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Item 1. Business

2026-01-28 compared with 2025-01-28 · 178 added, 197 removed, 935 unchanged (29% of the section changed)

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Our wholly owned, clinical stage pipeline includes three investigational drug candidates designed with the goal to be first-in-class or best-in-class therapeutics:

NX-5948, a highly selective degrader of Bruton’s tyrosine kinase (BTK);

NX-2127, a dual degrader of BTK and transcription factors IKZF1(Ikaros) and IKZF3 (Aiolos);

bexobrutideg (NX-5948), a highly selective degrader of Bruton’s tyrosine kinase (BTK);

zelebrudomide (NX-2127), a dual degrader of BTK and transcription factors IKZF1(Ikaros) and IKZF3 (Aiolos);

and NX-1607, an inhibitor of Casitas B-lineage lymphoma proto-oncogene B (CBL-B), an E3 ligase that regulates activation of multiple immune cell types including T cells and NK cells.

We are also advancing multiple potentially first-in-class or best-in-class degraders and degrader antibody conjugates (DACs) in our preclinical pipeline.

Our partnered drug discovery pipeline consists of preclinical stage degraders of IRAK4, STAT6 and multiple currently undisclosed targets under collaboration agreements with Gilead Sciences, Inc.

Our partnered drug discovery pipeline consists of a clinical stage degrader of IRAK4 (NX-0479/GS-6791), a preclinical stage degrader of STAT6, currently in investigational new drug application (IND), enabling studies, and multiple currently undisclosed targets under collaboration agreements with Gilead Sciences, Inc.

(Gilead), Sanofi S.A.

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Clinical Pipeline

Our portfolio of targeted protein degraders of the B‑cell signaling protein BTK comprises NX‑5948, an investigational, orally bioavailable, highly selective BTK degrader for the treatment of relapsed or refractory B-cell malignancies and potentially autoimmune diseases, and NX‑2127, an investigational, orally bioavailable degrader that simultaneously degrades BTK and two well-characterized cereblon neosubstrates IKZF1 (Ikaros) and IKZF3 (Aiolos) that are clinically validated transcription factor targets for relapsed or refractory B‑cell malignancies.

Status of NX-5948:

We are currently conducting a Phase 1b cohort expansion study of NX-5948 in patients with relapsed or refractory B-cell malignancies.

In January 2024, the U.S.

Food and Drug Administration (FDA) granted Fast Track designation for NX-5948 for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two lines of therapy, including a BTK inhibitor and a B-cell lymphoma 2 (BCL2) inhibitor.

In November 2024, the European Medicines Agency (EMA) granted Priority Medicine (PRIME) designation for NX-5948 in CLL or SLL after at least a BTK inhibitor and a BCL-2 inhibitor.

In December 2024, the FDA granted Fast Track designation for NX-5948 for the treatment of adult patients with Waldenstrom’s macroglobulinemia (WM) after at least two lines of therapy, including a BTK inhibitor.

Status of NX‑2127:

We are currently conducting a Phase 1a/1b dose-escalation and cohort expansion study of NX-2127 in patients with relapsed or refractory B-cell malignancies.

Our portfolio of targeted protein degraders of the B‑cell signaling protein BTK comprises bexobrutideg, an investigational, orally bioavailable, highly selective BTK degrader for the treatment of relapsed or refractory B-cell malignancies and potentially autoimmune diseases, and zelebrudomide, an investigational, orally bioavailable degrader that simultaneously degrades BTK and two well-characterized cereblon neosubstrates IKZF1 (Ikaros) and IKZF3 (Aiolos) that are clinically validated transcription factor targets for relapsed or refractory B‑cell malignancies.

Status of Bexobrutideg:

We are currently conducting a Phase 2 study of bexobrutideg in patients with relapsed or refractory CLL having failed three previous lines of therapy, specifically a covalent BTK inhibitor (cBTKi), a BCL2 inhibitor (BCL2i) and a non-covalent BTK inhibitor (ncBTKi).

This study is designed as a potentially pivotal trial for Accelerated Approval in the United States and commenced in October 2025 upon agreement with the U.S.

Food and Drug Administration (FDA) for the use of the 600mg, once daily dose of bexobrutideg as determined by our Phase 1b study of both a 200mg and a 600mg dose in patients in accordance with the FDA’s Project Optimus.

In January 2024, the FDA granted Fast Track designation for bexobrutideg for the treatment of adult patients with relapsed or refractory chronic lymphocytic leukemia (CLL) or small lymphocytic lymphoma (SLL) after at least two lines of therapy, including a BTK inhibitor and a B-cell lymphoma 2 (BCL2) inhibitor.

In November 2024, the European Medicines Agency (EMA) granted Priority Medicine (PRIME) designation for bexobrutideg in CLL or SLL after at least a BTK inhibitor and a BCL-2 inhibitor.

In December 2024, the FDA granted Fast Track designation for bexobrutideg for the treatment of adult patients with Waldenstrom’s macroglobulinemia (WM) after at least two lines of therapy, including a BTK inhibitor.

Status of Zelebrudomide:

We are currently conducting a Phase 1a/1b dose-escalation and cohort expansion study of zelebrudomide in patients with relapsed or refractory B-cell malignancies.

We previously initiated Phase 1b expansion cohorts for patients with relapsed CLL, diffuse large B-cell lymphoma (DLBCL) and mantle cell lymphoma (MCL).

Enrollment was paused in 2023 due to a partial clinical hold stemming from a manufacturing change designed to produce a chirally controlled form of NX-2127.

Enrollment was paused in 2023 due to a partial clinical hold stemming from a manufacturing change designed to produce a chirally controlled form of zelebrudomide.

Enrollment of new patients in this clinical trial recommenced in August 2024 following resolution of the partial hold by the FDA.

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CBL-B is a RING-type E3 ligase that regulates the activation of multiple immune cell types including T cells and NK cells through protein degradation.

NX-1607 is an orally bioavailable inhibitor of CBL-B that has the potential to relieve T cell anergy and promote anti-cancer immune cell activity.

NX-1607 is an orally bioavailable inhibitor of CBL-B that has the potential to reduce T cell anergy and promote anti-cancer immune cell activity.

NX-1607 is currently being explored in a variety of solid tumor indications.

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Corporate Strategy

Our strategy is to discover and develop breakthrough therapies for patients with significant unmet clinical need by developing highly differentiated targeted protein degrader drugs that eliminate disease-causing or disease-associated biological targets that to date have been ineffectively drugged or have been considered undruggable with existing modalities.

Our strategy is to discover and develop breakthrough therapies for patients with significant unmet clinical need by developing highly differentiated degrader-based medicines that alter or remove disease-causing or disease-associated biological targets that to date have been ineffectively drugged or have been considered undruggable with existing modalities.

The key elements of our strategy are to:

• Advance our lead program, NX-5948, into late-stage clinical development in CLL and potentially other B-cell malignancies.

Enrollment is ongoing in our Phase 1b clinical trial of NX-5948 in adults with relapsed or refractory B-cell malignancies.

• Advance our lead program, bexobrutideg, into late-stage clinical development in CLL and potentially other B-cell malignancies.

Enrollment is ongoing in our Phase 2 clinical trial of bexobrutideg in adults with relapsed or refractory CLL.

In 2026, we intend to commence enrollment of a suite of additional trials designed to support the potential future registration of the drug in multiple regulatory jurisdictions.

We plan to leverage the Fast Track designation from the FDA in CLL and WM as well as the PRIME designation from the EMA to accelerate the clinical development and registrational path for NX-5948 in oncology.

• Explore the therapeutic applications of our lead BTK degrader, NX-5948, for the treatment of patients with diseases caused by inflammation and autoimmunity.

• Explore the therapeutic applications of bexobrutideg, for the treatment of patients with diseases caused by inflammation and autoimmunity.

BTK mediates signaling downstream of the B-cell receptor (BCR), toll-like receptors (TLRs), and Fc receptors (FcRs), making it an attractive therapeutic target in antibody-mediated autoimmune and inflammatory diseases.

Targeting BTK can reduce the production of new antibodies and mitigate inflammation induced by a variety of inflammatory signals, addressing key challenges in inflammatory and autoimmune diseases.

We believe that NX-5948 may offer unique advantages over currently available BTK inhibitors in these disease indications by addressing both the enzymatic and scaffold activities of BTK, which are key to its function.

