On December 6, 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). These data are being presented during an oral presentation at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition on Saturday, December 6, 2025 at 2:45 p.m. ET. Anito-cel is partnered with Kite, a Gilead Company.

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October 7, 2025, is the data cutoff date for this presentation and the BLA submission. These data are for all 117 patients with a median follow-up of 15.9 months. All patients received a single infusion of anito-cel (target dose of 115×106 CAR+ viable T cells). Within the study population, 102 of 117 patients (87%) were triple refractory, 48 of 117 patients (41%) were penta refractory, 21 of 117 patients (18%) had extramedullary disease, and 47 of 117 patients (40%) had high risk cytogenetics. Patients received a median of three prior lines of therapy, with 65 of 117 patients (56%) having received three prior lines.

Overall response rate (ORR) was 96% (112/117) with a complete response/stringent complete response (CR/sCR) rate of 74% (86/117) and a very good partial response or higher (≥VGPR) rate of 88% (103/117), per Independent Review Committee (IRC) assessment. Of those evaluable for minimal residual disease (MRD) testing at the time of this data cut, 95% (91/96) achieved overall MRD negativity. Of the MRD evaluable group with sufficient follow up, 83% (54/65) sustained MRD negativity for >6 months, at a minimum of 10-5 sensitivity. Six-month progression-free survival (PFS) and overall survival (OS) rates were 93.1% and 95.7%, respectively; 12-month PFS and OS rates were 82.1% and 94.0%, respectively; 18-month PFS and OS rates were 67.4% and 88.0% respectively, and 24-month PFS and OS rates were 61.7% and 83.0% respectively. Median PFS and median OS have not been reached.

To date, no delayed or non-ICANS neurotoxicities, including no Parkinsonism, no cranial nerve palsies, no Guillain-Barré syndrome, and no immune effector cell-associated enterocolitis have been observed with anito-cel with all patients dosed more than 12 months ago.

Conclusions

Preliminary results from the Phase 2 iMMagine-1 study continue to 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-refractory disease. Notably, no delayed or non-ICANS neurotoxicities, including no Parkinsonism, no cranial nerve palsies, no Guillain-Barré syndrome, and no immune effector cell-associated enterocolitis have been observed with anito-cel to date.

"These data are compelling and are an important advancement for patients living with multiple myeloma," said Dr. Krina Patel, Associate Professor, Department of Lymphoma/Myeloma, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, and iMMagine-1 and iMMagine-3 clinical investigator. "I am encouraged by the depth of responses in the iMMagine-1 study. For clinicians, we rely on therapies that deliver continued meaningful efficacy, a predictable safety profile, and reliable manufacturing. Anito-cel demonstrates that it could become a significant new treatment option in our efforts to improve outcomes for patients with multiple myeloma."

Rami Elghandour, Arcellx’s Chairman and Chief Executive Officer, said, "The data from iMMagine-1 continue to reinforce our belief that anito-cel is poised to become a category leader in treating multiple myeloma patients. Our plans for a 2026 commercial launch are well underway. We are building a world-class commercial and medical affairs organization to ensure broad patient access and physician support. We remain committed to a launch of unparalleled scale and impact to meet the needs of the myeloma community and to demonstrate the true potential of cell therapy. We could not have reached this transformational moment without the collaboration of the physicians and patients who participated in the iMMagine-1 study, our team members who go above and beyond the status quo every day, and our partners at Kite. We believe we can set a new standard for what’s possible with a CAR T treatment option for multiple myeloma. We have come so far together, and the best is yet to come as we sit on the precipice of helping so many more patients in need."

ASH Presentation Details
Title: Phase 2 registrational study of anitocabtagene autoleucel for the treatment of patients with relapsed and/or refractory multiple myeloma: Updated results from iMMagine-1

Speaker: Krina K. Patel, MD, MSc, MD Anderson Cancer Center
Session Name: 655. Multiple Myeloma: Cellular Therapies: Clinical Trial Advances in CAR T-Cell Therapy for Multiple Myeloma
Session Date: Saturday, December 6, 2025
Session Time: 2:00 p.m. – 3:30 p.m. ET
Presentation Time: 2:45 p.m. ET
Location: OCCC – West Hall E1
Publication Number: 256
Submission ID: abs25-4541

Webcast Event:

Arcellx will host a live webcast event with a panel of clinician experts to discuss the iMMagine-1 clinical results on Saturday, December 6, 2025 at 8:00 p.m. ET. The event will be accessible from Arcellx’s website at www.arcellx.com in the Investors section. A replay of the webcast will be archived and available for 30 days following the event.

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 CART-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.

