On March 31, 2025 AstraZeneca reported that IMFINZI (durvalumab) in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by IMFINZI as adjuvant monotherapy after radical cystectomy (surgery to remove the bladder) has been approved in the US for the treatment of adult patients with muscle-invasive bladder cancer (MIBC) (Press release, AstraZeneca, MAR 31, 2025, View Source [SID1234651704]).

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The approval was granted by the Food and Drug Administration (FDA) after securing Priority Review and was based on results from the NIAGARA Phase III trial which were presented during a Presidential Symposium at the 2024 European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress and simultaneously published in The New England Journal of Medicine.

In 2024, over 20,000 people in the US were treated for MIBC.1 Bladder cancer is considered muscle-invasive when there is evidence of the tumor invading the muscle wall of the bladder but no distant metastases.2 This represents a curative-intent setting, where the current standard of care is neoadjuvant chemotherapy and radical cystectomy.3 However, even after surgery, patients experience high rates of disease recurrence and have a poor prognosis.3

Matthew ND. Galsky, Lillian and Howard Stratton Professor of Medicine, Director of Genitourinary Medical Oncology, The Tisch Cancer Institute at the Icahn School of Medicine at Mount Sinai, New York, and NIAGARA investigator and steering committee member, said: "This approval for the durvalumab-based perioperative regimen is a major breakthrough for people with muscle-invasive bladder cancer, nearly half of whom see their cancer return despite chemotherapy and surgery with curative-intent. This durvalumab regimen significantly extended patients’ lives in the NIAGARA trial and has the potential to transform care."

Dave Fredrickson, Executive Vice President, Oncology Hematology Business Unit, AstraZeneca, said: "Today’s approval for IMFINZI represents a paradigm shift, bringing the first perioperative immunotherapy to patients in the US with muscle-invasive bladder cancer and addressing a significant need for better treatment options. The NIAGARA trial showed more than 80 percent of patients were still alive at two years, underscoring the potential of this innovative perioperative regimen to become a new standard of care in this setting."

Meri-Margaret Deoudes, CEO of the Bladder Cancer Advocacy Network, said: "More than 20,000 people in the US were treated for muscle-invasive bladder cancer last year and there is a significant need for new treatment options that improve patient outcomes. The approval of the durvalumab perioperative regimen is welcome news, transforming how clinicians will tackle this disease in the future and offering new hope to patients and their loved ones."

In the trial, patients were treated with four cycles of IMFINZI in combination with neoadjuvant chemotherapy before radical cystectomy followed by eight cycles of IMFINZI monotherapy, or neoadjuvant chemotherapy before radical cystectomy. In a planned interim analysis, the IMFINZI-based perioperative regimen demonstrated a 32% reduction in the risk of disease progression, recurrence, not undergoing surgery, or death versus the comparator arm (based on event-free survival [EFS] hazard ratio [HR] of 0.68; 95% confidence interval [CI] 0.56-0.82; p<0.0001). Estimated median EFS was not yet reached for the IMFINZI arm versus 46.1 months for the comparator arm. An estimated 67.8% of patients treated with the regimen were event free at two years compared to 59.8% in the comparator arm.

Results from the key secondary endpoint of overall survival (OS) showed that the IMFINZI-based perioperative regimen reduced the risk of death by 25% versus neoadjuvant chemotherapy with radical cystectomy (based on OS HR of 0.75; 95% CI 0.59-0.93; p=0.0106). Median survival was not yet reached for either arm. An estimated 82.2% of patients treated with the regimen were alive at two years compared to 75.2% in the comparator arm.

IMFINZI was generally well tolerated, and no new safety signals were observed in the neoadjuvant and adjuvant settings. Further, adding IMFINZI to neoadjuvant chemotherapy was consistent with the known profile for this combination and did not compromise patients’ ability to complete surgery compared to neoadjuvant chemotherapy alone. Immune-mediated adverse events (imAEs) were consistent with the known profile of IMFINZI, manageable and mostly low-grade.

In February 2025, perioperative treatment with durvalumab (IMFINZI), neoadjuvant cisplatin-based chemotherapy and cystectomy was added to the NCCN Clinical Practical Guidelines in Oncology (NCCN Guidelines) as a NCCN Category 1 Recommended regimen for patients with MIBC based on the data from NIAGARA.4

IMFINZI is also approved in Brazil in this setting based on the NIAGARA results. Regulatory applications are currently under review in the EU, Japan and several other countries.

IMPORTANT SAFETY INFORMATION

There are no contraindications for IMFINZI (durvalumab).

Severe and Fatal Immune-Mediated Adverse Reactions

Important immune-mediated adverse reactions listed under Warnings and Precautions may not include all possible severe and fatal immune-mediated 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 or after discontinuation. 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 IMFINZI depending on severity. See USPI Dosing and Administration for specific details. In general, if IMFINZI requires interruption or discontinuation, administer systemic corticosteroid therapy (1 mg 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 corticosteroid therapy.

