On December 7, 2025 Regeneron Pharmaceuticals, Inc. (NASDAQ: REGN) reported encouraging data from the Phase 1/2 LINKER-MM4 trial evaluating Lynozyfic (linvoseltamab) in adults with newly diagnosed multiple myeloma (NDMM) who were transplant eligible or ineligible were shared in an oral presentation at the American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting. These data build on results from a broad clinical development program evaluating Lynozyfic in early lines of treatment, including precursor conditions, as monotherapy and in combination with standard-of-care or novel agents.

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"The treatment of newly diagnosed multiple myeloma often relies on complicated combinations of quadruplet or triplet regimens, each with its own toxicities, in order to achieve rapid and durable responses, which can be incredibly burdensome for these patients," said Robert Orlowski, M.D., Ph.D., Deputy Chair, Professor of Medicine, and Director of Translational Myeloma Research in the Departments of Lymphoma/Myeloma and Experimental Therapeutics at The University of Texas MD Anderson Cancer Center and the lead investigator for the LINKER-MM4 trial. "As the first to evaluate a BCMAxCD3 bispecific monotherapy in this setting, LINKER-MM4 seeks to understand whether frontline intervention with a single agent can deliver strong efficacy, enabling the simplification and potentially greater tolerability of these regimens. Lynozyfic monotherapy is already achieving MRD negativity rates comparable to quadruplet regimens but earlier in the treatment course, and these compelling results are expected to deepen with longer follow up. These results underscore Lynozyfic’s potential as a foundational component of frontline treatment regimens for multiple myeloma – or even a monotherapy regimen – for both transplant-eligible and transplant-ineligible patients."

LINKER-MM4 is an ongoing, open-label Phase 1/2 trial investigating Lynozyfic in adults with NDMM. During a Phase 1A (dose escalation) cohort, patients were treated with a step-up dosing regimen followed by 50 mg, 100 mg or 200 mg doses of Lynozyfic. The lowest (50 mg) and highest (200 mg) tolerated doses were selected for further evaluation in the Phase 1B (dose-expansion) cohort. Among the 45 treated patients in both Phase 1A and 1B, 28 were transplant eligible, and 17 were transplant ineligible.

Across all dose levels (n=45), there was a 1.2 months median time to onset of response (range: 1-4.5 months). All three dose groups (50 mg, 100 mg and 200 mg) showed impressive efficacy, with a VGPR+ (very good partial response or better) of ≥70% with limited follow-up. Evidence shows that these responses are expected to deepen over time. Across all dose groups, 95% (19 of 20 patients) of all minimum residual disease (MRD) evaluable VGPR+ patients achieved MRD negative status at 10-5 sensitivity.

Across all dose levels, the most common treatment-emergent adverse events (TEAEs) were cytokine release syndrome (CRS; all Grade 1: 44%) and neutropenia (any Grade: 38%; Grade 3/4: 33%). Among other adverse events of special interest, one patient in the 50 mg cohort experienced Grade 1 immune effector cell-associated neurotoxicity syndrome (ICANS). Infections occurred in 84% of patients (Grade 1/2: 51%; Grade 3: 33%) with the majority occurring within the first three months of treatment and the rate of infections decreased over time. There were no ≥Grade 4 infections, Grade 5 TEAEs or dose-limiting toxicities. Ten patients elected to undergo an autologous stem cell transplant, all of whom had an acceptable CD34+ stem cell yield post-induction (range: 2.5-11.5 x 106/kg).

A broad clinical development program investigating Lynozyfic in early stages of the disease is underway. This includes the Phase 2 portion of the LINKER-MM4 trial evaluating Lynozyfic at the recommended 200 mg dose, as well as LINKER-MM6 (EMN39), a trial evaluating a combination of daratumumab, lenalidomide and dexamethasone (DRd) followed by Lynozyfic monotherapy compared with continued DRd in transplant-ineligible NDMM.

The use of Lynozyfic described above is investigational, and its safety and efficacy has not been evaluated by any regulatory authority for this indication.

About the ‘Regeneron Roundtable’ Investor Event
Regeneron will host a virtual investor event to discuss its multiple myeloma program on Wednesday, December 10 at 8:30 a.m. ET. This is the next webcast in a new investor event series called the ‘Regeneron Roundtable,’ intended to highlight programs from the company’s innovative investigational pipeline.
 
Links to the webcast and to register via telephone may be accessed from the ‘Investors and Media’ page of Regeneron’s website at View Source Upon registration, all telephone participants will receive a confirmation email detailing how to join the conference call, including the dial-in number along with a unique passcode and registrant ID that can be used to access the call. A replay of the conference call and webcast will be archived on the company’s website for at least 30 days.

About Multiple Myeloma
As the second most common blood cancer, there are over 187,000 new cases of MM diagnosed globally every year, with more than 36,000 diagnosed and 12,000 deaths anticipated in the U.S. in 2025. The disease is characterized by the proliferation of cancerous plasma cells (MM cells) that crowd out healthy blood cells in the bone marrow, infiltrate other tissues and cause potentially life-threatening organ injury. Despite treatment advances, MM is not curable, and while current treatments are able to slow progression of the cancer, most patients will ultimately experience cancer progression and require additional therapies.