(Press release, Arcellx, DEC 6, 2025, View Source [SID1234661229])

On December 6, 2025 Vertex Pharmaceuticals Incorporated (Nasdaq: VRTX) reported data from multiple studies demonstrating the clinical benefits of CASGEVY (exagamglogene autotemcel) in people ages 5 years and older living with severe sickle cell disease (SCD) or transfusion-dependent beta thalassemia (TDT). The results, including the first presentation of clinical data from pivotal studies in children ages 5-11 years, and longer-term data from the pivotal studies of people with severe SCD and TDT ages 12 years and older, will be presented at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. CASGEVY is currently approved for eligible people ages 12 years and older with SCD or TDT in the United States, Great Britain, the European Union, the Kingdom of Saudi Arabia, the Kingdom of Bahrain, Kuwait, Qatar, Canada, Switzerland and the United Arab Emirates.

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"These results — the first clinical data ever presented on any genetic therapy for children ages 5-11 years with SCD — again demonstrate the transformative potential of CASGEVY," said Carmen Bozic, M.D., Executive Vice President, Global Medicines Development and Medical Affairs, and Chief Medical Officer at Vertex. "With dosing completed in the 5-11 age group and the Commissioner’s National Priority Voucher for CASGEVY in this population in hand, we are excited to begin global regulatory filings in the first half of next year and bring this potentially transformative therapy to eligible children as soon as possible."

"As an investigator in the clinical program for patients 12 years and older and after having real-world experience with CASGEVY as an early commercial treatment center, I have seen firsthand the transformative impact this therapy has had on older patients with SCD or TDT. I am excited to hopefully be able to offer this option to my younger patients soon, early in life, before some of the most devastating impacts of these diseases begin," said Haydar Frangoul, M.D., M.S., Medical Director of Pediatric Hematology and Oncology at Sarah Cannon Research Institute and HCA Healthcare’s TriStar Centennial Children’s Hospital, Member of Vertex’s SCD Program Steering Committee, and presenting author of the 5-11 years old CASGEVY data at ASH (Free ASH Whitepaper).

First presentation of data in children ages 5-11 years treated with CASGEVY

In children with SCD, 11 patients have been dosed with CASGEVY in the Phase 3 CLIMB-151 clinical study, and all (4/4) patients with sufficient follow-up achieved the primary endpoint of being free from vaso-occlusive crises (VOCs) for at least 12 consecutive months (VF12).
No patient experienced a VOC following infusion with CASGEVY, with the longest duration of VOC-free of approximately two years (range 3.2–24.1 months).
In children with TDT, 13 patients have been dosed with CASGEVY in the Phase 3 CLIMB-141 clinical study, and all (6/6) patients with sufficient follow-up achieved the primary endpoint of transfusion independence for at least 12 consecutive months while maintaining a weighted average hemoglobin (Hb) of at least 9 g/dL (TI12).
Following CASGEVY infusion, 12/13 are transfusion free, with the longest duration of transfusion free just under two years (range 2.3–22.5 months).
One patient died from pneumonia in the setting of multi-organ failure due to severe veno-occlusive disease related to the busulfan conditioning.
The safety profile of CASGEVY in younger patients is consistent with myeloablative conditioning and autologous transplant in both SCD and TDT, as established in clinical studies in older patients.
Consistent with studies in older patients, children treated with CASGEVY have durable increases in fetal hemoglobin (HbF) and stable allelic editing.
Longer-term data for people with SCD and TDT ages 12 years and older treated with CASGEVY

New longer-term data from the pivotal clinical studies of CASGEVY in people 12 years and older will also be presented at ASH (Free ASH Whitepaper). These data, as of April 2025, continue to demonstrate the transformative, durable clinical benefits that CASGEVY provides to people living with SCD or TDT. In SCD, 100% of patients (45/45) achieved VF12 in either CLIMB-121 or the long-term follow-up study CLIMB-131, with a mean duration of VOC-free for 35.3 months (range 12.9–67.7 months). In TDT, 98.2% (55/56) achieved TI12 in either CLIMB-111 or CLIMB-131 with a mean duration of transfusion independence of 41.4 months (range 13–72.3 months). The safety profile remained consistent with myeloablative conditioning and autologous transplant in both SCD and TDT.

About Sickle Cell Disease (SCD)
SCD is a debilitating, progressive and life-shortening disease. It is an inherited blood disorder that affects the red blood cells, which are essential for carrying oxygen to all organs and tissues of the body. SCD causes severe pain, organ damage and shortened life span due to misshapen or "sickled" red blood cells. The clinical hallmark of SCD is vaso-occlusive crises (VOCs), which are caused by blockages of blood vessels by sickled red blood cells and result in severe and debilitating pain that can happen anywhere in the body at any time. SCD requires a lifetime of treatment and results in a reduced life expectancy. In the U.S., the median age of death for patients living with SCD is approximately 45 years. SCD patients report health-related quality of life scores well below the general population, and the lifetime health care costs in the U.S. of managing SCD for patients with recurrent VOCs is estimated between $4 and $6 million.

