On March 5, 2025 Sanofi reported that it has successfully priced its offering of EUR 1.5 billion of notes across 2 tranches (Press release, Sanofi, MAR 5, 2025, View Source [SID1234650978]):

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€850 million floating rate notes, due March 2027, bearing interest at 3-month Euribor plus 0.300%

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€650 million fixed rate notes, due March 2031, bearing interest at an annual rate of 2.750%.

The notes are being issued off the company’s Euro Medium Term Note Program.

Sanofi intends to use the net proceeds of the offering for general corporate purposes.

The transaction has been led by Deutsche Bank and J.P. Morgan as Global Coordinators, and ING, Santander CIB and Unicredit, all as Joint Lead Managers.

On March 5, 2025 Fate Therapeutics, Inc. (NASDAQ: FATE), a clinical-stage biopharmaceutical company dedicated to bringing a pipeline of induced pluripotent stem cell (iPSC)-derived off-the-shelf cellular immunotherapies to patients, reported business highlights and financial results for the fourth quarter and full year ended December 31, 2024 (Press release, Fate Therapeutics, MAR 5, 2025, View Source [SID1234650907]).

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"We begin 2025 with resolve and focus to advance our lead clinical programs in autoimmunity and oncology," said Bob Valamehr, Ph.D. MBA, President and Chief Executive Officer of Fate Therapeutics. "The team continues to make great progress in our pursuit of achieving therapeutic differentiation for patients with B cell-mediated autoimmune diseases, and we look forward to providing clinical and regulatory updates as we advance our FT819 off-the-shelf CAR T-cell product candidate in SLE. We remain focused on driving patient enrollment and engaging with the FDA to further discuss novel development pathways for CAR T-cell therapy in autoimmune disease, including the use of fludarabine-free conditioning as well as add-on to maintenance therapy without conditioning. We also plan to explore FT819 clinical trial expansion in additional autoimmune diseases. In addition, our FT825 off-the-shelf CAR T-cell program for advanced solid tumors is advancing into higher-dose cohorts as monotherapy and in combination with monoclonal antibody therapy under our collaboration with Ono Pharmaceutical. We look forward to sharing clinical data from these two high-priority programs throughout the year."

FT819 iPSC-derived 1XX CAR T-cell Program

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Phase 1 Dose Expansion Initiated for SLE using Flu-free Conditioning Regimen. Based on clinical data from the first three patients treated with FT819 in its ongoing multi-center, Phase 1 clinical trial for moderate-to-severe systemic lupus erythematosus (SLE) (NCT06308978), the Company has initiated dose expansion in up to 10 patients at 360 million cells. The dose expansion stage is designed to evaluate the safety and efficacy of a fludarabine (flu)-free conditioning regimen, consisting of either bendamustine alone or cyclophosphamide alone, followed by a single dose of FT819. The Company is also assessing the safety, pharmacokinetics, and anti-B cell activity of FT819 at 900 million cells in dose escalation. FT819 is the Company’s off-the-shelf CD8αβ+ T-cell product candidate that incorporates a CD19-targeted chimeric antigen receptor (CAR) with a novel 1XX costimulatory domain into the T-cell receptor alpha constant (TRAC) locus.
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Clinical Data from First Three SLE Patients Presented at ASH (Free ASH Whitepaper). In December 2024, the Company highlighted clinical and translational data from the first three patients treated with FT819 for SLE at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. Each patient presented with active lupus nephritis (LN) despite having been treated with multiple standard-of-care therapies and received flu-free conditioning followed by a single dose of FT819 at 360 million cells. As of a data cutoff date of December 4, 2024, there were no dose-limiting toxicities (DLTs), and no events of any grade of cytokine release syndrome (CRS), immune effector-cell associated neurotoxicity syndrome (ICANS), or graft-versus-host disease (GvHD). All three patients showed rapid, deep, and sustained elimination of CD19+ B cells in the periphery during the first month of treatment. The first and only patient eligible for disease assessment at six-month follow-up as of the data cutoff date achieved DORIS (Definition Of Remission In SLE) clinical remission and was free of all immunosuppressive therapy.
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First Patient Treated with FT819 as Add-on to Maintenance Therapy. The Company amended the clinical protocol of its FT819 Phase 1 study to include a new treatment arm to assess the safety, pharmacokinetics, and anti-B cell activity of a single dose of FT819 as an add-on to maintenance therapy without conditioning chemotherapy in patients with SLE. The first patient in the new arm was on a stable dose of oral mycophenolate mofetil (MMF) and was treated with a single dose of FT819 at 360 million cells without administration of any conditioning chemotherapy. There were no DLTs and no events of CRS, ICANS, or GvHD. The patient remains on-study.
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Completed Type D Meeting with FDA for Inclusion of Additional Diseases in FT819 Phase 1 Study. In December 2024, the Company reached an agreement with the U.S. Food and Drug Administration (FDA) to allow for the clinical investigation of additional B cell-mediated autoimmune diseases under our current Phase 1 clinical trial of FT819. As a follow-up to the meeting, the Company has submitted an amended clinical protocol to the FDA that enables the conduct of independent dose-expansion cohorts for SLE as well as anti-neutrophilic cytoplasmic antibody-associated vasculitis (AAV), idiopathic inflammatory myositis (IIM), and systemic sclerosis (SSc). The Company plans to initiate dose-expansion cohorts in one or more of AAV, IIM, and SSc in 2025. Additionally, the FDA agreed to allow for investigation of a multi-dose treatment cycle as well as for re-treatment upon disease progression, making the treatment dosing paradigm more aligned with traditional biological therapies. The FDA also permitted the expansion of study eligibility criteria, including the inclusion of patients between the ages of 12 and 17.