About Lynozyfic
Lynozyfic was invented using Regeneron’s VelocImmune technology and is a fully human BCMAxCD3 bispecific antibody designed to bridge B-cell maturation antigen (BCMA) on MM cells with CD3-expressing T cells to facilitate T-cell activation and cancer-cell killing. Lynozyfic is approved to treat certain adults with R/R MM: in the U.S. after four lines of therapy and in the European Union after at least three prior therapies.

In the U.S., the generic name for Lynozyfic in its approved indications is linvoseltamab-gcpt, with gcpt as the suffix designated in accordance with Nonproprietary Naming of Biological Products Guidance for Industry issued by the U.S. FDA. Outside of the U.S., the generic name of Lynozyfic in its approved indications is linvoseltamab.

Lynozyfic is being investigated in a broad clinical development program exploring its use as a monotherapy as well as in combination regimens across different lines of therapy in MM, including earlier lines of treatment, as well as plasma cell precursor disorders. These potential uses are investigational, and their safety and efficacy have not been evaluated by any regulatory authority. 

In addition to LINKER-MM4, ongoing trials include:

LINKER-MM1: Phase 1/2 dose-escalation and dose-expansion trial evaluating the safety, tolerability, dose-limiting toxicities and anti-tumor activity of Lynozyfic monotherapy in R/R MM
LINKER-MM2: Phase 1b, open-label trial evaluating Lynozyfic in combination with other cancer treatments in patients with R/R MM
LINKER-MM3: Phase 3 confirmatory trial evaluating Lynozyfic monotherapy compared to the combination of elotuzumab, pomalidomide and dexamethasone in R/R MM
LINKER-MM5: Phase 3 trial evaluating Lynozyfic monotherapy or in combination with carfilzomib compared to standard of care combination regimens in patients with R/R MM
LINKER-MM6 (EMN39): Phase 3 trial, in collaboration with the European Myeloma Network, evaluating daratumumab, lenalidomide and dexamethasone induction followed by Lynozyfic monotherapy compared to continued daratumumab, lenalidomide, and dexamethasone in NDMM who are transplant-ineligible
Phase 1 trial evaluating Lynozyfic in combination with a Regeneron CD38xCD28 costimulatory bispecific in R/R MM
LINKER-SMM1: Phase 2 trial evaluating Lynozyfic monotherapy in high-risk smoldering MM
LINKER-MGUS1: Phase 2 dose-ranging trial evaluating Lynozyfic monotherapy in high-risk monoclonal gammopathy of unknown significance and non-high-risk SMM
LINKER-AL2: Phase 1/2 trial evaluating Lynozyfic monotherapy in R/R systemic light chain amyloidosis
For more information on Regeneron’s clinical trials in blood cancer, visit the clinical trials website, or contact via [email protected] or 844-734-6643.

IMPORTANT SAFETY INFORMATION FOR U.S. PATIENTS

What is the most important information I should know about LYNOZYFIC?
LYNOZYFIC may cause serious or life-threatening side effects, including Cytokine Release Syndrome (CRS) and infusion-related reactions (IRR), or neurologic problems.

Cytokine Release Syndrome (CRS) and infusion related reactions (IRR). CRS is common during treatment with LYNOZYFIC and can also be serious or life-threatening. Tell your healthcare provider or get medical help right away if you develop any signs or symptoms of CRS or IRR, including:

fever of 100.4ºF (38ºC) or higher
fast heartbeat
chills or shaking
dizziness or light-headedness
trouble breathing

Neurologic problems. LYNOZYFIC can cause neurologic problems that can be serious or life-threatening. Tell your healthcare provider or get medical help right away if you develop any signs or symptoms of neurologic problems, including:

headache
agitation, trouble staying awake, confusion or disorientation, seeing or hearing things that are not real (hallucinations)
trouble speaking, writing, thinking, remembering things, paying attention, or understanding things
problems walking, muscle weakness, shaking (tremors), loss of balance, or muscle spasms
numbness and tingling (feeling like "pins and needles")
burning, throbbing, or stabbing pain
changes in your handwriting
seizures
Due to the risk of CRS and neurologic problems, you will receive LYNOZYFIC on a "step-up dosing schedule" and should be hospitalized for 24 hours after the first and second "step-up" doses.

During the "step-up dosing schedule":
For your first dose, you will receive a smaller "step-up" dose of LYNOZYFIC on Day 1 of your treatment.
For your second dose, you will receive a larger "step-up" dose of LYNOZYFIC, which is usually given on Day 8 of your treatment.
For your third dose, you will receive the first treatment dose of LYNOZYFIC, which is usually given on Day 15 of your treatment.
Your healthcare provider may repeat one or both of the "step-up" doses depending on side effects or if your treatment is delayed.
Before the "step-up" doses and the first two treatment doses of LYNOZYFIC, you will receive medicines to help reduce your risk of CRS and IRR. Your healthcare provider will decide if you need to receive medicine to help reduce your risk of side effects with future doses.
LYNOZYFIC is available only through the LYNOZYFIC Risk Evaluation and Mitigation Strategy (REMS) due to the risk of side effects of CRS and neurologic problems. You will receive a Patient Wallet Card from your healthcare provider. Carry the LYNOZYFIC Patient Wallet Card with you at all times and show it to all of your healthcare providers. The LYNOZYFIC Patient Wallet Card lists signs and symptoms of CRS and neurologic problems. Get medical help right away if you develop any of the signs and symptoms listed on the LYNOZYFIC Patient Wallet Card. You may need to be treated in a hospital.

