Arcellx Announces New Positive Data for Its iMMagine-1 Study in Patients with Relapsed and/or Refractory Multiple Myeloma

On May 14, 2025 Arcellx, Inc. (NASDAQ: ACLX), a biotechnology company reimagining cell therapy through the development of innovative immunotherapies for patients with cancer and other incurable diseases, reported new positive data from its pivotal Phase 2 iMMagine-1 study of anitocabtagene autoleucel (anito-cel), in patients with relapsed or refractory multiple myeloma (RRMM) (Press release, Arcellx, MAY 14, 2025, View Source [SID1234653052]). These data will be presented during an oral presentation at the EHA (Free EHA Whitepaper)2025 Congress in Milan on June 14, 2025. Anito-cel is partnered with Kite, a Gilead Company.

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The Phase 2 iMMagine-1 data are from a May 1, 2025 data cutoff date, including all 117 patients with a median follow-up of 12.6 months and a minimum follow-up of four months after treatment with anito-cel. All patients received a single infusion of anito-cel (target dose of 115×106 CAR+ viable T cells). 101 of 117 patients (86%) were triple refractory, and 48 of 117 patients (41%) were penta refractory. Patients received a median of three prior lines of therapy, with 60 of 117 patients (51%) having received three prior lines.

Overall response rate (ORR) was 97% (114/117) with a complete response/stringent complete response (CR/sCR) rate of 68% (79/117) and a very good partial response or higher (≥VGPR) rate of 85% (100/117), per International Myeloma Working Group (IMWG) criteria as investigator-assessed. Of those evaluable for minimal residual disease (MRD) testing at the time of this data cut, 93.3% (70/75) achieved MRD negativity at a minimum of 10-5 sensitivity. Six-month progression-free survival (PFS) and overall survival (OS) rates were 91.9% and 96.6%, respectively, and 12-month PFS and OS rates were 78.8% and 95.2%, respectively. Median PFS and median OS have not been reached.

No delayed or non-immune effector cell-associated neurotoxicity syndrome (ICANS) neurotoxicities, including no Parkinsonism, no cranial nerve palsies, and no Guillain-Barré syndrome, and no immune-mediated enterocolitis have been observed to date with anito-cel. No additional treatment- or therapy-related deaths or Grade ≥3 cytokine release syndrome (CRS) or ICANS events have occurred since the previous data presentation in December 2024.

Conclusions

Preliminary results from the Phase 2 iMMagine-1 study demonstrate deep and durable responses with a predictable and manageable safety profile in a fourth-line or higher (4L+) RRMM population, including triple- and penta-class refractory disease. Notably, no delayed or non-ICANS neurotoxicities, including no Parkinsonism, no cranial nerve palsies, and no Guillain-Barré syndrome, and no immune-mediated enterocolitis have been observed with anito-cel to date.

"These clinical data from our registrational study continue to support our belief that anito-cel has the potential to address the needs of myeloma patients and the physicians who serve them," said Rami Elghandour, Arcellx’s Chairman and Chief Executive Officer. "There is no cure for multiple myeloma. We believe there remains an unmet medical need for CAR-T therapies that are efficacious, safe, and accessible. Anito-cel has the unique potential to address these needs thanks to our differentiated technology, our incredible and entrepreneurial team, the robust clinical data generated to date, and our strong partnership with Kite. Our 2026 commercial launch plans for anito-cel with our partners at Kite are well underway and we are excited for the opportunity to advance anito-cel in support of the myeloma community. We look forward to sharing these data with the clinical community at EHA (Free EHA Whitepaper) and are honored that the iMMagine-1 data will be presented during an oral presentation on Saturday, June 14."

EHA2025 Presentation Details

Phase 2 Registrational Study of Anitocabtagene Autoleucel for the Treatment of Patients with Relapsed and/or Refractory Multiple Myeloma: Preliminary Results from the iMMagine-1 Trial

Speaker: Gurbakhash Kaur, M.D., Assistant Professor of Internal Medicine, Mount Sinai Health System

Session Title: s431 Treatment of relapsed and/or refractory multiple myeloma (RRMM)

Session Date: June 14, 2025

Session Time: 17:00-18:15 CEST

Publication Number: S201

Presentation Title: S201 Phase 2 Registrational Study of Anitocabtagene Autoleucel for Relapsed and/or Refractory Multiple Myeloma (RRMM): Updated Results from iMMagine-1

About Multiple Myeloma

Multiple Myeloma (MM) is a type of hematological cancer in which diseased plasma cells proliferate and accumulate in the bone marrow, crowding out healthy blood cells and causing bone lesions, loss of bone density, and bone fractures. These abnormal plasma cells also produce excessive quantities of an abnormal immunoglobulin fragment, called a myeloma protein (M protein), causing kidney damage and impairing the patient’s immune function. MM is the third most common hematological malignancy in the United States and Europe, representing approximately 10% of all hematological cancer cases and 20% of deaths due to hematological malignancies. The median age of patients at diagnosis is 69 years with one-third of patients diagnosed at an age of at least 75 years. Because MM tends to afflict patients at an advanced stage of life, patients often have multiple co-morbidities and toxicities that can quickly escalate and become life-endangering.