Immune-Mediated Pneumonitis

IMFINZI can cause immune-mediated pneumonitis. The incidence of pneumonitis is higher in patients who have received prior thoracic radiation. In patients who did not receive recent prior radiation, the incidence of immune-mediated pneumonitis was 2.4% (34/1414), including fatal (<0.1%), and Grade 3-4 (0.4%) adverse reactions. The frequency and severity of immune-mediated pneumonitis in patients who did not receive definitive chemoradiation prior to IMFINZI were similar in patients who received IMFINZI as a single agent or with ES-SCLC or BTC when given in combination with chemotherapy.

Immune-Mediated Colitis

IMFINZI can cause immune-mediated colitis that is frequently associated with diarrhea. Cytomegalovirus (CMV) infection/reactivation has been reported in patients with corticosteroid-refractory immune-mediated colitis. In cases of corticosteroid-refractory colitis, consider repeating infectious workup to exclude alternative etiologies. Immune-mediated colitis occurred in 2% (37/1889) of patients receiving IMFINZI, including Grade 4 (<0.1%) and Grade 3 (0.4%) adverse reactions.

Immune-Mediated Hepatitis

IMFINZI can cause immune-mediated hepatitis. Immune-mediated hepatitis occurred in 2.8% (52/1889) of patients receiving IMFINZI, including fatal (0.2%), Grade 4 (0.3%) and Grade 3 (1.4%) adverse reactions.

Immune-Mediated Endocrinopathies

Adrenal Insufficiency: IMFINZI can cause primary or secondary adrenal insufficiency. For Grade 2 or higher adrenal insufficiency, initiate symptomatic treatment, including hormone replacement as clinically indicated. Immune-mediated adrenal insufficiency occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
Hypophysitis: IMFINZI can cause immune-mediated hypophysitis. Hypophysitis can present with acute symptoms associated with mass effect such as headache, photophobia, or visual field cuts. Hypophysitis can cause hypopituitarism. Initiate symptomatic treatment including hormone replacement as clinically indicated. Grade 3 hypophysitis/hypopituitarism occurred in <0.1% (1/1889) of patients who received IMFINZI.
Thyroid Disorders (Thyroiditis, Hyperthyroidism, and Hypothyroidism): IMFINZI can cause immune-mediated thyroid disorders. Thyroiditis can present with or without endocrinopathy. Hypothyroidism can follow hyperthyroidism. Initiate hormone replacement therapy for hypothyroidism or institute medical management of hyperthyroidism as clinically indicated.
Thyroiditis: Immune-mediated thyroiditis occurred in 0.5% (9/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
Hyperthyroidism: Immune-mediated hyperthyroidism occurred in 2.1% (39/1889) of patients receiving IMFINZI.
Hypothyroidism: Immune-mediated hypothyroidism occurred in 8.3% (156/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.
Type 1 Diabetes Mellitus, which can present with diabetic ketoacidosis: Monitor patients for hyperglycemia or other signs and symptoms of diabetes. Initiate treatment with insulin as clinically indicated. Grade 3 immune-mediated Type 1 diabetes mellitus occurred in <0.1% (1/1889) of patients receiving IMFINZI.
Immune-Mediated Nephritis with Renal Dysfunction

IMFINZI can cause immune-mediated nephritis. Immune-mediated nephritis occurred in 0.5% (10/1889) of patients receiving IMFINZI, including Grade 3 (<0.1%) adverse reactions.

Immune-Mediated Dermatology Reactions

IMFINZI can cause immune-mediated rash or dermatitis. Exfoliative dermatitis, including Stevens-Johnson Syndrome (SJS), drug rash with eosinophilia and systemic symptoms (DRESS), and toxic epidermal necrolysis (TEN), has occurred with PD-1/L-1 and CTLA-4 blocking antibodies. Topical emollients and/or topical corticosteroids may be adequate to treat mild to moderate non-exfoliative rashes. Immune-mediated rash or dermatitis occurred in 1.8% (34/1889) of patients receiving IMFINZI, including Grade 3 (0.4%) 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 patients who received IMFINZI or were reported with the use of other immune-checkpoint inhibitors.

Cardiac/vascular: Myocarditis, pericarditis, 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 to include 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 disorders: Myositis/polymyositis, rhabdomyolysis and associated sequelae including renal failure, arthritis, polymyalgia rheumatic.
Endocrine: Hypoparathyroidism.
Other (hematologic/immune): Hemolytic anemia, aplastic anemia, hemophagocytic lymphohistiocytosis, systemic inflammatory response syndrome, histiocytic necrotizing lymphadenitis (Kikuchi lymphadenitis), sarcoidosis, immune thrombocytopenia, solid organ transplant rejection, other transplant (including corneal graft) rejection.
Infusion-Related Reactions

IMFINZI can cause severe or life-threatening infusion-related reactions. Monitor for signs and symptoms of infusion-related reactions. Interrupt, slow the rate of, or permanently discontinue IMFINZI based on the severity. See USPI Dosing and Administration for specific details. For Grade 1 or 2 infusion-related reactions, consider using pre-medications with subsequent doses. Infusion-related reactions occurred in 2.2% (42/1889) of patients receiving IMFINZI, including Grade 3 (0.3%) adverse reactions.

