacturing Facility Poised for Launch in 2H22. The Company’s state-of-the-art, multi-drug product manufacturing facility located in Poway, California is undergoing qualification, and is expected to be fully operational and producing GMP material in the second half of 2022. The facility is designed to supply drug product for the conduct of pivotal studies and initial commercial launch, and is located on the campus of the Company’s corporate headquarters allowing for full operational integration among the technical operations, regulatory and quality, research and development, and corporate teams.
First Quarter 2022 Financial Results

Cash & Investment Position: Cash, cash equivalents and investments as of March 31, 2022 were $641.7 million.
Total Revenue: Revenue was $18.4 million for the first quarter of 2022, which was derived from the Company’s collaborations with Janssen and Ono Pharmaceutical.
R&D Expenses: Research and development expenses were $72.1 million for the first quarter of 2022, which includes $12.7 million of non-cash stock-based compensation expense.
G&A Expenses: General and administrative expenses were $20.7 million for the first quarter of 2022, which includes $6.6 million of non-cash stock-based compensation expense.
Shares Outstanding: Common shares outstanding were 96.5 million, and preferred shares outstanding were 2.8 million, as of March 31, 2022. Each preferred share is convertible into five common shares.
Today’s Conference Call and Webcast
The Company will conduct a conference call today, Wednesday, May 4, 2022 at 5:00 p.m. ET to review financial and operating results for the quarter ended March 31, 2022. In order to participate in the conference call, please dial (877) 303-6235 (domestic) or (631) 291-4837 (international) and refer to conference ID 9978043. 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 multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell lymphoma as a monotherapy and in combination with rituximab, and for the treatment of relapsed / refractory chronic lymphocytic leukemia (CLL) as a monotherapy and in combination with obinutuzumab (NCT04245722).

About 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 multi-center Phase 1 clinical trial for the treatment of relapsed / refractory B-cell malignancies, including B-cell lymphoma, chronic lymphocytic leukemia, and acute lymphoblastic leukemia (NCT04629729).

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 in 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 multi-center Phase 1 clinical trial for the treatment of relapsed / refractory multiple myeloma as a monotherapy and in combination with daratumumab (NCT05182073).

On May 4, 2022 Cytokinetics, Incorporated (Nasdaq: CYTK) reported financial results for the first quarter of 2022. Net loss for the first quarter was $89.4 million, or $1.05 per share, compared to net loss for the first quarter of 2021 of $47.1 million, or $0.66 per share (Press release, Cytokinetics, MAY 4, 2022, View Source [SID1234613588]). Cash, cash equivalents and investments totaled $686.1 million at March 31, 2022.

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"We achieved meaningful progress during the first quarter of 2022 with especially notable milestones relating to our cardiovascular pipeline, including the acceptance and filing of our NDA for omecamtiv mecarbil with FDA and the opening to enrollment in both SEQUOIA-HCM and Cohort 4 of REDWOOD-HCM. Additionally we shared positive data from Cohort 3 of REDWOOD-HCM demonstrating a substantial treatment effect with aficamten in patients taking disopyramide, and additional data from GALACTIC-HF reinforcing its safety, ease of initiation in the hospital setting and potential to reduce costs associated with fewer hospitalizations," said Robert I. Blum, Cytokinetics’ President and Chief Executive Officer. "Having secured long-term capital from Royalty Pharma also in the first quarter, our stronger balance sheet enables us to both accelerate our development of aficamten as well as to advance commercial readiness activities supportive of the potential approval of omecamtiv mecarbil this year."

Q1 and Recent Highlights

Cardiac Muscle Programs

omecamtiv mecarbil (cardiac myosin activator)

The U.S. Food and Drug Administration (FDA) accepted and filed our New Drug Application (NDA) for omecamtiv mecarbil for the treatment of heart failure with reduced ejection fraction (HFrEF). The NDA was assigned standard review with a Prescription Drug User Fee Act (PDUFA) target action date of November 30, 2022.

Continued building our commercial infrastructure and launch readiness capabilities for omecamtiv mecarbil in the U.S. including initiation of hiring first line field-based sales force leaders, selection of a patient services partner, and activities related to field force operations and market access.

Doubled the size of our therapeutic Medical Scientist team, hired a Field Director, and began recruitment for our Managed Healthcare Medical Scientist team.

Completed risk assessment of an end-to-end supply chain and advanced appropriate mitigating actions; initiated several major digital systems supportive of supply chain logistics.