Your healthcare provider will monitor you for signs and symptoms of CRS and neurologic problems during treatment with LYNOZYFIC, as well as other side effects, and may treat you in a hospital if needed. Your healthcare provider may temporarily stop or completely stop your treatment with LYNOZYFIC if you develop CRS, neurologic problems, or any other severe side effects.

If you have any questions about LYNOZYFIC, ask your healthcare provider.

Before receiving LYNOZYFIC, tell your healthcare provider about all of your medical conditions, including if you:

have an infection.
are pregnant or plan to become pregnant. LYNOZYFIC may harm your unborn baby. Tell your healthcare provider right away if you become pregnant or think that you may be pregnant during treatment with LYNOZYFIC.
Females who are able to become pregnant:
Your healthcare provider should do a pregnancy test before you start treatment with LYNOZYFIC.
You should use an effective form of birth control (contraception) during treatment with LYNOZYFIC and for 3 months after your last dose of LYNOZYFIC.
are breastfeeding or plan to breastfeed. It is not known whether LYNOZYFIC passes into your breast milk. Do not breastfeed during treatment with LYNOZYFIC and for 3 months after your last dose of LYNOZYFIC.
Tell your healthcare provider about all the medicines you take, including prescription and over-the-counter medicines, vitamins, and herbal supplements.

How will I receive LYNOZYFIC?

LYNOZYFIC will be given to you by your healthcare provider by infusion through a needle placed in a vein (intravenous infusion).
After the "step-up dosing schedule", the treatment dose of LYNOZYFIC is usually given 1 time each week for 11 doses, and then 1 time every other week for 5 doses. After these doses and based on how your disease responds, your healthcare provider will decide if you are able to receive LYNOZYFIC less often (every 4 weeks) or will continue to have every other week treatment.
Your healthcare provider will decide how long you will receive treatment with LYNOZYFIC.
If you miss any appointments, call your healthcare provider as soon as possible to reschedule your appointment. It is important for you to be monitored closely for side effects during treatment with LYNOZYFIC.
What should I avoid while receiving LYNOZYFIC?
Do not drive, or operate heavy or potentially dangerous machinery, or do other dangerous activities for 48 hours after completing each of your "step-up" doses or at any time during treatment with LYNOZYFIC if you develop new neurologic symptoms, until the symptoms go away.

What are the possible side effects of LYNOZYFIC?
LYNOZYFIC may cause serious side effects, including:

Infections. LYNOZYFIC can cause bacterial, viral, or fungal infections that are serious, life-threatening, or that may lead to death. Upper respiratory tract infections and pneumonia are common during treatment with LYNOZYFIC.
Your healthcare provider will monitor you for signs and symptoms of infection before and during treatment with LYNOZYFIC.
Your healthcare provider may prescribe medicines for you to help prevent infections and treat you as needed if you develop an infection during treatment with LYNOZYFIC.
Tell your healthcare provider right away if you develop any signs or symptoms of infection during treatment with LYNOZYFIC, including:
fever of 100.4 °F (38 °C) or higher
chills
cough
shortness of breath
chest pain
sore throat
pain during urination
feeling weak or generally unwell
Decreased white blood cell counts. Decreased white blood cell counts are common during treatment with LYNOZYFIC and can also be severe. Fever can happen with low white blood cell counts and may be a sign that you have an infection. Your healthcare provider will check your blood cell counts before you start treatment and during treatment with LYNOZYFIC, and will treat you as needed.
Liver problems. LYNOZYFIC can cause increased liver enzymes and bilirubin in your blood. These increases can happen with or without you also having CRS. Your healthcare provider will do blood tests to check your liver before starting and during treatment with LYNOZYFIC. Tell your healthcare provider if you develop any of the following signs or symptoms of liver problems:
tiredness
loss of appetite
pain in your right upper stomach-area (abdomen)
dark urine yellowing of your skin or the white part of your eyes
The most common side effects of LYNOZYFIC include:

muscle and bone pain
nausea
cough
headache
diarrhea
tiredness or weakness
shortness of breath
The most common severe abnormal blood test results with LYNOZYFIC include: low white blood cell counts and low red blood cell counts.

These are not all of the possible side effects of LYNOZYFIC.

Call your doctor for medical advice about side effects. You may report side effects to FDA at 1-800-FDA-1088.

Please see full Prescribing Information, including Boxed WARNING, and Medication Guide for LYNOZYFIC.

What is LYNOZYFIC?
LYNOZYFIC is a prescription medicine used to treat adults with multiple myeloma who:

have already received at least 4 treatment regimens, including a proteasome inhibitor, an immunomodulatory agent and an anti-CD38 monoclonal antibody to treat their multiple myeloma, and
their cancer has come back or did not respond to prior treatment.
It is not known if LYNOZYFIC is safe and effective in children.