About Transfusion-Dependent Beta Thalassemia (TDT)
TDT is a serious, life-threatening genetic disease. It requires frequent blood transfusions and iron chelation therapy throughout a person’s life. Due to anemia, patients living with TDT may experience fatigue and shortness of breath, and infants may develop failure to thrive, jaundice and feeding problems. Complications of TDT can also include an enlarged spleen, liver and/or heart, misshapen bones and delayed puberty. TDT requires lifelong treatment and significant use of health care resources, and ultimately results in reduced life expectancy, decreased quality of life and reduced lifetime earnings and productivity. In the U.S., the median age of death for patients living with TDT is 37 years. TDT patients report health-related quality of life scores below the general population and the lifetime health care costs in the U.S. of managing TDT are estimated between $5 and $5.7 million.

About CASGEVY (exagamglogene autotemcel)
CASGEVY is a non-viral, ex vivo CRISPR/Cas9 gene-edited cell therapy for eligible patients with SCD or TDT, in which a patient’s own hematopoietic stem and progenitor cells are edited at the erythroid specific enhancer region of the BCL11A gene through a precise double-strand break. This edit results in the production of high levels of fetal hemoglobin (HbF; hemoglobin F) in red blood cells. HbF is the form of the oxygen-carrying hemoglobin that is naturally present during fetal development, which then switches to the adult form of hemoglobin after birth. CASGEVY has been shown to reduce or eliminate VOCs for patients with SCD and transfusion requirements for patients with TDT.

The use of CASGEVY in children ages 5-11 years is investigational.

About the CLIMB Studies
The Phase 1/2/3 open-label studies, CLIMB-111 and CLIMB-121, are designed to assess the safety and efficacy of a single dose of CASGEVY in patients ages 12-35 years with TDT or with SCD and recurrent VOCs. Patients will be followed for approximately two years after CASGEVY infusion in these studies. CLIMB-141 and CLIMB-151 are ongoing Phase 3 open-label studies, designed to assess the safety and efficacy of a single dose of exagamglogene autotemcel in patients ages 2-11 years with TDT or with SCD and recurrent VOCs. Enrollment and dosing are complete for the 5-11-years-old cohort in both studies with the plan to extend to ages 2-4 years.

Each patient will be asked to participate in the ongoing long-term, open-label study, CLIMB-131. CLIMB-131 is designed to evaluate the long-term safety and efficacy of CASGEVY in patients with up to 15 years of follow up after CASGEVY infusion.

Next steps for CASGEVY in children ages 5-11 years
Enrollment and dosing are complete for the 5-11 years cohort in both studies. Vertex expects to initiate global regulatory filings for this age group, including a supplemental Biologics License Application (sBLA) in the U.S., in the first half of next year. Vertex recently received a Commissioner’s National Priority Voucher for CASGEVY in the 5-11 years age group from the U.S. Food and Drug Administration to accelerate the review of the sBLA once submitted. Products under the program will be subject to a 1–2-month review clock from the start of FDA’s review and will also benefit from enhanced communication opportunities with the agency.

U.S. INDICATIONS AND IMPORTANT SAFETY INFORMATION FOR CASGEVY

WHAT IS CASGEVY?

CASGEVY is a one-time therapy used to treat people ages 12 years and older with:

sickle cell disease (SCD) who have frequent vaso-occlusive crises or VOCs
beta thalassemia (β-thalassemia) who need regular blood transfusions
CASGEVY is made specifically for each patient, using the patient’s own edited blood stem cells, and increases the production of a special type of hemoglobin called hemoglobin F (fetal hemoglobin or HbF). Having more HbF increases overall hemoglobin levels and has been shown to improve the production and function of red blood cells. This can eliminate VOCs in people with sickle cell disease and eliminate the need for regular blood transfusions in people with beta thalassemia.

IMPORTANT SAFETY INFORMATION

What is the most important information I should know about CASGEVY?

After treatment with CASGEVY, you will have fewer blood cells for a while until CASGEVY takes hold (engrafts) into your bone marrow. This includes low levels of platelets (cells that usually help the blood to clot) and white blood cells (cells that usually fight infections). Your doctor will monitor this and give you treatment as required. The doctor will tell you when blood cell levels return to safe levels.

Tell your healthcare provider right away if you experience any of the following, which could be signs of low levels of platelet cells:
severe headache
abnormal bruising
prolonged bleeding
bleeding without injury such as nosebleeds; bleeding from gums; blood in your urine, stool, or vomit; or coughing up blood
Tell your healthcare provider right away if you experience any of the following, which could be signs of low levels of white blood cells:
fever
chills
infections
You may experience side effects associated with other medicines administered as part of the treatment regimen for CASGEVY. Talk to your physician regarding those possible side effects. Your healthcare provider may give you other medicines to treat your side effects.

How will I receive CASGEVY?

Your healthcare provider will give you other medicines, including a conditioning medicine, as part of your treatment with CASGEVY. It’s important to talk to your healthcare provider about the risks and benefits of all medicines involved in your treatment.

After receiving the conditioning medicine, it may not be possible for you to become pregnant or father a child. You should discuss options for fertility preservation with your healthcare provider before treatment.