Complications of Allogeneic HSCT after IMFINZI

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/L-1 blocking antibody. Transplant-related complications include hyperacute graft-versus-host disease (GVHD), acute GVHD, chronic GVHD, hepatic veno-occlusive disease (VOD) after reduced intensity conditioning, and steroid-requiring febrile syndrome (without an identified infectious cause). These complications may occur despite intervening therapy between PD-1/L-1 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/L-1 blocking antibody prior to or after an allogeneic HSCT.

Embryo-Fetal Toxicity

Based on its mechanism of action and data from animal studies, IMFINZI can cause fetal harm when administered to a pregnant woman. Advise pregnant women of the potential risk to a fetus. In females of reproductive potential, verify pregnancy status prior to initiating IMFINZI and advise them to use effective contraception during treatment with IMFINZI and for 3 months after the last dose of IMFINZI.

Lactation

There is no information regarding the presence of IMFINZI in human milk; however, because of the potential for serious adverse reactions in breastfed infants from IMFINZI, advise women not to breastfeed during treatment and for 3 months after the last dose.

Adverse Reactions

The most common adverse reactions, including laboratory abnormalities, in the overall study (occurring in ≥20% of patients) were decreased hemoglobin, decreased neutrophils, increased blood creatinine, decreased sodium, nausea, increased ALT, decreased calcium, decreased platelets, fatigue, increased potassium, decreased lymphocytes, increased AST, constipation, decreased magnesium, decreased appetite, increased alkaline phosphate, rash, pyrexia, diarrhea, vomiting and abdominal pain.
In patients with MIBC in the neoadjuvant phase of the NIAGARA study receiving IMFINZI in combination with gemcitabine and cisplatin (n=530), permanent discontinuation of IMFINZI due to an adverse reaction occurred in 9% of patients. Serious adverse reactions occurred in 24% of patients; the most frequent (≥1%) serious adverse reactions were pulmonary embolism (1.9%), febrile neutropenia (1.5%), acute kidney injury (1.3%), thrombocytopenia (1.3%), urinary tract infection (1.3%), and pneumonia (1.3%). Fatal adverse reactions occurred in 1.1% of patients including sepsis, myocardial infarction, and pulmonary embolism (0.2% each). One fatal adverse reaction of pneumonia was reported in 1 (0.2%) patient in the post-surgery phase before adjuvant treatment started. Of the 530 patients in the IMFINZI treatment arm and 526 patients in the chemotherapy treatment arm who received neoadjuvant treatment, 1 (0.2%) patient in each treatment arm did not receive surgery due to adverse reactions. The adverse reaction that led to cancellation of surgery in the IMFINZI treatment arm was interstitial lung disease.
In patients with MIBC in the adjuvant phase of the NIAGARA study receiving IMFINZI as a single agent (n=383), permanent discontinuation of adjuvant IMFINZI due to an adverse reaction occurred in 5% of patients. Serious adverse reactions occurred in 26% of patients. The most frequent serious adverse reactions (occurring in ≥1% of patients) were urinary tract infection (7%), acute kidney injury (3.7%), hydronephrosis (2.1%), pyelonephritis (2.1%), urosepsis (1.8%) and sepsis (1.6%). Fatal adverse reactions occurred in 1.8% of patients, including COVID-19, severe acute respiratory syndrome, cardiopulmonary failure, gastrointestinal hemorrhage, and chronic hepatic failure (0.3% each).
The safety and effectiveness of IMFINZI has not been established in pediatric patients.

Indication:

IMFINZI in combination with gemcitabine and cisplatin as neoadjuvant treatment, followed by single-agent IMFINZI as adjuvant treatment following radical cystectomy, is indicated for the treatment of adult patients with muscle-invasive bladder cancer (MIBC).

Please see Full Prescribing Information including Medication Guide for IMFINZI.

You may report side effects related to AstraZeneca products.

Notes

Muscle-invasive bladder cancer

Bladder cancer is the 9th most common cancer in the world, with more than 614,000 patients diagnosed each year.5 The most common type of bladder cancer is urothelial carcinoma, which begins in the urothelial cells of the urinary tract.6 In MIBC, approximately 50% of patients who undergo bladder removal surgery experience disease recurrence.3 Treatment options that prevent disease recurrence after surgery are critically needed in this curative-intent setting.