About Regeneron in Hematology
At Regeneron, we’re applying more than three decades of biology expertise with our proprietary VelociSuite technologies to develop medicines for patients with diverse blood cancers and rare blood disorders.

Our blood cancer research is focused on bispecific antibodies that are being investigated both as monotherapies and in various combinations and emerging therapeutic modalities. Together, they provide us with unique combinatorial flexibility to develop customized and potentially synergistic cancer treatments.

Our research and collaborations to develop potential treatments for rare blood disorders include explorations in antibody medicine, gene editing and gene-knockout technologies, and investigational RNA-approaches focused on depleting abnormal proteins or blocking disease-causing cellular signaling.

(Press release, Regeneron, DEC 7, 2025, View Source [SID1234661207])

On December 7, 2025 Orna Therapeutics (Orna), a biotechnology company dedicated to engineering immune cells in vivo to treat autoimmune and oncology diseases, reported new preclinical data supporting the Company’s in vivo CAR programs to target and treat a broad range of B cell-mediated autoimmune diseases and plasma cell or BCMA-related diseases at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting taking place in Orlando, Florida from December 6-9, 2025.

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"The preclinical data presented at this year’s ASH (Free ASH Whitepaper) Annual Meeting further highlights our potent, non-viral, transient, tunable, and scalable approach to in vivo CAR therapies in both autoimmune diseases and oncology," said Joseph Bolen, Ph.D., Chief Executive Officer of Orna. "Our panCAR platform has demonstrated robust activity in B cell autoimmunity and BCMA-related diseases without the need for preconditioning lymphodepletion. Additionally, the non-human primate (NHP) data presented across both programs demonstrated specific and targeted depletion of B cells or plasma cells. As we look ahead, we anticipate submitting our first Clinical Trial Application for ORN-252, our anti-CD19 panCAR program this year and entering the clinic in early 2026."

Oral Presentation details:

In Vivo panCAR Therapy Utilizing Circular RNA for Treatment of Autoimmune Diseases

In this presentation, Orna highlighted preclinical data demonstrating the potential of its proprietary circular (oRNA) technology paired with its best-in-class lipid nanoparticle (LNP) delivery platform to enable the next generation of in vivo therapies and treat a variety of B cell-mediated autoimmune diseases.

Key findings in the study include:

ORN-252, Orna’s anti-CD19 panCAR mediated robust B cell depletion in humanized mice in vivo at doses as low as 0.03 mg/kg.
In a humanized mouse lupus model, ORN-252 showed robust B cell depletion with concurrent reduction in dsDNA titers in contrast to rituximab.
Treatment with ORN-252 led to complete peripheral and splenic B cell depletion in NHP at doses as low as 0.1 mg/kg.
CAR+ T cells upregulated cytotoxicity markers after the first dose when the majority of cell killing occurs.
ORN-252 demonstrated durable B cell depletion with a reduction in switched memory and an increase in naïve B cell phenotype upon repopulation.
ORN-252 showed superior binding affinity, expression, and killing of CD19 cells in human vs. NHP cells, potentially providing increased potency upon translation to humans.
Orna anticipates filing a Clinical Trial Application for this program by the end of 2025 and expects to initiate a first-in-human study in early 2026.

Poster Presentation details:

In Vivo panCARTM Therapy Utilizing Circular RNA for Treatment of Multiple Myeloma

In today’s poster presentation, Orna will showcase preclinical data demonstrating the potential of its in vivo panCARTM therapy to treat a range of plasma cell or BCMA-related diseases including multiple myeloma.

Key findings in the study include:

High surface expression of anti-BCMA panCAR was observed in a dose-dependent manner on human and cynomolgus immune cells and was maintained at least 72 hours in vitro.
In a humanized mouse model engrafted with BCMA-expressing tumor cells, anti-BCMA panCAR demonstrated superior tumor control, eliminating tumors for at least 30 days, functionally outperforming a clinically validated anti-BCMA binder.
In NHPs, treatment with BCMA panCAR resulted in specific and targeted plasma cell depletion.
Anti-BCMA panCAR is highly selective, demonstrating no significant impact on the overall B cell repertoire in NHPs.

(Press release, Orna Therapeutics, DEC 7, 2025, View Source [SID1234661206])

On December 7, 2025 Nurix Therapeutics, Inc. (Nasdaq: NRIX), a clinical-stage biopharmaceutical company focused on the discovery, development and commercialization of targeted protein degradation medicines in oncology and autoimmune disease, reported new clinical data from the Company’s ongoing Phase 1a/1b NX-5948-301 study of bexobrutideg (NX-5948) in patients with relapsed or refractory B-cell malignancies. These data will be presented in an oral session at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition in Orlando, FL, on December 6, 2025, at 9:45 a.m. ET, by Zulfa Omer, M.D., Assistant Professor of Internal Medicine at the University of Cincinnati and a principal investigator in the study.