About Anitocabtagene Autoleucel (anito-cel)

Anitocabtagene autoleucel (anito-cel, previously ddBCMA) is the first BCMA-directed CAR T-cell therapy to be investigated in multiple myeloma that utilizes Arcellx’s novel and compact binder known as the D-Domain. The small, stable D-Domain binder enables high CAR expression without tonic signaling and is designed to quickly release from the BCMA target. This combination may allow for the effective elimination of multiple myeloma cells without severe immunotoxicity. Anito-cel has been granted Fast Track, Orphan Drug, and Regenerative Medicine Advanced Therapy Designations by the U.S. Food and Drug Administration.

Arbutus Reports First Quarter 2025 Financial Results and Provides Corporate Update

On May 14, 2025 Arbutus Biopharma Corporation (Nasdaq: ABUS) ("Arbutus" or the "Company"), a clinical-stage biopharmaceutical company focused on infectious disease, reported first quarter 2025 financial results and provided a corporate update (Press release, Arbutus Biopharma, MAY 14, 2025, View Source [SID1234653051]).

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"To date, eight patients have reached functional cure following imdusiran combination therapy. Of particular note, two of those functional cure patients did not receive any interferon during the trial," said Lindsay Androski, President and CEO of Arbutus. "There are more than 250 million people suffering from cHBV globally. This type of functional cure data, in patients who successfully discontinued all cHBV treatments including NUCs, is an exciting milestone for Arbutus, clinicians, and patients.

"In addition, our oral PD-L1 inhibitor, AB-101, achieved 100% receptor occupancy in 11 of 13 evaluable healthy volunteers in our Phase 1a/1b clinical trial at the 40 mg dose. The trial continues in cHBV patients, and across all cohorts there have been no AB-101-related SAEs and no evidence of liver dysfunction to date.

"Lastly, I am pleased to announce that Andrew Sung has joined Arbutus as General Counsel. Andrew brings a wealth of life sciences deal experience, from collaboration and licensing agreements to large M&A transactions and is an important and valuable addition to our team."

2025 Clinical Development Milestones

Imdusiran (AB-729)

At the European Association for the Study of the Liver (EASL) Congress 2025, the Company presented two posters with data from the IM-PROVE I Phase 2a clinical trial that evaluated imdusiran with nucleos(t)ide analogue (NA) therapy and pegylated interferon alfa-2a (IFN). One poster characterized the demographics and virological markers of six cHBV patients who achieved functional cure. The data showed that HBsAg at baseline was the only apparent marker in common associated with functional cure. In a second poster, the Company reported that patients who achieved functional cure in the 24-week IFN treatment cohorts experienced HBsAg loss that was associated with transient HBV RNA elevations that were preceded by or coincided with increases in immunological markers.
Also at EASL, the Company presented a poster in the late-breaker session with data from the IM-PROVE II Phase 2a clinical trial that evaluated imdusiran, ongoing NA therapy and Barinthus Biotherapeutics’ VTP-300, with or without low dose nivolumab. The data showed that 25% (2/8) of the patients who had baseline HBsAg <1000 IU/mL and received the addition of low dose nivolumab to the treatment regimen reached functional cure.
To date, the Company has reported a total of eight patients with cHBV who have been functionally cured following treatment with imdusiran and ongoing NA therapy in combination with either IFN or nivolumab plus an immunotherapeutic. Two of the eight patients received no IFN as part of the combination therapy. Seven of the eight patients who achieved functional cure had HBsAg <1000 IU/mL at baseline. According to the literature, patients with HBsAg levels <1000 IU/mL represent a significant portion of the cHBV population.
AB-101 (oral PD-L1 inhibitor)

AB-101-001 is a Phase 1a/1b double-blind, randomized, placebo-controlled clinical trial designed to investigate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single- and multiple-ascending doses of AB-101, the Company’s oral PD-L1 inhibitor, in healthy subjects and patients with cHBV.
Data from Part 1 and Part 2 of this clinical trial which evaluated single- and multiple-ascending doses of AB-101 in healthy subjects showed that AB-101 was well-tolerated with evidence of dose-dependent receptor occupancy. In Part 1, all five evaluable subjects in the 40mg cohort showed evidence of 100% receptor occupancy. In Part 2, all subjects in the 40mg cohort showed evidence of high receptor occupancy between 74-100%, with six of the eight subjects demonstrating 100% receptor occupancy during the seven-day dosing period. Across Parts 1 and 2, eleven of the thirteen evaluable healthy subjects that received either single or multiple doses of 40mg of AB-101 achieved 100% receptor occupancy.
At EASL, the Company presented a poster with data from Part 3 of the clinical trial showing that 10mg of AB-101 once daily for 28 days was also well tolerated in patients with cHBV, with PD-L1 receptor occupancy similar to that observed in healthy volunteers who received multiple doses of AB-101 10mg once daily.
There were no serious adverse events or early discontinuations due to AB-101 and no evidence of liver dysfunction across the cohorts presented.
Part 3 of this clinical trial is ongoing.
LNP Litigation