In 2025, we plan to expand the current Phase 1b trial in patients with CLL to include patients who are also suffering from immune-mediated cytopenias such as anemia, a common co-morbidity associated with CLL.

In 2025, we may further explore the utility of NX-5948 in autoimmune and inflammatory diseases with a separate clinical program which will require an IND with a separate division at the FDA.

• Continue development of NX-2127 through dose escalation with a focus on aggressive lymphomas including MCL and DLBCL.

Enrollment of new patients in our Phase 1a/1b clinical trial of NX-2127 has resumed in adults with relapsed or refractory B-cell malignancies.

We believe that bexobrutideg may offer unique advantages over currently available BTK inhibitors in these disease indications by addressing both the enzymatic and scaffold activities of BTK, which are key to its function.

In 2025, we expanded the current Phase 1b trial in patients with CLL to include patients who are also suffering from immune-mediated cytopenias such as anemia, a common co-morbidity associated with CLL.

In 2026, we may further explore the utility of bexobrutideg in autoimmune and inflammatory diseases with a separate clinical program which will require an IND with a separate division at the FDA.

• Continue development of zelebrudomide through dose escalation with a focus on aggressive lymphomas including MCL and DLBCL.

Enrollment of new patients in our Phase 1a/1b clinical trial of NX-2127 has continued in adults with relapsed or refractory B-cell malignancies.

In 2026, we expect to define doses to enable a Phase 1b cohort expansion.

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Enrollment is ongoing in our Phase 1a/1b trial for NX-1607 in adults with multiple solid tumor types.

In 2025, we expect to define doses and potential indications to enable a Phase 1b cohort expansion.

In 2025, we continued dose escalation and expect to define doses and potential indications to enable a Phase 1b cohort expansion in 2026.

• Advance our portfolio of preclinical programs to generate development candidates and license agreements for our partnered pipeline.

Our partnership efforts are focused on the advancement of a robust and sustainable pipeline in collaboration with our partners Gilead, Sanofi, and Pfizer.

In our more mature partnerships with Gilead and Sanofi, multiple disclosed and undisclosed programs are advancing through lead optimization and IND-enablement.

In March 2023, Gilead licensed our IRAK4 TPD program under the collaboration, and in March of 2024, Gilead extended the research term of multiple TPD programs.

In April 2024, Sanofi extended its research term for a STAT6 targeted protein degrader with the goal of selecting a development candidate in the first half of 2025.

In our partnership with Pfizer, which was announced in September 2023 under an agreement with Seagen, Inc., we have achieved two preclinical milestones to date, qualifying for $10.0 million in milestone payments.

We expect to earn multiple additional preclinical and clinical milestones across our three active partnerships in 2025, which may allow us to secure additional license and development candidate events in subsequent years.

In our more mature partnerships with Gilead and Sanofi, multiple disclosed and undisclosed programs are advancing through lead optimization, IND-enablement and Phase 1 clinical studies.

In March 2023, Gilead licensed our IRAK4 TPD program under the collaboration, and in April 2025 we announced FDA clearance of an IND for GS-6791/NX-0479 a novel IRAK4 degrader for inflammatory conditions.

In addition, in March of 2024, Gilead extended the research term of multiple TPD programs.

In April 2024, Sanofi extended its research term for a STAT6 targeted protein degrader and in June 2025 licensed a development candidate, NX-3911, and commenced IND enabling studies.

In addition, Sanofi licensed a second program in May 2025 for an undisclosed target.

In our partnership with Pfizer, which was announced in September 2023 under an agreement with Seagen, Inc., we have achieved three preclinical milestones to date, qualifying for $15.0 million in milestone payments.

We expect to earn multiple additional preclinical and clinical milestones across our three active partnerships in 2026, which may allow us to secure additional license and development candidate events in 2026 and subsequent years.

• Advance our proprietary portfolio of preclinical programs toward additional INDs.

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By combining Nurix’s experience in machine learning, automated chemistry and targeted protein degraders with Pfizer’s expertise in antibody conjugate design, optimization and development, we believe we can achieve technical synergies that could allow us to redefine the application of antibody conjugates for not only oncology but also non-oncology indications.

In addition to the DACs in the Pfizer collaboration, we are pursuing multiple wholly owned DAC programs.

• Grow our proprietary pipeline by expanding the capabilities of our DEL-AI platform.

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We believe we are uniquely positioned to identify novel chemical starting points to undruggable proteins and ligases.

We have developed a suite of AI tools applicable across the breadth of our technical workflows, but with a specific focus on prospective ligand discovery informed by our years of accumulated DEL know-how and screening data.

Using our SP3-enriched, proprietary DNA-encoded libraries and complementary E3 ligase-enriched DEL screening data, we have created a leading AI-powered platform which is designed to quickly generate multiple potential starting points for degrader drugs, thereby opening access to hundreds of unprecedented drug targets and target families.

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Our DEL-AI platform can reduce reliance on serial wet-lab protein chemistry and screening efforts on challenging targets and instead can provide nearly instant access to drug-like and selective DEL binders to potentially any target or target class.

By employing advanced machine learning models informed by empirical degrader assay datasets we amassed, which include a compendium of in vitro and in vivo pharmacokinetic and pharmacodynamic readouts from tens of thousands of targeted protein degrader compounds, we have the ability to reduce the number of design-make-test cycles in our optimization campaigns, eliminate optimization bottlenecks, and shorten the overall project timelines required to achieve desired TPD target product profiles.

By employing advanced machine learning models informed by empirical degrader assay datasets that we have amassed, which include a compendium of in vitro and in vivo pharmacokinetic and pharmacodynamic readouts from tens of thousands of targeted protein degrader compounds, we have the ability to reduce the number of design-make-test cycles in our optimization campaigns, eliminate optimization bottlenecks, and shorten the overall project timelines required to achieve desired TPD target product profiles.

We plan to continue to invest in and leverage our purpose-built machine learning capabilities and DEL-AI research engine, which we believe will enable us to enhance our position as a leader in degrader drug discovery and deliver a robust and sustainable drug pipeline.

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BTK’s role in B-cell malignancy

BTK is a key component of the B-cell receptor signaling pathway and has been clinically validated as a target in the treatment of B-cell malignancies, most notably in CLL but also in NHL.

BTK is a key component of the B-cell receptor signaling pathway and has been clinically validated as a target in the treatment of B-cell malignancies, most notably in CLL but also in non-Hodgkin lymphoma (NHL).

It is estimated that in 2024, in the United States, over 20,000 patients were diagnosed with CLL and over 80,000 patients were diagnosed with NHLs.

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• Addresses scaffold function of BTK .

Removal of the BTK protein rather than inactivating the kinase domain addresses the scaffolding activity of BTK, more completely blocking the signaling activity of both wild-type and mutant forms of BTK.

Removal of the BTK protein rather than inactivating the kinase domain addresses the scaffolding activity of BTK, more completely eliminating the signaling activity of both wild-type and mutant forms of BTK.

• Address BTK inhibitor resistance mutations through event-driven pharmacology.

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A single degrader molecule is able to trigger degradation of thousands of BTK target proteins sequentially without the need to be constantly bound to the target.

We believe that targeted protein degradation of BTK may be a superior approach to existing covalent or noncovalent BTK inhibitors, particularly in the relapsed and refractory setting, and in the setting of resistance mutations to both covalent and noncovalent inhibitors.

We believe that targeted protein degradation of BTK may be a superior approach to existing covalent or noncovalent BTK inhibitors as well as in the setting of resistance mutations to both covalent and noncovalent inhibitors.

Immunomodulatory drugs, including Revlimid, or lenalidomide, and Pomalyst, or pomalidomide, are analogs of Thalomid, or thalidomide.

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Based on reported sales to date, global sales of this drug class, including Revlimid and Pomalyst, peaked in 2021 at approximately $16.2 billion, prior to the introduction of generic competition.

Subsequent to their approval and successful commercialization, studies demonstrated that these immunomodulatory drugs exert their therapeutic effect by triggering the degradation of specific proteins including Ikaros and Aiolos through the E3 ligase activity of cereblon, and hence were identified retrospectively as the first approved drugs to target an E3 ligase.

Recently published studies have reported early clinical data showing that combining a BTK inhibitor with an immunomodulatory drug may have the potential to augment clinical activity of certain standard of care agents in some hematologic malignancies such as non-germinal center B-cell like (non-GCB) DLBCL.

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We have conducted extensive preclinical studies of our two clinical stage BTK degraders.