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"The clinical activity and durability observed with bexobrutideg in this study are highly encouraging for patients with relapsed or refractory CLL/SLL, many of whom have limited treatment options," said Dr. Omer. "The responses we are seeing across heavily pretreated patients, including those with prior exposure to both covalent and non-covalent BTK inhibitors and BCL-2 inhibitors, support continued evaluation of bexobrutideg as a therapeutic approach for patients with relapsed or refractory CLL/SLL and ultimately earlier line patients."

The new and updated data from the Phase 1a/1b study (NX-5948-301) in patients with relapsed or refractory chronic lymphocytic leukemia (CLL) and small lymphocytic lymphoma (SLL) include safety findings across all patients, safety findings for patients treated at the RP2D of 600 mg once daily, updated Phase 1a results with extended follow-up, and emerging efficacy results from the randomized Phase 1b cohort 1 comparing 200 mg and 600 mg once-daily dosing. Collectively, these results provide a maturing clinical picture of bexobrutideg’s efficacy, durability, and tolerability, which form the foundation for Nurix’s advancing pivotal clinical program.

"We are excited to share this important data update for bexobrutideg, which continues to demonstrate compelling efficacy and durability for patients with relapsed or refractory CLL/SLL" said Paula O’Connor, M.D., chief medical officer of Nurix. "Advancing the 600 mg dose into our pivotal DAYBreak program reflects our conviction that this regimen offers patients the greatest opportunity for sustained clinical benefit, supported by a favorable safety profile."

Data presented at the 2025 ASH (Free ASH Whitepaper) Annual Meeting include baseline demographics and safety findings for all patients with CLL/SLL in the ongoing Phase 1a/1b study (n=126) and safety findings for patients treated at the RP2D of 600 mg (n=70). Efficacy results are presented for patients treated with bexobrutideg at doses ranging from 50 mg to 600 mg in the Phase 1a study (n=48) and for patients in the Phase 1b cohort 1, who were randomized and treated with either a 200 mg or 600 mg dose (n=42) in accordance with FDA’s Project Optimus.

Phase 1a/1b demographics and safety findings
Overall, the heavily pretreated Phase 1a/1b population had received a median of three prior lines of therapy (range = 1–17) including prior BTK inhibitors (85.7%), prior BCL-2 inhibitors (61.9%), and prior non-covalent BTK inhibitors (27.0%). The Phase 1a population was more heavily pretreated with a median of four prior lines of therapy (range = 2-12) including prior BTK inhibitors (97.9%), prior BCL-2 inhibitors (83.3%), and prior non-covalent BTK inhibitors (27.1%). At baseline, many patients had mutations associated with BTK inhibitor resistance, including mutations in BTK (39.6% overall, 38.3% in the Phase 1a population) and PLCG2 (8.1% overall, 14.9% in the Phase 1a population). Poor prognostic features were common, including TP53 mutations (39.6% overall, 44.7% in the Phase 1a population). Of the five patients (4.0%) in the trial who had central nervous system (CNS) involvement, all five were in the Phase 1a population.

Bexobrutideg was well tolerated across all dose levels evaluated, consistent with prior disclosures. The treatment emergent adverse event (TEAE) profile was similar between the RP2D of 600 mg and the overall study population with the most common treatment emergent adverse events being purpura/contusion, neutropenia, and petechiae. There were no dose-limiting toxicities, no systemic fungal infections or Grade 4 infections of any kind, and a single event of new onset atrial fibrillation was consistent with the rate in the age-matched general population.

Phase 1a efficacy update (n=48)
The updated Phase 1a dataset includes patients treated at starting dose levels ranging from 50 mg to 600 mg once daily with a median follow-up of 19.0 months (range = 13.5 – 32.3). Among the 47 efficacy evaluable patients, the objective response rate (ORR) was 83.0% including two patients (4.3%) with a complete response, an improvement from earlier disclosures due to additional follow-up and deepening of response. Overall, the disease control rate (DCR) was 95.7%. Importantly, the median progression-free survival was 22.1 months, and the median duration of response (DOR) was 20.1 months. Responses were observed across clinically challenging subgroups including patients who had progressed on prior BTK inhibitors, patients who were double-exposed to both BTK inhibitors and BCL-2 inhibitors, patients who had received prior non-covalent BTK inhibitors, patients with baselines mutations associated with BTK inhibitor resistance including non-C481 BTK mutations, and patients with high-risk molecular features such as TP53 mutations. Meaningful reductions in lymph node burden were also observed independent of baseline mutations associated with BTK inhibitor resistance and poor prognosis.

Phase 1b Cohort 1: Randomized evaluation of 200 mg vs 600 mg once daily (n=42)
In the randomized Phase 1b cohort, 42 patients were assigned to receive either 200 mg (n = 22) or 600 mg (n = 20) once daily. Among the 37 efficacy evaluable patients, preliminary data showed the 600 mg dose with an ORR of 83.3% compared to 73.7% for the 200 mg dose. With a median follow up of 9.8 months, the preliminary PFS curves suggest longer progression free survival for the 600 mg group compared to the 200 mg group.

