On August 7, 2024 2seventy bio, Inc. (Nasdaq: TSVT), reported financial results and recent highlights for the second quarter ended June 30, 2024 (Press release, 2seventy bio, AUG 7, 2024, View Sourcenews-releases/news-release-details/2seventy-bio-reports-second-quarter-financial-results-and-1" target="_blank" title="View Sourcenews-releases/news-release-details/2seventy-bio-reports-second-quarter-financial-results-and-1" rel="nofollow">View Source [SID1234645481]).

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"This year has been transformative for 2seventy, and we enter the second half in a strong financial and operational position, poised for commercial growth," said Chip Baird, CEO. "We dramatically reduced our cost structure and strengthened our balance sheet with the completion of the sale of our oncology R&D business to Regeneron and the sale of our Hemophilia A program and gene editing technology to Novo Nordisk. These changes move us closer to achieving quarterly profitability by the end of 2025. We were pleased to see that Abecma turned a corner in the second quarter, recording modest growth in revenue in the U.S. Importantly, we saw a meaningful increase in patients undergoing apheresis, which we expect to translate to additional revenue growth in the third quarter. We look forward to the continued execution of our third line launch in the second half of 2024 and a continued return to growth for Abecma."

ABECMA COMMERCIAL AND REGULATORY HIGHLIGHTS

Second quarter Abecma (idecabtagene vicleucel; ide-cel) U.S. revenues, as reported by Bristol Myers Squibb (BMS), were $54 million. Demand, as measured by new patients undergoing apheresis in the quarter, saw meaningful growth.
In order to restore growth for Abecma, 2seventy bio and BMS are focused on competitively differentiating Abecma’s safety and efficacy profile supported by the strength of the KarMMa-3 and real-world data, and anticipates continued growth in the second half of 2024.
2seventy bio and BMS share equally in all profits and losses related to development, manufacturing, and commercialization of Abecma in the U.S. The Company reported collaborative arrangement revenue of $4.4 million related to the collaboration with BMS for the three months ended June 30, 2024.
SELECT SECOND QUARTER FINANCIAL RESULTS

Total revenues were $9.0 million for the three months ended June 30, 2024, compared to $36.0 million for the three months ended June 30, 2023. Total revenues were $21.4 million for the six months ended June 30, 2024, compared to $77.7 million for the six months ended June 30, 2023.
Research and development expenses were $16.0 million for the three months ended June 30, 2024, compared to $60.0 million for the three months ended June 30, 2023. Research and development expenses were $59.9 million for the six months ended June 30, 2024, compared to $128.2 million for the six months ended June 30, 2023.
Selling, general and administrative expenses were $9.9 million for the three months ended June 30, 2024, compared to $19.5 million for the three months ended June 30, 2023. Selling, general and administrative expenses were $22.5 million for the six months ended June 30, 2024, compared to $40.2 million for the six months ended June 30, 2023.
Restructuring expenses were $7.4 million for the three months ended June 30, 2024, and $11.6 million for the six months ended June 30, 2024. There were no restructuring expenses in the comparable three- and six-month periods in 2023.
The Company recognized a $48.0 million one-time gain on sale to Novo Nordisk for the three months ended June 30, 2024. Additionally, the Company recognized a $5.0 million one-time loss on assets held for sale to Regeneron for the six months ended June 30, 2024.
Net income was $24.9 million for the three months ended June 30, 2024, compared to net loss of $42.1 million for the three months ended June 30, 2023. Net loss was $27.8 million for the six months ended June 30, 2024, compared to net loss of $89.1 million for the six months ended June 30, 2023.
The Company has lowered its net cash spend range to $40-60 million for 2024.
Cash, cash equivalents, and marketable securities totaled $201.9 million as of June 30, 2024; the Company continues to expect to have cash runway beyond 2027.
Conference Call Information
2seventy bio will host a conference call and live webcast today, August 7 at 8:00 a.m. ET to discuss second quarter 2024 financial results and recent business highlights. Participants can access the conference call live via webcast which is available on the Investors and Media page of the company’s website at View Source Participants who wish to ask a question may register here to receive dial-in numbers and a unique pin to join the call.

A replay of the webcast may be accessed from the "News and Events" page in the Investors and Media section of our website at View Source and will be available for 30 days following the event.

ABECMA U.S. INDICATION
ABECMA is a B-cell maturation antigen (BCMA)-directed genetically modified autologous T cell immunotherapy indicated for the treatment of adult patients with relapsed or refractory multiple myeloma after two or more prior lines of therapy including an immunomodulatory agent, a proteasome inhibitor, and an anti-CD38 monoclonal antibody.

U.S. Important Safety Information

BOXED WARNING: CYTOKINE RELEASE SYNDROME, NEUROLOGIC TOXICITIES, HLH/MAS, PROLONGED CYTOPENIA and SECONDARY HEMATOLOGICAL MALIGNANCIES

Cytokine Release Syndrome (CRS), including fatal or life-threatening reactions, occurred in patients following treatment with ABECMA. Do not administer ABECMA to patients with active infection or inflammatory disorders. Treat severe or life-threatening CRS with tocilizumab or tocilizumab and corticosteroids.
Neurologic Toxicities, which may be severe or life-threatening, occurred following treatment with ABECMA, including concurrently with CRS, after CRS resolution, or in the absence of CRS. Monitor for neurologic events after treatment with ABECMA. Provide supportive care and/or corticosteroids as needed.
Hemophagocytic Lymphohistiocytosis/Macrophage Activation Syndrome (HLH/MAS) including fatal and life-threatening reactions, occurred in patients following treatment with ABECMA. HLH/MAS can occur with CRS or neurologic toxicities.
Prolonged Cytopenia with bleeding and infection, including fatal outcomes following stem cell transplantation for hematopoietic recovery, occurred following treatment with ABECMA.
T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including ABECMA
ABECMA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ABECMA REMS.
Warnings and Precautions:

Early Death: In KarMMa-3, a randomized (2:1), controlled trial, a higher proportion of patients experienced death within 9 months after randomization in the ABECMA arm (45/254; 18%) compared to the standard regimens arm (15/132; 11%). Early deaths occurred in 8% (20/254) and 0% prior to ABECMA infusion and standard regimen administration, respectively, and 10% (25/254) and 11% (15/132) after ABECMA infusion and standard regimen administration, respectively. Out of the 20 deaths that occurred prior to ABECMA infusion, 15 occurred from disease progression, 3 occurred from adverse events and 2 occurred from unknown causes. Out of the 25 deaths that occurred after ABECMA infusion, 10 occurred from disease progression, 11 occurred from adverse events, and 4 occurred from unknown causes.