We have demonstrated that both NX-5948 and NX-2127 can induce BTK degradation and inhibit tumor growth with oral administration in xenograft mouse models implanted with both wild-type and ibrutinib-resistant lymphoma cell lines.

We have also demonstrated the ability of both NX-5948 and NX-2127 to degrade BTK in circulating B cells of non-human primates and in B-cell lymphoma patients following once daily oral dosing in ongoing Phase 1 trials.

We have specifically designed NX-5948 to degrade BTK with limited or no degradation of cereblon neosubstrates.

We have designed NX-2127 as a dual degrader of BTK and the cereblon neosubstrates Ikaros and Aiolos, for potential applications in indications where adding immunomodulatory activity may be beneficial.

We have optimized NX-5948 and NX-2127 to be able to degrade both wild-type BTK and the C481S variant of BTK that has been identified as the most common mutation in patients who have become resistant to ibrutinib therapy over time.

We have demonstrated that both bexobrutideg and zelebrudomide can induce BTK degradation and inhibit tumor growth with oral administration in xenograft mouse models implanted with both wild-type and ibrutinib-resistant lymphoma cell lines.

We have also demonstrated the ability of both bexobrutideg and zelebrudomide to degrade BTK in circulating B cells of non-human primates and in B-cell lymphoma patients following once daily oral dosing in ongoing Phase 1 trials.

We have specifically designed bexobrutideg to degrade BTK with limited or no degradation of cereblon neosubstrates.

We have designed zelebrudomide as a dual degrader of BTK and the cereblon neosubstrates Ikaros and Aiolos, for potential applications in indications where adding immunomodulatory activity may be beneficial.

We have optimized bexobrutideg and zelebrudomide to be able to degrade both wild-type BTK and the C481S variant of BTK that has been identified as the most common mutation in patients who have become resistant to ibrutinib therapy over time.

Both agents have subsequently demonstrated the ability to degrade additional mutant variants of BTK associated with resistance to BTK inhibitors including L528W, T474I, M437R and V416L.

In our model of DLBCL cell line (TM8) harboring the most common resistance mutations, both NX-5948 and NX-2127 retained activity against all of the common clinical BTK inhibitor resistance mutations, while all tested inhibitors demonstrated a major decrease in activity against at least one of these prevalent mutations.

The figure below shows a heat map of the relative activity of NX-5948 and NX-2127 compared to a panel of both covalent and non-covalent BTK inhibitors.

Clinical development studies for NX-5948

We are studying the pharmacology, safety, and clinical activity of NX-5948 in multiple subtypes of relapsed and refractory B-cell malignancies, including those in which ibrutinib has shown only modest effects or is ineffective, as in the case of CLL patients with BTK inhibitor resistance mutations.

As illustrated in the diagram below, we are conducting a Phase 1a/1b dose-escalation and cohort expansion study of NX-5948 in patients with relapsed or refractory CLL and NHL.

We completed enrollment in the Phase 1a portion and commenced the Phase 1b portion of the trial in the second half of 2024 with two doses, 200 mg and 600 mg, in patients with CLL, MZL, FL, and WM.

In our model of DLBCL cell line (TM8) harboring the most common resistance mutations, both bexobrutideg and zelebrudomide retained activity against all of the common clinical BTK inhibitor resistance mutations, while all tested inhibitors demonstrated a major decrease in activity against at least one of these prevalent mutations.

The figure below shows a heat map of the relative activity of bexobrutideg compared to a panel of both covalent and non-covalent BTK inhibitors.

Clinical development studies for bexobrutideg

We are studying the pharmacology, safety, and clinical activity of bexobrutideg in multiple subtypes of relapsed and refractory B-cell malignancies, including those in which ibrutinib has shown only modest effects or is ineffective, as in the case of CLL patients with BTK inhibitor resistance mutations.

As illustrated in the diagram below, we are conducting a Phase 1a/1b dose-escalation and cohort expansion study of bexobrutideg in patients with relapsed or refractory CLL and NHL.

We completed enrollment in the Phase 1a portion and commenced the Phase 1b portion of the trial in the second half of 2024 randomized between two once daily (QD) doses of 200 mg and 600 mg in patients with CLL.

Additional cohorts of patients with CLL, MZL, FL, and WM were initiated at the 600mg QD dose.

The patients in the study represent a heavily pre-treated population with a variety of previous treatments.

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The study is currently enrolling in the United States, the UK, and in selected sites in Europe.

NX-5948 Phase 1 Clinical Study Design

NX-5948 Phase 1 clinical findings in chronic lymphocytic leukemia

Clinical findings from the NX-5948 Phase 1 trial were presented at the 66th American Society of Hematology annual meeting in December 2024 (ASH 2024).

These results included safety findings from a total of 125 patients as of the October 10, 2024 data cut and included efficacy findings from among the 60 CLL patients enrolled at that time.

NX-5948 was well tolerated across all doses evaluated, and safety findings in the CLL/SLL cohort were consistent with the overall population as well as previous safety analyses.

Among the CLL/SLL patients, the most common treatment emergent adverse events were purpura/contusion (36.7%, all grade 1 or 2), fatigue (26.7%, all grade 1 or 2), petechiae (26.7%, all grade 1 or 2), neutropenia (23.3%, 18.3% grade 3 or higher), and rash (23.3%, 1.7% grade 3 or higher).

Importantly, across the entire population, there was only one case of grade 1 atrial fibrillation in a patient with pre-existing atrial fibrillation.

Among the efficacy evaluable patients with CLL/SLL (n=49), NX-5948 treatment resulted in an objective response rate (ORR) of 75.5% across all doses tested (see table below), with the majority of responses occurring at the first assessment (Week 8).

With longer time on treatment, the ORR increased to 84.2% based on an exploratory efficacy analysis of patients who had at least two response assessments (Week 16).

Bexobrutideg Phase 1 Clinical Study Design

Bexobrutideg Phase 1a clinical findings in chronic lymphocytic leukemia

Clinical findings from the bexobrutideg Phase 1a trial were presented at the 67th American Society of Hematology annual meeting in December 2025 (ASH 2025).

These results included safety findings from a total of 126 CLL/SLL patients treated at all doses and 70 CLL/SLL patients treated at the 600mg dose, as of the September 19, 2025 data cut, and included efficacy findings from among the 47 CLL response evaluable patients enrolled in the Phase 1a at that time.

Bexobrutideg was well tolerated across all doses evaluated, and safety findings in the CLL/SLL cohort were consistent with the overall population as well as previous safety analyses (see table below).

Bexobrutideg Comparable AE Profile for Patients Overall and at the 600mg Dose Selected per Project Optimus

a Purpura/contusion includes episodes of contusion or purpura;

b Aggregate of ‘neutrophil count decreased’ or ‘neutropenia’;

c Fatigue was transient;

d Aggregate of ‘thrombocytopenia’ and ‘platelet count decreased’;

e Aggregate of ‘rash’ and ‘rash maculopapular’ and ‘rash pustular’;

f Aggregate of ‘COVID-19’ and ‘COVID-19 pneumonia’ AE , adverse event;

RP2D , recommended Phase 2 dose;

TEAE , treatment-emergent adverse event

Among the efficacy evaluable patients with CLL/SLL in the Phase 1a portion of the study (n=47), bexobrutideg treatment resulted in an objective response rate (ORR) of 83.0% across all doses tested including two complete responses (4.3%), with the majority of responses occurring at the first assessment (Week 8).

The median progression free survival (PFS) was 22.1 months across all doses tested (50-600 mg, see tables below).

Responses were observed across all populations regardless of prior treatment, baseline mutations, high-risk molecular features, or central nervous system (CNS) involvement.

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Robust BTK degradation was observed in all patients, including those with baseline BTK mutations.

NX-5948 was well tolerated across B-cell malignancies, with no additional safety signals observed with longer duration on study or increased dose.

NX-5948 Overall Response Assessment

a Objective response rate includes CR + PR + PR-L

b Patients who progressed prior to their first response assessment and patients who discontinued for any reason after their first response assessment are included in the denominators

c Patients without identified target lesion(s) at baseline are evalueated as disease-evaluable per iwCLL, while they may not be represented in waterfall plot

CLL , chronic lymphocytic leukemia;

CR , complete response;

iwCLL , International Workshop on CLL;

Bexobrutideg Phase 1a Overall Response Assessment

a Patients who were treated with bexobrutideg having ≥1 post-baseline disease assessment or documented clinical PD.

b Objective response rate was evaluated using iwCLL criteria and included CR + PR + PR-L.

c Kaplan-Meier estimate

Emerging data from the randomized Phase 1b cohorts points to higher ORR and longer progression free survival at the 600 mg RP2D compared to the 200 mg dose.