Across Phase 1a and Phase 1b, the totality of clinical data supports 600 mg once daily as the optimal dose for further development. At this dose level, bexobrutideg demonstrated the strongest clinical activity observed to date, including higher response rates and a favorable trend toward longer progression-free survival in the randomized Phase 1b cohort. Importantly, the 600 mg dose maintained a tolerable safety profile comparable to the overall study population, with no dose-limiting toxicities, no systemic fungal infections, and no Grade 4 infections reported. Taken together, in accordance with FDA’s Project Optimus, these results provide a robust foundation for advancing 600 mg as the recommended Phase 2 dose and for the ongoing pivotal DAYBreak development program.

"These exciting, positive results reinforce the potential for bexobrutideg to be best-in-class and form a strong foundation to support our pivotal development program," said Arthur T. Sands, M.D., Ph.D., president and chief executive officer, Nurix. "Nurix has entered this next phase of clinical development with momentum and a commitment to deliver a transformative new medicine for patients with B-cell malignancies."

Webcast Details
Date and time: Monday, December 8, 2025, 8:15 p.m. ET
Access Details: The live webcast and subsequent archived replay will be available in the Investors section of the Nurix website under Events.

About Bexobrutideg (NX-5948)
Bexobrutideg is an investigational, orally bioavailable, brain penetrant, highly selective small molecule degrader of BTK currently being evaluated in the DAYBreak CLL-201 clinical trial (NCT07221500), a pivotal single-arm Phase 2 study of bexobrutideg in patients with relapsed or refractory chronic lymphocytic leukemia. Nurix also continues enrollment in the NX-5948-301 Phase 1a/1b clinical trial (NCT05131022) of bexobrutideg in patients with relapsed or refractory B cell malignancies. Additional information on the ongoing clinical trials can be accessed at clinicaltrials.gov.

(Press release, Nurix Therapeutics, DEC 7, 2025, View Source [SID1234661204])

On December 7, 2025 Lyell Immunopharma, Inc. (Nasdaq: LYEL), a clinical-stage company advancing a pipeline of next-generation chimeric antigen receptor (CAR) T-cell therapies for patients with cancer, reported new clinical and translational data from the ongoing clinical trial of rondecabtagene autoleucel (ronde-cel, also known as LYL314) in patients with large B-cell lymphoma (LBCL), which were presented today in two oral presentations at the 67th American Society of Hematology (ASH) (Free ASH Whitepaper) Annual Meeting and Exposition. As of the data cutoff date of September 5, 2025, ronde-cel continued to demonstrate robust clinical responses with a manageable safety profile appropriate for outpatient administration. A 93% overall response rate, a 76% complete response rate, and median progression-free survival of 18 months were reported for patients with relapsed and/or refractory (R/R) LBCL in the third- or later-line (3L+) setting. Patients evaluated in the second-line (2L) setting (94% with difficult-to-treat primary refractory disease) achieved an 83% overall response rate and a 61% complete response rate, and 70% of patients with a complete response remained in complete response at 6 months or longer.

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Ronde-cel is an autologous dual-targeting CD19/CD20 CAR T-cell product candidate in pivotal development for patients with R/R LBCL. Ronde-cel CAR T cells are designed to have enhanced antitumor activity through a proprietary manufacturing process that enriches for CD62L-positive cells to produce a CAR T-cell product with a higher proportion of naïve and central memory T cells. The United States Food and Drug Administration (FDA) has granted ronde-cel Regenerative Medicine Advanced Therapy (RMAT) designation for the treatment of patients with R/R LBCL in the 3L+ and 2L settings.

"These data from the ongoing clinical trial showing high rates of durable complete responses along with a manageable safety profile in patients with high-risk large B-cell lymphoma represent the potential of ronde-cel to improve patient outcomes," commented Sarah M. Larson, MD, Associate Professor, Department of Medicine, Medical Director, Immune Effector Cell Therapy Program, Division of Hematology/Oncology, David Geffen School of Medicine at UCLA. "The two pivotal trials underway, including the first-of-its kind head-to-head CAR T-cell trial, are expected to provide a comprehensive and robust evaluation of the potential for ronde-cel to demonstrate differentiated benefit over approved CD19 CAR T-cell therapies."

Sixty-nine CAR T-cell naïve patients with R/R LBCL received ronde-cel as of the data cutoff date for the presentation. The efficacy evaluable population, defined as those patients with Day 84 assessments or prior disease progression or death, consisted of 47 patients (29 in the 3L+ and 18 in the 2L settings). Imaging assessments were performed locally by the sites. Patient demographics and baseline disease characteristics were consistent with a high-risk, heavily pre-treated patient population, particularly as compared to historical trials of CD19 CAR T-cell products: median ages of 64 and 65 years with 20% (9/45) and 21% (5/24) of patients being 75 years or older in the 3L+ and 2L settings, respectively; and primary refractory disease in 49% (22/45) and 92% (22/24) of patients in the 3L+ and 2L settings, respectively.