FT825 / ONO-8250 iPSC-derived CAR T-cell Program

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First Patient Treated with FT825 / ONO-8250 in Combination with Monoclonal Antibody Therapy. Under its collaboration with Ono Pharmaceutical Co., Ltd. (Ono), the Company is conducting a multi-center, Phase 1 study to assess the safety, pharmacokinetics, and activity of FT825 / ONO-8250, a multiplexed-engineered CAR T-cell product candidate targeting human epidermal growth factor receptor 2 (HER2), in patients with advanced solid tumors (NCT06241456). Enrollment is currently ongoing at the third dose level of 900 million cells as monotherapy and at the second dose level of 300 million cells in combination with epidermal growth factor receptor (EGFR)-targeted monoclonal antibody therapy.
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Initial Phase 1 Clinical Data Presented at 2024 SITC (Free SITC Whitepaper). At the 2024 Society of Immunotherapy of Cancer (SITC) (Free SITC Whitepaper) in November, the Company presented initial clinical data from three heavily pre-treated patients, all of whom were previously treated with at least five prior lines of therapy including HER2-targeted therapy. Each patient was administered conditioning chemotherapy and a single dose of FT825 / ONO-8250 as monotherapy at the first dose level of 100 million cells. As of a data cutoff date of October 25, 2024, FT825 / ONO-8250 demonstrated a favorable safety profile with no DLTs and no events of any grade of CRS, ICANS, or GvHD. In addition, at Day 8 following treatment, peak CAR T-cell expansion was observed and phenotyping of FT825 / ONO-8250 sourced from the patients’ peripheral blood was indicative of an activated state (as evidenced by high levels of Granzyme B expression and maintenance of CAR expression) with no evidence of exhaustion (as evidenced by low levels of PD-1 and TIM3 expression).

FT522 iPSC-derived CAR NK Cell Program

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Initial Translational Data of FT522 without Conditioning Chemotherapy Presented at ACR Convergence. FT522 is the Company’s off-the-shelf, CD19-targeted CAR NK cell product candidate and first product candidate to incorporate Alloimmune Defense Receptor (ADR) technology, which is designed to reduce or eliminate the need for administration of conditioning chemotherapy to patients receiving cell therapies. In November 2024, the Company presented initial translational data from its ongoing multi-center, Phase 1 clinical trial of FT522 in patients with relapsed / refractory B-cell lymphoma (BCL) (NCT05950334). The presentation illustrated that live FT522 cells with anti-B cell activity were detected in the patients’ peripheral blood through Day 15, demonstrating the potential of FT522 to persist and function in the presence of an unmatched, fully-intact immune system. The Company intends to assess any further clinical development of FT522 in relapsed / refractory BCL upon completion of dose escalation at the second dose level of 900 million cells.
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Unique Clinical Development Opportunities for FT522 in Autoimmunity under Evaluation. The FDA has allowed the Company’s Investigational New Drug (IND) application to assess the safety, pharmacokinetics, and activity of FT522 across a basket of B cell-mediated autoimmune diseases. The Phase 1 clinical protocol allows for treatment of patients with up to four weekly doses of FT522, without administration of conditioning chemotherapy, as an add-on to rituximab induction therapy (Regimen A) and as an add-on to maintenance therapy in combination with rituximab (Regimen B). The Company is currently evaluating opportunities and timelines for the clinical development of FT522 in autoimmunity.