Arbutus continues to consult closely with and support our exclusive licensee, Genevant Sciences, to protect and defend Arbutus’s intellectual property, which is the subject of on-going lawsuits against Moderna and Pfizer/BioNTech. The Company, together with Genevant, is seeking fair compensation for Moderna’s and Pfizer/BioNTech’s use of Arbutus’s patented LNP technology that was developed with great effort and at a great expense, and without which Moderna’s and Pfizer/BioNTech’s COVID-19 vaccines would not have been successful.
The claim construction hearing for the lawsuit against Pfizer/BioNTech occurred in December 2024. The court is expected to provide its ruling on the claim construction and issue a further scheduling order in 2025.
The jury trial in the Moderna U.S. litigation is scheduled for September 29, 2025. Expert discovery has concluded and the case is entering the summary judgment stage. In March 2025, the Company, alongside Genevant Sciences, filed five international lawsuits against Moderna and its affiliates seeking to enforce patents protecting the Company’s patented LNP technology across 30 countries. In the Unified Patent Court, Moderna’s Statement of Defense is due on July 8, 2025.
Corporate Updates

In April, the Company hired Andrew J. Sung as General Counsel. Mr. Sung brings over 20 years of legal experience representing and advising companies on corporate matters, intellectual property, compliance, contracting, litigation and employment issues. Mr. Sung, an MIT-trained chemist, has conducted multiple life sciences transactions including over $24 billion of M&A deals and licensing and collaboration agreements exceeding $4 billion in potential payments. Prior to Arbutus, Mr. Sung served as General Counsel of Harmonix Music Systems, Inc. for several years, leading the company’s sale to Epic Games, Inc., where he continued through the post-merger integration and transition. Mr. Sung was previously a Life Sciences Corporate Associate at Ropes & Gray LLP and a Senior Consultant in the Life Sciences practice at Cap Gemini Ernst & Young. Mr. Sung earned his J.D. from Harvard Law School and his B.S in Chemistry from the Massachusetts Institute of Technology.
Financial Results

Cash, Cash Equivalents and Investments

As of March 31, 2025, the Company had cash, cash equivalents and investments in marketable securities of $112.7 million compared to $122.6 million as of December 31, 2024. During the quarter ended March 31, 2025, the Company used $13.4 million in operating activities, which was partially offset by $2.7 million of proceeds from the exercise of employee stock options.

Revenue

Total revenue was $1.8 million for the quarter ended March 31, 2025, compared to $1.5 million for the same period in 2024. The increase of $0.3 million was due to an increase in revenue recognition of the upfront license fee received in 2022 from Qilu, the Company’s collaboration partner in China, Hong Kong, Macau and Taiwan, partially offset by a decrease in license royalty revenues in the 2025 period compared to the same period in 2024 due to a decrease in Alnylam’s sales of ONPATTRO.

Operating Expenses

Research and development expenses were $9.0 million for the quarter ended March 31, 2025 compared to $15.4 million for the same period in 2024. The decrease of $6.4 million was due primarily to cost savings from the Company’s decision in August 2024 to streamline the organization to focus its efforts on advancing the clinical development of imdusiran and AB-101, which included ceasing all discovery efforts, discontinuing its IM-PROVE III clinical trial and reducing the Company’s workforce.

General and administrative expenses were $5.8 million for the quarter ended March 31, 2025, compared to $5.3 million for the same period in 2024. This increase was due primarily to an increase in litigation-related legal fees, partially offset by a decrease in employee compensation-related expenses.

Restructuring costs in the quarter ended March 31, 2025 were $12.4 million, consisting of: (i) $6.0 million of cash severance and benefits; (ii) $2.3 million of non-cash stock-based compensation expenses for employee equity award modifications; and (iii), in connection with the decision to exit its corporate headquarters, (a) $3.8 million of non-cash impairment charges for laboratory equipment, leasehold improvements and its right-of-use asset and (b) $0.4 million of lease-related cash operating expenses. Substantially all of the termination severance payments and other employee benefits costs are expected to be paid during the second quarter of 2025, with the remainder to be paid in the second half of 2025.

Net Loss

For the quarter ended March 31, 2025, the Company’s net loss was $24.5 million, or a loss of $0.13 per basic and diluted common share, as compared to a net loss of $17.9 million, or a loss of $0.10 per basic and diluted common share, for the quarter ended March 31, 2024.

Outstanding Shares

As of March 31, 2025, the Company had 191.5 million common shares issued and outstanding, as well as 15.2 million stock options and unvested restricted stock units outstanding. Roivant Sciences Ltd. owned approximately 20% of the Company’s outstanding common shares as of March 31, 2025.