NIAGARA

NIAGARA is a randomized, open-label, multi-center, global Phase III trial evaluating perioperative IMFINZI as treatment for patients with MIBC before and after radical cystectomy. In the trial, 1,063 patients were randomized to receive IMFINZI plus neoadjuvant chemotherapy prior to cystectomy followed by IMFINZI, or neoadjuvant chemotherapy alone prior to cystectomy with no further treatment after surgery. NIAGARA is the largest global Phase III trial in this setting.

The trial is being conducted at 192 centers across 22 countries including in North America, South America, Europe, Australia and Asia. Its dual primary endpoints are EFS and pathologic complete response (pCR) at the time of cystectomy. Key secondary endpoints are OS and safety.

IMFINZI

IMFINZI (durvalumab) is a human monoclonal antibody that binds to the PD-L1 protein and blocks the interaction of PD-L1 with the PD-1 and CD80 proteins, countering the tumor’s immune-evading tactics and releasing the inhibition of immune responses.

In addition to the indication in bladder cancer, IMFINZI is the global standard of care based on OS in the curative-intent setting of unresectable, Stage III non-small cell lung cancer (NSCLC) in patients whose disease has not progressed after chemoradiotherapy (CRT). Additionally, IMFINZI is approved as a perioperative treatment in combination with neoadjuvant chemotherapy in resectable NSCLC, and in combination with a short course of tremelimumab-actl and chemotherapy for the treatment of metastatic NSCLC. IMFINZI is also approved for limited-stage small cell lung cancer (SCLC) in patients whose disease has not progressed following concurrent platinum-based CRT; and in combination with chemotherapy (etoposide and either carboplatin or cisplatin) for the treatment of extensive-stage SCLC.

In addition to its indications in lung cancers, IMFINZI is approved in combination with chemotherapy (gemcitabine plus cisplatin) in locally advanced or metastatic biliary tract cancer and in combination with tremelimumab-actl in unresectable hepatocellular carcinoma (HCC). IMFINZI is also approved as a monotherapy in unresectable HCC in Japan and the EU.

In March 2025, perioperative IMFINZI added to standard-of-care chemotherapy met the primary endpoint of event-free survival in the MATTERHORN Phase III trial in resectable gastric and gastroesophageal junction cancers.

IMFINZI in combination with chemotherapy followed by IMFINZI monotherapy is approved as a 1st-line treatment for primary advanced or recurrent endometrial cancer (mismatch repair deficient disease only in US and EU). IMFINZI in combination with chemotherapy followed by olaparib and IMFINZI is approved for patients with mismatch repair proficient advanced or recurrent endometrial cancer in EU and Japan.

Since the first approval in May 2017, more than 374,000 patients have been treated with IMFINZI. As part of a broad development program, IMFINZI is being tested as a single treatment and in combinations with other anti-cancer treatments for patients with SCLC, NSCLC, bladder cancer, breast cancer, several gastrointestinal and gynecologic cancers, and other solid tumors.

On March 31, 2025 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 for the treatment of cancer and autoimmune disease, reported fourth quarter and full year 2024 financial results (Press release, Cue Biopharma, MAR 31, 2025, View Source [SID1234651667]).
•
Prioritized resources on potentially disruptive autoimmune programs while enabling maturation of clinical data from oncology programs to further support prospective strategic partnerships
•
Appointed key industry leaders to management team and board of directors
•
Lucinda Warren, Chief Business Officer
Industry veteran, with extensive experience and proven expertise in strategic transactions, portfolio optimization and alliance management.
•
Daniel Baker, M.D., Interim Chief Development Officer
Over 20 years of drug development experience in the pharmaceutical industry.

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•
Pasha Sarraf, M.D., Ph.D., Member of Board of Directors
Physician-scientist with extensive experience in the business of science and biotechnology.
•
Successfully regained worldwide development and commercialization rights for CUE-401, the Company’s lead autoimmune program with potential to transform treatment across a broad spectrum of autoimmune and inflammatory diseases
•
Advanced research and development of CUE-501 as lead program of the CUE-500 series, demonstrating the potential to harness anti-viral specific T cells against pathogenic cells in both autoimmune and oncology
•
Company plans to announce business update call and webcast within the next couple of weeks

"During 2024 and Q1 2025, we made significant progress shaping the company for success," said Daniel Passeri, chief executive officer of Cue Biopharma. "We believe that the ongoing advancement of our prioritized autoimmune programs and the implementation of a highly focused strategic business model, support our ability to exploit the potentially disruptive opportunity of our Immuno-STAT platform, specifically CUE-401."

Fourth Quarter 2024 Financial Results

The Company reported collaboration revenue of $1.6 million and $1.8 million for the three months ended December 31, 2024 and 2023, respectively. The decrease was due to revenue earned from the strategic collaboration agreement entered into with Ono Pharmaceutical in the first quarter of 2023.

Research and development expenses were $7.2 million and $10.9 million for the three months ended December 31, 2024 and 2023, respectively. The decrease was primarily due to decreases in both drug substance manufacturing and clinical trial costs.