Cytokine Release Syndrome (CRS): CRS, including fatal or life-threatening reactions, occurred following treatment with ABECMA. Among patients receiving ABECMA for relapsed refractory multiple myeloma in the KarMMa and KarMMa-3 studies (N=349), CRS occurred in 89% (310/349), including ≥ Grade 3 CRS (Lee grading system) in 7% (23/349) of patients and Grade 5 CRS in 0.9% (3/349) of patients. The median time-to-onset of CRS, any grade, was 1 day (range: 1 to 27 days), and the median duration of CRS was 5 days (range: 1 to 63 days). In the pooled studies, the rate of ≥Grade 3 CRS was 10% (7/71) for patients treated in dose range of 460 to 510 x 106 CAR-positive T cells and 5.4% (13/241) for patients treated in dose range of 300 to 460 x 106 CAR-positive T cells.

The most common manifestations of CRS (greater than or equal to 10%) included pyrexia (87%), hypotension (30%), tachycardia (26%), chills (19%), hypoxia (16%). Grade 3 or higher events that may be associated with CRS include hypotension, hypoxia, hyperbilirubinemia, hypofibrinogenemia, ARDS, atrial fibrillation, hepatocellular injury, metabolic acidosis, pulmonary edema, coagulopathy, renal failure, multiple organ dysfunction syndrome and HLH/MAS.

Identify CRS based on clinical presentation. Evaluate for and treat other causes of fever, hypoxia, and hypotension. CRS has been reported to be associated with findings of HLH/MAS, and the physiology of the syndromes may overlap. HLH/MAS is a potentially life-threatening condition. In patients with progressive symptoms of CRS or refractory CRS despite treatment, evaluate for evidence of HLH/MAS.

Of the 349 patients who received ABECMA in clinical trials, 226 (65%) patients received tocilizumab; 39% (135/349) received a single dose, while 26% (91/349) received more than 1 dose of tocilizumab. Overall, 24% (82/349) of patients received at least 1 dose of corticosteroids for treatment of CRS. Almost all patients who received corticosteroids for CRS also received tocilizumab. For patients treated in dose range of 460 to 510 x 106 CAR-positive T cells, 76% (54/71) of patients received tocilizumab and 35% (25/71) received at least 1 dose of corticosteroids for treatment of CRS. For patients treated in dose range of 300 to 460 x 106 CAR-positive T cells, 63% (152/241) of patients received tocilizumab and 20% (49/241) received at least 1 dose of corticosteroid for treatment of CRS.

Monitor patients at least daily for 7 days following ABECMA infusion at the REMS-certified healthcare facility for signs or symptoms of CRS and monitor patients for signs or symptoms of CRS for at least 4 weeks after ABECMA infusion. At the first sign of CRS, institute treatment with supportive care, tocilizumab and/or corticosteroids as indicated. Ensure that a minimum of 2 doses of tocilizumab are available prior to infusion of ABECMA. Counsel patients to seek immediate medical attention should signs or symptoms of CRS occur at any time.

Neurologic Toxicities: Neurologic toxicities, including immune-effector cell-associated neurotoxicity (ICANS), which may be severe or life- threatening, occurred concurrently with CRS, after CRS resolution, or in the absence of CRS following treatment with ABECMA.

In patients receiving ABECMA in the KarMMa and KarMMa-3 studies, CAR T cell-associated neurotoxicity occurred in 40% (139/349), including Grade 3 in 4% (14/349) and Grade 4 in 0.6% (2/349) of patients. The median time to onset of neurotoxicity was 2 days (range: 1 to 148 days). The median duration of CAR T cell-associated neurotoxicity was 8 days (range: 1 to 720 days) in all patients including those with ongoing neurologic events at the time of death or data cut off. CAR T cell-associated neurotoxicity resolved in 123 of 139 (88%) patients and median time to resolution was 5 days (range: 1 to 245 days). One-hundred and thirty four out of 349 (38%) patients with neurotoxicity had CRS. The onset of neurotoxicity during CRS was observed in 93 patients, before the onset of CRS in 12 patients, and after the CRS event in 29 patients. The rate of Grade 3 or 4 CAR T cell-associated neurotoxicity was 5.6% (4/71) and 3.7% (9/241) for patients treated in dose range of 460 to 510 x 106 CAR-positive T cells and 300 to 460 x 106 CAR-positive T cells, respectively. The most frequent (greater than or equal to 5%) manifestations of CAR T cell-associated neurotoxicity include encephalopathy (21%), headache (15%), dizziness (8%), delirium (6%), and tremor (6%).

At the safety update for KarMMa-3 study, one patient developed fatal neurotoxicity 43 days after ABECMA. In KarMMa, one patient had ongoing Grade 2 neurotoxicity at the time of death. Two patients had ongoing Grade 1 tremor at the time of data cutoff.

Cerebral edema has been associated with ABECMA in a patient in another study in multiple myeloma. Grade 3 myelitis and Grade 3 parkinsonism have occurred after treatment with ABECMA in another study in multiple myeloma.

Monitor patients at least daily for 7 days following ABECMA infusion at the REMS-certified healthcare facility for signs or symptoms of neurologic toxicities and monitor patients for signs or symptoms of neurologic toxicities for at least 4 weeks after ABECMA infusion and treat promptly. Rule out other causes of neurologic symptoms. Neurologic toxicity should be managed with supportive care and/or corticosteroids as needed. Counsel patients to seek immediate medical attention should signs or symptoms occur at any time.