Fourth Quarter 2024 Financial Results

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Cash & Investment Position: Cash, cash equivalents, and investments as of December 31, 2024 were $306.7 million.
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Total Revenue: Revenue was $1.9 million for the fourth quarter of 2024, which was derived from the conduct of preclinical development activities for a second collaboration candidate targeting an undisclosed solid tumor antigen under the Company’s collaboration with Ono Pharmaceutical.
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Total Operating Expenses: Total operating expenses were $63.6 million for the fourth quarter of 2024, including research and development expenses of $33.6 million and general and administrative expenses of $15.3 million. Such amount included $9.1 million of non-cash stock-based compensation expense and a one-time non-cash asset impairment charge of $14.7 million related to equipment and right-of-use assets.
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Shares Outstanding: As of December 31, 2024, common shares outstanding were 113.9 million, pre-funded warrants outstanding were 3.9 million, and preferred shares outstanding were 2.8 million. Each preferred share is convertible into five common shares.

On March 4, 2025 Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in cellular metabolism and PK activation pioneering therapies for rare diseases, reported that its management team is scheduled to present at the following conferences (Press release, Agios Pharmaceuticals, MAR 4, 2025, View Source [SID1234650872]):

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Leerink Global Healthcare Conference 2025: Fireside chat on Tuesday, March 11, 2025, at 10:50 a.m. ET
Barclays 27th Annual Global Healthcare Conference: Fireside chat on Wednesday, March 12, 2025, at 12:30 p.m. ET

The live webcast for each event will be accessible on the Investors section of the company’s website (www.agios.com) under the "Events & Presentations" tab. Replays of the webcasts will be archived on the company’s website for at least two weeks following the presentation.

On March 4, 2025 BeiGene, Ltd. (NASDAQ: ONC; HKEX: 06160; SSE: 688235), a global oncology company that intends to change its name to BeOne Medicines Ltd., reported the U.S. Food and Drug Administration (FDA) has approved TEVIMBRA (tislelizumab-jsgr), in combination with platinum-containing chemotherapy, for the first-line treatment of adults with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1 (≥1) (Press release, BeiGene, MAR 4, 2025, View Source [SID1234650874]).

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"The approval of TEVIMBRA in combination with chemotherapy for adult patients with ESCC expands first-line treatment options for patients with this disease," said Dr. Nataliya Uboha, Associate Professor, University of Wisconsin, Carbone Cancer Center. "There is a critical need for effective treatments of ESCC, and TEVIMBRA has been shown to improve outcomes in this patient population."

The additional indication is based on results from BeiGene’s RATIONALE-306 (NCT03783442), a randomized, placebo-controlled, double-blind, global Phase 3 study to evaluate the efficacy and safety of TEVIMBRA in combination with platinum-containing chemotherapy as a first-line treatment in adult patients (n=649) with unresectable, locally advanced recurrent or metastatic ESCC. The study met its primary endpoint and demonstrated a statistically significant improvement in overall survival (OS) for adult patients randomized to TEVIMBRA in combination with chemotherapy compared to placebo in combination with chemotherapy. Exploratory analyses indicated that the improvement in the intent-to-treat (ITT) population was primarily attributed to the results observed in the subgroup of patients with PD-L1 ≥1. Analysis of OS in the PD-L1 positive (≥1) population (n=481) showed a median OS of 16.8 months for patients treated with TEVIMBRA plus chemotherapy compared to 9.6 months for patients treated with placebo plus chemotherapy (HR: 0.66, [95% CI: 0.53, 0.82]), resulting in a 34% reduction in the risk of death. These results represent an unprecedented improvement in OS in first-line ESCC patients.

"Today’s approval, our third from the FDA in less than a year, reflects our dedication to advancing innovative therapies and addressing critical needs in cancer care," said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. "FDA approval of TEVIMBRA for the first-line treatment of advanced esophageal squamous cell carcinoma marks a significant step forward in tackling the unmet needs in this challenging disease area. We are grateful to the patients, clinicians, and researchers whose commitment and courage have made this progress possible."

The safety of TEVIMBRA in combination with chemotherapy was evaluated in the same global clinical trial, RATIONALE-306. The most frequent serious adverse reactions (≥2%) were pneumonia, dysphagia, diarrhea, fatigue, and esophageal stenosis. The most common (≥20%) adverse reactions were anemia, fatigue, decreased appetite, nausea, constipation, decreased weight, diarrhea, peripheral sensory neuropathy, vomiting, and stomatitis.

TEVIMBRA is also approved in the U.S. as monotherapy for the treatment of adult patients with unresectable or metastatic esophageal squamous cell carcinoma after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor and in combination with chemotherapy for the first-line treatment of adults with gastric and gastroesophageal junction (G/GEJ) cancers.