General and administrative expenses were $4.0 million and $4.6 million for the three months ended December 31, 2024 and 2023, respectively. The decrease was primarily due to a decrease in professional fees.

Full Year 2024 Financial Results

The Company reported collaboration revenue of $9.3 million and $5.5 million for the years ended December 31, 2024 and 2023, respectively. The increase was due to revenue earned from our strategic collaboration agreement entered into with Ono Pharmaceutical in the first quarter of 2023.

Research and development expenses were $36.3 million and $40.8 million for the years ended December 31, 2024 and 2023, respectively. The decrease was primarily due to decreases in clinical trial costs, employee compensation, which includes stock-based compensation, and manufacturing costs.

General and administrative expenses were $14.6 million and $16.7 million for the years ended December 31, 2024 and 2023, respectively. The decrease was primarily due to decreases in employee compensation, which includes stock-based compensation, and professional fees.

As of December 31, 2024, the Company had $22.5 million in cash and cash equivalents.

Cue Biopharma, Inc.

Consolidated Statements of Operations and Comprehensive Loss

(In thousands, except share and per share amounts)

Three Months Ended December 31,

Years Ended December 31,

2024

2023

2024

2023

Collaboration revenue

$

1,576

$

1,821

$

9,287

$

5,490

Operating expenses (income):

General and administrative

4,021

4,609

$

14,585

16,680

Research and development

7,184

10,887

$

36,295

40,802

(Gain) loss on fixed asset disposal

4

157

$

(93

)

157

Total operating expenses

11,209

15,653

50,787

57,639

Loss from operations

(9,633

)

(13,832

)

(41,500

)

(52,149

)

Other income (expense):

Interest income

290

905

1,622

2,661

Interest expense

(153

)

(507

)

(796

)

(1,245

)

Total other income, net

137

398

826

1,416

Net loss

$

(9,496

)

$

(13,434

)

$

(40,674

)

$

(50,733

)

Unrealized gain from available-for-sale securities

96

Comprehensive loss

$

(9,496

)

$

(13,434

)

$

(40,674

)

$

(50,637

)

Net loss per common share – basic and diluted

$

(0.13

)

$

(0.28

)

$

(0.72

)

$

(1.11

)

Weighted average common shares outstanding – basic and diluted

74,238,329

47,181,633

56,328,348

45,754,794

Cue Biopharma, Inc.

Consolidated Balance Sheets

(In thousands)

December 31,
2024

December 31,
2023

Assets

Cash and cash equivalents

$

22,459

$

48,514

Other assets

9,732

13,016

Total assets

$

32,191

$

61,530

Liabilities and stockholders’ equity

Liabilities

$

14,692

$

24,445

Stockholders’ equity

17,499

37,085

Total Liabilities and stockholders’ equity

$

32,191

$

61,530

On March 31, 2025 CASI Pharmaceuticals, Inc. (NASDAQ:CASI), ("CASI" or the "Company"), a Cayman incorporated biopharmaceutical company focused on developing and commercializing innovative therapeutics and pharmaceutical products, reported business and financial results for the fourth quarter ended December 31, 2024, and provided an update on key highlights for 2024 (Press release, CASI Pharmaceuticals, MAR 31, 2025, https://feeds.issuerdirect.com/news-release.html?newsid=5642877492672387&symbol=CASI [SID1234652235]).

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Wei-Wu He, Ph.D., CASI’s Chairman and Chief Executive Officer, commented, "2024 was a transformative year for CASI as we strategically pivoted our company toward the development of CID-103 for organ transplant rejection and autoimmune disease. CID-103 is an anti-CD38 antibody with the potential to be a best-in-class treatment for a myriad of autoimmune diseases as well as antibody mediated rejection (AMR). We are encouraged by our clinical progress, achieving a milestone with the first Immune Thrombocytopenia (ITP) patient dosed in January 2025. Simultaneously, we are diligently working towards resolution of the FDA renal allograft AMR clinical hold."

Dr. He continued, "As we advance into 2025, we remain firmly committed to progressing CID-103 at an accelerated pace. We expect to reach multiple important milestones this year. Our focused approach and prudent capital allocation position CASI to deliver sustainable long-term value creation for both patients and shareholders."

Key Business Highlights

CASI reported the fourth quarter revenue of $13.4 million and full-year revenue of $28.5 million.

Received a proposal with respect to the acquisition of CASI’s China business from Dr. Wei-Wu He on June 21, 2024.

Completed a $15.0 million private placement financing with leading healthcare investors including Venrock Healthcare Capital Partners, Foresite Capital, Panacea Venture and Dr. Wei-Wu He, on July 15, 2024.

Pipeline and Program Updates

Received FDA IND clearance of ITP on May 15, 2024.

Received CTA approval from China’s NMPA on ITP on October 24, 2024.

First patient dosed in Phase 1/2 clinical trial in ITP on January 3, 2025. Patient enrollment and treatment continues.