STEP 1: Before CASGEVY treatment, a doctor will give you mobilization medicine(s). This medicine moves blood stem cells from your bone marrow into the blood stream. The blood stem cells are then collected in a machine that separates the different blood cells (this is called apheresis). This entire process may happen more than once. Each time, it can take up to one week.

During this step rescue cells are also collected and stored at the hospital. These are your existing blood stem cells and are kept untreated just in case there is a problem in the treatment process. If CASGEVY cannot be given after the conditioning medicine, or if the modified blood stem cells do not take hold (engraft) in the body, these rescue cells will be given back to you. If you are given rescue cells, you will not have any treatment benefit from CASGEVY.

STEP 2: After they are collected, your blood stem cells will be sent to the manufacturing site where they are used to make CASGEVY. It may take up to 6 months from the time your cells are collected to manufacture and test CASGEVY before it is sent back to your healthcare provider.

STEP 3: Shortly before your stem cell transplant, your healthcare provider will give you a conditioning medicine for a few days in hospital. This will prepare you for treatment by clearing cells from the bone marrow, so they can be replaced with the modified cells in CASGEVY. After you are given this medicine, your blood cell levels will fall to very low levels. You will stay in the hospital for this step and remain in the hospital until after the infusion with CASGEVY.

STEP 4: One or more vials of CASGEVY will be given into a vein (intravenous infusion) over a short period of time.

After the CASGEVY infusion, you will stay in hospital so that your healthcare provider can closely monitor your recovery. This can take 4-6 weeks, but times can vary. Your healthcare provider will decide when you can go home.

What should I avoid after receiving CASGEVY?

Do not donate blood, organs, tissues, or cells at any time in the future
What are the possible or reasonably likely side effects of CASGEVY?

The most common side effects of CASGEVY include:

Low levels of platelet cells, which may reduce the ability of blood to clot and may cause bleeding
Low levels of white blood cells, which may make you more susceptible to infection
Your healthcare provider will test your blood to check for low levels of blood cells (including platelets and white blood cells). Tell your healthcare provider right away if you get any of the following symptoms:

fever
chills
infections
severe headache
abnormal bruising
prolonged bleeding
bleeding without injury such as nosebleeds; bleeding from gums; blood in your urine, stool, or vomit; or coughing up blood
These are not all the possible side effects of CASGEVY. Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

General information about the safe and effective use of CASGEVY

Talk to your healthcare provider about any health concerns.

Please see full Prescribing Information including Patient Information for CASGEVY.

(Press release, Vertex Pharmaceuticals, DEC 6, 2025, View Source [SID1234661228])

On December 6, 2025 Deciphera Pharmaceuticals, a member of Ono Pharmaceutical Co., Ltd. (Headquarters: Osaka, Japan; President and COO: Toichi Takino; "Ono"), reported the oral presentation of positive results from the Phase 2a IMPRSSION study of sapablursen in patients with polycythemia vera (PV) at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting, taking place December 6-9, 2025, in Orlando, FL.

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The results were presented by Ionis Pharmaceuticals, who discovered and developed sapablursen and conducted the IMPRSSION study. In March 2025, Ionis and Ono entered into a license agreement in which Ono obtained exclusive global rights for the development and commercialization of sapablursen.

"In the treatment of PV, phlebotomy and cytoreductive therapy are performed as treatments for preventing thrombosis. Phlebotomy is the most common treatment for PV, in which blood is regularly removed from the vein, but it imposes significant physical and psychological burdens on patients. These Phase 2a study results demonstrate the ability of sapablursen to reduce the rate of blood withdrawals and control the hematocrit, which is the percentage of red blood cells in the total blood volume of the body, in phlebotomy-dependent patients including those undergoing cytoreductive therapy," said Tatsuya Okamoto, Corporate Officer / Executive Director, Clinical Development of Ono. "We believe sapablursen has the potential to be an important new treatment option for patients with PV and we look forward to advancing this promising treatment in a Phase 3 study."

Sapablursen was granted Fast Track designation in January 2024 and orphan drug designation in August 2024 by the U.S. Food and Drug Administration (FDA), along with Breakthrough Therapy designation in May 2025. Based on the positive Phase 2a study, Deciphera plans to initiate a Phase 3 study of sapablursen in patients with PV in 2026.

Summary of Data and Findings from Phase 2a IMPRSSION Study

The Phase 2a IMPRSSION study is a multicenter, randomized, open-label trial evaluating the safety and efficacy of sapablursen in patients with phlebotomy-dependent PV. Forty-nine (49) patients were accrued to Cohort A (N=32) and Cohort B (N=17). Cohort A initially assessed 120 mg before the dose was reduced to 80 mg, and Cohort B tested 40 mg. Sapablursen was administered subcutaneously every four weeks. The treatment period was 37 weeks, with an endpoint window between weeks 17 and 37, followed by a 36-week treatment extension period.