Patients Evaluated in the 3L+ Setting

There were 29 efficacy-evaluable 3L+ patients with R/R LBCL (diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, Grade 3B follicular lymphoma, or transformed follicular lymphoma) with a median follow up time of 12 months as of the data cutoff date. In these patients:

The overall response rate was 93% (27/29 patients), with 76% (22/29) of patients achieving a complete response
72% (13/18) of patients with complete response remained in complete response at 6 months or longer
Median progression-free survival was 18 months
Patients Evaluated in the 2L Setting

There were 18 efficacy-evaluable patients enrolled in the 2L setting with a median follow-up time of 9 months as of the data cutoff date. Of these efficacy-evaluable patients, 94% had primary refractory disease. In these patients:

The overall response rate was 83% (15/18 patients), with 61% (11/18) achieving a complete response
70% (7/10) of patients with complete response remained in complete response at 6 months or longer
The median duration of complete response was not reached
Safety Data

In 69 patients, including patients from both the 3L+ and the 2L cohorts, a manageable safety profile appropriate for outpatient administration was observed. No Grade 3 or greater cytokine release syndrome (CRS) was observed in any patient. Twenty-five of the 69 patients received protocol-directed dexamethasone prophylaxis (10 mg/day for 3 days). One case (4%) of Grade 3 or greater ICANS was reported in a patient with high disease burden; no case of Grade 2 ICANS was reported.

In all 69 patients, as of the data cutoff date, low rates of Grade 1 (32%) or Grade 2 (29%) CRS were reported; ICANS rates were reported as follows: Grade 1 (9%), Grade 2 (3%), and Grade 3 or greater (12%) of patients. The median time to complete resolution of all reports of ICANS was 4 days. Cell pharmacodynamic data demonstrated robust CAR T-cell expansion and persistence that were similar in patients with or without dexamethasone prophylaxis. No deaths were determined to be related to ronde-cel administration.

Pivotal Clinical Trials

Lyell has initiated two pivotal clinical trials of ronde-cel: PiNACLE – H2H and PiNACLE.

PiNACLE – H2H is a Phase 3 head-to-head CAR T-cell therapy randomized controlled clinical trial of ronde-cel versus investigator’s choice of either lisocabtagene maraleucel (liso-cel) or axicabtagene ciloleucel (axi-cel) in patients with R/R LBCL receiving treatment in the 2L setting. Patients randomized to ronde-cel will be treated with a dose of 100 x 106 CAR T cells; patients in the control arm will be treated as per the product label. The primary endpoint of the trial is event-free survival and the trial is expected to enroll approximately 200 patients per arm (N = 400) with R/R LBCL, including diffuse large B-cell lymphoma, primary mediastinal B-cell lymphoma, high grade B-cell lymphoma, Grade 3B follicular lymphoma, or transformed follicular or transformed mantle cell lymphoma who have not previously received CAR T-cell therapy. Patients may be treated with ronde-cel in either the inpatient or outpatient setting. More information about the PiNACLE – H2H trial can be found on clinicaltrials.gov (NCT07188558) here.

PiNACLE is a single-arm trial of ronde-cel that is enrolling up to 120 patients receiving treatment in the 3L+ setting. This registration trial is a seamless expansion of the 3L+ cohort from the Phase 1/2 trial. The dose is 100 x 106 CAR+ cells and the primary endpoint is overall response rate. Patients may be treated with ronde-cel in either the inpatient or outpatient setting. More information about the PiNACLE trial can be found on clinicaltrials.gov (NCT05826535) here.

Ronde-cel Translational Data

Translational data from the ongoing Phase 1/2 clinical trial showed that ronde-cel manufactured with CD62L enrichment achieved robust expansion and high expression of memory-related genes after infusion in patients with LBCL. An evaluation of ronde-cel and published data for CD19 CAR T-cell products demonstrated that ronde-cel had a higher proportion of CD62L-positive T cells with a higher proportion of memory-cell phenotype prior to infusion (ronde-cel, N = 34; axi-cel, N = 110 and tisagenlecleucel (tisa-cel), N = 31). In addition, ronde-cel had up to a three-fold higher expansion in patients after infusion compared to the expansion of approved CD19 CAR T-cell products. The product memory-cell phenotype was positively correlated with expansion. Peripheral blood samples collected from patients one month after infusion (N = 9) also had a higher proportion of CAR T cells with a memory phenotype compared to cells from axi-cel-treated patients (N = 4). Ronde-cel CAR-positive T cells collected from patients one (N = 7) and two months (N = 3) after infusion demonstrated sustained capacity to proliferate, kill tumor cells over 72 hours, and secrete cytokines (N = 3).

The clinical data were highlighted in an oral presentation by Sarah M. Larson, MD, Associate Professor, Department of Medicine, Medical Director, Immune Effector Cell Therapy Program, Division of Hematology/Oncology, David Geffen School of Medicine at UCLA, Los Angeles, CA. Translational data were presented in a separate oral presentation by Akil Merchant, MD, Associate Professor and Co-Director of the Lymphoma Program at the Samuel Oschin Cancer Center, Cedars-Sinai Medical Center, Los Angeles, CA.

Conference Call Details

Lyell’s management will host an investor conference call and webcast to review these data at 8:30 AM ET on Monday, December 8th. The webcast registration link can be accessed here. A replay of the event and presentation materials will be available on the Investor page of the Lyell Website following the end of the event.