Upcoming Milestones

Anticipate FDA feedback on clinical hold for AMR in Q2, 2025.

Target IND submission for Aplastic Anemia in Q2, 2025.

Report the interim data from the ongoing ITP phase 1 study in mid-2025.

Anticipate finalizing the equity transfer agreement regarding Precision Autoimmune Therapeutics ("PAT") in Q2 2025. Upon completion of this transaction, CASI will have the sole global ownership of all indications in CID-103.

Product and Pipeline Highlights

CID-103 (Anti-CD38 antibody)

CID 103 is a full human IgG1 anti-CD38 monoclonal antibody recognizing a unique epitope that has demonstrated an encouraging preclinical efficacy and safety profile compared to other anti-CD38 monoclonal antibodies, and which we have exclusive global rights. CID 103 is being developed for the treatment of patients with chronic Immune Thrombocytopenia (ITP), renal allograft antibody mediated rejection (AMR). In May 2024, we announced the clearance of IND application with the US FDA for the initiation of a phase 1/2 study of CID-103 in adults with ITP. In October 2024, the Center for Drug Evaluation (CDE) approved the Clinical Trial Application (CTA) for a phase 1/2 study of CID-103 in patients with chronic ITP in China. The Chinese ITP study is part of the global development program which has been approved by the US FDA in May 2024. In January 2025, CASI announced the first patient was enrolled and dosed in the ITP clinical study. Furthermore, we are making steady progress towards resolution of the FDA clinical hold.

EVOMELA (melphalan for injection)

On December 3, 2018, CASI received the NMPA approval for importation, marketing and sales in China for EVOMELA , and on August 12, 2019, CASI announced the commercial launch of EVOMELA in China. Prior to EVOMELA’s entry into the Chinese market, an average of 800 stem cell transplants per year were conducted in the multiple myeloma (MM) treatment setting. Following EVOMELA’s launch in August of 2019, CASI worked closely with KOLs to improve market awareness and expedite adoption in the Chinese market. In 2023, nearly 10,000 patients were treated with EVOMELA. In 2024, the launch of an undifferentiated generic formulation of melphalan for injection product by a Chinese domestic manufacture has presented challenges, resulting in a decline of EVOMELA sales.

FOLOTYN (Pralatrexate)

On July 31, 2023, CASI entered into a tripartite assignment agreement with Mundipharma International Corporation Limited ("MICL"), Mundipharma Medical Company (MMCo), and Acrotech Biopharma Inc. (Acrotech) for the commercialization of FOLOTYN (Pralatrexate) in China. FOLOTYN (Pralatrexate) is a dihydrofolate reductase inhibitor indicated for the treatment of patients with relapsed or refractory peripheral T-cell lymphoma (PTCL). This product was approved by both the FDA and China’s NMPA for PTCL. CASI announced the first patient was dosed with FOLOTYN in China on February 15, 2024.

Fourth Quarter and Full-Year 2024 Financial Results

Revenue for the fourth quarter of 2024 was $13.4 million, representing a 94% increase compared to $6.9 million in the same period last year. The quarterly growth reflects a successful execution of commercial strategy implemented in the second half of the year. Full-year revenue was $28.5 million, compared to $33.9 million in 2023, a decrease of 16%. The annual performance was impacted by intensified competition following the market entry of domestically produced injectable melphalan, which created pricing pressure throughout the year.

R&D expenses for the fourth quarter was $3.7 million, a 61% increase from $2.3 million in the same period last year. The increase is primarily for the development of CID-103, supporting the company’s focused pivot toward opportunities in organ transplant rejection and autoimmune indications. Full-year R&D expenses was $8.9 million, compared to $9.9 million in 2023, representing a decrease of 10%. The reduction primarily resulted from lower amortization expenses following the decision to write off generic portfolio at the end of 2023.

G&A expenses for the fourth quarter of 2024 was $7.1 million, compared to $6.4 million in the same period in 2023, a 11% increase. This quarter-over-quarter increase is primarily attributable to legal expenses associated with ongoing arbitration proceedings with Juventas. Full-year G&A expenses was $23.6 million, compared to $25.4 million in 2023, representing a decrease of 7%. This year-over-year improvement demonstrates the effectiveness of our operational efficiency initiatives and cost control measures, reinforcing our commitment to disciplined financial management.

Net loss for the year ended December 31, 2024 was $39.3 million compared to $26.3 million for the year ended December 31, 2023.

As of December 31, 2024, CASI had cash and cash equivalents of $13.5 million compared to cash and cash equivalents plus short term investments of $29.1 million as of December 31, 2023.

Further information regarding the Company, including its Annual Report on Form 20-F for the year ended December 31, 2024, can be found at www.casipharmaceuticals.com. The Company will provide a hard copy of its annual report containing the audited consolidated financial statements, free of charge, to its shareholders upon request. Requests should be directed to Investor Relations Department, CASI Pharmaceuticals, Inc., Rm 1701-1702, China Central Office Tower 1, No.81 Jianguo Road Chaoyang District, Beijing, 100025, China.