Preliminary Efficacy in Phase 1b Randomized Cohort of 200mg vs.

a Objective response rate includes CR + nPR + PR + PR-L.

CI , confidence interval;

ORR , objective response rate;

PD , progressive disease;

PR , partial response;

PR-L , partial response with rebound lymphocytosis;

SD , stable disease

NX-5948 Phase 1 clinical findings in Waldenstrom’s macroglobulinemia

Clinical findings from the NX-5948 Phase 1 trial were presented at the 12th International Workshop on Waldenstrom’s Macroglobulinemia in Prague, Czech Republic, in October 2024.

These results, also from the October 10, 2024 data cut included the baseline characteristics of the first 13 patients with WM enrolled across both the Phase 1a and Phase 1b portions of the trial, clinical response assessments in nine response-evaluable patients, and duration on study for all 13 patients.

Among the nine patients who were evaluable for response, seven patients (77.8%) had an objective response, and two patients experienced stable disease (22.2%).

All seven responses were observed at the first assessment at eight weeks, and five remained on treatment, with two patients on treatment for longer than one year.

Clinical development of NX-2127

We are studying the pharmacology, safety and clinical activity of NX-2127 in multiple subtypes of relapsed and refractory B‑cell malignancies, including CLL, DLBCL, MCL, MZL and FL.

We plan to focus development in indications where NX-2127 shows evidence of compelling clinical activity and where there is high unmet need.

PFS progression free survival

Bexobrutideg Pivotal Phase 2 commencement

In October 2025, enrollment was initiated in the DAYBreak CLL-201 Phase 2 study (NCT07221500), evaluating bexobrutideg at the 600 mg recommended Phase 2 dose (RP2D) and designed to support accelerated approval of bexobrutideg in triple-exposed CLL/SLL patients (post cBTKi, ncBTKi and BCL-2i).

DAYBreak Phase 2 Study Designed to Support Accelerated Approval

r/r CLL , relapsed or refractory chronic lymphocytic leukemia;

ORR , objective response rate;

iwCLL , International Workshop on CLL;

IRC , Independent Review Committee;

QD ,once daily;

SLL , small lymphocytic lymphoma;

cBTKi , covalent BTK inhibitor;

ncBTKi , non-covalent BTK inhibitor;

BCL-2i , BCL-2 inhibitor

Bexobrutideg Phase 1 clinical findings in Waldenström macroglobulinemia

Clinical findings from the bexobrutideg Phase 1 trial in patients with Waldenström macroglobulinemia (WM) were also presented at the 67th American Society of Hematology annual meeting in December 2025 (ASH 2025).

These results, also from the September 19, 2025 data cut, included the baseline characteristics of the 31 patients with WM enrolled across both the Phase 1a and Phase 1b portions of the trial, primary efficacy analysis in all response-evaluable patients, and duration on study for all 31 patients.

Among the 28 patients who were evaluable for response the ORR was 75.0% and for 23 patients with two or more response assessments the ORR was 82.6%.

A steady reduction in IgM levels occurred in most patients starting from the first IgM assessment (four weeks) which continued to deepen at eight weeks and beyond.

The median duration of response was not reached with 14 patients continuing on treatment for more than six months.

Clinical development of zelebrudomide

We are studying the pharmacology, safety and clinical activity of zelebrudomide in multiple subtypes of relapsed and refractory B‑cell malignancies, including CLL, DLBCL, MCL, MZL and FL.

We plan to focus development in NHL indications where zelebrudomide shows evidence of compelling clinical activity and where there is high unmet need.

The Phase 1a/1b dose escalation and cohort expansion study was initiated in 2021.

Enrollment was paused in the fourth quarter of 2023 due to a partial clinical hold stemming from a manufacturing change designed to produce a chirally controlled form of NX-2127.

Enrollment of new patients in the NX-2127 clinical trial recommenced in August 2024, following resolution of the partial hold by the FDA.

Enrollment was paused in the fourth quarter of 2023 due to a partial clinical hold stemming from a manufacturing change designed to produce a chirally controlled form of zelebrudomide.

Enrollment of new patients in the zelebrudomide clinical trial recommenced in August 2024, following resolution of the partial hold by the FDA.

Dose escalation with the new drug form is ongoing with a focus on patients with aggressive forms of B-cell lymphoma.

As illustrated in the diagram below, the Phase 1a/1b trial is currently evaluating doses of the new drug product ranging from 100 mg to 450 mg, with potential expansion cohorts for patients with DLBCL, MCL, FL, MZL, and WM.

Patients enrolled in the clinical study who are deriving clinical benefit on the original drug product may continue to receive treatment in accordance with the ongoing study protocol, but all new patients are being treated with the new drug product.

NX-2127 Phase 1 Study Design

Patients enrolled in the clinical study who are deriving clinical benefit on the original drug product may continue to receive treatment in accordance with the ongoing study protocol, however all new patients are being treated with the new drug product.

Zelebrudomide Phase 1 Study Design

a Planned number of evaluable patients (i.e., meeting DLT evaluability criteria);

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WM , Waldenstrom's macroglobulinemia

NX-2127 Clinical findings

Positive data from the NX-2127 clinical study was presented at the 65th ASH annual meeting in December 2023 (ASH 2023) and ASH 2024, in patients with NHL and CLL, confirming a manageable safety profile that is consistent with previous reports for BTK-targeted and immunomodulatory therapies.

Zelebrudomide Clinical findings

Positive data from the zelebrudomide clinical study was presented at the 65th ASH annual meeting in December 2023 (ASH 2023) and ASH 2024, in patients with NHL and CLL, confirming a manageable safety profile that is consistent with previous reports for BTK-targeted and immunomodulatory therapies.

BTK degradation was demonstrated at all dose levels in patient samples, as shown in the figure below.

Danilov et al., ASH 2023, Poster #4463

To evaluate the immunomodulatory effects of NX-2127, circulating patient PBMCs were collected at baseline, after 1 week (C1D8, acute assessment), and following one treatment cycle (C2D1, sustained effects;

28-day cycle).

Single-cell sequencing analysis was performed to compare gene signatures between responders (R;

patients achieving a best response of PR or PR with lymphocytosis) and non-responders (NR;

patients achieving SD or PD).

The analysis revealed distinct differences between responders and non-responders within CD4+ and CD8+ T-cell subpopulations.

In CD4+ T cells, as shown in Figure A, responders exhibited increased expression of activation markers, including CD69 and ICOS, as well as upregulation of oxidative phosphorylation-related genes, such as COX7B and NDUFA5.

In CD8+ T cells, as shown in Figure B, non-responders displayed higher expression of exhaustion markers, including TOX, PD-1, and TIGIT, consistent with immune dysfunction.

The fold-change plot in Figure B illustrates the progressive increase in TOX expression in non-responders relative to responders over time, highlighting these differences.

These findings provide evidence supporting the potential of NX-2127 to modulate T-cell function, which may contribute to its observed clinical activity in patients with CLL.

NX-2127 modulates patient T cells, contributing to its clinical efficacy in CLL patients

Tiana et al., ASH 2024, Oral Presentation

The findings from the study confirmed the manageable and predictable safety profile.

The most common TEAEs (any grade) were fatigue, neutropenia, hypertension, bruising/contusion, and diarrhea.

The most common grade ≥3 TEAEs were neutropenia, hypertension and anemia.

Atrial fibrillation was observed in six patients (11.1%;

down from 17% reported previously), with three patients (5.6%) having grade ≥3 events.

Twenty-one patients (38.9%) had serious TEAEs, of whom eight (14.8%) had SAEs considered related to NX-2127 treatment.

Two patients experienced dose limiting toxicities (cognitive disturbance, neutropenia;

both at the 300 mg dose).

Efficacy findings showed promising clinical activity:

For patients with NHL, encouraging and durable responses were observed, including two complete responses and two partial responses, each at week eight.

For patients with CLL, despite a median of five prior lines of treatment and BTK mutations present in 36% of patients, NX-2127 treatment resulted in an objective overall response rate of 40.7%, including partial responses in 11 patients, with treatment ongoing in 13 patients.