UNAUDITED CONDENSED CONSOLIDATED STATEMENTS OF LOSS
(in thousands, except share and per share data)

Three Months Ended March 31,
2025 2024
Revenue
Collaborations and licenses $ 1,316 $ 939
Non-cash royalty revenue 448 593
Total revenue 1,764 1,532
Operating expenses
Research and development 8,959 15,403
General and administrative 5,832 5,312
Change in fair value of contingent consideration 299 180
Restructuring costs 12,373 —
Total operating expenses 27,463 20,895
Loss from operations (25,699) (19,363)
Other income (loss)
Interest income 1,197 1,545
Interest expense (28) (44)
Foreign exchange gain/(loss) 4 (13)
Total other income 1,173 1,488
Net loss $ (24,526) $ (17,875)
Net loss per common share
Basic and diluted $ (0.13) $ (0.10)
Weighted average number of common shares
Basic and diluted 190,707,085 175,625,552

UNAUDITED CONDENSED CONSOLIDATED BALANCE SHEETS
(in thousands)

March 31,
2025 December 31,
2024
Cash, cash equivalents and marketable securities, current $ 112,707 $ 122,623
Accounts receivable and other current assets 4,101 4,693
Total current assets 116,808 127,316
Property and equipment, net of accumulated depreciation 168 3,309
Right of use asset — 1,048
Other non-current assets 34 34
Total assets $ 117,010 $ 131,707

Accounts payable and accrued liabilities $ 12,109 $ 7,564
Deferred license revenue, current 6,759 7,571
Lease liability, current 563 483
Total current liabilities 19,431 15,618
Liability related to sale of future royalties 4,409 4,829
Deferred license revenue, non-current 2,863 2,863
Contingent consideration 10,524 10,225
Lease liability, non-current 626 806
Total stockholders’ equity 79,157 97,366
Total liabilities and stockholders’ equity $ 117,010 $ 131,707

UNAUDITED CONDENSED CONSOLIDATED STATEMENTS OF CASH FLOWS
(in thousands)

Three Months Ended March 31,
2025 2024
Net loss $ (24,526) $ (17,875)
Non-cash items 5,866 1,439
Change in deferred license revenue (812) (244)
Other changes in working capital 6,081 (2,615)
Net cash used in operating activities (13,391) (19,295)
Net cash provided by investing activities 11,349 11,694
Issuance of common shares pursuant to the Open Market Sale Agreement — 21,765
Cash provided by other financing activities 2,784 2,665
Net cash provided by financing activities 2,784 24,430
Effect of foreign exchange rate changes on cash and cash equivalents 4 (13)
Increase in cash and cash equivalents 746 16,816
Cash and cash equivalents, beginning of period 36,330 26,285
Cash and cash equivalents, end of period 37,076 43,101
Investments in marketable securities 75,631 94,816
Cash, cash equivalents and marketable securities, end of period $ 112,707 $ 137,917

About Imdusiran (AB-729)  

Imdusiran is an RNAi therapeutic specifically designed to reduce all HBV viral proteins and antigens including hepatitis B surface antigen, which is thought to be a key prerequisite to enable reawakening of a patient’s immune system to control the virus. Imdusiran targets hepatocytes using Arbutus’ novel covalently conjugated N-Acetylgalactosamine (GalNAc) delivery technology enabling subcutaneous delivery. To date, Arbutus has reported a total of eight patients with cHBV who have achieved a functional cure following treatment with imdusiran and NA therapy in combination with either IFN or low dose nivolumab plus an immunotherapeutic. Clinical data generated thus far has shown imdusiran to be generally safe and well-tolerated, while also providing meaningful reductions in hepatitis B surface antigen and hepatitis B DNA.

About AB-101  

AB-101 is an oral PD-L1 inhibitor candidate that is designed to allow for controlled checkpoint blockade while minimizing the systemic safety issues typically seen with checkpoint antibody therapies. Immune checkpoints such as PD-1/PD-L1 play an important role in the induction and maintenance of immune tolerance and in T-cell activation, for example against HBV. In Arbutus’ ongoing Phase 1a/1b clinical trial, AB-101 has been generally safe and well-tolerated with evidence of high receptor occupancy.

About HBV  

Hepatitis B is a potentially life-threatening liver infection caused by the hepatitis B virus (HBV). HBV can cause chronic infection which leads to a higher risk of death from cirrhosis and liver cancer. Chronic HBV infection represents a significant unmet medical need. The World Health Organization estimates that over 250 million people worldwide suffer from chronic HBV infection, while other estimates indicate that approximately 2 million people in the United States suffer from chronic HBV infection. Approximately 1.1 million people die every year from complications related to chronic HBV infection despite the availability of effective vaccines and current treatment options.

Aptose Selected for Prestigious Oral Presentation of Data from TUSCANY Phase 1/2 Clinical Trial of Tuspetinib Triplet Therapy in Newly Diagnosed AML at the 2025 EHA Congress

On May 14, 2025 Aptose Biosciences Inc. ("Aptose" or the "Company") (TSX: APS; OTC: APTOF), a clinical-stage precision oncology company, reported that data from its Phase 1/2 TUSCANY trial in newly diagnosed patients treated with tuspetinib (TUS) in combination with standard of care dosing venetoclax and azacitidine (TUS+VEN+AZA triplet) has been selected for oral presentation at the European Hematology Association (EHA) (Free EHA Whitepaper) Congress (EHA 2025), being held June 12-15, 2025, in Milan, Italy (Press release, Aptose Biosciences, MAY 14, 2025, View Source [SID1234653050]).