Hemophagocytic Lymphohistiocytosis (HLH)/Macrophage Activation Syndrome (MAS): In patients receiving ABECMA in the KarMMa and KarMMa-3 studies, HLH/MAS occurred in 2.9% (10/349) of patients. All events of HLH/MAS had onset within 10 days of receiving ABECMA, with a median onset of 6.5 days (range: 4 to 10 days) and occurred in the setting of ongoing or worsening CRS. Five patients with HLH/MAS had overlapping neurotoxicity. The manifestations of HLH/MAS include hypotension, hypoxia, multiple organ dysfunction, renal dysfunction and cytopenia.

In KarMMa-3, one patient had Grade 5, two patients had Grade 4 and two patients had Grade 3 HLH/MAS. The patient with Grade 5 HLH/MAS also had Grade 5 candida sepsis and Grade 5 CRS. In another patient who died due to stroke, the Grade 4 HLH/MAS had resolved prior to death. Two cases of Grade 3 and one case of Grade 4 HLH/MAS had resolved.

In KarMMa, one patient treated in the 300 x 106 CAR-positive T cells dose cohort developed fatal multi-organ HLH/MAS with CRS. In another patient with fatal bronchopulmonary aspergillosis, HLH/MAS was contributory to the fatal outcome. Three cases of Grade 2 HLH/MAS resolved.

HLH/MAS is a potentially life-threatening condition with a high mortality rate if not recognized early and treated. Treatment of HLH/MAS should be administered per institutional guidelines.

ABECMA REMS: Due to the risk of CRS and neurologic toxicities, ABECMA is available only through a restricted program under a Risk Evaluation and Mitigation Strategy (REMS) called the ABECMA REMS. Further information is available at www.AbecmaREMS.com or contact Bristol-Myers Squibb at 1-866-340-7332.

Hypersensitivity Reactions: Allergic reactions may occur with the infusion of ABECMA. Serious hypersensitivity reactions, including anaphylaxis, may be due to dimethyl sulfoxide (DMSO) in ABECMA.

Infections: ABECMA should not be administered to patients with active infections or inflammatory disorders. Severe, life-threatening, or fatal infections occurred in patients after ABECMA infusion.

In all patients receiving ABECMA in the KarMMa and KarMMa-3 studies, infections (all grades) occurred in 61% of patients. Grade 3 or 4 infections occurred in 21% of patients. Grade 3 or 4 infections with an unspecified pathogen occurred in 12%, viral infections in 7%, bacterial infections in 4.3%, and fungal infections in 1.4% of patients. Overall, 15 patients had Grade 5 infections (4.3%); 8 patients (2.3%) with infections of pathogen unspecified, 3 patients (0.9%) with fungal infections, 3 patients (0.9%) with viral infections, and 1 patient (0.3%) with bacterial infection.

Monitor patients for signs and symptoms of infection before and after ABECMA infusion and treat appropriately. Administer prophylactic, pre-emptive, and/or therapeutic antimicrobials according to standard institutional guidelines.

Febrile neutropenia was observed in 38% (133/349) of patients after ABECMA infusion and may be concurrent with CRS. In the event of febrile neutropenia, evaluate for infection and manage with broad-spectrum antibiotics, fluids, and other supportive care as medically indicated.

Viral Reactivation: Cytomegalovirus (CMV) infection resulting in pneumonia and death has occurred following ABECMA administration. Monitor and treat for CMV reactivation in accordance with clinical guidelines. Hepatitis B virus (HBV) reactivation, in some cases resulting in fulminant hepatitis, hepatic failure, and death, can occur in patients treated with drugs directed against plasma cells. Perform screening for CMV, HBV, hepatitis C virus (HCV), and human immunodeficiency virus (HIV) in accordance with clinical guidelines before collection of cells for manufacturing. Consider antiviral therapy to prevent viral reactivation per local institutional guidelines/clinical practice.

Prolonged Cytopenias: In patients receiving ABECMA in the KarMMa and KarMMa-3 studies, 40% of patients (139/349) experienced prolonged Grade 3 or 4 neutropenia and 42% (145/349) experienced prolonged Grade 3 or 4 thrombocytopenia that had not resolved by Month 1 following ABECMA infusion. In 89% (123/139) of patients who recovered from Grade 3 or 4 neutropenia after Month 1, the median time to recovery from ABECMA infusion was 1.9 months. In 76% (110/145) of patients who recovered from Grade 3 or 4 thrombocytopenia, the median time to recovery was 1.9 months. Five patients underwent stem cell therapy for hematopoietic reconstitution due to prolonged cytopenia. The rate of Grade 3 or 4 thrombocytopenia was 62% (44/71) and 56% (135/241) for patients treated in dose range of 460 to 510 x 106 CAR-positive T cells and 300 to 460 x 106 CAR-positive T cells, respectively.

Monitor blood counts prior to and after ABECMA infusion. Manage cytopenia with myeloid growth factor and blood product transfusion support according to local institutional guidelines.

Hypogammaglobulinemia: In all patients receiving ABECMA in the KarMMa and KarMMa-3 studies, hypogammaglobulinemia was reported as an adverse event in 13% (46/349) of patients; laboratory IgG levels fell below 500 mg/dL after infusion in 37% (130/349) of patients treated with ABECMA.

Hypogammaglobulinemia either as an adverse reaction or laboratory IgG level below 500 mg/dL after infusion occurred in 45% (158/349) of patients treated with ABECMA. Forty-one percent of patients received intravenous immunoglobulin (IVIG) post-ABECMA for serum IgG <400 mg/dL.

Monitor immunoglobulin levels after treatment with ABECMA and administer IVIG for IgG <400 mg/dl. Manage appropriately per local institutional guidelines, including infection precautions and antibiotic or antiviral prophylaxis.

Use of Live Vaccines: The safety of immunization with live viral vaccines during or after ABECMA treatment has not been studied. Vaccination with live virus vaccines is not recommended for at least 6 weeks prior to the start of lymphodepleting chemotherapy, during ABECMA treatment, and until immune recovery following treatment with ABECMA.

Secondary Malignancies: Patients treated with ABECMA may develop secondary malignancies. In KarMMa-3, myeloid neoplasms (four cases of myelodysplastic syndrome and one case of acute myeloid leukemia) occurred in 2.2% (5/222) of patients following treatment with ABECMA compared to none in the standard regimens arm at the time of the safety update. The median time to onset of myeloid neoplasm from ide-cel infusion was 338 days (Range: 277 to 794 days). Three of these five patients have died following the development of myeloid neoplasm. One out of the five cases of myeloid neoplasm occurred after initiation of subsequent antimyeloma therapy.