For patients with CLL, despite a median of five prior lines of treatment and BTK mutations present in 36% of patients, zelebrudomide treatment resulted in an objective overall response rate of 40.7%, including partial responses in 11 patients, with treatment ongoing in 13 patients.

Tumor shrinkage and clinical responses were observed in patients regardless of prior lines of therapy or baseline BTK mutations.

NX-2127 NHL efficacy

NX-2127 CLL efficacy

Zelebrudomide NHL efficacy

Zelebrudomide CLL efficacy

Danilov et al, ASH 2023, Poster #4463

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NX-1607 does not appear to activate T cells in the absence of TCR engagement.

The in vivo effects of orally administered NX-1607 were evaluated as a single agent in several mouse models of cancer.

In the experiments shown in the figure below on the left, oral treatment with NX-1607 significantly increased survival in this neoadjuvant model of metastatic triple-negative breast cancer in which treatment was initiated just prior to surgical primary tumor resection (shaded area indicates dosing period).

Without further treatment, all mice in the vehicle group (black line) died by day 60 as a result of disseminated tumor metastases in the lung, liver and brain.

By contrast, animals treated with NX-1607 (blue line) administered as a daily oral dose starting at day seven and continuing through day 46 demonstrated a highly significant prolongation of survival.

In the figure below on the right, oral treatment with NX-1607 (blue squares) significantly reduced the size of tumors and the rate of tumor growth compared to the vehicle group (black circles) in a B-cell lymphoma model.

The in vivo effects of orally administered NX-1607 were evaluated in combination with an antibody to PD-1 in several mouse models of cancer as shown in the figure below.

In the left and middle panels, the combination of oral NX-1607 plus anti-PD-1 (light blue lines) demonstrated increased survival in two separate colorectal cancer models compared with animals treated with either NX-1607 alone (blue line), anti-PD-1 alone (red line) or vehicle (black line).

Clinical development of NX-1607

We are studying the pharmacology, safety and clinical activity of single-agent NX-1607 and the combination of NX-1607 with taxane chemotherapy in multiple solid tumor indications.

We are studying the pharmacology, safety and clinical activity of single-agent NX-1607 and have studied the combination of NX-1607 with taxane chemotherapy in multiple solid tumor indications.

The solid tumors selected for this initial assessment include three different immune phenotypes:

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We are currently enrolling patients in the Phase 1a dose escalation portion of the monotherapy trial, which includes assessment of both once daily (QD) and twice daily (BID) dosing.

NX-1607 Phase 1 Clinical Study Design

Interim data from patients treated at 5, 15, 25, and 50 mg QD show linear pharmacokinetics (half-life of four to nine hours), dose-proportional exposure, and no apparent accumulation as indicated in figure below.

Interim PK results suggest linear PK (Cycle 1 Day 1)

Biomarker Strategy:

Proximal Markers of CBL-B Inhibition

Nurix identified multiple proximal biomarkers of CBL-B inhibition that correlate with anti-tumor activity in syngeneic models.

Using flow cytometry-based phosphorylation profiling and mass spectrometry–based ubiquitination assays, phosphorylated hematopoietic lineage cell-specific protein 1 (pHS1) emerged as a robust indicator of CBL-B inhibition in whole blood.

Pharmacodynamic analyses in the Phase 1a NX-1607-101 trial (below figure) shows maximal pharmacodynamic profiles in patients treated with 5 to 60 mg of total daily dose of NX-1607, either once daily (QD) or twice daily (BID).

Whole blood was collected at pre- and post-dosing timepoints in TruCulture tubes containing no stimulant (Null) or anti-CD3/CD28 (CD3/CD28).

Collectively, these findings demonstrate the dose-dependent pharmacodynamic activity of NX-1607, providing robust evidence of target engagement and aligning with preclinical data supporting its potential efficacy in patients.

Interim PD results show dose-proportionate increases of proximal biomarker pHS1, which correspond with levels associated with potent anti-tumor activity in mouse models

We are also exploring step-up dosing and the use of anti-emetic prophylaxis medication to achieve target drug levels and minimize potential gastrointestinal tolerability issues.

We have also explored step-up dosing and the use of anti-emetic prophylaxis medication to achieve target drug levels and minimize potential gastrointestinal tolerability issues.

NX-1607 Phase 1a Clinical Study Design

ECOG PS, Eastern Cooperative Oncology Group (ECOG) performance status

New Phase 1a clinical trial data for NX-1607 were presented at the European Society for Medical Oncology (ESMO) Congress and the 2025 Society for Immunotherapy of Cancer (SITC) Annual Meeting, demonstrating that NX-1607 exhibited dose-dependent pharmacologic activity consistent with target engagement and immune modulation, showing clinical activity through reductions in tumor-specific biomarkers such as prostate-specific antigen (PSA) in prostate cancer and carcinoembryonic antigen (CEA) in colorectal cancer.

Notably, there was a confirmed partial response in a patient with micro-satellite stable colorectal cancer (MSS CRC), a tumor type typically unresponsive to immune checkpoint therapy.

Furthermore, treatment with NX-1607 led to increased peripheral T cell activation and proliferation, significantly greater in patients with stable disease compared to those with progressive disease, indicating active T-cell receptor engagement and immune responsiveness.

NX-1607 demonstrated on-target peripheral immune activation, suggesting its potential as an active immune-oncology agent with a unique mechanism distinct from PD-1/PD-L1 therapies.

The data support the initiation of expansion cohorts at the two highest doses tested for both monotherapy and combination treatments in advanced solid tumors.

NX-1607 Demonstrates a Disease Control Rate of 49.3% Across Doses and Tumor Types

Our DEL-AI Platform and Research Engine

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• Degraders can eliminate all of a protein’s functionality.

Removing a protein from the cell by targeting it for proteasomal destruction eliminates all of a protein’s functionality, in contrast to small molecule inhibitors that only block enzymatic function.

Removing a protein from the cell by targeting it for proteasomal destruction eliminates all of a protein’s functionality, including scaffolding or structural functions, in contrast to small molecule inhibitors that only block enzymatic function.

• Degraders can access an expanded range of target space.

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TPDs act catalytically to eliminate their corresponding target proteins from a cell, requiring just a few degrader molecules to eliminate thousands of protein molecules and forcing the cell to resynthesize the target protein to restore functionality.

This creates a disconnect between degrader pharmacokinetics and degrader pharmacodynamics, greatly reducing the amplitude and duration of drug exposure required to maintain target suppression.

This creates a unique degrader pharmacokinetics and degrader pharmacodynamics, greatly reducing the amplitude and duration of drug exposure required to maintain target suppression as compared to traditional small molecule inhibitors.

• Degraders are mutationally tolerant.

Minor changes in the amino acid sequence of a target protein, as a consequence of somatic or inhibitor-induced resistance mutations, do not necessarily preclude degrader activity, even in cases where the mutations occur within the degrader binding site.

This is in strong contrast to the propensity of amino acid point mutations to disrupt the in vivo activity and efficacy of inhibitor drugs.

Minor changes in the amino acid sequence of a target protein, as a consequence of somatic or inhibitor-selected resistance mutations, do not necessarily preclude degrader activity, even in cases where the mutations occur within the degrader binding site.

This desirable property relates to the event-driven pharmacology of degraders and is in stark contrast to the propensity of amino acid point mutations to disrupt the in vivo activity and efficacy of inhibitor drugs.

• Degraders can penetrate the CNS.

Small molecule drugs and, most prominently beyond-the-rule-of-five compounds rarely achieve potent CNS exposure or activity.

However, TPDs are increasingly cited for their ability to penetrate and show pharmacology in the CNS, in part due to the minimal plasma exposure required for these catalytic agents to exhibit target coverage.

However, TPDs are increasingly cited for their ability to penetrate and show pharmacology in the CNS, in part due to the minimal plasma and cerebral spinal fluid (CSF) exposure required for these catalytic agents to exhibit target coverage.

• Inhibiting E3 ligases to control pathway activation.

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Upon signing the Gilead Agreement, Gilead paid us an upfront payment of $45.0 million, plus $3.0 million in additional fees.

In addition, from the signing of the Gilead Agreement to November 30, 2024, we received payments of $47.0 million for research milestones and additional payments, $20.0 million for a license option exercise payment and $15.0 million in research term extension fees.

In addition, from the signing of the Gilead Agreement to November 30, 2025, we received payments of $47.0 million for research milestones and additional payments, $20.0 million for a license option exercise payment, $15.0 million in research term extension fees and $5.0 million for a clinical milestone payment.