Presented additional data from GALACTIC-HF (Global Approach to Lowering Adverse Cardiac Outcomes Through Improving Contractility in Heart Failure) at the American College of Cardiology 71st Annual Scientific Session (ACC.22) including:

An analysis showing that a subgroup of patients in GALACTIC-HF treated with omecamtiv mecarbil led to a reduction in resource intensity, with an estimated cost offset of $3,085, or 19% reduction per patient. The majority of these cost reductions were due to heart failure hospitalizations avoided by patients who were treated with omecamtiv mecarbil.

An analysis showing that the effect of treatment with omecamtiv mecarbil was associated with similar risk reduction in the primary composite endpoint in both hospitalized patients and in outpatients, indicating that initiation of omecamtiv mecarbil was safe and well tolerated in both hospitalized patients and outpatients.
Announced results of METEORIC-HF (Multicenter Exercise Tolerance Evaluation of Omecamtiv Mecarbil Related to Increased Contractility in Heart Failure), a Phase 3 clinical trial of omecamtiv mecarbil in patients with HFrEF that evaluated the effect of treatment with omecamtiv mecarbil compared to placebo on exercise capacity as determined by cardiopulmonary exercise testing (CPET). After 20 weeks of treatment, there was no change in peak oxygen uptake (pVO2) in patients treated with omecamtiv mecarbil versus placebo. Adverse events, including major cardiac events, were similar between the treatment arms, and the safety profile of omecamtiv mecarbil was consistent with prior clinical trials, including GALACTIC-HF.

Published a manuscript entitled "Influence of Atrial Fibrillation on Efficacy and Safety of Omecamtiv Mecarbil in Heart Failure: The GALACTIC-HF Trial" in the European Heart Journal.

Published a manuscript entitled "Developments in Exercise Capacity Assessment in Heart Failure Clinical Trials and the Rationale for the Design of METEORIC-HF" in Circulation: Heart Failure.
aficamten (cardiac myosin inhibitor)

Announced positive data from Cohort 3 of REDWOOD-HCM (Randomized Evaluation of Dosing With CK-274 in Obstructive Outflow Disease in HCM), which enrolled patients with symptomatic obstructive hypertrophic cardiomyopathy (HCM) and a resting left ventricular outflow tract gradient (LVOT-G) ≥50, or resting LVOT-G ≥30 mmHg and post-Valsalva LVOT-G ≥50 mmHg, whose background therapy included disopyramide and in the majority a beta-adrenergic blocker. Results showed that substantial reductions in the average resting LVOT-G as well as the post-Valsalva LVOT-G (defined as resting gradient <30 mmHg and post-Valsalva gradient <50 mmHg) were achieved. The safety and tolerability of aficamten were consistent with prior experience in REDWOOD-HCM with no treatment interruptions and no serious adverse events attributed to treatment reported by the investigators.

Opened enrollment in Cohort 4 of REDWOOD-HCM (Randomized Evaluation of Dosing With CK-274 in Obstructive Outflow Disease in HCM), which will enroll, in an open label fashion, 30-40 patients with symptomatic non-obstructive hypertrophic cardiomyopathy receiving background medical therapy. The primary objective is to determine the safety and tolerability of aficamten in patients with non-obstructive hypertrophic cardiomyopathy.

Opened enrollment in SEQUOIA-HCM (Safety, Efficacy, and Quantitative Understanding of Obstruction Impact of Aficamten in HCM), a Phase 3 randomized, placebo-controlled, double-blind, multi-center clinical trial designed to evaluate the effect of aficamten on exercise capacity, heart failure symptoms, and New York Heart Association (NYHA) Functional Class in patients with symptomatic obstructive HCM on background medical therapy for 24 weeks.
Skeletal Muscle Program

reldesemtiv (fast skeletal muscle troponin activator (FSTA))

Continued conduct and enrollment of COURAGE-ALS (Clinical Outcomes Using Reldesemtiv on ALSFRS-R in a Global Evaluation in ALS), the Phase 3 clinical trial of reldesemtiv in patients with amyotrophic lateral sclerosis (ALS).
Pre-Clinical Development and Ongoing Research

Continued to advance new muscle directed compounds and conduct IND-enabling studies with the expectation of our potentially moving 1-2 drug candidates into clinical development in the next year.

Continued research activities directed to our other muscle biology research programs.
Corporate

Secured long-term capital from entities affiliated with Royalty Pharma to support the potential commercialization of omecamtiv mecarbil and the further development of aficamten. Royalty Pharma will provide Cytokinetics long-term capital and debt financing of up to $300 million, subject to certain conditions, to support the potential commercialization of omecamtiv mecarbil and the further development of aficamten, and other general corporate purposes. Royalty Pharma also purchased a royalty on aficamten of 4.5% on sales up to $1 billion and 3.5% on sales above $1 billion, subject to certain potential step-downs, in exchange for payments of up to $150 million.