On March 31, 2025 Curis, Inc. (NASDAQ: CRIS), a biotechnology company focused on the development of emavusertib (CA-4948), an orally available, small molecule IRAK4 inhibitor, reported its business update and financial results for the quarter ended December 31, 2024 (Press release, Curis, MAR 31, 2025, View Source [SID1234651668]).

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Operational Highlights

Emavusertib (IRAK4 Inhibitor)

TakeAim Lymphoma

Curis successfully concluded meetings with both the U.S. Food and Drug Administration (FDA) and the Committee for Medicinal Products for Human Use of the European Medicines Agency (EMA) on the suitability of using the ongoing TakeAim Lymphoma study (NCT 03328078) to support a potential accelerated approval path in PCNSL.
Curis also announced that emavusertib has been granted Orphan Drug Designation for PCNSL in both the US and Europe.
Curis provided a data update for 27 patients enrolled in the ongoing TakeAim Lymphoma study in relapsed/refractory (R/R) PCNSL as of January 2, 2025 (data cutoff).
In 20 BTKi-experienced patients:
13 patients had change in tumor burden data available as of data cutoff;
9 of these 13 patients demonstrated a reduction in tumor burden, including 6 objective responses, 4 complete responses (CR) and 2 partial responses (PR), with 3 of 4 CRs lasting more than six months.
In 7 BTKi-naïve patients:
6 patients had change in tumor burden data available as of data cutoff;
5 of these 6 patients demonstrated a reduction in tumor burden, including 5 objective responses, 1 CR and 4 PRs.
TakeAim Leukemia

In December 2024, the Company announced data from the TakeAim Leukemia study (NCT 04278768) in R/R Acute Myeloid Leukemia (AML) at the 66th ASH (Free ASH Whitepaper) annual meeting for 21 patients with a FLT3 mutation who had received fewer than 3 lines of prior therapy and were treated with emavusertib as monotherapy at the Recommended Phase 2 Dose (RP2D) of 300 mg BID.
19 patients were response-evaluable:
10 of 19 patients achieved objective response, including 6 CRs, 2 CRs with incomplete hematological recovery or partial hematological recovery (CRi/CRh) and 2 morphologic leukemia-free state (MLFS);
7 of the 10 objective responses were reported at the first assessment.
2 patients were not response-evaluable, as they discontinued treatment prior to first disease assessment (death occurred at Day 8 and Day 13, respectively).
Ema-Ven-Aza Triplet Study in Frontline AML

The Company initiated a Phase 1 clinical study of emavusertib in combination with venetoclax and azacitidine (ema-ven-aza) in frontline AML (CA-4948-104, 2023-505828-58). The study is currently being conducted in Spain, Germany, and Italy to assess the safety and tolerability of different dosing regimens by adding emavusertib to a patient’s ven-aza regimen after they have achieved a CR on ven-aza but remain positive for minimal residual disease. The first dosing cohort was completed and well tolerated, with no unexpected adverse events. As a result, the external Clinical Safety Review Committee recommended escalation to the next dosing cohort. Enrollment for this cohort is currently ongoing.

Corporate

On March 28, 2025, Curis priced a registered direct offering of common stock and concurrent private placement of pre-funded warrants and warrants ("March 2025 Offerings") with gross proceeds of approximately $10.0 million. The offerings are expected to close concurrently on March 31, 2025, subject to the satisfaction of customary closing conditions.

In October 2024, Curis completed a registered direct offering and concurrent private placement with net proceeds of approximately $10.8 million.

"Curis had a very productive 2024. We started the year seeing early responses in our PCNSL trial. As more patients enrolled, and we continued to see positive data, we initiated discussions with the FDA and EMA to discuss the possibility of pursuing an accelerated approval path for emavusertib. We are pleased to announce today that we have received supportive feedback from both agencies. Over the next 12-18 months, we will be focused on enrolling 30-40 additional patients to support the regulatory filing for accelerated approval," said James Dentzer, Chief Executive Officer of Curis.

Additional details of the Company’s discussions with EMA and FDA and the March 2025 Offerings were reported on Form 8-K filed by the Company with the SEC on March 28, 2025.

Fourth Quarter 2024 Financial Results

For the year ended December 31, 2024, Curis reported a net loss of $43.4 million, or $6.88 per share on both a basic and diluted basis, as compared to a net loss of $47.4 million, or $8.96 per share on both a basic and diluted basis in 2023. For the fourth quarter of 2024, Curis reported a net loss of $9.6 million or $1.25 per share on both a basic and diluted basis as compared to a net loss of $11.7 million or $2.03 on both a basic and diluted basis for the same period in 2023.