As of November 30, 2025, we are eligible to receive up to approximately $1.8 billion in total additional payments based on certain additional fees, payments and the successful completion of certain preclinical, clinical, development and sales milestones.

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The collaboration excludes our current internal protein degradation programs for which we retain all rights, and also excludes our future internal programs, provided that we distinguished future programs as excluded from the scope of the collaboration.

In March 2025, Sanofi exercised its right to exclusively license one target (the First Sanofi License Extension), the first development candidate resulting from the Sanofi Agreement.

Pursuant to the Sanofi Agreement, we received a license extension fee payment of $15.0 million in March 2025 for the First Sanofi License Extension.

In May 2025, Sanofi exercised its right to exclusively license a second target (the Second Sanofi License Extension, and together with the First Sanofi License Extension, the Sanofi License Extensions), the second development candidate resulting from the Sanofi Agreement.

Pursuant to the Sanofi Agreement, we received a license extension fee payment of $15.0 million in June 2025 for the Second Sanofi License Extension.

The license to the functional intellectual property and all goods and services related to both the First Sanofi License Extension and the Second Sanofi License Extension were transferred during the second quarter of fiscal year 2025.

For drug targets that are subject to the collaboration, we have primary responsibility for conducting preclinical research activities (including target validation, drug discovery, identification or synthesis) in accordance with the applicable research plan agreed to by the parties and established on a target-by-target basis.

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Subsequently in January 2021, Sanofi paid us an additional $22.0 million to exercise its option to expand the number of targets beyond the initial targets included in the collaboration.

In addition, from the signing of the Sanofi Agreement to November 30, 2024, we received payments of $13.0 million for research milestones.

As of November 30, 2024, we are eligible to receive up to approximately $1.9 billion in total additional payments based on certain additional fees, payments and the successful completion of certain research development, regulatory and sales milestones.

In addition, from the signing of the Sanofi Agreement to November 30, 2025, we received payments of $20.0 million for research milestones and $30.0 million for license extension fees.

As of November 30, 2025, we are eligible to receive up to approximately $930.0 million in total additional payments based on certain additional fees, payments and the successful completion of certain research development, regulatory and sales milestones.

We are also eligible to receive mid-single digit to low teen percentage tiered royalties on annual net sales of any commercial products that may result from the collaboration, subject to certain reductions and excluding sales in the United States of any products for which we exercise our option to co-develop and co-promote, for which the parties share profits and losses evenly.

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Under the terms of the Pfizer Agreement, we received an upfront payment of $60.0 million.

In addition, from the signing of the Pfizer Agreement to November 30, 2024, we received a payment of $5.0 million in connection with the achievement of a research milestone in May 2024.

In addition, from the signing of the Pfizer Agreement to November 30, 2025, we received payments of $10.0 million for research milestones.

We are eligible to receive up to approximately $3.4 billion in contingent payments based on specified research, development, regulatory and commercial milestones across multiple programs.

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We have personnel or engaged consultants with extensive technical, manufacturing, analytical and quality experience and good project management to oversee contract manufacturing and testing activities.

We have engaged third-party manufacturers to supply the drug substances for NX-5948, NX-2127 and NX-1607 and to develop and manufacture finished drug products for use in our clinical trials.

We have engaged third-party manufacturers to supply the drug substances for bexobrutideg, zelebrudomide, and NX-1607 and to develop and manufacture finished drug products for use in our clinical trials.

Should any of these manufacturers become unavailable to us for any reason, we believe that there are a number of potential replacements, although we may incur some delay in identifying and qualifying such replacements.

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patents, 24 U.S.

patent applications, 10 foreign patents and 134 foreign applications that we own, and three U.S.

patents, four pending U.S.

patent applications, one foreign patent and 26 foreign patent applications that we co-own with Gilead.

The expected expirations for issued patents and patents that may issue from pending applications covering our clinical candidates are between the years 2039 and 2044 for NX-5948;

2039 and 2042 for NX-2127;

patent applications, 23 foreign patents and 121 foreign applications that we own, three U.S.

patents, eight pending U.S.

patent applications, five foreign patents and 88 foreign patent applications that we co-own with Gilead.

The expected expirations for issued patents and patents that may issue from pending applications covering our clinical candidates are between the years 2039 and 2044 for bexobrutideg;

2039 and 2042 for zelebrudomide;

and 2040 and 2043 for NX-1607.

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If a Member State does not recognize the marketing authorization, the disputed points are eventually referred to the European Commission, whose decision is binding.

Since the UK has left the EU, Great Britain is no longer covered by centralized marketing authorizations.

This is not the case for Northern Ireland as under the Northern Ireland Protocol, centralized marketing authorizations continued to be recognized in Northern Ireland until December 31, 2024.

Medicines with existing centralized marketing authorizations were automatically converted to Great Britain marketing authorizations on January 1, 2021.

Since the UK has left the EU, it is no longer covered by centralized marketing authorizations.

A separate marketing authorization application is required in respect of the UK.

The UK government reached a new agreement with the EU, the “Windsor Framework,” which replaced the Northern Ireland protocol.

According to the Windsor Framework, medicinal products intended for the UK market including Northern Ireland will be authorized by the MHRA and will bear a “UK only” label.

This means that medicinal products placed on the market in Northern Ireland will no longer need to be compliant with EU law.

The UK government recently reached a new agreement with the EU, the “Windsor Framework,” which replaced the Northern Ireland protocol, according to which, the EU pharmaceutical legal framework acquis continued to apply to Northern Ireland.

Since the implementation of the Windsor Framework, medicinal products intended for the UK market including Northern Ireland are now authorized by the MHRA and must bear a “UK only” label.

This means that medicinal products placed on the market in Northern Ireland no longer need to be compliant with EU law.

These new measures have been implemented as of January 1, 2025.

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Since then, the MHRA has launched the Innovative Licensing and Access Pathway (ILAP), a new accelerated assessment procedure for marketing authorization applications that enables eligible products to be authorized in and potentially placed on the UK market faster.

This pathway is currently closed, as of November 20, 2024, until March 2025, when it will reopen for applications under a new refreshed pathway.

On January 1, 2024, the MHRA launched an International Recognition Procedure for marketing authorization applications whereby the MHRA will, when considering such applications, take into account the approval of medicines by trusted reference regulators in Australia, Canada, Switzerland, Singapore, Japan, United States and EU into its own abbreviated assessment.

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Commercially confidential information and protected personal data, however, may not be accessed.

On May 3, 2022, the European Commission published a proposal for a regulation on the European Health Data Space (EHDS), which aims to further enable exchange of electronic health data both for primary use (among national EU healthcare systems for patient care) and secondary use (among private companies and regulators to enable scientific research).

While the text of the regulation has provisionally been agreed to among the EU legislators, it is expected that the EHDS will be formally adopted by the European Parliament and the European Council and enter into force within 2025.

EHDS will then apply two years after entry into force, with certain provisions becoming applicable within four or six years after entry into force.

This will impose new obligations, but also create opportunities, for entities engaged in health-related research to share and access health data on a scale much larger than what is foreseen under current applicable transparency provisions.

The European Health Data Space Regulations (the EHDS Regulations) came into force on March 26, 2025.

The aims of the EHDS Regulations are to provide individuals with more control over their electronic health data, enable cross-border sharing of European Health Data (EHD) between national EU healthcare systems and facilitate the sharing of EHD for secondary research purposes.

The EHDS Regulations impose new obligations, but also create opportunities for companies engaged in health-related research to share and access health data on a large scale.

Although the EHDS Regulations have come into force, key obligations will not apply until March 2029.

Regulatory framework in the UK following Brexit

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The EU regulatory framework for medicinal products in place before the end of the transition period has been preserved in UK domestic legislation as “retained EU law” but the UK may diverge from EU law in the future should it wish to do so.

Pursuant to the Northern Ireland Protocol, the EU pharmaceutical legal framework acquis continues to apply in Northern Ireland and medicines can only be placed in the Northern Ireland market if they comply with EU law.

Pursuant to the Northern Ireland Protocol, the EU pharmaceutical legal framework acquis continued to apply in Northern Ireland and medicines could only be placed in the Northern Ireland market if they complied with EU law.

The UK government reached a new agreement with the EU, the “Windsor Framework,” which has replaced the Northern Ireland protocol.