Announced changes to the Board of Directors including the retirement of L. Patrick Gage, Ph.D., former Chairman of the Board, the appointment of John T. Henderson, M.B., Ch.B. as the company’s new Chairman, and the appointment of Robert A. Harrington, M.D., Arthur L. Bloomfield Professor and Chair, Department of Medicine, Stanford University, to the Board.

Joined with the European Organisation for Rare Diseases (EURORDIS) and the National Organization for Rare Disorders (NORD) to recognize Rare Disease Day, an international campaign elevating the public understanding of rare diseases.

Announced a three-year collaboration with the American Heart Association (AHA) Bay Area to accelerate education and awareness of heart disease, in which Cytokinetics will provide funding and support for several initiatives led by AHA Bay Area.

Awarded Cytokinetics Communications Fellowship Grants to patient advocacy organizations serving the heart failure, HCM and ALS communities to support increased capacity in communications, awareness building and community engagement for nonprofit organizations serving the patient community.
2022 Corporate Milestones

Cardiac Muscle Programs

omecamtiv mecarbil (cardiac myosin activator)

Launch omecamtiv mecarbil in the U.S. pending FDA approval in Q4 2022.
aficamten (cardiac myosin inhibitor)

Continue enrolling patients with obstructive HCM in SEQUOIA-HCM through 2022.

Continue enrolling patients with non-obstructive HCM in Cohort 4 of REDWOOD-HCM.

Begin second Phase 3 clinical trial of aficamten in obstructive HCM in 2H 2022.

Expect to share data from the open label extension study of aficamten, REDWOOD-HCM OLE, at Heart Failure 2022 on May 23, 2022.
CK-3828136 (CK-136) (cardiac troponin activator)

Reactivate development program for CK-136 in 2H 2022.
Skeletal Muscle Program

reldesemtiv (fast skeletal muscle troponin activator (FSTA))

Expect the Data Monitoring committee to conduct the first interim analysis from COURAGE-ALS in 2H 2022, assessing for futility, 12 weeks after approximately one-third or more of the planned sample size is randomized.
Financials

Revenues for the first quarter 2022 were $1.1 million compared to $6.5 million for the corresponding period in 2021. The decrease in revenues was primarily due to the termination of the Amgen agreement effective May 20, 2021.

Research and development expenses for the first quarter 2022 increased to $45.9 million compared to $31.6 million for the same period in 2021, due primarily to increases in spending for clinical development activities for our cardiac muscle inhibitor programs, facility expenses, COURAGE-ALS, and early research programs.

General and administrative expenses for the first quarter 2022 increased to $33.1 million from $15.6 million for the same period in 2021 due primarily to higher outside services spending in anticipation of the potential commercial launch of omecamtiv mecarbil, an increase in personnel related costs including stock-based compensation and facilities expenses for our new headquarters.

Conference Call and Webcast Information

Members of Cytokinetics’ senior management team will review the company’s first quarter results on a conference call today at 4:30 PM Eastern Time. The call will be simultaneously webcast and can be accessed from the homepage and in the Investors & Media section of Cytokinetics’ website at www.cytokinetics.com. The live audio of the conference call can also be accessed by telephone by dialing either (866) 999-CYTK (2985) (United States and Canada) or (706) 679-3078 (international) and typing in the passcode 5771758.

An archived replay of the webcast will be available via Cytokinetics’ website until May 18, 2022. The replay will also be available via telephone by dialing (855) 859-2056 (United States and Canada) or (404) 537-3406 (international) and typing in the passcode 5771758 from May 4, 2022 at 8:00 PM Eastern Time until May 18, 2022.

On May 4, 2022 Aligos Therapeutics, Inc. (Nasdaq: ALGS), a clinical stage biopharmaceutical company focused on developing novel therapeutics to address unmet medical needs in viral and liver diseases, reported recent business progress and financial results for the first quarter March 31, 2022 (Press release, Aligos Therapeutics, MAY 4, 2022, View Source [SID1234613587]).