T cell malignancies have occurred following treatment of hematologic malignancies with BCMA- and CD19-directed genetically modified autologous T cell immunotherapies, including ABECMA. Mature T cell malignancies, including CAR-positive tumors, may present as soon as weeks following infusion, and may include fatal outcomes.

Monitor life-long for secondary malignancies. In the event that a secondary malignancy occurs, contact Bristol-Myers Squibb at 1‑888‑805‑4555 for reporting and to obtain instructions on collection of patient samples for testing of secondary malignancy.

Effects on Ability to Drive and Operate Machinery: Due to the potential for neurologic events, including altered mental status or seizures, patients receiving ABECMA are at risk for altered or decreased consciousness or coordination in the 8 weeks following ABECMA infusion. Advise patients to refrain from driving and engaging in hazardous occupations or activities, such as operating heavy or potentially dangerous machinery, during this initial period.

Adverse Reactions: The most common nonlaboratory adverse reactions (incidence greater than or equal to 20%) include pyrexia, CRS, hypogammaglobulinemia, infections – pathogen unspecified, musculoskeletal pain, fatigue, febrile neutropenia, hypotension, tachycardia, diarrhea, nausea, headache, chills, upper respiratory tract infection, encephalopathy, edema, dyspnea and viral infections.

Please see full Prescribing Information, including Boxed WARNINGS and Medication Guide.

On August 7, 2024 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical‑stage T-cell reprogramming company advancing a diverse pipeline of cell therapies for patients with solid tumors or hematologic malignancies, reported financial results and business highlights for the second quarter ended June 30, 2024 (Press release, Lyell Immunopharma, AUG 7, 2024, View Source [SID1234645498]).

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"We are pleased that initial data from our Phase 1 trial of LYL797 demonstrated dose-dependent clinical activity and that LYL797 CAR T cells expanded, infiltrated solid tumors and killed cancer cells in patients. Based on these promising initial data, we have expanded the cancer indications under evaluation in this trial to include patients with ovarian and endometrial cancers, and we plan to file an IND to initiate a new trial evaluating LYL797 in multiple myeloma and chronic lymphocytic leukemia," said Lynn Seely, M.D., Lyell’s President and CEO. "In addition, our IND for LYL119, a next generation ROR1-targeted CAR T‑cell product candidate designed with four technologies to generate T cells with even greater capacity to resist exhaustion, has been cleared by the FDA, and we expect to report initial clinical data from the Phase 1 trial in the second half of 2025. We remain on track to report initial clinical data from our lead TIL program in the second half of this year. Our strong cash position enables us to advance multiple product candidates through critical clinical milestones and fund operations into 2027."

Second Quarter Updates and Recent Business Highlights

Lyell is advancing four wholly-owned product candidates. Two product candidates, LYL797 and LYL845, are in Phase 1 clinical development, and LYL119 is entering Phase 1 clinical development. A second-generation tumor infiltrating lymphocyte (TIL) product candidate is in preclinical development.
LYL797 – A ROR1-targeted CAR T-cell product candidate enhanced with anti-exhaustion technology designed for improved tumor infiltration and tumor cell killing

•Enrollment in the Phase 1 clinical trial of LYL797 is ongoing. The study was initiated in patients with relapsed/refractory triple-negative breast cancer (TNBC) or non-small cell lung cancer (NSCLC). Based on the initial clinical data that demonstrated dose-dependent anti-tumor activity, the trial has been expanded to include patients with platinum-resistant ovarian or endometrial cancers and an investigational new drug (IND) application is expected to be submitted in the second half of this year to initiate a second Phase 1 clinical trial of LYL797 in multiple myeloma and chronic lymphocytic leukemia (CLL).

•Initial clinical and translational data from the Phase 1 clinical trial of LYL797 were reported in June 2024. The initial dataset of 20 patients (16 patients with TNBC and four patients with NSCLC) demonstrated dose-dependent antitumor clinical activity and the ability of LYL797 CAR T cells to proliferate, infiltrate tumors and kill cancer cells in patients with relapsed/refractory disease. Patients with TNBC treated with LYL797 had an objective response rate (ORR) of 40% and a clinical benefit rate (CBR) of 60% at the 150 x 106 CAR T cell dose level, with a CBR of 38% across all dose levels evaluable at the time data were reported. Common treatment-related adverse events (TRAE) in patients without lung metastases included Grade 1 and 2 cytokine release syndrome (CRS) and headache, and the expected cytopenia from lymphodepletion. There were no reports of immune effector cell‑associated neurotoxicity syndrome (ICANS) attributed to LYL797. Pneumonitis occurred in some patients with lung metastases, including the index patient who experienced Grade 5 respiratory failure on Day 41. All patients are now given dexamethasone prophylaxis and dose escalation is continuing separately and more gradually in patients with lung involvement. No dose‑limiting toxicities have been reported in patients without lung involvement.
•Updated data from the ongoing Phase 1 trial in solid tumor indications, including the initiation of dose expansion, are expected in late 2024 – early 2025.
LYL845 – A TIL product candidate epigenetically reprogrammed using Lyell’s proprietary Epi-R manufacturing protocol, designed for differentiated potency and durability
•Enrollment in the Phase 1 clinical trial of LYL845 is ongoing. The trial is designed to include patients with relapsed or refractory metastatic or locally advanced melanoma, NSCLC and colorectal cancer.
•Initial clinical and translational data from the Phase 1 trial of LYL845 in patients with advanced melanoma are expected in the second half of 2024.
LYL119 – A next-generation ROR1-targeted CAR T-cell product candidate incorporating four stackable and complementary anti-exhaustion technologies designed for enhanced potency
•LYL119 is a ROR1-targeted CAR T-cell product enhanced with four novel genetic and epigenetic reprogramming technologies: c-Jun overexpression, NR4A3 knockout, Epi-R manufacturing protocol and Stim‑RTM T-cell activation technology.
•An IND application for LYL119 has received clearance from the U.S. Food and Drug Administration (FDA).
•The Phase 1 trial is designed as an open‑label dose‑escalation and ‑expansion trial in patients with ROR1‑positive solid tumors and will initially enroll patients with ROR1‑positive platinum‑resistant ovarian cancer or endometrial cancer. It is estimated that approximately 50% of patients with ovarian cancer and approximately 50% of patients with endometrial cancer have ROR1‑positive tumors.
•Initial clinical data are expected in the second half of 2025.
Second Quarter Financial Results
Lyell reported a net loss of $45.8 million for the second quarter ended June 30, 2024, compared to a net loss of $63.9 million for the same period in 2023. Non‑GAAP net loss, which excludes non-cash stock-based compensation, non‑cash expenses related to the change in the estimated fair value of success payment liabilities and certain non-cash investment gains and charges, was $39.1 million for the second quarter ended June 30, 2024, compared to $45.6 million for the same period in 2023.

