On September 27, 2024 Poseida Therapeutics, Inc. (Nasdaq: PSTX), a clinical-stage allogeneic cell therapy and genetic medicines company advancing differentiated non-viral treatments for patients with cancer and rare diseases, reported new interim clinical data from its ongoing Phase 1 trial of P-BCMA-ALLO1 in patients with relapsed/refractory multiple myeloma (RRMM) (Press release, Poseida Therapeutics, SEP 27, 2024, View Source [SID1234646898]). Data1 demonstrated a 91% overall response rate (ORR) and compelling safety results in the 23 heavily pretreated patients in Arm C, an optimized lymphodepletion arm. The new clinical data were presented today in an oral session at the 21st International Myeloma Society (IMS) Annual Meeting in Rio de Janeiro.

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P-BCMA-ALLO1 is an investigational non-viral, stem cell memory T cell (TSCM)-rich allogeneic CAR-T cell therapy in Phase 1/1b clinical development for the treatment of patients with RRMM. The Company is developing this investigational off-the-shelf allogeneic CAR-T cell therapy with Roche as part of a broader collaboration focused on addressing blood cancers with Poseida’s TSCM-rich CAR-T platform.

"The compelling and differentiated results from the optimized lymphodepletion arms of the ongoing Phase 1 trial of P-BCMA-ALLO1 showed deep responses and a high response rate in patients with heavily pre-treated relapsed or refractory multiple myeloma, regardless of prior exposure to B-cell maturation antigen (BCMA)-targeting therapy. The high overall response rate of 91% is remarkable because most study participants in my center had rapidly proliferative refractory disease, in contrast with those treated in the pivotal clinical trials of FDA-approved autologous CAR-T therapies. Such patients treated in the current trial of P-BCMA ALLO1 would not have qualified for standard of care autologous CAR T therapy," said Bhagirathbhai R. Dholaria, M.D., Associate Professor of Medicine, Malignant Hematology & Stem Cell Transplantation at Vanderbilt University Medical Center in Nashville, Tenn., and trial investigator. "All patients in the Phase 1 trial have been treated quickly once enrolled, with no waiting for manufacturing, with no need for apheresis or bridging therapy, demonstrating key advantages of allogeneic CAR-T cell therapy."

"P-BCMA-ALLO1 is one of the most advanced allogeneic CAR-T in clinical development for multiple myeloma, manufactured using non-viral technology to produce a TSCM-rich therapy that has shown a compelling emerging product profile," said Kristin Yarema, Ph.D., president and chief executive officer of Poseida Therapeutics. "We are encouraged to see such a high overall response rate in an arm of the Phase 1 trial with optimized lymphodepletion, along with standout safety results across all arms, given that the study population was heavily pretreated, high-risk, and in general had many features that historically have led to a poor prognosis. We are excited to build on these data as we advance P-BCMA-ALLO1 in the Phase 1b part of the trial, which is currently enrolling patients."

New Interim Clinical Data from Phase 1 P-BCMA-ALLO1 Trial
The ongoing open-label, multicenter Phase 1/1b dose-escalation and expansion trial in patients with RRMM is assessing the safety and maximum tolerated dose of P-BCMA-ALLO1 (primary objective) and its anti-myeloma activity (secondary objective). As of September 6, 2024, 72 unique patients were enrolled as an intent-to-treat (ITT) population and were treated across four study arms (S, A, B and C) that included different P-BCMA-ALLO1 doses and lymphodepletion regimen combinations. Study participants were required to have received three or more prior lines of therapy, including a prior proteasome inhibitor, immunomodulatory drug and anti-CD38 monoclonal antibody. The trial enrolled a heavily pretreated patient population with 43% of patients having received prior BCMA-and/or GPRC5D targeting therapy. Most prior BCMA therapies included autologous CAR-T and/or T-cell engagers (TCE). Additionally, 33% of study participants were racial minorities, demonstrating Poseida’s commitment to underserved patient populations.

In the ITT population, 100% of patients enrolled as of the data cutoff were infused with P-BCMA-ALLO1. No patients required anti-myeloma bridging therapy or prophylaxis with steroids or tocilizumab, and there was no invasive apheresis or manufacturing wait time. The median time from enrollment to the start of study treatment was one day.