Efficacy

In both cohorts, the study achieved its primary endpoint of significantly decreasing weekly phlebotomy rate from baseline to weeks 17-37; with a decrease from 0.15 to 0.05 in Cohort A (p<0.0001) and from 0.17 to 0.07 in Cohort B (p=0.0001).
In patients who completed the 37-week treatment period, the median number of phlebotomies during the last 20 weeks of treatment (weeks 17-37) decreased to 0 and 1.5 phlebotomies in Cohort A and B, respectively, compared to 5 phlebotomies in the 26 weeks (6 months) prior to treatment for both cohorts.
Sapablursen caused a dose- and time-dependent increase in hepcidin with a corresponding reduction in hematocrit.
When assessing the symptoms of PV via Myeloproliferative Neoplasm Symptom Assessment Form – Total Symptom Score (MPN-SAF-TSS), the mean change from baseline was statistically significant in Cohort A and not statistically significant for Cohort B.
In Cohort A there was a mean change of -6.2.
In Cohort B there was a mean change of -2.7.
Safety

Sapablursen was generally safe and well tolerated.
During the study, one death occurred due to transformation to acute myeloid leukemia, which was deemed not related to the study drug.
The incidence of injection site reactions was low.
Injection site reactions were all mild in severity, not progressive, resolved spontaneously, and did not recur.
No laboratory trends suggesting adverse effects on liver or renal function were observed.
About Sapablursen

Sapablursen is designed to reduce the production of TMPRSS6 resulting in increased expression of hepcidin, which is the key regulator of iron homeostasis. By increasing production of hepcidin, sapablursen has the potential to positively impact blood diseases such as PV.

About Polycythemia Vera

Polycythemia vera (PV) is a rare and potentially life-threatening hematologic disease characterized by the overproduction of red blood cells, which significantly increases the risk of serious blood clots, especially in critical organs like the lungs, heart and brain. Patients with PV also experience severe iron deficiency and commonly have symptoms of fatigue, which can lead to reduced quality of life (QOL).

(Press release, Deciphera Pharmaceuticals, DEC 6, 2025, View Source [SID1234661227])

On December 6, 2025 Protagonist Therapeutics, Inc. ("Protagonist") (NASDAQ:PTGX) and Takeda (TSE:4502/NYSE:TAK) reported that new 52-week results from the pivotal Phase 3 VERIFY study evaluating rusfertide in patients with polycythemia vera (PV) will be presented in an oral presentation at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. These findings further reinforce rusfertide’s efficacy and safety and demonstrate durability of response, with 61.9% of patients continuously treated with rusfertide maintaining absence of phlebotomy eligibility from baseline to Week 52.

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"The 52-week data demonstrated the sustained efficacy of rusfertide, reducing the need for patients to receive phlebotomy while maintaining hematocrit control," said Dr. Andrew T. Kuykendall, M.D., VERIFY Lead Investigator and Associate Member in the Department of Hematology at Moffitt Cancer Center. "The 32-week VERIFY primary results were already promising, and this deeper understanding of the durability of response with rusfertide is critical to inform clinical decision-making for polycythemia vera. In totality, these findings, including the long-term extension data from THRIVE, reaffirm rusfertide as a potential new addition to the standard of care for patients with PV."

Achieving and maintaining controlled hematocrit (HCT) levels of <45% is the primary treatment goal in PV to prevent thrombotic events and help alleviate symptoms. However, many patients still experience uncontrolled hematocrit levels and burdensome symptoms with current standard of care treatments. The VERIFY study, designed to evaluate the efficacy and safety of rusfertide in patients with uncontrolled hematocrit who are phlebotomy-dependent despite receiving current standard of care treatment, met the primary endpoint and all four key secondary endpoints in its previously-reported 32-week primary analysis. During Part 1a (Weeks 0-32) of the VERIFY study, 293 patients were randomized to receive either rusfertide (147 patients) or placebo (146 patients), as an add-on to their current treatment. During Part 1b (Weeks 32-52), all participants were eligible to receive open-label rusfertide to evaluate the durability of the treatment response. 274 patients (94%) continued into Part 1b, and 267 patients (91%) remained in the study through Week 52, with 254 continuing to receive rusfertide in Part 2 (Weeks 52-156).

Key findings at 52 Weeks include1,2:

Phlebotomy Eligibility

61.9% of patients treated with rusfertide plus current standard of care throughout Parts 1a and 1b of the study experienced a durable clinical response, defined as absence of phlebotomy eligibility.
84.1% of patients treated with rusfertide who experienced a clinical response in the Part 1a assessment window (Weeks 20-32) maintained their response.
77.9% of patients who crossed over from placebo to rusfertide at Week 32 for Part 1b experienced a clinical response during the Part 1b assessment window (Weeks 40-52).
Median time to first phlebotomy was 16 Weeks in the placebo group, while median time to first phlebotomy was not reached in either the rusfertide group in Part 1a or 1b, or the placebo to rusfertide crossover group in Part 1b.
HCT Control

Mean hematocrit remained <43% through Week 52 in patients treated with rusfertide throughout Part 1a and Part 1b and those who switched from placebo to rusfertide for Part 1b.
Median time to first hematocrit ≥ 45% was 8.3 Weeks in the placebo group in Part 1a, while median time to first hematocrit ≥ 45% was not reached in the rusfertide group during Parts 1a or 1b.
Quality of Life Endpoints

Patients treated with rusfertide in Parts 1a and 1b maintained improvements in patient reported outcomes as measured by PROMIS Fatigue SF-8a and MFSAF TSS7.
Rusfertide was generally well-tolerated through 52 Weeks of treatment. The most common treatment-emergent adverse events (AE) in rusfertide-treated patients were injection site reactions (47.4%), anemia (25.6%) and fatigue (19.6%), which were primarily grade 1 or 2. Serious AEs occurred in 8.1% of overall rusfertide-treated patients.