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The TUS+VEN+AZA triplet is being developed as the only safe and mutation agnostic frontline therapy to treat large, mutationally diverse populations of newly diagnosed AML patients who are ineligible to receive induction chemotherapy. As reported prior, the first two dose cohorts at 40 mg of TUS or 80 mg of TUS in the TUS+VEN+AZA triplet, have demonstrated safety, complete remissions, and MRD negativity across patients with diverse mutations, including TP53-mutated/CK AML and FLT3-wildtype AML patients. The oral presentation at EHA (Free EHA Whitepaper) will include updated safety, complete remission, minimal residual disease (MRD) clinical findings, and longer duration of follow-up.

Details of the presentation are as follows:
Title: TUSCANY Study of Safety and Efficacy of Tuspetinib Plus Standard of Care Venetoclax and Azacitidine in Study Participants with Newly Diagnosed AML Ineligible for Induction Chemotherapy
Session: Oral Presentations: Acute Myeloid Leukemia – Clinical
Session Date and Time: Thursday, June 12, 2025, 5:00 – 6:15 pm CEST
Presenter: Dr. Gabriel Mannis, Associate Professor of Medicine, Stanford University School of Medicine
Abstract #: S139

Abstracts are available on the EHA (Free EHA Whitepaper)2025 website here.

TUSCANY: TUS+VEN+AZA Triplet Phase 1/2 Study

The tuspetinib-based TUS+VEN+AZA triplet therapy is being advanced in the TUSCANY Phase 1/2 clinical study with the goal of creating an improved frontline therapy for newly diagnosed AML patients that is active across diverse AML populations, durable, and well tolerated. Earlier APTIVATE trials of TUS as a single agent and in combination as TUS+VEN demonstrated favorable safety and broad activity in diverse relapsed or refractory (R/R) AML populations that went beyond the more prognostically favorable NPM1 and IDH mutant subgroups. Indeed, responses were also in R/R AML patients with highly adverse TP53 and RAS mutations, and those with mutated or unmutated (wildtype) FLT3 genes.

The TUSCANY Phase 1/2 study, being conducted at 10 leading U.S. clinical sites by elite clinical investigators, is designed to test various doses and schedules of TUS in combination with standard dosing of AZA and VEN for patients with AML who are ineligible to receive induction chemotherapy. A convenient, once daily oral agent, TUS is being administered in 28-day cycles. Multiple U.S. sites are enrolling in the TUSCANY trial with anticipated enrollment of 18-24 patients by mid-late 2025. Data will be released as it becomes available.

More information on the TUSCANY Phase 1/2 study can be found on www.clinicaltrials.gov (here).

Aprea Therapeutics Reports First Quarter 2025 Financial Results and Provides a Clinical Update

On May 14, 2025 Aprea Therapeutics, Inc. (Nasdaq: APRE) ("Aprea", or the "Company"), a clinical-stage biopharmaceutical company developing innovative treatments that exploit specific cancer cell vulnerabilities while minimizing damage to healthy cells, reported financial results for the first quarter ended March 31, 2025, and provided a business update (Press release, Aprea, MAY 14, 2025, View Source [SID1234653049]).

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"2025 is off to a strong start with significant clinical progress across both of our lead therapeutic candidates," said Oren Gilad, Ph.D., President and Chief Executive Officer of Aprea. "In our ongoing ATRN-119 clinical program, three patients in the latest twice daily cohort demonstrated stable disease, with tumor shrinkage of 7%, 14% and 21%, marking early evidence of single agent, anti-tumor activity. Notably, these encouraging results were achieved at a dose level below the recommended Phase 2 dose, reinforcing our belief in ATRN-119’s potential to address the urgent needs of patients with DDR-deficient cancers. As we progress to a dose level where clinical activity is emerging, our focus is shifting toward RP2D selection. Enrollment also continues in the ACESOT-1051 trial of our WEE1 inhibitor, APR-1051, and we expect to report preliminary efficacy data in the second half of 2025. At Aprea, we aim to redefine what is possible for patients with limited treatment options and we see ATRN-119 and APR-1051 as important clinical assets that may help us achieve this goal."