The Company recently announced its intent to change its name to BeOne Medicines Ltd., reaffirming its commitment to develop innovative medicines to eliminate cancer by partnering with the global community to serve as many patients as possible.

About Esophageal Squamous Cell Carcinoma (ESCC)

Globally, esophageal cancer is the sixth most common cause of cancer-related deaths, and ESCC is the most common histologic subtype, accounting for nearly 90% of esophageal cancers. An estimated 957,000 new esophageal cancer cases are projected in 2040, an increase of nearly 60% from 2020, underscoring the need for additional effective treatments.1 Esophageal cancer is a rapidly fatal disease, and more than two-thirds of patients have advanced or metastatic disease at the time of diagnosis, with an expected five-year survival rate of less than 6% for those with distant metastases.2

About TEVIMBRA (tislelizumab-jsgr)

TEVIMBRA is a uniquely designed humanized immunoglobulin G4 (IgG4) anti-programmed cell death protein 1 (PD-1) monoclonal antibody with high affinity and binding specificity against PD-1. It is designed to minimize binding to Fc-gamma (Fcγ) receptors on macrophages, helping the body’s immune cells detect and fight tumors.

TEVIMBRA is the foundational asset of BeiGene’s solid tumor portfolio and has shown potential across multiple tumor types and disease settings. The global TEVIMBRA clinical development program includes almost 14,000 patients enrolled to date in 34 countries and regions across 66 trials, including 20 registration-enabling studies. TEVIMBRA is approved in more than 42 countries, and more than 1.3 million patients have been treated globally.

U.S. Indication and Important Safety Information for TEVIMBRA (tislelizumab-jsgr) injection

IMPORTANT SAFETY INFORMATION

WARNINGS AND PRECAUTIONS

Severe and Fatal Immune-Mediated Adverse Reactions

TEVIMBRA is a monoclonal antibody that belongs to a class of drugs that bind to either the programmed death receptor-1 (PD-1) or PD-ligand 1 (PD-L1), blocking the PD-1/PD-L1 pathway, thereby removing inhibition of the immune response, potentially breaking peripheral tolerance and inducing immune-mediated adverse reactions.

Immune-mediated adverse reactions, which may be severe or fatal, can occur in any organ system or tissue. Immune-mediated adverse reactions can occur at any time after starting treatment with a PD-1/PD-L1 blocking antibody. While immune-mediated adverse reactions usually manifest during treatment with PD-1/PD-L1 blocking antibodies, immune-mediated adverse reactions can also manifest after discontinuation of PD-1/PD-L1 blocking antibodies. Important immune-mediated adverse reactions listed here may not include all possible severe and fatal immune-mediated reactions.

Early identification and management of immune-mediated adverse reactions are essential to ensure safe use of PD-1/PD-L1 blocking antibodies. Monitor patients closely for symptoms and signs that may be clinical manifestations of underlying immune-mediated adverse reactions. Evaluate liver enzymes, creatinine, and thyroid function at baseline and periodically during treatment. In cases of suspected immune-mediated adverse reactions, initiate appropriate workup to exclude alternative etiologies, including infection. Institute medical management promptly, including specialty consultation as appropriate.

Withhold or permanently discontinue TEVIMBRA depending on severity. In general, if TEVIMBRA requires interruption or discontinuation, administer systemic corticosteroid therapy (1 to 2 mg/kg/day prednisone or equivalent) until improvement to Grade 1 or less. Upon improvement to Grade 1 or less, initiate corticosteroid taper and continue to taper over at least 1 month. Consider administration of other systemic immunosuppressants in patients whose immune-mediated adverse reactions are not controlled with corticosteroids.

Immune-Mediated Pneumonitis

TEVIMBRA can cause immune-mediated pneumonitis, which can be fatal. In patients treated with other PD-1/PD-L1 blocking antibodies, the incidence of pneumonitis is higher in patients who have received prior thoracic radiation.

Immune-mediated pneumonitis occurred in 4.9% (96/1972) of patients receiving TEVIMBRA, including fatal (0.1%), Grade 4 (0.3%), Grade 3 (1.6%) and Grade 2 (1.9%) adverse reactions. Pneumonitis led to permanent discontinuation of TEVIMBRA in 38 (1.9%) patients and withholding of TEVIMBRA in 32 (1.6%) patients.

Seventy-four (77.1%) of the 96 patients received systemic corticosteroids. Sixty-five (67.7%) of the 96 patients received high-dose systemic corticosteroids. Immune-mediated pneumonitis resolved in 50% of the 96 patients. Of the 32 patients in whom TEVIMBRA was withheld for pneumonitis, 20 (62.5%) reinitiated TEVIMBRA after symptom improvement; of these, 2 (10%) patients had recurrence of pneumonitis.