GAAP and Non-GAAP Operating Expenses
•Research and development (R&D) expenses were $40.3 million for the second quarter ended June 30, 2024, compared to $47.5 million for the same period in 2023. The decrease in second quarter 2024 R&D expenses of $7.2 million was primarily driven by a decrease in personnel-related expenses associated with Lyell’s November 2023 reduction in workforce. Non‑GAAP R&D expenses, which exclude non-cash stock-based compensation and non-cash expenses related to the change in the estimated fair value of success payment liabilities for the second quarter ended June 30, 2024, were $37.2 million, compared to $41.6 million for the same period in 2023. The decrease in second quarter 2024 non-GAAP R&D expenses was primarily driven by a decrease in personnel-related expenses.

•General and administrative (G&A) expenses were $12.3 million for the second quarter ended June 30, 2024, compared to $19.0 million for the same period in 2023. The decrease in second quarter 2024 G&A expenses was primarily driven by decreases in non-cash stock-based compensation. Non‑GAAP G&A expenses, which exclude non-cash stock‑based compensation, for the second quarter ended June 30, 2024, were $7.8 million, compared to $10.1 million for the same period in 2023. The decrease in second quarter 2024 non-GAAP G&A expenses was primarily driven by a decrease in personnel-related expenses associated with Lyell’s November 2023 reduction in workforce.
A discussion of non-GAAP financial measures, including reconciliations of the most comparable GAAP measures to non‑GAAP financial measures, is presented below under "Non-GAAP Financial Measures."

Cash, cash equivalents and marketable securities
Cash, cash equivalents and marketable securities as of June 30, 2024, were $491.1 million, compared to $562.7 million as of December 31, 2023. Lyell believes that its cash, cash equivalents and marketable securities balances will be sufficient to meet working capital and capital expenditure needs into 2027.

On August 7, 2024 Halda Therapeutics, a biotechnology company developing a novel class of cancer therapies called RIPTACTM (Regulated Induced Proximity TArgeting Chimeras) therapeutics, reported the publication of data demonstrating proof-of-mechanism and pharmacology of a RIPTAC therapeutic, published in the peer-reviewed journal Cell Chemical Biology (Press release, Halda Therapeutics, AUG 7, 2024, View Source [SID1234645520]). The manuscript entitled, "Regulated Induced Proximity Targeting Chimeras (RIPTACs): a Heterobifunctional Small Molecule Strategy for Cancer Selective Therapies," describes the creation of a chemical biology model of RIPTAC therapeutics and illustrates the mechanism of action of this novel drug modality to enable selective killing of cancer cells.

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RIPTAC therapeutics are heterobifunctional small molecules that work by a novel "hold and kill" mechanism, bringing together two proteins, a tumor-specific protein and a protein with essential function, resulting in abrogation of the essential cell function, and subsequently, cancer cell death. This unique pharmacology does not require the target protein to be the driver of the cancer, unlike the majority of precision oncology medicines that rely on an oncogene driver as the target protein. In addition, the novel mode of action of RIPTAC therapeutics is designed to overcome the known bypass mechanisms of resistance that evolve during a course of therapy, a common limitation of today’s precision oncology medicines, thereby opening the potential for their use in both late and early stages of cancer treatment.

"We are excited to share data demonstrating the mechanism of action of RIPTAC molecules, as well as how the protein proximity paradigm can be extended into direct cancer cell killing," said Kanak Raina, PhD, lead author and Head of Biology at Halda. "Insights gained from the detailed interrogation of this chemical biology model have provided Halda with a robust foundation that has resulted in our pipeline of RIPTAC therapeutics for major cancers."

The publication details several chemical biology approaches using a model with a HaloTag‑FKBP target protein to dissect the mechanism of action and pharmacology of RIPTAC molecules. Key findings from the study include:

RIPTAC therapeutics demonstrated selective anti-proliferative activity in cells expressing the target protein.
A ternary complex formed by the target protein, the RIPTAC molecule, and a pan-essential protein abrogated the function of the essential protein selectively in target-expressing cells, causing cell death.
Several different pan-essential cellular proteins were shown to be amenable for selective cancer cell killing when incorporated into RIPTAC ternary complexes.
Halda’s scientific founder, Craig Crews, PhD, Professor of Molecular, Cellular, and Developmental Biology at Yale University, is an author on the paper in Cell Chemical Biology and is a pioneer of induced proximity biology that has led to the vision and invention of heterobifunctional drugs. Professor Crews commented, "RIPTAC therapeutics address a shortcoming shared by most current precision medicines for cancer, namely, the reliance on oncogenic driver proteins which can result in drug resistance in a large percentage of patients. The RIPTAC modality offers a new oral, selective, and widely applicable cancer cell-killing mechanism that can overcome drug resistance and can be used in advanced cancer where resistance has emerged, as well as in early stage disease where the tumor-specific protein is expressed."

On August 7, 2024 Aclaris Therapeutics, Inc. (NASDAQ: ACRS), a clinical-stage biopharmaceutical company focused on developing novel drug candidates for immuno-inflammatory diseases, reported its financial results for the second quarter of 2024 and provided a corporate update (Press release, Aclaris Therapeutics, AUG 7, 2024, View Source [SID1234645482]).