The durability of response and safety profile of rusfertide in patients with PV from the 52-week VERIFY data are further supported by the four-year analysis of 46 patients who continued from REVIVE to the long-term extension study, THRIVE.

The results show that after transitioning to THRIVE, continued treatment with rusfertide with or without cytoreductive therapy demonstrated consistent, long-term hematocrit control with a greater than 13-fold reduction in estimated annual therapeutic phlebotomy rate compared to baseline prior to study entry in REVIVE. Prior to study entry in REVIVE, the mean annualized phlebotomy rate (i.e., phlebotomy/year) for the 46 patients who eventually rolled over to THRIVE was 9.2 phlebotomies/year. The mean annualized phlebotomy rate during THRIVE was 0.7 phlebotomies/year.3 Rusfertide’s safety profile was consistent with prior observations.

"The totality of these data further demonstrates rusfertide’s well tolerated safety profile and ability to deliver durable hematocrit control and clinical response as defined by absence of phlebotomy eligibility and support its potential to expand the treatment armamentarium for PV and positively impact the lives of patients with PV," said Arturo Molina, M.D., M.S., Chief Medical Officer at Protagonist. "We look forward to continuing to work with our partner, Takeda, to prepare for submission of an NDA to the FDA."

"We are committed to making a difference for patients with PV who face serious risks from thrombotic events if they are unable to adequately control hematocrit levels with currently available treatment options," said Phuong Khanh (P.K.) Morrow, M.D., Head of the Oncology Therapeutic Area Unit at Takeda. "The comprehensive data presented at ASH (Free ASH Whitepaper), from the pivotal VERIFY and long-term THRIVE studies, strongly underscore the potential of rusfertide to provide a sustained response, addressing a critical unmet need in managing this chronic cancer. We are excited to advance rusfertide towards regulatory approval in collaboration with Protagonist, bringing us one step closer to improving the care of patients suffering from PV."

Rusfertide has received Breakthrough Therapy Designation, Orphan Drug Designation and Fast Track Designation from the U.S. Food & Drug Administration (FDA).

About VERIFY
The Phase 3 VERIFY study (NCT05210790) is an ongoing, three-part, global, randomized, placebo-controlled study evaluating rusfertide in 293 patients with polycythemia vera over a 156-week period, with treatment extension for participants who are continuing to derive benefit from rusfertide beyond the 156-week treatment period. The study is evaluating the efficacy and safety of once-weekly, subcutaneously self-administered rusfertide in patients with uncontrolled hematocrit who are phlebotomy-dependent despite current standard of care treatment, which could include hydroxyurea, interferon and/or ruxolitinib. The primary endpoint of the study was the proportion of patients achieving a response during Weeks 20-32, which was defined as the absence of "phlebotomy eligibility." To meet phlebotomy eligibility, patients in the study were required to have: confirmed hematocrit ≥45% that was ≥3% higher than their baseline hematocrit value, or hematocrit ≥48%.

All patients have completed their participation in the randomized, placebo-controlled portion of the study evaluating the efficacy and safety of rusfertide plus current standard of care versus placebo plus current standard of care and are now in the open-label portions of the study.

About THRIVE
The THRIVE study (NCT06033586) is an ongoing, open-label extension study evaluating the long-term durability of response and safety profile of rusfertide in patients with polycythemia vera. The study includes 46 patients who previously participated in the Phase 2 REVIVE study (NCT04057040). Patients eligible to transition to the THRIVE study completed the open-label extension portion of REVIVE, ≥12 months of rusfertide therapy and had an end-of-treatment visit. THRIVE is designed to further assess the maintenance of hematocrit control, reduction in the need for therapeutic phlebotomy and overall safety of once-weekly, subcutaneous rusfertide over an additional two-year treatment period.

About Polycythemia Vera (PV)
Polycythemia vera (PV) is characterized by the overproduction of red blood cells (erythrocytosis), which increases blood viscosity, or thickness, that can result in life threatening thrombotic events such as stroke, deep vein thrombosis and pulmonary embolism. Hematocrit (HCT) is the ratio of red blood cells to total amount of blood in the body. Achieving and maintaining controlled HCT levels of <45% is the primary treatment goal in PV to prevent thrombotic events and alleviate burdensome symptoms, including severe fatigue, difficulty in concentrating, night sweats and pruritus.