Immune-Mediated Colitis

TEVIMBRA can cause immune-mediated colitis, which can be fatal. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis treated with PD-1/PD-L1 blocking antibodies. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies.

Immune-mediated colitis occurred in 0.8% (16/1972) of patients receiving TEVIMBRA, including Grade 3 (0.3%) and Grade 2 (0.4%) adverse reactions. Colitis led to permanent discontinuation of TEVIMBRA in 4 (0.2%) patients and withholding of TEVIMBRA in 5 (0.3%) patients. Twelve (75%) of the 16 patients received systemic corticosteroids. Eight (50%) of the 16 patients received high-dose systemic corticosteroids. Two (12.5%) of the 16 patients received immunosuppressive treatment. Immune-mediated colitis resolved in 93.8% of the 16 patients. All 5 patients in whom TEVIMBRA was withheld for colitis reinitiated TEVIMBRA after symptom improvement; of these, none of the patients had recurrence of colitis.

Immune-Mediated Hepatitis

TEVIMBRA can cause immune-mediated hepatitis, which can be fatal.

Immune-mediated hepatitis occurred in 1.2% (24/1972) of patients receiving TEVIMBRA, including fatal (0.1%), Grade 4 (0.2%), Grade 3 (0.5%) and Grade 2 (0.4%) adverse reactions. Immune-mediated hepatitis led to permanent discontinuation in 3 (0.2%) patients and withholding of TEVIMBRA in 13 (0.7%) patients. Eighteen (75%) of the 24 patients received systemic corticosteroids. Thirteen (54.2%) of the 24 patients received high-dose systemic corticosteroids. Two patients (8.3%) of the 24 patients received immunosuppressive treatment. Immune-mediated hepatitis resolved in 70.8% of the 24 patients. Of the 13 patients in whom TEVIMBRA was withheld for hepatitis, 7 (53.8%) reinitiated TEVIMBRA after symptom improvement; of these, none of the patients had recurrence of hepatitis.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency

TEVIMBRA can cause immune-mediated adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Withhold TEVIMBRA depending on severity.

Immune-mediated adrenal insufficiency occurred in 0.4% (8/1972) of patients receiving TEVIMBRA, including Grade 4 (0.1%), Grade 3 (0.1%) and Grade 2 (0.3%) adverse reactions. Adrenal insufficiency did not lead to permanent discontinuation of TEVIMBRA. TEVIMBRA was withheld in 7 (0.4%) patients. All 8 patients received systemic corticosteroids. Three (37.5%) of the 8 patients received high-dose systemic corticosteroids. Adrenal insufficiency resolved in 25% of the 8 patients. Of the 7 patients in whom TEVIMBRA was withheld for adrenal insufficiency, 5 (71.4%) reinitiated TEVIMBRA after symptom improvement; of these, none of the patients had recurrence of adrenal insufficiency.

Hypophysitis

TEVIMBRA can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field defects. Hypophysitis can cause hypopituitarism. Initiate hormone replacement as clinically indicated. Withhold or permanently discontinue TEVIMBRA depending on severity.

Hypophysitis/hypopituitarism occurred in 0.2% (4/1972) of patients receiving TEVIMBRA, including a Grade 2 (0.2%) adverse reaction. No TEVIMBRA treatment discontinuation was required, while treatment was withheld in 1 (0.1%) patient. Three (75%) of the 4 patients received systemic corticosteroids. One (25%) of the 4 patients received high-dose systemic corticosteroids. Hypophysitis/hypopituitarism did not resolve in the 4 patients. For the 1 patient where TEVIMBRA was withheld for hypophysitis/hypopituitarism, there was no recurrence of hypophysitis/hypopituitarism.

Thyroid Disorders

TEVIMBRA can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated. Withhold or permanently discontinue TEVIMBRA depending on severity.

Thyroiditis: Immune-mediated thyroiditis occurred in 1.2% (24/1972) of patients receiving TEVIMBRA, including Grade 2 (0.5%) adverse reactions. Thyroiditis did not lead to permanent discontinuation of TEVIMBRA. TEVIMBRA was withheld in 3 (0.2%) patients. Two (8.3%) of the 24 patients received systemic corticosteroids. Thyroiditis resolved in 41.7% of the 24 patients. All three patients in whom TEVIMBRA was withheld for thyroiditis reinitiated TEVIMBRA after symptom improvement; of these, none of the patients had recurrence of thyroiditis.