The ORR across all four study arms was 54%; 11% of patients achieved a complete response (CR) or a stringent complete response (sCR), and 33% achieved a very good partial response or higher (VGPR+). The median duration of response (DoR) was 232 days for study Arms A and B – the cohorts with six or more months of follow-up at the time of data cut-off. Expansion and persistence of the CAR-T cells in patients after infusion has been dependent upon the conditioning dose of cyclophosphamide. P-BCMA-ALLO1 levels measured in the peripheral blood and were much higher in patients in Arm C (cyclophosphamide 750 mg/m2/day) and Arm B (cyclophosphamide 1000 mg/m2/day) than in patients in Arm S (cyclophosphamide 300 mg/m2/day), and Arm A (cyclophosphamide 500 mg/m2/day). Arm C was identified as the optimized lymphodepletion arm based on cellular kinetics, safety and efficacy.

Data from Arm C of the Phase 1 P-BCMA-ALLO1 Trial
Results from 23 study participants in Arm C were highlighted in the oral session at IMS. Patients received cyclophosphamide 750 mg/m2/day and fludarabine 30 mg/m2/day and approximately 2×106 cells/kg P-BCMA-ALLO1. Some patients were treated in an outpatient setting. Arm C patient details include:

Nearly half (48%) were age 65 or older
All were heavily pretreated, with a median of six prior lines of anti-myeloma therapy and a maximum of 14
62% of patients had received prior BCMA-targeting therapy
29% had failed both a BCMA CAR-T and a bispecific TCE, and 29% had failed both a BCMA-targeting therapy and the GPRC5D-targeting TCE, talquetamab
Approximately two-thirds of patients (62%) had high-risk disease by cytogenetics and 38% had extramedullary disease
Efficacy results, which are still evolving, for the 23 patients in Arm C showed:

An ORR of 91%, with a 100% ORR in BCMA-naïve patients, an 86% ORR in those who had received at least one prior BCMA-targeting treatment (all had received prior CAR-T and/or TCE), and an 86% ORR in those who had received at least one prior BCMA-targeting treatment and/or talquetamab
22% achieved a CR or an sCR
48% achieved VGPR+
Median DoR could not be estimated at the time of data cut-off because the current median follow-up is less than 3.5 months (for pooled arms A and B, the median DoR was more than seven months (estimated range of five-10 months), with a median time to response of only 16 days)
P-BCMA-ALLO1 was well-tolerated with key safety results from Arm C, including:

No dose-limiting toxicities, Grade 3 or higher cytokine release syndrome (CRS) or immune effector cell neurotoxicity syndrome (ICANS). The incidence of Grade 1 or 2 CRS was 39% and the incidence of Grade 1 or 2 ICANS was 13%
The incidence of infections was 48%, including 30% that were Grade 1 or 2 and 17% that were Grade 3
Rapid cytopenia recovery in the vast majority of cases
No graft-vs-host disease (GvHD), hemophagocytic lymphohistiocytosis (HLH), Parkinsonism or cranial neuropathies observed
The safety results of P-BCMA-ALLO1 in arm C have been consistent with those observed in the other three arms of the Phase 1 trial, with a total safety database, including 72 unique patients
The ongoing P-BCMA-ALLO1 Phase 1/1b trial is enrolling patients using the Arm C lymphodepletion regimen described above, across two dosing cohorts, with dose optimization ongoing in Arm C.

Company-Hosted IMS Live Webcast and Conference Call Information
Poseida will host a live webcast and conference call tomorrow, Saturday, September 28, 2024, at 1 p.m. ET / 10 a.m. PT. The webcast will feature an expert panel of clinicians who will discuss the new clinical data and multiple myeloma treatment landscape. The panel will be moderated by Dr. Rizvi and include Dr. Dholaria and Thomas G. Martin, M.D., Clinical Professor of Medicine, Adult Leukemia and Bone Marrow Transplantation Program and Associate Director of the Myeloma Program at the University of California, San Francisco (UCSF), and Co-Leader of the Cancer Immunology & Immunotherapy Program at the UCSF Helen Diller Family Comprehensive Cancer Center.

The conference call can be accessed by dialing 800-225-9448 or 203-518-9708 (International) with the conference ID PSTX0928. The live webcast can be accessed using the link here, or by visiting the Events and Presentations section of the Poseida website at investors.poseida.com. After the live webcast, the event will remain archived on the Poseida website for approximately 90 days.