(Press release, Takeda, DEC 6, 2025, View Source [SID1234661226])

On December 6, 2025 Partner Therapeutics, Inc. (PTx), a private, fully-integrated biotechnology company, reported new data from a post hoc analysis of the Phase 2 eNRGy trial (NCT02912949) evaluating zenocutuzumab in patients with treatment-naïve non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion. Results were presented in a late-breaking oral session at the IASLC-ASCO North America Conference on Lung Cancer (NACLC), in Chicago, Illinois.

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The new analysis evaluated the efficacy and safety of zenocutuzumab-zbco in treatment-naïve and previously treated NRG1+ NSCLC. Among 20 treatment-naïve and 121 previously treated patients, zenocutuzumab demonstrated an overall response rate (ORR) of 35% and 31%, respectively. The clinical benefit rate, defined as partial/complete response or stable disease for ≥24 weeks, was 65% in treatment-naïve and 58% in previously treated patients. Median duration of response was 17.1 months in treatment naïve patients, notably longer than in previously treated patients, 7.4 months. All treatment-related adverse events were grade 1 or 2. Zenocutuzumab safety profile was favorable and consistent with prior data.

"These data underscore the potential of zenocutuzumab as a first-line option for patients with NRG1-positive NSCLC, a patient population that typically responds poorly to standard first-line therapy," said Stephen Liu, MD, of Georgetown University. "Early and durable responses, coupled with a favorable safety profile are encouraging and highlight the importance of targeted therapy in this rare molecular subset."

"Consistent with other therapies targeting key oncogenic drivers, early intervention can lead to better outcomes — and we see the same with zenocutuzumab," said Pritesh J. Gandhi, Chief Development Officer at Partner Therapeutics. "These findings strengthen our conviction that early targeted inhibition of the NRG1 pathway with zenocutuzumab has the potential to meaningfully improve outcomes for patients with NRG1+ NSCLC."

"For patients and families facing NRG1+ lung cancer, these results mark meaningful progress," said Danielle Hicks, Chief Patient Officer of GO2 for Lung Cancer. "The durable responses and manageable safety profile of zenocutuzumab offer renewed hope and reinforce the need for continued innovation in biomarker-driven lung cancer care."

The abstract will be available on the Partner Therapeutics website under the research tab following the conference. Additional meeting information can be found on the IASLC-ASCO NACLC website.

In December 2024, zenocutuzumab-zbco (BIZENGRI) received U.S. Food and Drug Administration accelerated approval for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) and pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy. The indications were approved under accelerated approval based on ORR and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

For more information on the eNRGy trial and zenocutuzumab-zbco, please visit www.partnertx.com.

About NRG1 Gene Fusions

NRG1 fusions are unique cancer drivers that create oncogenic chimeric ligands rather than the more widely described chimeric receptors (NTRK, RET, ROS1, ALK, and FGFR fusions). The chimeric ligands bind to HER3, triggering HER2/HER3 heterodimerization and activate downstream signaling pathways that cause cancer cells to grow and proliferate. Zenocutuzumab-zbco is a bispecific antibody that blocks HER2/HER3 dimerization and NRG1 fusion interactions with HER3, resulting in the suppression of these pathways. Comprehensive molecular testing, notably tissue-based RNA next generation sequencing, is essential to identify rare and actionable gene fusions like NRG1.

About BIZENGRI (zenocutuzumab-zbco)

INDICATIONS

BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic non-small cell lung cancer (NSCLC) harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy.

BIZENGRI is indicated for the treatment of adults with advanced unresectable or metastatic pancreatic adenocarcinoma harboring a neuregulin 1 (NRG1) gene fusion with disease progression on or after prior systemic therapy.

These indications are approved under accelerated approval based on overall response rate and duration of response. Continued approval for these indications may be contingent upon verification and description of clinical benefit in a confirmatory trial(s).

Important Safety Information

BOXED WARNING: EMBRYO-FETAL TOXICITY

Embryo-Fetal Toxicity: Exposure to BIZENGRI during pregnancy can cause embryo-fetal harm. Advise patients of this risk and the need for effective contraception.

WARNINGS AND PRECUATIONS

Infusion-Related Reactions/Hypersensitivity/Anaphylactic Reactions

BIZENGRI can cause serious and life-threatening infusion-related reactions (IRRs), hypersensitivity and anaphylactic reactions. Signs and symptoms of IRR may include chills, nausea, fever, and cough.

In the eNRGy study, 13% of patients experienced IRRs, all were Grade 1 or 2; 91% occurred during the first infusion.

Administer BIZENGRI in a setting with emergency resuscitation equipment and staff who are trained to monitor for IRRs and to administer emergency medications. Monitor patients closely for signs and symptoms of infusion reactions during infusion and for at least 1 hour following completion of first BIZENGRI infusion and as clinically indicated. Interrupt BIZENGRI infusion in patients with ≤ Grade 3 IRRs and administer symptomatic treatment as needed. Resume infusion at a reduced rate after resolution of symptoms. Immediately stop the infusion and permanently discontinue BIZENGRI for Grade 4 or life-threatening IRR or hypersensitivity/anaphylaxis reactions.