Hyperthyroidism: Immune-mediated hyperthyroidism occurred in 4.8% (95/1972) of patients receiving TEVIMBRA, including Grade 3 (0.1%) and Grade 2 (0.9%) adverse reactions. Hyperthyroidism led to the permanent discontinuation of TEVIMBRA in 1 (0.1%) patient and withholding of TEVIMBRA in 4 (0.2%) patients. One (1.1%) of the 95 patients received systemic corticosteroids. Hyperthyroidism resolved in 75.8% of the 95 patients. Of the 4 patients in whom TEVIMBRA was withheld for hyperthyroidism, 3 (75%) reinitiated TEVIMBRA after symptom improvement; of these, none of the patients had recurrence of hyperthyroidism.

Hypothyroidism: Immune-mediated hypothyroidism occurred in 12.7% (250/1972) of patients receiving TEVIMBRA, including Grade 4 (0.1%) and Grade 2 (6.8%) adverse reactions. TEVIMBRA was not permanently discontinued in any patient, while treatment was withheld in 7 (0.4%) patients. Two (0.8%) of the 250 patients received systemic corticosteroids and 158 patients (63.2%) received hormone replacement therapy. Hypothyroidism resolved in 31.6% of the 250 patients. The majority (51.6%) of patients with hypothyroidism required long-term thyroid hormone replacement. Of the 7 patients in whom TEVIMBRA was withheld for hypothyroidism, 6 (85.7%) reinitiated TEVIMBRA after symptom improvement; of these, none of the patients had recurrence of hypothyroidism.

Type 1 Diabetes Mellitus, which can present with Diabetic Ketoacidosis

Diabetes mellitus has been reported with PD-1/PD-L1 blocking antibodies. Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Withhold or permanently discontinue TEVIMBRA depending on severity.

Diabetes mellitus occurred in 0.9% (18/1972) of patients receiving TEVIMBRA, including Grade 4 (0.1%), Grade 3 (0.4%) and Grade 2 (0.4%) adverse reactions. TEVIMBRA was permanently discontinued in 3 (0.2%) patients and TEVIMBRA treatment was withheld in 3 (0.2%) patients. Twelve (66.7%) patients received insulin therapy for diabetes mellitus. Diabetes mellitus resolved in 27.8% of the 18 patients. Of the 3 patients in whom TEVIMBRA was withheld for diabetes mellitus, none of the patients reinitiated TEVIMBRA after symptom improvement.

Immune-Mediated Nephritis with Renal Dysfunction

TEVIMBRA can cause immune-mediated nephritis, which can be fatal.

Immune-mediated nephritis with renal dysfunction occurred in 0.3% (5/1972) of patients receiving TEVIMBRA, including Grade 3 (0.1%) and Grade 2 (0.2%) adverse reactions. TEVIMBRA was permanently discontinued in 1 (0.1%) patient and treatment was withheld in 3 (0.2%) patients. Three (60%) of the 5 patients received systemic corticosteroids. All 3 (60%) of the 5 patients received high-dose systemic corticosteroids. Nephritis with renal dysfunction resolved in 40.0% of the 5 patients. Of the 3 patients in whom TEVIMBRA was withheld for nephritis, 2 (66.7%) reinitiated TEVIMBRA after symptom improvement and one (50%) patient had recurrence of nephritis.

Immune-Mediated Dermatologic Adverse Reactions

TEVIMBRA can cause immune-mediated rash or dermatitis. Cases of severe cutaneous adverse reactions (SCARs), including exfoliative dermatitis, Stevens-Johnson Syndrome (SJS), and toxic epidermal necrolysis (TEN), have been reported, some with fatal outcome. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Withhold or permanently discontinue TEVIMBRA depending on severity.

Immune-mediated dermatologic adverse reactions occurred in 15.3% (301/1972) of patients receiving TEVIMBRA, including Grade 4 (0.1%), Grade 3 (0.9%) and Grade 2 (3.5%) adverse reactions. Dermatologic adverse reactions led to permanent discontinuation of TEVIMBRA in 2 (0.1%) patients and withholding of TEVIMBRA in 18 (0.9%) patients. Thirty (10.0%) of the 301 patients received systemic corticosteroids. Thirteen (4.3%) of the 301 patients received high-dose systemic corticosteroids. Immune-mediated skin reactions resolved in 190 (63.1%) of the 301 patients. Of the 18 patients in whom TEVIMBRA was withheld for dermatologic adverse reactions, 15 (83.3%) reinitiated TEVIMBRA after symptom improvement; of these, 1 (6.7%) patient had recurrence of immune-mediated dermatologic adverse reactions.

Other Immune-Mediated Adverse Reactions

The following clinically significant immune-mediated adverse reactions occurred at an incidence of less than 1% each in 1972 patients who received TEVIMBRA: myositis, myocarditis, arthritis, polymyalgia rheumatica, and pericarditis.