According to the Windsor Framework, medicinal products intended for the UK market including Northern Ireland will be authorized by the MHRA and will bear a “UK only” label.

According to the Windsor Framework, medicinal products intended for the UK market including Northern Ireland are now authorized by the MHRA and must bear a “UK only” label.

This means that medicinal products placed on the market in Northern Ireland no longer need to be compliant with EU law.

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We will also be subject to certain ex-U.S.

privacy laws in connection with our clinical trial activities outside the United States such as the EU General Data Protection Regulation (EU GDPR), non-compliance with which could result in administrative fines of up to the greater of €20.0 million or 4% of global annual revenues.

The EU GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies and obtain compensation for damages resulting from violations of the EU GDPR.

privacy laws in connection with our clinical trial activities outside the United States such as the EU and UK General Data Protection Regulation (GDPR), non-compliance with which could result in administrative fines of up to the greater of 4% of global annual revenues or €20.0 million (under the EU GDPR) or £17.5m (under the UK GDPR).

The GDPR also confers a private right of action on data subjects and consumer associations to lodge complaints with supervisory authorities, seek judicial remedies and obtain compensation for damages resulting from violations of the GDPR.

Reimbursement of medicines in Europe

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The outcome of HTAs is decided on a national basis and some Member States may decide not to reimburse the use of medicines or may reduce the rate of reimbursement.

In December 2021, the EU adopted a new Regulation on Health Technology Assessment which allows Member States to carry out joint clinical assessments and operate joint clinical consultations.

It is expected that the new Regulation will go into effect in January 2025.

As of January 12, 2025, EU Health Technology Regulation No.

2021/2282 has become applicable in respect of new oncology medicines.

Regulation 2021/2282 imposes a new procedure, a joint clinical assessment at a centralized level, as a mandatory step for the assessment of the pricing and reimbursement of medicinal products by national authorities.

It requires companies applying for products in scope to make relevant submissions for the joint clinical assessment, in line with a number of prespecified criteria.

In the UK, NICE is the body in England and Wales, which conducts HTAs and issues guidance on whether a product is considered to be “cost-effective” and therefore recommended for use and reimbursement under the national health service.

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The law also prohibits avoiding, decreasing or concealing an obligation to pay money to the federal government.

The government can bring claims directly or through a civil whistleblower or qui tam action, and potential liability includes mandatory treble damages and significant per claim penalties currently set at $13,946 up to $27,894 per false claim or statement for penalties assessed after January 15, 2024, and which we expect will increase incrementally in early 2025 due to inflationary adjustments.

The government can bring claims directly or through a civil whistleblower or qui tam action, and potential liability includes mandatory treble damages and significant per claim penalties currently set at $14,308 up to $28,619 per false claim or statement for penalties assessed after July 3, 2025.

Numerous pharmaceutical and other healthcare companies have been investigated under these laws for purportedly, among other things, concealing price concessions in the pricing information submitted to the government for government price reporting purposes, and for allegedly providing free product to customers with the expectation that the customers would bill federal programs for the product.

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Department of Health and Human Services (HHS) issued proposed revisions to the HIPAA Privacy Rule aimed at reducing regulatory burdens that may exist in discouraging coordination of care and patient access to their health information, among other changes, which could affect not just covered entities and business associates, but broader entities in the life sciences space.

While a final rule has not yet been issued, if adopted, these proposed changes may require us to update our policies and procedures to comply with the new requirements.

Moreover, on December 27, 2024, HHS issued proposed revisions to the HIPAA Security Rule aimed at strengthening required cybersecurity protections for protected health information.

While a final rule has not yet been issued for either proposed rule, if adopted, these proposed changes may require us to update our policies and procedures to comply with the new requirements.

In addition, many state laws govern the privacy and security of health information and other personal information in certain circumstances (such as the California Consumer Privacy Act of 2018, the Virginia Consumer Data Protection Act, and similar state privacy laws in several other states, along with health privacy focused laws such as the Washington My Health My Data Act), and these state laws may differ from each other in significant ways and may not have the same effect.

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Some of these cost-savings pilots and projects, such as the Enhancing Oncology Model, are directed specifically at oncology.

The ACA and certain of its provisions have been subject to judicial challenges as well as legislative and regulatory efforts to repeal or replace them or to alter their interpretation or implementation.

For example, the Tax Cuts and Jobs Act (TCJA), among other things, included a provision repealing, effective January 1, 2019, the tax-based shared responsibility payment, or penalty, imposed by the ACA on certain individuals who fail to maintain qualifying health coverage for all or part of a year that is commonly referred to as the “individual mandate.” Further, the Bipartisan Budget Act of 2018, among other things, amended the ACA, effective January 1, 2019, to increase from 50% to 70% the point-of-sale discount that is owed by pharmaceutical manufacturers who participate in Medicare Part D and to close the coverage gap in most Medicare drug plans, commonly referred to as the “donut hole.” Additionally, the Further Consolidated Appropriations Act of 2020, signed into law December 20, 2019, fully repealed the ACA’s “Cadillac Tax” on certain high-cost employer-sponsored insurance plans (for tax years beginning after December 31, 2019), the annual fee imposed on certain health insurance providers based on market share (for calendar year 2021) and the medical device excise tax on non-exempt medical devices.

On June 17, 2021, the U.S.

Supreme Court dismissed a judicial challenge to the ACA brought by several states who argued that, without the individual mandate, the entire ACA was unconstitutional.

The Supreme Court’s dismissal of the lawsuit did not specifically rule on the constitutionality of the ACA.

On March 11, 2021, Congress enacted the American Rescue Plan Act of 2021, which included among its provisions a sunset of the ACA’s cap on pharmaceutical manufacturers’ rebate liability under the Medicaid Drug Rebate Program.

The ACA and certain of its provisions have been subject to judicial challenges as well as legislative and regulatory efforts to repeal or replace them, to alter their interpretation, or to otherwise impact the implementation of the ACA.

For example, on March 11, 2021, Congress enacted the American Rescue Plan Act of 2021, which included among its provisions a sunset of the ACA’s cap on pharmaceutical manufacturers’ rebate liability under the Medicaid Drug Rebate Program.

Under the ACA, manufacturers’ rebate liability was capped at 100% of the average manufacturer price for a covered outpatient drug.

Effective January 1, 2024, manufacturers’ MDRP rebate liability is no longer capped, potentially resulting in a manufacturer paying more in MDRP rebates than it receives on the sale of certain covered outpatient drugs.

Effective January 1, 2024, manufacturers’ MDRP rebate liability is no longer capped, meaning manufacturers may pay more in MDRP rebates than they receive on the sale of certain covered outpatient drugs.

The American Rescue Plan Act also temporarily increased premium tax credit assistance for individuals eligible for subsidies under the ACA for 2021 and 2022 and removed the 400% federal poverty level limit that otherwise applies for purposes of eligibility to receive premium tax credits.

The Inflation Reduction Act of 2022 (IRA) extended this increased tax credit assistance and removal of the 400% federal poverty limit through 2025.

This tax credit assistance expired on December 31, 2025, and additional action from Congress would be needed to restore such assistance in the future.

In the future, there may be additional challenges and/or amendments to the ACA.

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Other legislative changes have been proposed and adopted in the United States since the ACA was enacted to reduce healthcare expenditures.

These changes include the Budget Control Act of 2011, which, among other things, led to aggregate reductions of Medicare payments to providers of up to 2% per fiscal year that started in 2013 and, due to subsequent statutory amendments, will remain in effect through the first eight months of the fiscal year 2032 sequestration order unless additional congressional action is taken, with the exception of a temporary suspension, and later a temporary reduction instituted during the COVID-19 pandemic that expired on July 1, 2022.

These changes include the Budget Control Act of 2011, which, among other things, led to aggregate reductions of Medicare payments to providers of up to 2% per fiscal year that started in 2013 and, due to subsequent statutory amendments, will remain in effect through the first eleven months of the fiscal year 2032 sequestration order unless additional congressional action is taken, with the exception of a temporary suspension, and later a temporary reduction instituted during the COVID-19 pandemic that expired on July 1, 2022.

The American Taxpayer Relief Act of 2012 made other changes, including the reduction of Medicare payments to several types of providers and an increase in the statute of limitations period for the government to recover overpayments to providers from three to five years.