Interstitial Lung Disease/Pneumonitis

BIZENGRI can cause serious and life-threatening interstitial lung disease (ILD)/pneumonitis.

In the eNRGy study, ILD/pneumonitis occurred in 2 (1.1%) patients treated with BIZENGRI. Grade 2 ILD/pneumonitis (Grade 2) resulting in permanent discontinuation of BIZENGRI occurred in 1 (0.6%) patient. Monitor for new or worsening pulmonary symptoms indicative of ILD/pneumonitis (e.g., dyspnea, cough, fever). Immediately withhold BIZENGRI in patients with suspected ILD/pneumonitis and administer corticosteroids as clinically indicated.

Permanently discontinue BIZENGRI if ILD/pneumonitis ≥ Grade 2 is confirmed.

Left Ventricular Dysfunction

BIZENGRI can cause left ventricular dysfunction.

Left ventricular ejection fraction (LVEF) decrease has been observed with anti-HER2 therapies, including BIZENGRI. Treatment with BIZENGRI has not been studied in patients with a history of clinically significant cardiac disease or LVEF less than 50% prior to initiation of treatment.

In the eNRGy study, Grade 2 LVEF decrease (40%-50%; 10 – 19% drop from baseline) occurred in 2% of evaluable patients. Cardiac failure without LVEF decrease occurred in 1.7% of patients, including 1 (0.6%) fatal event.

Before initiating BIZENGRI, evaluate LVEF and monitor at regular intervals during treatment as clinically indicated. For LVEF of less than 45% or less than 50% with absolute decrease from baseline of 10% or greater which is confirmed, or in patients with symptomatic congestive heart failure (CHF), permanently discontinue BIZENGRI.

Embryo-Fetal Toxicity

Based on its mechanism of action, BIZENGRI can cause fetal harm when administered to a pregnant woman. No animal reproduction studies were conducted with BIZENGRI. In post marketing reports, use of a HER2-directed antibody during pregnancy resulted in cases of oligohydramnios manifesting as fatal pulmonary hypoplasia, skeletal abnormalities, and neonatal death. In animal models, studies have demonstrated that inhibition of HER2 and/or HER3 results in impaired embryo-fetal development, including effects on cardiac, vascular and neuronal development, and embryolethality. Advise patients of the potential risk to a fetus. Verify the pregnancy status of females of reproductive potential prior to the initiation of BIZENGRI. Advise females of reproductive potential to use effective contraception during treatment with BIZENGRI and for 2 months after the last dose.

ADVERSE REACTIONS

NRG1 Gene Fusion Positive Unresectable or Metastatic NSCLC

Serious adverse reactions occurred in 25% of patients with NRG1 gene fusion positive NSCLC who received BIZENGRI. Serious adverse reactions in ≥ 2% of patients included pneumonia (n=4) dyspnea and fatigue (n=2 each). Fatal adverse reactions occurred in 3 (3%) patients and included respiratory failure (n=2), and cardiac failure (n=1). Permanent discontinuation of BIZENGRI due to an adverse reaction occurred in 3% of patients. Adverse reactions resulting in permanent discontinuation of BIZENGRI included dyspnea, pneumonitis and sepsis (n=1 each).

In patients with NRG1 gene fusion positive NSCLC who received BIZENGRI, the most common (>20%) adverse reactions, including laboratory abnormalities, were decreased hemoglobin (35%), increased alanine aminotransferase (30%), decreased magnesium (28%), increased alkaline phosphatase (27), decreased phosphate (26%), diarrhea (25%), musculoskeletal pain (23%), increased gamma-glutamyl transpeptidase (23%), increased aspartate aminotransferase (22%), and decreased potassium (21%).

NRG1 Gene Fusion Positive Unresectable or Metastatic Pancreatic Adenocarcinoma

Serious adverse reactions occurred in 23% of patients with NRG1 gene fusion positive pancreatic adenocarcinoma who received BIZENGRI.

There were 2 fatal adverse reactions, one due to COVID-19 and one due to respiratory failure. In patients with NRG1 gene fusion positive pancreatic adenocarcinoma who received BIZENGRI the most common (≥20%) adverse reactions, including laboratory abnormalities, were increased alanine aminotransferase (51%), diarrhea (36%), increased aspartate aminotransferase (31%), increased bilirubin (31%), decreased phosphate (31%), increased alkaline phosphatase (28%), decreased sodium (28%), musculoskeletal pain (28%), decreased albumin (26%), decreased potassium (26%), decreased platelets (26%), decreased magnesium (24%), increased gamma-glutamyl transpeptidase (23%), decreased hemoglobin (23%), vomiting (23%), nausea (23%), decreased leukocytes (21%), and fatigue (21%).

Please see full Prescribing Information, including Boxed Warning

(Press release, Partner Therapeutics, DEC 6, 2025, View Source [SID1234661223])