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"With study activities underway for our ATI-2138 Phase 2a trial in moderate to severe atopic dermatitis and the strengthening of our balance sheet through the completion of our royalty purchase agreement with OMERS, we’re well-positioned to drive our strategic initiatives forward," said Dr. Neal Walker, Interim President & CEO and Chair of the Board of Directors of Aclaris. "Our focus remains on leveraging our resources to maximize the potential of our innovative drug candidates, pursue available opportunities, and create long-term value for patients and shareholders alike."

Research and Development Highlights:

ITK Inhibitor Programs
ATI-2138, an investigational oral covalent ITK/JAK3 inhibitor
ATI-2138-AD-201: Aclaris is activating clinical sites and expects to enroll patients in the coming weeks in this Phase 2a open-label trial to investigate the safety, tolerability, pharmacokinetics, efficacy, and pharmacodynamics of ATI-2138 in subjects with moderate to severe atopic dermatitis (AD).
ITK Selective Compound
Aclaris is progressing to development candidate selection a second generation ITK selective inhibitor for autoimmune indications.
Lepzacitinib (ATI-1777), an investigational topical "soft" JAK 1/3 inhibitor
In January 2024, Aclaris reported positive top-line results from its Phase 2b trial of lepzacitinib in atopic dermatitis (AD).
Aclaris is currently seeking a global development and commercialization partner for this program (excluding Greater China). As previously announced, in 2022 Aclaris granted Pediatrix Therapeutics exclusive rights to develop and commercialize lepzacitinib in Greater China.
Zunsemetinib (ATI-450), an investigational oral small molecule MK2 inhibitor
Aclaris plans to support Washington University in St. Louis in its investigator-initiated Phase 1b/2 trials of zunsemetinib as a potential treatment for pancreatic cancer and metastatic breast cancer. Aclaris expects these trials to be primarily funded by grants awarded to Washington University.
Financial Highlights:

Liquidity and Capital Resources

As of June 30, 2024, Aclaris had aggregate cash, cash equivalents and marketable securities of $149.9 million compared to $181.9 million as of December 31, 2023. In July 2024, Aclaris received an upfront payment of $26.5 million and is eligible to receive up to an additional $5.0 million upon the achievement of certain sales milestones in connection with the sale of OLUMIANT royalties and milestones to OMERS Life Sciences.

Aclaris anticipates that its cash, cash equivalents and marketable securities as of June 30, 2024 in combination with the $26.5 million from the sale of OLUMIANT royalties and milestones will be sufficient to fund its operations into 2028, without giving effect to any potential new business development transactions, additional financing activities or the outcome of its strategic review.

Financial Results

Second Quarter 2024

Net loss was $11.0 million for the second quarter of 2024 compared to $29.6 million for the second quarter of 2023.
Total revenue was $2.8 million for the second quarter of 2024 compared to $1.9 million for the second quarter of 2023. The increase was primarily driven by an increase in royalties under the Lilly license agreement during the three months ended June 30, 2024.
Research and development (R&D) expenses were $8.8 million for the quarter ended June 30, 2024 compared to $25.3 million for the prior year period.
The $16.5 million decrease was primarily the result of lower:
Zunsemetinib development expenses associated with clinical activities for a Phase 2a trial for hidradenitis suppurativa which was completed in March 2023, a Phase 2b trial for rheumatoid arthritis which was completed in November 2023, a Phase 2b trial for psoriatic arthritis which was discontinued in December 2023, and drug candidate manufacturing costs;
Costs associated with lepzacitinib preclinical development activities and a Phase 2b clinical trial for AD which was completed in January 2024;
ATI-2138 development expenses, including costs associated with a Phase 1 MAD trial which was completed in September 2023 and other preclinical activities; and
Compensation-related expenses due to a decrease in headcount and higher forfeiture credits.
General and administrative (G&A) expenses were $4.8 million for the quarter ended June 30, 2024 compared to $8.3 million for the prior year period. The decrease was primarily due to a reduction in compensation-related expenses due to lower headcount and higher forfeiture credits, along with the recognition of bad debt expense recorded in the prior year period from Aclaris’ determination that collection of amounts due from EPI Health are uncertain as a result of their filing for Chapter 11 bankruptcy protection.
Licensing expenses were $1.3 million for the quarter ended June 30, 2024 compared to $0.6 million for the prior year period. The increase was due to an increase in royalties earned under the Lilly license agreement.
Revaluation of contingent consideration resulted in a $0.2 million loss for the quarter ended June 30, 2024 compared to a gain of $1.5 million for the prior year period.
Year-to-date 2024

Net loss was $27.9 million for the six months ended June 30, 2024 compared to $57.7 million for the six months ended June 30, 2023.
Total revenue was $5.2 million for the six months ended June 30, 2024 compared to $4.4 million for the six months ended June 30, 2023. The increase was primarily driven by an increase in royalties under the Lilly license agreement during the six months ended June 30, 2024.
R&D expenses were $18.6 million for the six months ended June 30, 2024 compared to $47.9 million for the prior year period.
The $29.3 million decrease was primarily the result of lower:
Zunsemetinib development expenses associated with clinical activities for a Phase 2a trial for hidradenitis suppurativa which was completed in March 2023, a Phase 2b trial for rheumatoid arthritis which was completed in November 2023, a Phase 2b trial for psoriatic arthritis which was discontinued in December 2023, and drug candidate manufacturing costs;
Costs associated with lepzacitinib preclinical development activities and a Phase 2b clinical trial for AD which was completed in January 2024;
ATI-2138 development expenses, including costs associated with a Phase 1 MAD trial which was completed in September 2023 and other preclinical activities; and
Compensation-related expenses due to a decrease in headcount and higher forfeiture credits.
G&A expenses were $11.6 million for the six months ended June 30, 2024 compared to $17.1 million for the prior year period. The decrease was primarily due to a reduction in compensation-related expenses due to lower headcount and higher forfeiture credits, a decrease in patent, legal and accounting related expenses, and the recognition of bad debt expense recorded in the prior year period from Aclaris’ determination that collection of amounts due from EPI Health are uncertain as a result of their filing for Chapter 11 bankruptcy protection.
Licensing expenses were $2.3 million for the six months ended June 30, 2024 compared to $1.6 million for the prior year period. The increase was due to an increase in royalties earned under the Lilly license agreement.
Revaluation of contingent consideration resulted in a $3.0 million loss for the six months ended June 30, 2024 compared to a gain of $2.3 million for the prior year period.
OLUMIANT is a registered trademark of Eli Lilly and Company.