Key Business Updates and Potential Upcoming Key Milestones

ACESOT-1051: A Biomarker Focused, Phase 1 Trial of Oral WEE1 inhibitor, APR-1051

APR-1051 is a potent and selective small molecule WEE1 inhibitor designed to potentially solve tolerability challenges of the WEE1 class and may achieve greater clinical activity than other programs currently in development. Aprea is advancing APR-1051 as monotherapy in cancers with well-defined biomarkers that may predict sensitivity to WEE1 inhibition. Among these, cancers over-expressing Cyclin E represent a high unmet medical need. Patients with Cyclin E over-expression have poor prognosis and, currently, lack effective therapies options.
Patients are now being enrolled into the 100 mg QD dose level in the ACESOT-1051 (A Multi-Center Evaluation of WEE1 Inhibitor in Patients with Advanced Solid Tumors, APR-1051) Phase 1 clinical trial evaluating single-agent APR-1051 in advanced solid tumors harboring cancer-associated gene alterations. Given the encouraging tolerability profile to date, we are in a position to accelerate dose escalation and explore higher doses, potentially improving APR-1051 therapeutic impact. Informed by pharmacokinetic (PK) data, the dose escalation in ACESOT-1051 has been revised to get to potential therapeutic levels of drug earlier. After successfully clearing the 100 mg once-daily dose level, patients in the next cohort are expected to be dosed at 150 mg. The first patient at the 70 mg once-daily dose level had HPV+ head and neck squamous cell carcinoma (HNSCC), in line with a clinical strategy to include populations most likely to benefit from WEEI inhibition.
The primary objectives of ACESOT-1051 are to assess safety, dose-limiting toxicities (DLTs), maximum tolerated dose or maximum administered dose (MTD/MAD), and determine recommended Phase 2 dose (RP2D); secondary objectives are to evaluate pharmacokinetics and preliminary efficacy according to RECIST or PCWG3 criteria; pharmacodynamic parameters are exploratory objectives.
Preliminary safety and efficacy data from the ACESOT-1051 study are anticipated in the second half of 2025, with completion of the dose-escalation phase expected in the first half of 2026. Aprea intends to submit an abstract to a major oncology conference.
For more information, refer to ClinicalTrials.gov NCT06260514.
ABOYA-119: Ongoing Clinical Trial Evaluating ATR inhibitor, ATRN-119

ATRN-119 is a potent and highly selective first-in-class macrocyclic ATR inhibitor, designed and developed, to be used in patients with mutations in DDR-related genes. Cancers with mutations in DDR-related genes represent a high unmet medical need. These patients often have a poor prognosis and currently lack effective therapeutics options.
ATRN-119 is being evaluated in the open-label Phase 1/2a clinical trial (ABOYA-119) as monotherapy in patients with advanced solid tumors having at least one mutation in a defined panel of DDR-related genes.
Six patients have demonstrated stable disease to date, with three patients in the 550 mg twice daily cohort showing tumor shrinkage of 7%, 14% and 21%. The individual results include:
A female patient with leiomyosarcoma harboring RB1/ATM mutations achieved a 21% tumor reduction at her first follow-up scan after two months of therapy.
A male patient with acinar cell carcinoma of the pancreas harboring ATM mutation experienced a 14% tumor reduction at his first follow-up scan.
A female patient with ovarian cancer harboring BRIP1 mutation showed a 7% tumor reduction at her first follow-up scan.
Importantly, these results were observed at a dose level that is below the recommended Phase 2 dose, as dose escalation continues in the trial.

Preliminary safety and efficacy data from ABOYA-119 are expected in the second half of 2025 and RP2D is expected to be identified in the first half of 2026. For more information on ABOYA-119, please refer to clinicaltrials.gov NCT04905914.
Material Transfer Agreement with MD Anderson Cancer Center

In March 2025, Aprea entered into a Material Transfer Agreement (MTA) with MD Anderson Cancer Center. Aprea has agreed to supply APR-1051 to support preclinical research aimed at exploring its potential in treating HPV+ and HPV- head and neck squamous cell carcinoma (HNSCC) expressing genomic markers of replication stress.
The agreement will enable the research group at MD Anderson to conduct a series of pre-clinical experiments designed to generate preliminary efficacy and mechanistic data to support future clinical trials and treatment regimens. The project is being overseen by Professors Jeffrey N. Myers, M.D., Ph.D., F.A.C.S., and Abdullah A. Osman, Ph.D., both from the Department of Head and Neck Surgery, MD Anderson Cancer Center. Prof. Myers is the leading expert on head and neck cancers.
Select Financial Results for the First Quarter Ended March 31, 2025

As of March 31, 2025, the Company reported cash and cash equivalents of $19.3 million compared to $22.8 million as of December 31, 2024. The Company believes its cash and cash equivalents as of March 31, 2025 will be sufficient to meet its currently projected operating expenses and capital expenditure requirements into early second quarter of 2026.
For the first quarter ended March 31, 2025, the Company reported an operating loss of $4.1 million, compared to an operating loss of $3.1 million in the first quarter of 2024.
Research and Development (R&D) expenses were $2.5 million for the quarter ended March 31, 2025, compared to $1.6 million for the first quarter of 2024. The increase in R&D expense was primarily related to the initiation of our second clinical trial program for APR-1051, our small molecule WEE1 inhibitor, and the ABOYA-119 clinical trial to evaluate ATRN-119, our clinical-stage oral small molecule inhibitor of ATR.
General and Administrative (G&A) expenses were $1.8 million for the quarter ended March 31, 2025, compared to $1.9 million for the first quarter of 2024.
The Company reported a net loss of $3.9 million ($0.66 per basic share) on approximately 6.0 million weighted-average common shares outstanding for the quarter ended March 31, 2025, compared to a net loss of $2.8 million ($0.67 per basic share) on approximately 4.2 million weighted average common shares outstanding for the comparable period in 2024.