About P-BCMA-ALLO1
P-BCMA-ALLO1 is an allogeneic CAR-T product candidate licensed to Roche targeting B-cell maturation antigen (BCMA) for the treatment of relapsed/refractory multiple myeloma. This allogeneic program includes a VH-based binder that targets BCMA, and interim clinical data presented at IMS in September 2024 support the Company’s belief that T stem cell (TSCM)-rich allogeneic CAR-Ts have the potential to offer effective, safe and reliable treatment addressing unmet needs in multiple myeloma. The U.S. Food and Drug Administration (FDA) has granted P-BCMA-ALLO1 Orphan Drug designation for multiple myeloma and Regenerative Medicine Advanced Therapy (RMAT) designation for adult patients with relapsed/refractory multiple myeloma after three or more prior lines of therapies including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 antibody.

P-BCMA-ALLO1 is currently being evaluated in a Phase 1/1b trial in patients with multiple myeloma. Additional information about the Phase 1/1b trial is available at www.clinicaltrials.gov using identifier: NCT04960579.

On September 26, 2024 Theriva Biologics, Inc. (NYSE American: TOVX) ("Theriva" or the "Company"), a diversified clinical-stage company developing therapeutics designed to treat cancer and related diseases in areas of high unmet need, reported the pricing of its "reasonable best efforts" public offering for the purchase and sale of up to 1,428,600 shares of common stock (or pre-funded warrants in lieu thereof) and warrants to purchase up to 1,428,600 shares of common stock at a combined offering price of $1.75 per share and accompanying warrant (the "Offering") (Press release, Theriva Biologics, SEP 26, 2024, View Source [SID1234646881]). The Company expects to receive aggregate gross proceeds of approximately $2.5 million, before deducting placement agent fees and other offering expenses, and assuming no exercise of the warrants. The warrants will have an exercise price of $2.00 per share, will be exercisable immediately and will expire five years from the issuance date.

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The closing of the Offering is expected to occur on or about September 27, 2024, subject to the satisfaction of customary closing conditions. The Company intends to use the net proceeds from this Offering primarily for working capital and general corporate purposes, including for research and development and manufacturing scale-up. The Company may also use a portion of the net proceeds to invest in or acquire other products, businesses or technologies, although it currently has no commitments or agreements with respect to any such investments or acquisitions.

A.G.P./Alliance Global Partners is acting as the sole placement agent for the Offering.

The securities described above are being offered pursuant to a registration statement on Form S-1 (File No. 333-282024) previously filed with the Securities and Exchange Commission ("SEC") on September 10, 2024, as amended, which became effective on September 25, 2024. The Offering is being made only by means of a prospectus forming part of the effective registration statement. Copies of the preliminary prospectus and, when available, copies of the final prospectus, relating to the Offering may be obtained on the SEC’s website located at View Source Electronic copies of the final prospectus relating to the Offering may be obtained, when available, from A.G.P./Alliance Global Partners, 590 Madison Avenue, 28th Floor, New York, NY 10022, or by telephone at (212) 624-2060, or by email at [email protected].

This press release shall not constitute an offer to sell or the solicitation of an offer to buy nor shall there be any sale of these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On September 26, 2024 BeiGene, Ltd. (NASDAQ: BGNE; HKEX: 06160; SSE: 688235), a global oncology company, reported the U.S. Food and Drug Administration (FDA) Oncologic Drugs Advisory Committee (ODAC) recognizes the favorable benefit-risk profile of PD-1 inhibitors, including TEVIMBRA (tislelizumab-jsgr), for the first-line treatment of patients with locally advanced unresectable or metastatic esophageal squamous cell carcinoma (ESCC) expressing PD-L1 (>1%) and gastric/gastroesophageal junction (G/GEJ) cancers expressing PD-L1 >1% (Press release, BeiGene, SEP 26, 2024, View Source [SID1234646882]).

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The committee reviewed efficacy and safety data from the Phase 3 RATIONALE-305 (G/GEJ) and RATIONALE-306 (ESCC) studies, as well as other pivotal studies from the two other PD-1 inhibitors approved in these indications. The Advisory Committee voted 10 to 2, with one abstaining, that the risk benefit assessment was not favorable for the use of PD-1 inhibitors in G/GEJ with PD-L1 expression less than 1%. The ODAC members voted 11 to 1, with one abstaining, that the risk benefit profile was not favorable for ESCC patients with a PD-L1 expression less than 1%. The vote represents a recommended class-wide PD-L1 expression level cut-off across PD-1 inhibitors reviewed during the meeting for these patient populations.