The following additional clinically significant immune-mediated adverse reactions have been reported with other PD-1/PD-L1 blocking antibodies, including severe or fatal cases.

Cardiac/Vascular: Vasculitis.

Nervous System: Meningitis, encephalitis, myelitis and demyelination, myasthenic syndrome/myasthenia gravis (including exacerbation), Guillain-Barré syndrome, nerve paresis, autoimmune neuropathy.

Ocular: Uveitis, iritis, and other ocular inflammatory toxicities can occur. Some cases can be associated with retinal detachment. Various grades of visual impairment, including blindness, can occur. If uveitis occurs in combination with other immune-mediated adverse reactions, consider a Vogt-Koyanagi-Harada-like syndrome, as this may require treatment with systemic steroids to reduce the risk of permanent vision loss.­­

Gastrointestinal: Pancreatitis including increases in serum amylase and lipase levels, gastritis, duodenitis.

Musculoskeletal and Connective Tissue: Polymyositis, rhabdomyolysis and associated sequelae including renal failure.

Endocrine: Hypoparathyroidism.

Other (Hematologic/Immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenic purpura, solid organ transplant rejection, other transplant (including corneal graft) rejection.

Infusion-Related Reactions

TEVIMBRA can cause severe or life-threatening infusion-related reactions. Infusion-related reactions occurred in 5% (99/1972) patients receiving TEVIMBRA, including Grade 3 or higher (0.2%) reactions. Monitor patients for signs and symptoms of infusion-related reactions.

Slow the rate of infusion for mild (Grade 1) and interrupt the infusion for moderate (Grade 2) infusion-related reactions. For severe (Grade 3) or life-threatening (Grade 4) infusion-related reactions, stop infusion and permanently discontinue TEVIMBRA.

Complications of Allogeneic HSCT

Fatal and other serious complications can occur in patients who receive allogeneic hematopoietic stem cell transplantation (HSCT) before or after being treated with a PD-1/PD-L1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/PD-L1 blockade and allogeneic HSCT.

Follow patients closely for evidence of transplant-related complications and intervene promptly. Consider the benefit versus risks of treatment with a PD-1/PD-L1 blocking antibody prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on its mechanism of action, TEVIMBRA can cause fetal harm when administered to a pregnant woman. Animal studies have demonstrated that inhibition of the PD-1/PD-L1 pathway can lead to increased risk of immune-mediated rejection of the developing fetus resulting in fetal death. Advise pregnant women of the potential risk to a fetus. Advise females of reproductive potential to use effective contraception during treatment with TEVIMBRA and for 4 months after the last dose.

ADVERSE REACTIONS

First-line Treatment of Unresectable Advanced or Metastatic Esophageal Carcinoma (ESCC)

Permanent discontinuation of TEVIMBRA due to adverse reactions occurred in 13% of patients. The adverse reaction which resulted in discontinuation in ≥2% of patients was pneumonitis (2.2%).

Dosage interruptions of TEVIMBRA due to adverse reactions occurred in 52% of patients. Adverse reactions which required dosage interruption in ≥2% of patients were neutrophil count decreased (7%), fatigue (6%), pneumonia (6%), anemia (4.3%), neutropenia (4.3%), white blood cell count decreased (4.3%), rash (3.7%), dysphagia (2.8%), platelet count decreased (2.8%), pyrexia (2.8%), and diarrhea (2.2%).

The most common (≥20%) adverse reactions, including laboratory abnormalities were decreased neutrophil count, decreased sodium, increased glucose, anemia, fatigue, decreased appetite, increased AST, decreased potassium, increased serum creatinine, decreased calcium, increased ALT, diarrhea, stomatitis, and vomiting.

Previously Treated Unresectable Advanced or Metastatic ESCC

Permanent discontinuation of TEVIMBRA due to an adverse reaction occurred in 19% of patients. Adverse reactions which resulted in permanent discontinuation in ≥1% of patients were hemorrhage, pneumonitis (including pneumonitis and immune-mediated pneumonitis), and pneumonia.

Dosage interruptions of TEVIMBRA due to an adverse reaction occurred in 23% of patients. Adverse reactions which required dosage interruptions in ≥2% of patients were pneumonia, pneumonitis, and fatigue.

The most common (≥20%) adverse reactions, including laboratory abnormalities, were increased glucose, decreased hemoglobin, decreased lymphocytes, decreased sodium, decreased albumin, increased alkaline phosphatase, anemia, fatigue, increased AST, musculoskeletal pain, decreased weight, increased ALT, and cough.