Agios to Highlight Pyruvate Kinase Activation Portfolio with New Data in Rare Blood Disorders at 30th EHA Congress

On May 14, 2025 Agios Pharmaceuticals, Inc. (Nasdaq: AGIO), a leader in cellular metabolism and pyruvate kinase (PK) activation pioneering therapies for rare diseases, reported that new data on the company’s PK activators, mitapivat and tebapivat, will be featured in oral and poster presentations during the 30th European Hematology Association (EHA) (Free EHA Whitepaper) Congress (EHA 2025) in Milan, Italy, June 12-15, 2025 (Press release, Agios Pharmaceuticals, MAY 14, 2025, View Source [SID1234653048]).

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"The clinical results and scientific insights being presented at EHA (Free EHA Whitepaper) add to the robust body of efficacy and safety data demonstrating the promise of PK activation in treating both adults and children with rare blood disorders," said Sarah Gheuens, M.D., Ph.D., Chief Medical Officer and Head of R&D, Agios. "The presentations span serious conditions with limited or no treatment options, including sickle cell disease, thalassemia, PK deficiency, and myelodysplastic syndromes, offering meaningful results that highlight the therapeutic potential of mitapivat and tebapivat. We look forward to this important opportunity to share these new data and strengthen our collaboration with the global hematology community at EHA (Free EHA Whitepaper)."

Select presentations and publications at EHA (Free EHA Whitepaper) 2025 will include:

An oral presentation of results from the ACTIVATE-KidsT Phase 3 study of mitapivat in children aged 1 to <18 years with PK deficiency who are regularly transfused. The study showed a clinically meaningful reduction in transfusion burden with mitapivat, with a higher proportion of patients achieving the primary endpoint of transfusion reduction response compared to placebo, though the prespecified statistical criterion was not met. Safety results were consistent with the safety profile for mitapivat previously observed in adults with PK deficiency who are regularly transfused. The ACTIVATE-KidsT study, along with the positive ACTIVATE-Kids Phase 3 trial, represents the successful execution of Agios’ first pediatric clinical program.
An oral presentation of long-term data from the investigator-led ESTIMATE Phase 2 trial, an open-label study investigating mitapivat in patients with sickle cell disease. In the study, mitapivat showed sustained efficacy and tolerability over three years, including improvements in anemia, hemolysis, painful vaso-occlusive crises, and markers of kidney damage.
A poster presentation with preclinical data demonstrating that tebapivat reduced red blood cell sickling and adhesion in blood samples from sickle cell disease patients, highlighting its therapeutic potential in this patient population.
A preclinical publication examining expression patterns of PKM2, an isoform (or variant) of the PK enzyme. The study found that, compared with healthy controls, patients with myelodysplastic syndromes (MDS) have significantly reduced PKM2 expression in CD34+ hematopoietic stem cells, which may be implicated in the development of MDS. These findings further support the ongoing investigation of tebapivat in lower-risk MDS, as it activates PKM2 in addition to PKR (the PK isoform found in red blood cells).
In total, 14 presentations and publications led by Agios and external collaborators will be shared at EHA (Free EHA Whitepaper) 2025.

EHA 2025 Accepted Abstracts

Title Number Date/Time Presenter Acceptance
Thalassemia
Overall survival and morbidity among adults with thalassemia in England: A retrospective analysis using routinely collected healthcare data from 2008 to 2020 PS2183

Saturday, June 14, 2025, 6:30 – 7:30 PM CEST

Khaled M. Musallam, M.D., Ph.D., Burjeel Medical City, Abu Dhabi, United Arab Emirates

Poster
Impact of non-transfusion-dependent thalassemia on adult patients’ health-related quality of life and work productivity: A multi-region real-world survey PF1192

Friday, June 13, 2025, 6:30 – 7:30 PM CEST

Khaled M. Musallam, M.D., Ph.D., Burjeel Medical City, Abu Dhabi, United Arab Emirates

Poster
ENERGIZE-T/ENERGIZE: Roxyscan assesses pyruvate kinase activator’s effect on oxidative stress sensitivity in β-thalassemia patients PS2192

Saturday, June 14, 2025, 6:30 – 7:30 PM CEST

Eduard J. van Beers, M.D., Ph.D., University Medical Center of Utrecht, Netherlands Poster
Understanding health literacy among patients with thalassemia: Initial key learnings from a global patient survey by the Thalassemia Advocacy Advisory Council PB3545

N/A Maria Domenica Cappellini, M.D., University of Milan, Italy Publication
Sickle Cell Disease
Three-year safety, efficacy, and renal outcomes of mitapivat treatment in sickle cell disease: Results from a phase 2, open-label study S299

Thursday, June 12, 2025, 5:00 – 6:15 PM CEST Geoffrey Kuppens, University Medical Center Utrecht, Netherlands

Oral
Patient-reported vaso-occlusive events, their associated pain severity, and impact of sickle cell disease on fatigue and quality of life: A real-world survey in the United States PS2179

Saturday, June 14, 2025, 6:30 – 7:30 PM CEST

Oladipo Cole, M.D., University of Connecticut Health Center

Poster
Optimizing hydroxyurea therapy in sickle cell disease: Insights from metabolite detection, treatment response and clinical outcomes* PF1176