"The survival rates for gastric and esophageal cancer remain strikingly low for the majority of patients who are diagnosed with late-stage disease and there is a need for additional treatments that can extend life," said Sally Werner, RN, BSN, MSHA, CEO at Cancer Support Community. "We appreciate the FDA’s recognition of the need for safe and effective treatments for these cancers. Additional treatment options offer physicians and their patients choices on the treatment that is right for them."

"The vote by ODAC members to recommend a class-level cut-off of PD-L1 expression for PD-1 inhibitors used in the treatment of gastric/GEJ cancers and ESCC will help to establish a standard for clinicians and the patients they treat," said Mark Lanasa, M.D., Ph.D., Chief Medical Officer, Solid Tumors at BeiGene. "We look forward to working with the FDA as it completes its review of our BLAs for TEVIMBRA, and we strive to bring this therapy to applicable patients in the U.S."

Both the RATIONALE-305 and RATIONALE-306 studies met their endpoints of overall survival (OS), demonstrating a statistically significant reduction in the risk of death across both indications. The safety profile for TEVIMBRA in combination with chemotherapy is consistent with the known safety profile of anti-PD-1 antibodies, and no new safety signals were identified.

The Biologics License Applications (BLAs) for TEVIMBRA in these indications remain under review with the FDA. TEVIMBRA is currently approved in the U.S. for the treatment of adult patients with unresectable or metastatic ESCC after prior systemic chemotherapy that did not include a PD-L1 inhibitor.

About RATIONALE-305

RATIONALE-305 (NCT03777657) is a randomized, double-blind, placebo-controlled, global Phase 3 that enrolled 997 patients with advanced unresectable or metastatic G/GEJ adenocarcinoma. The primary endpoint was OS, with prespecified hierarchy testing for the PD-L1 high population followed by the intent-to-treat (ITT) population. Results of the final analysis of the ITT population were presented as a late-breaking oral presentation during the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023.

About RATIONALE-306

RATIONALE-306 (NCT03783442) is a randomized, placebo-controlled, double-blind, global Phase 3 study to evaluate the efficacy and safety of tislelizumab in combination with chemotherapy as a first-line treatment in patients with advanced or metastatic ESCC. The primary endpoint of the trial is overall survival. Secondary endpoints include progression free survival, overall response rate, and duration of response per RECIST v1.1, as well as health-related quality of life measures and safety. The trial enrolled 649 patients at research centers across Asia-Pacific, Europe, and North America. Patients were randomized 1:1 to receive either tislelizumab plus chemotherapy or placebo plus chemotherapy.

About TEVIMBRA (tislelizumab-jsgr)

Tislelizumab 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 to aid the body’s immune cells to detect and fight tumors.

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

INDICATION

TEVIMBRA (tislelizumab-jsgr), as a single agent, is indicated 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.

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 3.8% (75/1972) of patients receiving TEVIMBRA, including fatal (0.2%), Grade 4 (0.3%), Grade 3 (1.4%), and Grade 2 (1.7%) adverse reactions. Pneumonitis led to permanent discontinuation of TEVIMBRA in 35 (1.8%) patients and withholding of TEVIMBRA in 27 (1.4%) patients.

Systemic corticosteroids were required in all patients with pneumonitis. Immune-mediated pneumonitis resolved in 47% of the 75 patients. Of the 27 patients in whom TEVIMBRA was withheld for pneumonitis, 18 reinitiated TEVIMBRA after symptom improvement; of these, 3 (17%) 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 0.9% (17/1972) of patients receiving TEVIMBRA, including Grade 3 (0.4%), and Grade 2 (0.5%) adverse reactions. Colitis led to permanent discontinuation of TEVIMBRA in 2 (0.1%) patients and withholding of TEVIMBRA in 10 (0.5%) patients. All 17 patients received systemic corticosteroids. Twelve (71%) of the 17 patients received high-dose systemic corticosteroids. Two (12%) of the 17 patients received immunosuppressive treatment. Immune-mediated colitis resolved in 88% of the 17 patients. Of the 10 patients in whom TEVIMBRA was withheld for colitis, 8 reinitiated TEVIMBRA after symptom improvement; of these, 1 (13%) patient had recurrence of colitis.