On August 7, 2024 Omeros Corporation (Nasdaq: OMER), a clinical-stage biopharmaceutical company committed to discovering, developing and commercializing small-molecule and protein therapeutics for large-market and orphan indications targeting immunologic disorders including complement-mediated diseases, as well as cancers and addictive and compulsive disorders, reported recent highlights and developments as well as financial results for the second quarter ended June 30, 2024, which include (Press release, Omeros, AUG 7, 2024, View Source [SID1234645499]):

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● Net loss for the second quarter of 2024 was $56.0 million, or $0.97 per share, compared to a net loss of $37.3 million, or $0.59 per share for the second quarter of 2023. For the six months ended June 30, 2024, our net loss was $93.2 million, or $1.60 per share, compared to a net loss of $71.0 million, or $1.13 per share in the prior year period. The second quarter of 2024 includes a $17.6 million charge for narsoplimab drug substance delivered during the quarter, the manufacturing of which commenced in October 2023, a $21.2 million payment for term loan-related debt repurchase, and $1.9 million of term loan-related transaction costs. These significant cash outlays, representing a total of $40.7 million dollars, are not expected to be repeated in the foreseeable future.

● On June 3, 2024, we entered into a Credit and Guaranty Agreement (the "Credit Agreement") with funds managed by Athyrium Capital Management (collectively, "Athyrium") and funds managed by Highbridge Capital Management (collectively, "Highbridge") as lenders (the "Lenders"). Under the Credit Agreement, we entered into an initial senior secured term loan of $67.1 million (the "Initial Term Loan") and paid $21.2 million to the Lenders in exchange for $118.1 million aggregate principal amount of Omeros’ existing 5.25 percent convertible senior notes due on February 15, 2026 (the "2026 Notes") held by the Lenders and representing 55 percent of our total 2026 Notes. The Credit Agreement also provides for a $25.0 million delayed draw term loan available to be drawn on request by Omeros on or prior to June 3, 2025 contingent on regulatory approval of narsoplimab in hematopoietic stem cell transplant-associated thrombotic microangiopathy ("TA-TMA"). All loans under the Credit Agreement have a stated maturity date of June 3, 2028.

ο The purchase price in the debt exchange and repurchase of our outstanding 2026 Notes represents a discount from notional value of approximately 25 percent.

ο Neither the Initial Term Loan nor the delayed draw term loan includes equity consideration for the Lenders, preventing any shareholder dilution as a consequence of these transactions.

ο After giving effect to the repurchase, we had approximately $98 million principal amount of our 2026 Notes outstanding.

● At June 30, 2024, we had $158.9 million of cash and short-term investments available for operations and debt servicing, a decrease of $12.9 million from December 31, 2023.

● As previously disclosed, we submitted an analysis plan to assess our existing clinical trial data along with other evidence proposed to be included in a resubmission of our biologics license application ("BLA") for narsoplimab in TA-TMA. We are engaged in ongoing discussions with the FDA regarding the analysis plan and the other evidence proposed to be included in the submission. An additional meeting with FDA has been scheduled and we expect to provide a further update on our plans for resubmission and anticipated timing when more definitive information becomes available.

● We continued advancing our lead MASP-3 inhibitor antibody zaltenibart (also known as OMS906) through a Phase 2 development program in paroxysmal nocturnal hemoglobinuria ("PNH") comprised of two fully enrolled clinical trials and a long-term extension study in which patients who have completed either of the first two studies are eligible to enroll. Patients continue to accrue to the extension study and we remain on track to initiate our Phase 3 program for zaltenibart in PNH later this year.

● Enrollment is ongoing in our Phase 2 clinical trial evaluating zaltenibart for the treatment of complement 3 glomerulopathy ("C3G"). A Phase 3 program in C3G is planned to begin in early 2025.

"Throughout the second quarter, we continued rapidly progressing our clinical programs while significantly strengthening our balance sheet," said Gregory A. Demopulos, M.D., Omeros’ chairman and chief executive officer. "Through the term loan and note repurchase transaction completed in June, we reduced by more than half the outstanding balance of our 2026 convertible notes at a substantial discount to par value without diluting shareholders. With the new secured term loan in place, a substantial portion of our outstanding debt is now maturing in 2028, the Company is well positioned to address the remaining balance of our 2026 convertible notes, and we have access to an additional term loan of up to $25 million to fund the commercial launch of narsoplimab in TA-TMA. Although the lengthy regulatory process is a continuing source of frustration for our team, our shareholders and, most especially, the TA-TMA patients in need of an effective treatment for this often-lethal condition, we believe that the evidence we have proposed to submit with our BLA is highly compelling and we remain dedicated to making narsoplimab the first approved product for the treatment of TA-TMA. We look forward to providing a further update on the outcome of our ongoing discussions with FDA. In parallel, our MASP-3 inhibitor zaltenibart continues to advance rapidly, generating consistently – and compared to other marketed and developing alternative pathway inhibitors – strong data, and it remains on track to initiate a Phase 3 program in PNH later this year and, in C3G, early in 2025."

Second Quarter and Recent Clinical Developments

● Recent developments regarding narsoplimab, our lead monoclonal antibody targeting mannan-binding lectin-associated serine protease-2 ("MASP-2"), include the following:

o We previously submitted to FDA an analysis plan to assess already existing clinical trial data, existing data from an historical control population available from an external source, data from the narsoplimab expanded access (i.e., compassionate use) program, and data directed to the mechanism of action of narsoplimab. We are having ongoing discussions with the agency regarding the proposed analysis plan and FDA’s requirements for our resubmission of our BLA. An additional meeting with FDA has been scheduled and we expect to provide a further update on our plans for resubmission and the anticipated timing when more definitive information becomes available.

o FDA recently announced the establishment of the Rare Disease Innovation Hub, which will serve as a single point of connection and engagement within the FDA to support the development of treatments and products for rare diseases. The hub will have a particular focus on products intended for smaller populations or for diseases where the natural history is variable and not fully understood. FDA’s focus on these issues and their responsiveness to the rare disease community’s advocacy is encouraging, and we view the establishment of the hub as a tangible demonstration of FDA’s commitment to recognizing and addressing the unique challenges faced in developing therapies for these conditions.