Revenues, net were $10.9 million and $10.0 million for the years ended December 31, 2024 and 2023, respectively. Revenues are comprised of royalty revenues related to Genentech and Roche’s net sales of Erivedge. Revenues were $3.3 million and $2.7 million for the fourth quarters of 2024 and 2023, respectively.

Research and development expenses were $38.6 million and $39.5 million for the years ended December 31, 2024 and 2023, respectively. The decrease was primarily attributable to lower clinical and consulting costs, partially offset by higher manufacturing costs. Research and development expenses were $9.0 million and $10.0 million for the fourth quarters of 2024 and 2023, respectively.

General and administrative expenses were $16.8 million and $18.6 million for the years ended December 31, 2024 and 2023, respectively. The decrease was primarily attributable to lower consulting, legal, facility, insurance and employee-related costs. General and administrative expenses were $3.4 million and $4.9 million for the fourth quarters of 2024 and 2023, respectively.

Other income, net was $1.2 million and $0.9 million for the years ended December 31, 2024 and 2023, respectively. The increase was attributable to a decrease in expense related to the sale of future royalties partially offset by a decrease in interest income. Other expense, net was $0.6 million for the fourth quarter of 2024 and other income, net was $0.5 million for the fourth quarter of 2023.

As of December 31, 2024, Curis’s cash and cash equivalents totaled $20.0 million, and the Company had approximately 8.5 million shares of common stock outstanding.

Cash Runway Guidance

Curis expects its cash and cash equivalents as of December 31, 2024, together with the expected proceeds from the March 2025 Offerings will enable the Company to fund its planned operations into the fourth quarter of 2025.

Conference Call Information

Curis management will host a conference call today, March 31, 2025, at 8:30 a.m. ET, to discuss the business update and these financial results.

To access the live conference call, please dial (800)-836-8184 from the United States or (646)-357-8785 from other locations, shortly before 8:30 a.m. ET. The conference call can also be accessed here on the Curis website in the Investors section.

On March 31, 2025 Oncotelic Therapeutics, Inc. (OTCQB:OTLC) ("Oncotelic," the "Company," or "We"), a leader in RNA-based therapeutics, reported the publication of its latest research paper, titled, "Positive Prognostic Overall Survival Impacts of Methylated TGFB2 and MGMT in Adult Glioblastoma Patients (Press release, Oncotelic, MAR 31, 2025, View Source [SID1234651690])." The paper, authored by Sanjive Qazi, Michael Potts, Scott Myers, Stephen Richardson, and Vuong Trieu, is available online at: View Source

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To facilitate deeper exploration and discussion of this research by the research community, Oncotelic is introducing its proprietary communication platform powered by PDAOAI. PDAOAI enables users to query this paper and dozens of referenced articles through a single interactive interface. Scientists and clinicians are invited to engage at: View Source

A Simple Summary

Glioblastoma (GBM) is one of the most aggressive brain tumors in adults. It is well established that methylation of the O-6-methylguanine-DNA methyltransferase (MGMT) gene is predictive of overall survival (OS) benefits in patients receiving standard temozolomide and radiotherapy. Transforming growth factor beta (TGFB) is a family of cytokines involved in vital cellular processes and the regulation of growth factors.

The study’s novel discovery demonstrates that high TGFB2 gene methylation correlates with an improved OS risk, surpassing the predictive value of MGMT and TGFB1 methylation when controlling for age and sex. Several genes and pathways linked to TGFB2 methylation, including immune mechanisms such as T-cell activation, antigen processing, and Toll-like receptor pathways, were identified as improving survival outcomes in GBM patients. Of note, mucosa-associated lymphoid tissue lymphoma translocation protein, also referred to as MALT1, mRNA negatively impacted survival rates, suggesting a potential avenue for targeted therapies.

"The complexity of the publication was simplified into a concise statement by our PDAOAI platform, demonstrating the power of this platform for scientific communication: The findings underscore the importance of TGFB2 methylation as a prognostic marker in GBM treatment. High levels of TGFB2 methylation are associated with improved overall survival, particularly in young adult males. This suggests that TGFB2 methylation could be a valuable biomarker for risk stratification and therapeutic targeting in GBM, potentially guiding treatment decisions and improving patient outcomes." – Dr. Vuong Trieu, CEO of Oncotelic and co-author of the study.

"Our findings present an actionable opportunity to improve GBM patient outcomes by integrating sophisticated predictive analytical platforms and tools with clinical data. By uncovering insightful methylation patterns and elucidating gene-expression profiles at the biochemical pathway level, we expand our capacity to identify potential therapeutic targets. This approach supports the development of tailored treatment strategies through our nano-technology drug delivery platform. Ultimately, these insights enhance innovation in targeted therapies, driving improved clinical efficacy and patient survival rates in this devastating disease." – Dr. Sanjive Qazi, lead researcher

"This is the first paper we have published that utilized our proprietary AI technology. We are excited to see our technology being applied in real-world scenarios, and we look forward to the advancements it can potentially bring in the future." – Scott Myers, Product Manager