About Rondecabtagene Autoleucel (Ronde-cel)

Rondecabtagene autoleucel (ronde-cel, also known as LYL314) is a next-generation dual-targeting CD19/CD20 CAR T-cell product candidate designed to increase complete response rates and prolong the duration of the responses as compared to the approved CD19 targeted CAR T-cell therapies for the treatment of R/R LBCL.

Ronde-cel is designed with an ‘OR’ logic gate to target B cells that express either CD19, CD20 or both, each with full potency. Ronde-cel is manufactured to produce a CAR T-cell product with higher proportions of naïve and central memory T cells through a proprietary process that enriches for CD62L-expressing cells. This manufacturing process is designed to generate CAR T cells with enhanced antitumor activity.

Ronde-cel has received RMAT designation from the FDA for the treatment of patients with R/R LBCL in the 3L+ and 2L settings, as well as Fast Track Designation for the treatment of patients with R/R LBCL in the 3L+ setting.

(Press release, Lyell Immunopharma, DEC 7, 2025, View Source [SID1234661203])

On December 7, 2025 Immix Biopharma, Inc. ("ImmixBio", "Company", "We" or "Us" or "IMMX"), a global leader in relapsed/refractory AL Amyloidosis, reported positive phase 2 NXC-201 results in an oral presentation at ASH (Free ASH Whitepaper) 2025 presented by Heather Landau, MD, of Memorial Sloan Kettering Cancer Center. NXC-201 demonstrated a complete response (CR) rate of 75% (15/20) (at s/u IFE(-) level) by independent review committee. In four out of five pending patients, MRD negativity in bone marrow predicts future complete response, potentially increasing future CR rate to 95%. NEXICART-2 final readout and BLA submission are planned for 2026.

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"In the larger patient set Phase 2 results presented today at ASH (Free ASH Whitepaper), we are thrilled to see complete response rates continue to improve in NEXICART-2. These excellent results demonstrate the potential of NXC-201 to address the significant unmet medical need in relapsed/refractory AL Amyloidosis," said Ilya Rachman, MD, PhD, Chief Executive Officer of Immix Biopharma. Gabriel Morris, Chief Financial Officer of Immix Biopharma, added, "This exciting Phase 2 milestone brings us one step closer to delivering this promising therapy to patients upon planned BLA submission in 2026."

ASH Presentation Results – Phase 2

Prior to NXC-201 treatment, all patients were exposed to an anti-CD38 antibody and a proteasome inhibitor. Median prior lines of therapy was 4 (range: 1-10). All patients had baseline relapsed/refractory AL Amyloidosis organ involvement. After NXC-201 treatment, complete responses (CRs) were observed in 75% (15 out of 20 patients) (at s/u IFE(-) level) by independent review committee. In four out of five pending patients, minimum residual disease (MRD) negativity in bone marrow predicts future complete response, potentially increasing the future CR rate to 95%. Downstream clinical improvement, including organ responses, were observed in 70% of evaluable patients (7/10). No neurotoxicity was observed. Only low-grade cytokine release syndrome has been observed with a median duration of 1 day. The ASH (Free ASH Whitepaper) presentation contains clinical data as of November 13, 2025.

Current treatments typically result in a 10% or lower complete response (CR) rate in relapsed/refractory AL Amyloidosis according to Zanwar, et al 2024, indicating a high unmet medical need.

KOL Event Discussing NXC-201 ASH (Free ASH Whitepaper) 2025 Oral Presentation of Phase 2 Clinical Results

A Key Opinion Leader (KOL) event with lead investigator Heather Landau, MD, of Memorial Sloan Kettering Cancer Center, Shahzad Raza, MD, of Cleveland Clinic, and Vaishali Sanchorawala, MD, of Boston Medical Center will be held Sunday, December 7, 2025 8:00pm ET to discuss the significance of the NEXICART-2 Phase 2 Clinical Results. Register to attend here.

About NEXICART-2
NEXICART-2 (NCT06097832) is an ongoing multi-site U.S. Phase 2 clinical trial of sterically-optimized CAR-T NXC-201 in relapsed/refractory AL Amyloidosis, with a registrational design. NEXICART-2 is expected to enroll 40 patients.

About NXC-201
NXC-201 is a sterically-optimized BCMA-targeted chimeric antigen receptor T (CAR-T) cell therapy with a "digital filter" that is designed to filter out non-specific activation. NXC-201 teaches the immune system to recognize and eliminate the source of the toxic light chains. NXC-201 has been awarded Regenerative Medicine Advanced Therapy (RMAT) by the FDA, and Orphan Drug Designation (ODD) by the US FDA and in the EU by the EMA.

About AL Amyloidosis
AL amyloidosis is a devastating disease where the immune system, that’s supposed to protect, instead continuously produces toxic light chains, clogging up the heart, kidney and liver, causing organ failure and death.

The number of patients in the U.S. with relapsed/refractory AL Amyloidosis is estimated to be growing at 12% per year according to Staron, et al Blood Cancer Journal, to approximately 38,500 patients in 2026.

The Amyloidosis market was $3.6 billion in 2017, and is expected to reach $6 billion in 2025, according to Grand View Research.

(Press release, Immix Biopharma, DEC 7, 2025, View Source [SID1234661202])