Immune-Mediated Hepatitis

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

Immune-mediated hepatitis occurred in 1.7% (34/1972) of patients receiving TEVIMBRA, including fatal (0.1%), Grade 4 (0.1%), Grade 3 (1%), and Grade 2 (0.6%) adverse reactions. Immune-mediated hepatitis led to permanent discontinuation in 9 (0.5%) patients and withholding of TEVIMBRA in 20 (1%) patients. All patients received systemic corticosteroids. Twenty-nine (85%) of the 34 patients received high-dose systemic corticosteroids. One patient (2.9%) of the 34 patients received immunosuppressive treatment. Immune-mediated hepatitis resolved in 59% of the 34 patients. Of the 20 patients in whom TEVIMBRA was withheld for hepatitis, 12 reinitiated TEVIMBRA after symptom improvement; of these, 2 (17%) 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 0.3% (6/1972) of patients receiving TEVIMBRA, including Grade 4 (0.1%), Grade 3 (0.1%), and Grade 2 (0.2%) adverse reactions. Adrenal insufficiency did not lead to permanent discontinuation of TEVIMBRA. TEVIMBRA was withheld in 5 out of the 6 patients. All 6 patients received systemic corticosteroids. Two (33%) of the 6 patients received high-dose systemic corticosteroids. Adrenal insufficiency resolved in 17% of the 6 patients.

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 0.1% (1/1972) of patients receiving TEVIMBRA, including a Grade 2 (0.1%) adverse reaction. No TEVIMBRA treatment discontinuation or withholding was required.

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 0.4% (7/1972) of patients receiving TEVIMBRA, including Grade 2 (0.3%) adverse reactions. Thyroiditis did not lead to permanent discontinuation of TEVIMBRA. TEVIMBRA was withheld in 1 (0.1%) patient. One (14%) of the 7 patients received systemic corticosteroids. Thyroiditis resolved in 29% of the 7 patients.

Hyperthyroidism: Immune-mediated hyperthyroidism occurred in 0.6% (12/1972) of patients receiving TEVIMBRA, including Grade 3 (0.1%), and Grade 2 (0.5%) adverse reactions. Hyperthyroidism led to the permanent discontinuation of TEVIMBRA in 1 (0.1%) patient and withholding of TEVIMBRA in 1 (0.1%) patient. One (8%) of the 12 patients received systemic corticosteroids. Hyperthyroidism resolved in 92% of the 12 patients.

Hypothyroidism: Immune-mediated hypothyroidism occurred in 7% (132/1972) of patients receiving TEVIMBRA, including Grade 4 (0.1%) and Grade 2 (5%) adverse reactions. TEVIMBRA was not permanently discontinued in any patient, while treatment was withheld in 6 (0.3%) patients. Two (1.5%) of the 132 patients received systemic corticosteroids. All 132 patients received hormone replacement therapy. Hypothyroidism resolved in 27% of the 132 patients. The majority (86%) of patients with hypothyroidism required long-term thyroid hormone replacement.

Type 1 Diabetes Mellitus, which can present with Diabetic Ketoacidosis

Type 1 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.

Immune-Mediated Nephritis with Renal Dysfunction

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

Immune-mediated nephritis with renal dysfunction occurred in 0.4% (7/1972) of patients receiving TEVIMBRA, including Grade 4 (0.1%), Grade 3 (0.1%), and Grade 2 (0.2%) adverse reactions. TEVIMBRA was permanently discontinued in 3 (0.2%) patients and treatment was withheld in 3 (0.2%) patients. All patients received systemic corticosteroids. Nephritis with renal dysfunction resolved in 57% of the 7 patients. Of the 3 patients in whom TEVIMBRA was withheld for nephritis, 2 reinitiated TEVIMBRA after symptom improvement and one 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 1.2% (24/1972) of patients receiving TEVIMBRA, including Grade 4 (0.2%), Grade 3 (0.4%), and Grade 2 (0.4%) adverse reactions. Dermatologic adverse reactions led to permanent discontinuation of TEVIMBRA in 3 (0.2%) patients and withholding of TEVIMBRA in 9 (0.5%) patients. Twenty-three (96%) of the 24 patients received systemic corticosteroids. Immune-mediated skin reactions resolved in 58% of the 24 patients. Of the 9 patients in whom TEVIMBRA was withheld for dermatologic adverse reactions, 8 reinitiated TEVIMBRA after symptom improvement; of these, 2 (25%) patients had recurrence of immune-mediated rash.