ο In addition to previous publications on narsoplimab in TA-TMA, international transplant experts are preparing two manuscripts – one directed to the results of a survival comparison between our pivotal trial of narsoplimab in TA-TMA and an external control population of TA-TMA patients and the second detailing the survival data obtained from narsoplimab treatment of TA-TMA patients in our expanded access program. Physicians continue to request access to narsoplimab under this program for their patients with TA-TMA. Given that there is no approved treatment for this life-threatening condition, we continue to do what we can to help these patients.

● Recent developments regarding OMS1029, our long-acting, next-generation MASP-2 inhibitor, include:

o Both the single- and multiple-ascending-dose Phase 1 studies of OMS1029 have now been completed. The results support once-quarterly dosing, administered either subcutaneously or intravenously. Data from the multiple-ascending-dose study will be utilized to inform dose selection for continued clinical development. Consistent with the results of the single-ascending-dose Phase 1 clinical trial of OMS1029 completed in early 2023, OMS1029 was generally well tolerated at all doses evaluated in the multiple-ascending-dose study, with no significant safety concern identified to date.

o We continue to evaluate large market indications for Phase 2 clinical development of OMS1029. These include neovascular age-related macular degeneration, sometimes referred to as "wet AMD." MASP-2 inhibition previously showed efficacy in a pre-clinical murine model of wet AMD and we are currently engaged in a primate study comparing OMS1029 to Eylea (afibercept), a product currently approved to treat wet AMD. If shown to be effective, OMS1029 administered systemically (e.g., either intravenously or subcutaneously) could represent a significantly more attractive treatment experience compared to Eylea and other currently approved treatments for wet AMD, which require frequent injections directly into the posterior chamber of the eye.

● Recent developments regarding OMS906, our lead monoclonal antibody targeting mannan-binding lectin-associated serine protease-3 ("MASP-3"), the key activator of the alternative pathway, include:

o The United States Adopted Names Council ("USAN"), in consultation with the World Health Organization’s International Nonproprietary Names Expert Committee ("INN"), recently selected the nonproprietary name "zaltenibart" for OMS906. The USAN Council, by working closely with the INN Programme of the World Health Organization and various national nomenclature groups, aims for global standardization and unification of drug nomenclature to ensure that drug information is communicated accurately and unambiguously. Going forward, we will use the name zaltenibart to refer to our lead MASP-3 antibody in publications, at conferences and across other forums.

o Our Phase 2 trial evaluating two doses of zaltenibart in PNH patients who have had an unsatisfactory response to the C5 inhibitor ravulizumab has continued to produce encouraging data. The study utilizes a "switch-over" design, enrolling PNH patients who are receiving ravulizumab and adding zaltenibart to provide combination therapy with ravulizumab for 24 weeks. Those patients who demonstrate a hemoglobin response with the combination therapy are then switched to zaltenibart monotherapy. In June, at the annual congress of the European Hematology Association (EHA) (Free EHA Whitepaper), interim analysis results from the combination therapy portion of the trial were presented by Dr. Morag Griffin, an internationally recognized PNH expert from St. James University Hospital in England. During the adjunctive therapy period, the statistically significant mean hemoglobin improvement from baseline was 3.27 g/dL and 10 of 12 patients advanced to monotherapy. Absolute reticulocyte count also demonstrated statistically significant improvement. Zaltenibart was safe and well tolerated. An abstract providing results of the zaltenibart monotherapy stage has been submitted to the American Society of Hematology (ASH) (Free ASH Whitepaper) for presentation at their annual meeting in December. The efficacy and safety profiles of zaltenibart as monotherapy remain strong, including demonstration of sustained and clinically meaningful improvements in hemoglobin levels and absolute reticulocyte counts, as well as prevention of both extravascular and intravascular hemolysis.

o Our Phase 2 study of zaltenibart in PNH patients who have not previously received treatment with a complement inhibitor (i.e., naïve patients) is also ongoing and continues to progress well. Results from an interim analysis of subcutaneous zaltenibart treatment were presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) meeting held in December 2023. Following that presentation, we amended the study protocol to identify the plasma concentrations and the level of MASP-3 inhibition required to inhibit breakthrough hemolysis. These data, in combination with data derived from our "switch-over" PNH study and from our Phase 1 studies in healthy subjects, are expected to provide all the data needed to finalize selection of the zaltenibart dose for our upcoming Phase 3 clinical trials.

o We plan to conduct two trials in our Phase 3 program for zaltenibart in PNH. Similar to our Phase 2 program, one will enroll complement inhibitor-naïve patients and the other will employ a "switch over" design. Through our recent advisory boards with experts in PNH and focus-group PNH patients, we have received valuable input to inform the design of our Phase 3 studies and our positioning of zaltenibart in the marketplace, if approved. The zaltenibart drug substance necessary to supply our Phase 3 clinical trials has been manufactured, upcoming pre-Phase 3 meetings with both European and U.S. regulators have been scheduled or requested, and the other activities required to initiate our Phase 3 program have also been completed or are progressing as planned. We remain on track to initiate the program later this year.

● Recent developments regarding OMS527, our phosphodiesterase 7 ("PDE7") inhibitor program focused on addictions and compulsive disorders as well as movement disorders, include:

o In April 2023 we were awarded a three-year, $6.69 million grant by the National Institute on Drug Abuse ("NIDA") to pursue development of our lead orally administered PDE7 inhibitor compound for the treatment of cocaine use disorder ("CUD"). We expect to complete by the end of this year a grant-funded preclinical cocaine interaction study, which is a safety prerequisite to initiation of the randomized, placebo-controlled, inpatient clinical study evaluating the safety and effectiveness of OMS527 in patients with CUD, which is also contemplated to be funded with proceeds of the NIDA award.