Friday, June 13, 2025, 6:30 – 7:30 PM CEST

Sigrid van der Veen, University Medical Center Utrecht, Netherlands

Poster
Ex-vivo activation of pyruvate kinase by tebapivat reduces sickling and red blood cell adhesion in sickle cell disease PS2170

Saturday, June 14, 2025, 6:30 – 7:30 PM CEST

Minke Rab, M.D., Ph.D., University Medical Center Utrecht, Netherlands

Poster
Pyruvate Kinase Deficiency
Efficacy and safety of mitapivat in pediatric patients with pyruvate kinase deficiency who are regularly transfused: Results from the phase 3 randomized global placebo-controlled ACTIVATE-KidsT trial S296 Thursday, June 12, 2025, 5:00 – 6:15 PM CEST Rachael F. Grace, M.D., MMSc; Dana-Farber/Boston Children’s Cancer and Blood Disorder Center, Harvard Medical School Oral
Cardiac magnetic resonance observations in a patient with pyruvate kinase deficiency and beta-thalassemia trait treated with mitapivat – a case report PB3570 N/A Paolo Ricchi, M.D., Ph.D., Center for Rare Red Blood Cell Diseases, AORN A. Cardarelli, Naples, Italy Publication
Myelodysplastic Syndromes
PKM and PKLR mRNA expression in CD34+ cells derived from patients with myelodysplastic syndromes PB2748

N/A Erin Tsai, M.S., Agios Pharmaceuticals Publication
Other
SATISFY: Mitapivat in adults with erythrocyte membranopathies and congenital dyserythropoietic anemia type II: A EuroBloodNet, multicenter, single-arm, phase 2 study S297

Thursday, June 12, 2025, 5:00 – 6:15 PM CEST Thomas Doeven, M.D., University Medical Center Utrecht, Netherlands

Oral
Red blood cell age distribution and metabolic features in hereditary spherocytosis, hereditary xerocytosis and congenital dyserythropoietic anemia – baseline results of exploratory analysis from the SATISFY study PS2199

Saturday, June 14, 2025, 6:30 – 7:30 PM CEST

Richard van Wijk, Ph.D., University Medical Center Utrecht, Netherlands

Poster
PIEZO1 gain-of-function drives glycolytic imbalance in late-stage erythropoiesis: The potential of mitapivat therapy in dehydrated hereditary stomatocytosis PS2201 Saturday, June 14, 2025, 6:30 – 7:30 PM CEST Barbara Eleni Rosato, Ph.D., University of Naples, Italy Poster

*This investigator-sponsored trial is part of a larger project funded by Agios

Please refer to the EHA (Free EHA Whitepaper) 2025 online program for full session details and data presentation listings, and visit the Agios booth (#C04) onsite.

About PYRUKYND (mitapivat)
U.S. INDICATION
PYRUKYND is a pyruvate kinase activator indicated for the treatment of hemolytic anemia in adults with pyruvate kinase (PK) deficiency.

U.S. IMPORTANT SAFETY INFORMATION
Acute Hemolysis: Acute hemolysis with subsequent anemia has been observed following abrupt interruption or discontinuation of PYRUKYND in a dose-ranging study. Avoid abruptly discontinuing PYRUKYND. Gradually taper the dose of PYRUKYND to discontinue treatment if possible. When discontinuing treatment, monitor patients for signs of acute hemolysis and anemia including jaundice, scleral icterus, dark urine, dizziness, confusion, fatigue, or shortness of breath.

Hepatocellular Injury in Another Condition: In patients with another condition treated with PYRUKYND at a higher dose than that recommended for patients with PK deficiency, liver injury has been observed. These events were characterized by a time to onset within the first 6 months of treatment with peak elevations of alanine aminotransferase of >5× upper limit of normal (ULN) with or without jaundice. All patients discontinued treatment with PYRUKYND, and these events improved upon treatment discontinuation.

Obtain liver tests prior to the initiation of PYRUKYND and monthly thereafter for the first 6 months and as clinically indicated. Interrupt PYRUKYND if clinically significant increases in liver tests are observed or alanine aminotransferase is >5x ULN. Discontinue PYRUKYND if hepatic injury due to PYRUKYND is suspected.

Adverse Reactions: The most common adverse reactions including laboratory abnormalities (≥10%) in patients with PK deficiency were estrone decreased (males), increased urate, back pain, estradiol decreased (males), and arthralgia.

Drug Interactions:

Strong CYP3A Inhibitors and Inducers: Avoid concomitant use.
Moderate CYP3A Inhibitors: Do not titrate PYRUKYND beyond 20 mg twice daily.
Moderate CYP3A Inducers: Consider alternatives that are not moderate inducers. If there are no alternatives, adjust PYRUKYND dosage.
Sensitive CYP3A, CYP2B6, CYP2C Substrates Including Hormonal Contraceptives: Avoid concomitant use with substrates that have narrow therapeutic index.
UGT1A1 Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.
P-gp Substrates: Avoid concomitant use with substrates that have narrow therapeutic index.
Hepatic Impairment: Avoid use of PYRUKYND in patients with moderate and severe hepatic impairment.

Please see full Prescribing Information for PYRUKYND.