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-Barre 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 4.2% (83/1972) patients receiving TEVIMBRA, including Grade 3 or higher (0.3%) 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 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

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.

Please see full U.S. Prescribing Information including Medication Guide.

On September 26, 2024 Cue Biopharma, Inc. (Nasdaq: CUE), a clinical-stage biopharmaceutical company developing a novel class of therapeutic biologics to selectively engage and modulate disease-specific T cells, reported the pricing of an underwritten public offering of (i) 11,564,401 shares of its common stock and accompanying common stock warrants to purchase an aggregate of 2,891,100 shares of common stock and, (ii) to certain investors in lieu of common stock, pre-funded warrants to purchase 12,435,599 shares of common stock and accompanying common stock warrants to purchase an aggregate of 3,108,900 shares of common stock (Press release, Cue Biopharma, SEP 26, 2024, View Source [SID1234646883]). Each share of common stock and accompanying common stock warrant are being sold together at a combined public offering price of $0.50, and each pre-funded warrant and accompanying common stock warrant are being sold together at a combined public offering price of $0.499. The aggregate gross proceeds of the offering are expected to be approximately $12.0 million, before deducting underwriting discounts and commissions and other offering expenses. Each pre-funded warrant will have an exercise price of $0.001 per share, will be exercisable immediately and will be exercisable until all of the pre-funded warrants are exercised in full. Each common stock warrant will have an exercise price of $0.50 per share, will be exercisable immediately and will expire five years from the date of issuance. The offering is expected to close on or about September 30, 2024, subject to satisfaction of customary closing conditions. All of the securities are being offered by Cue Biopharma.

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Oppenheimer & Co. Inc. is acting as sole book-running manager for the offering. Newbridge Securities Corporation is acting as co-manager for the offering.

A shelf registration statement on Form S-3 (File No. 333-271786) relating to the securities to be offered in the public offering was filed with the Securities and Exchange Commission (the "SEC") on May 9, 2023 and declared effective on May 26, 2023. The offering was made only by means of a prospectus supplement and accompanying prospectus that form a part of the registration statement. A preliminary prospectus supplement relating to and describing the terms of the offering has been filed with the SEC and may be obtained for free by visiting the SEC’s website at www.sec.gov. A final prospectus supplement relating to the offering will be filed with the SEC. When available, copies of the preliminary prospectus supplement and final prospectus supplement relating to the offering may also be obtained by contacting: Oppenheimer & Co. Inc., Attention: Syndicate Prospectus Department, 85 Broad Street, 26th Floor, New York, New York 10004, by telephone at (212) 667-8055, or by email at [email protected].

This press release does not constitute an offer to sell, or a solicitation of an offer to buy these securities, nor shall there be any sale of, these securities in any state or jurisdiction in which such offer, solicitation or sale would be unlawful prior to registration or qualification under the securities laws of any such state or jurisdiction.

On September 26, 2024 Fortress Biotech, Inc. (Nasdaq: FBIO) ("Fortress"), an innovative biopharmaceutical company focused on acquiring and advancing assets to enhance long-term value for shareholders through product revenue, equity holdings and dividend and royalty revenue, reported that Lindsay A. Rosenwald, M.D., Chairman, President and Chief Executive Officer, will participate in the following upcoming October 2024 investor conferences (Press release, Fortress Biotech, SEP 26, 2024, View Source [SID1234646885]):

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Early/Late Stage Pipeline Development - Target Scouting - Clinical Biomarkers - Indication Selection & Expansion - BD&L Contacts - Conference Reports - Combinatorial Drug Settings - Companion Diagnostics - Drug Repositioning - First-in-class Analysis - Competitive Analysis - Deals & Licensing

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Lytham Partners Fall 2024 Investor Conference
Date and Time: Tuesday, October 1, 2024 at 4:15 p.m. ET
Location: Virtual
Format: Fireside Chat and 1×1 Meetings
Registration link for the event: View Source

3rd Annual ROTH Healthcare Opportunities Conference
Date: Wednesday, October 9, 2024
Location: New York
Format: 1×1 Meetings

A replay of the fireside chat at the Lytham Partners Fall 2024 Investor Conference will be available shortly after the conference on the Events page under the News & Media section of Fortress’ website: www.fortressbiotech.com for approximately 30 days following the meeting.