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"From the very beginning, we designed Aligos to be a company with a diverse portfolio of drug candidates across a broad range of indications," said Lawrence Blatt, PhD, MBA, Chairman & CEO of Aligos. "This approach has allowed us to continue to advance promising new drug candidates from our portfolio even in the face of the recent discontinuation of our STOPS and antisense oligonucleotide (ASO) HBV programs in Q1. Our teams remain focused on advancing our pipeline and we look forward to achieving important milestones this year, including top line data for ALG-000184, our Class II CAM for HBV, and ALG-055009, our THR-β agonist for NASH. In addition, we are on track to file a clinical trial application in second half of 2022 to conduct a first in human study evaluating ALG-125755, our HBV siRNA. Finally, we are excited to see ALG-097558, a broad-spectrum coronavirus inhibitor that was identified in our collaboration with KU Leuven, advance towards the clinic."

Recent Business Progress

Aligos Portfolio of Drug Candidates:

HBV Programs

ALG-000184 (Class II CAM) – dosing in the 10-300 mg range for 28 days in chronic hepatitis B (CHB) patients continued in Q1 and is set to complete in Q3 2022. Cohorts evaluating doses of 10-300 mg given over 12 weeks are also set to begin in Q3. We plan to share top line results for 28 day and 12-week cohorts in Q2 and Q4 2022, respectively.

ALG-125755 (siRNA) – first in human enabling nonclinical studies continued in Q1 and are set to complete in Q3 2022 when we plan to file a clinical trial application (CTA) to enable dosing in healthy volunteers beginning in Q4 2022.

Our STOPS and ASO programs were terminated in Q1 due to insufficient antiviral activity and poor tolerability, respectively, being observed in Phase 1 studies.
NASH Programs

ALG-055009 (THR- β) – dosing in healthy volunteers (HVs) and subjects with hyperlipidemia continued in Q1 and is set to complete in Q2. Preliminary data after single and multiple oral doses will be shared as a poster presentation (Abstract #3109) at the upcoming EASL ILC meeting 22-26 June 2022. Topline results from this Phase 1 proof of concept study remain on track for release in Q3 2022.

Significant progress has been made in the nonalcoholic steatohepatitis (NASH) oligonucleotide research collaboration with Merck with respect to the two undisclosed targets, utilizing Aligos’ know-how and our proprietary oligonucleotide chemistry platform. Both collaboration programs are currently advancing further into lead optimization.
COVID Protease Inhibitor (PI) Program

ALG-097558 – we recently announced that we selected this broad-spectrum coronavirus protease inhibitor to move forward into development. ALG-097558 has shown superior potency compared to nirmatrelvir (PF-07321332) against SARS-CoV-2 and multiple resistant variants in all cell-based and biochemical assays tested to date. ALG-097558 is 7 to 20-fold more active than nirmatrelvir, depending on the variant. ALG-097558 exerts potent broad-spectrum activity against alpha and beta coronaviruses, and its highly conserved target site indicates a high probability that it will retain potent activity against potential future SARS-CoV-2 variants that may emerge. Projected efficacious doses of ALG-097558 can be achieved in humans without ritonavir boosting. Aligos expects to file a Phase 1 clinical trial application in second half of 2022.

Financial Results for the First Quarter 2022

Cash, cash equivalents and marketable securities totaled $183.2 million as of March 31, 2022, compared with $205.8 million as of December 31, 2021. We continue to believe our cash balance provides sufficient cash to fund planned operations into the first half of 2024.

Net losses for the three months ended March 31, 2022, were $35.6 million or basic and diluted net loss per common share of $0.84 compared to net losses of $27.7 million or basic and diluted net loss per common share of $0.74 for the three months ended March 31, 2021.

Research and development (R&D) expenses for the three months ended March 31, 2022, were $31.7 million compared with $22.9 million for the same period of 2021. The increase in R&D expenses for this comparative period is primarily attributable to an increase in third-party expenses primarily due to our continued increase in expenditures related to research, development and manufacturing activities associated with our CAM clinical trial activities as well as costs related to our NASH program, and our discontinued STOPS and ASO programs, leading to write off charges for non-cancelable purchase obligations. Total R&D stock-based compensation expense incurred for the three months ended March 31, 2022, was $2.0 million compared with $1.7 million for the same period for 2021.

General and administrative (G&A) expenses for the three months ended March 31, 2022, were $6.5 million compared with $5.8 million for the same period of 2021. The increase in G&A expenses for this comparative period is primarily attributable to an increase in ordinary routine employee-related costs partially offset by a decrease in in third-party expenses primarily due to decreased legal and accounting service costs. Total G&A stock-based compensation expense incurred for the three months ended March 31, 2022, was $1.8 million compared with $1.0 million for the same period of 2021.