Treatment of Previously Untreated Unresectable or Metastatic Gastric or Gastroesophageal Junction Adenocarcinoma (G/GEJ)

Permanent discontinuation of TEVIMBRA due to an adverse drug reaction occurred in 16% of patients. Adverse drug reactions which resulted in permanent discontinuation in ≥1% of patients were death, fatigue, and pneumonitis.

Dosage interruption of TEVIMBRA in the TEVIMBRA plus chemotherapy arm due to an adverse drug reaction occurred in 49% of patients. Adverse drug reactions which required dosage modifications in ≥2% of patients were, platelet count decreased (12%), neutrophil count decreased (10%), neutropenia (6%), white blood cell count decreased (6%), increased AST (4.8%), increased ALT (3.8%), increased blood bilirubin (3%), COVID-19 (3%), thrombocytopenia (2.8%), leukopenia (2.6%), pneumonitis (2.2%), and pneumonia (2%).

The most common (≥20%) adverse reactions, including laboratory abnormalities, for TEVIMBRA in combination with chemotherapy were nausea, fatigue, decreased appetite, anemia, peripheral sensory neuropathy, vomiting, decreased platelet count, decreased neutrophil count, increased aspartate aminotransferase, diarrhea, abdominal pain, increased alanine aminotransferase, decreased white blood cell count, decreased weight, and pyrexia.

INDICATIONS

TEVIMBRA is a programmed death receptor-1 (PD-1)-blocking antibody indicated for:

Esophageal Cancer

in combination with platinum-containing chemotherapy for the first-line treatment of adults with unresectable or metastatic esophageal squamous cell carcinoma (ESCC) whose tumors express PD-L1 (≥1).
as a single-agent, for the treatment of adults with unresectable or metastatic ESCC after prior systemic chemotherapy that did not include a PD-(L)1 inhibitor.
Gastric Cancer

in combination with platinum and fluoropyrimidine-based chemotherapy for the first-line treatment of adults with unresectable or metastatic HER2-negative gastric or gastroesophageal junction adenocarcinoma whose tumors express PD-L1 (≥1).
Please see full U.S. Prescribing Information including the U.S. Medication Guide.

On March 4, 2025 Aadi Bioscience, Inc. (Nasdaq: AADI) ("Aadi"), an oncology therapeutics company applying advanced technologies to established tumor biology to efficiently deliver advances in cancer treatment, reported the closing of its previously announced private placement (Press release, Aadi Bioscience, MAR 4, 2025, View Source [SID1234650890]). The private placement was led by Ally Bridge Group, with participation from new investors OrbiMed, Invus, Kalehua Capital and other accredited investors, Tae Han, co-founder of ProfoundBio, as well as existing investors, including Avoro Capital, KVP Capital and Acuta Capital Partners, for total gross proceeds of approximately $100 million.

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Aadi sold and issued an aggregate of 21,592,000 shares of its common stock ("Common Stock") at a price of $2.40 per share, and pre-funded warrants ("Pre-Funded Warrants") to purchase up to an aggregate of 20,076,500 shares of Common Stock at a purchase price of $2.3999 per Pre-Funded Warrant share in a private placement exempt from the registration requirements of the Securities Act of 1933, as amended (the "Securities Act").

Jefferies LLC acted as exclusive placement agent for the private placement.

Aadi intends to use the net proceeds from the private placement to fund certain upfront payments under its license agreement with WuXi Biologics (Shanghai FX) Co., Ltd. and for working capital and other general corporate purposes. The proceeds from this private placement and the sale of Aadi’s FYARRO business, together with Aadi’s existing cash, cash equivalents and marketable securities, are expected to fund operations into 2028, including anticipated clinical data readouts for its ADC portfolio.

The Common Stock and Pre-Funded Warrants sold in the private placement have not been registered under the Securities Act, or any state or other applicable jurisdiction’s securities laws and may not be offered or sold in the United States absent registration or an applicable exemption from the registration requirements of the Securities Act and applicable state or other jurisdictions’ securities laws. In connection with the private placement, Aadi and the investors entered into a registration rights agreement pursuant to which Aadi will file a registration statement (the "Resale Registration Statement") with the U.S. Securities and Exchange Commission (the "SEC") registering the resale of the shares of Common Stock sold in the private placement. Any offering of the shares sold in the private placement under the Resale Registration Statement will only be made by means of a prospectus.

This press release shall not constitute an offer to sell or a solicitation of an offer to buy Aadi’s Common Stock, nor shall there be any offer, solicitation, or sale of Aadi’s Common Stock in any jurisdiction in which such offer, solicitation or sale would be unlawful.