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Among other reforms, the IRA imposes inflation rebates on drug and biological product manufacturers for products reimbursed under Medicare Parts B and D if the prices of those products increase faster than inflation beginning in 2023;

implements changes to the Medicare Part D benefit that, beginning in 2025, will cap benefit annual out-of-pocket spending at $2,000, with new discount obligations for pharmaceutical manufacturers;

implements changes to the Medicare Part D benefit that, beginning in 2025, caps benefit annual out-of-pocket spending at $2,000, with new discount obligations for pharmaceutical manufacturers;

and, beginning in 2026, establishes a “maximum fair price” for a fixed number of pharmaceutical and biological products covered under Medicare Parts B and D following a price negotiation process with the CMS.

CMS has also taken steps to implement the IRA, including:

on August 29, 2023, releasing the initial list of ten drugs subject to price negotiations;

on August 15, 2024 releasing the negotiated maximum prices for such drugs that will be effective beginning in 2026;

on October 2, 2024, releasing final guidance outlining the process for the second round of price negotiations for products subject to the “maximum fair price” provision;

and on December 20, 2024, releasing a list of 64 Medicare Part B products that had an adjusted coinsurance rate based on the inflationary rebate provisions of the IRA for the time period of January 1, 2025, to March 31, 2025.

CMS has also taken steps to implement the IRA, including releasing the negotiated maximum prices, which are effective in 2026 for the first ten drugs that were subject to the IRA’s negotiation process, as well as the negotiated maximum prices for fifteen additional drugs to be effective in 2027, and releasing quarterly lists of Medicare Part B products that are subject to adjusted coinsurance rates based on the inflationary rebate provisions of the IRA.

While it remains to be seen how the drug pricing provisions imposed by the IRA will affect the broader pharmaceutical industry, several pharmaceutical manufacturers and other industry stakeholders have challenged the law, including through lawsuits brought against the HHS, the Secretary of the HHS, CMS, and the CMS Administrator challenging the constitutionality and administrative implementation of the IRA’s drug price negotiation provisions.

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Additionally, the cost of prescription pharmaceuticals and biological products has been the subject of considerable discussion in the United States.

For example, on February 2, 2022, the Biden administration signaled its continued commitment to the Cancer Moonshot initiative, which was initially launched in 2016.

In its announcement, the administration noted that its new goals under the initiative include addressing inequities in order to ensure broader access to cutting-edge cancer therapeutics and investing in a robust pipeline for new treatments.

In alignment with President Biden’s Cancer Moonshot initiative, on June 27, 2023, the Center for Medicare Innovation at CMS announced a new model, the Enhancing Oncology Model, that is designed to make high-quality cancer care more affordable to both patients and Medicare.

Additionally, on October 14, 2022, President Biden issued an Executive Order on Lowering Prescription Drug Costs for Americans, which instructed the Secretary of the HHS to consider whether to select for testing by the CMS Innovation Center new healthcare payment and delivery models that would lower drug costs and promote access to innovative drug therapies for beneficiaries enrolled in the Medicare and Medicaid programs.

On February 14, 2023, HHS issued a report in response to the October 14, 2022, Executive Order, which, among other things, selects three potential drug affordability and accessibility models to be tested by the CMS Innovation Center.

Specifically, the report addresses:

(1) a model that would allow Part D Sponsors to establish a “high-value drug list” setting the maximum co-payment amount for certain common generic drugs at $2;

(2) a Medicaid-focused model that would establish a partnership between CMS, manufacturers, and state Medicaid agencies that would result in multi-state outcomes-based agreements for certain cell and gene therapy drugs;

and (3) a model that would adjust Medicare Part B payment amounts for Accelerated Approval Program drugs to advance the developments of novel treatments.

For example, President Trump has signed multiple executive orders addressing prescription drug pricing and access, including:

on April 15, 2025, outlining several actions the Secretary of the Department of HHS must take to optimize healthcare regulations that will provide access to prescription drugs at lower costs;

on May 5, 2025, aiming to promote domestic production of critical medicines;

and on May 12, 2025, aiming to establish a “most favored nation” drug pricing policy that would tie U.S.

drug prices to the prices paid for drugs in other countries.

Since the May 12, 2025 “most favored nation” executive order, the Trump administration has continued to exert pressure on drug manufacturers to implement “most favored nation” pricing, including by suggesting that the administration may impose significant tariffs on pharmaceuticals if such manufacturers do not reach agreements to implement “most favored nation” pricing.

Additionally, in November 2025, CMS announced a new voluntary payment initiative called the GENEROUS Model (GENErating cost Reductions for U.S.

Medicaid Model) where drug manufacturers may voluntarily offer supplemental rebates to participating state Medicaid programs that are intended to provide such Medicaid programs with a “most favored nation” price for participating manufacturers’ products.

Moreover, there have been several recent U.S.

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It remains to be seen how these drug pricing initiatives will affect the broader pharmaceutical industry.

Moreover, results of the 2024 Presidential and Congressional elections, and potential subsequent developments, increase the uncertainty related to the healthcare regulatory environment.

In addition, on June 28, 2024, the U.S.

Supreme Court issued an opinion holding that courts reviewing agency action pursuant to the Administrative Procedure Act (APA) “must exercise their independent judgment” and “may not defer to an agency interpretation of the law simply because a statute is ambiguous.” The decision will have a significant impact on how lower courts evaluate challenges to agency interpretations of law, including those by CMS and other agencies with significant oversight of the healthcare industry.

The new framework is likely to increase both the frequency of such challenges and their odds of success by eliminating one way in which the government previously prevailed in such cases.

As a result, significant regulatory policies may be subject to increased litigation and judicial scrutiny.

Any resulting changes in regulation may result in unexpected delays, increased costs, or other negative impacts that are difficult to predict but could have a material adverse effect on our business and financial condition.

For example, certain of these changes could impose additional limitations on the rates we will be able to charge for our future products or the amounts of reimbursement available for our future products from governmental agencies or third-party payors.

At the state level, legislatures are increasingly passing legislation and implementing regulations designed to control pharmaceutical and biological product pricing, including price or patient reimbursement constraints, discounts, restrictions on certain product access and marketing cost disclosure and transparency measures and, in some cases, to encourage importation from other countries and bulk purchasing.

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The implementation of cost containment measures or other healthcare reforms may prevent us from being able to generate revenue, attain profitability, or commercialize any product that is ultimately approved, if approved.

In addition, several recently passed state laws require disclosures related to state agencies and/or commercial purchasers with respect to price increases and new product launches that exceed certain levels as identified in the relevant statutes.

Some of these laws and regulations contain ambiguous requirements that government officials have not yet clarified.

In addition, several state laws require disclosures related to state agencies and/or commercial purchasers with respect to price increases and new product launches that exceed certain levels as identified in the relevant statutes.

Another emerging trend at the state level is the establishment of prescription drug affordability boards, some of which will prospectively permit certain states to establish upper payment limits for drugs that the state has determined to be “high-cost.” Prescription drug affordability boards in several states, including Colorado, Maryland, Oregon, and Washington, have begun identifying products for affordability reviews and issuing information requests to manufacturers to determine whether upper payment limits may be justified.

Some of these state laws and regulations contain ambiguous requirements that government officials have not yet clarified.

Given the lack of clarity in the laws and their implementation, our future reporting actions could be subject to the penalty provisions of the pertinent federal and state laws and regulations.

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Of our vice president-level and above employees, approximately 45% were self-reported as female.

In addition, as of November 30, 2024, approximately 61% of our full-time employees were self-reported as ethnic or racial minorities in the United States, with 43% Asian, 2% Black or African American, 8% Hispanic or Latino and 5% of other minority groups or two or more races.

Of our vice president-level and above employees, 33% were self-reported as ethnic or racial minorities in the United States, with 21% Asian and 8% Black or African American.

In addition, as of November 30, 2025, approximately 50% of our full-time employees were self-reported as ethnic or racial minorities in the United States, with approximately 41% Asian, 2% Black or African American, 7% Hispanic or Latino and 1% of other minority groups or two or more races.

Of our vice president-level and above employees, approximately 33% were self-reported as ethnic or racial minorities in the United States, with approximately 30% Asian and 3% Black or African American.

Employee development and training

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Our focus on culture comes from our Board and flows throughout our company.

In evaluating our Chief Executive Officer and management team, significant emphasis is place on their contributions to our overall culture.

In evaluating our Chief Executive Officer and management team, significant emphasis is placed on their contributions to our overall culture.

Our Board’s Compensation Committee is responsible for reviewing with management our human resources activities, which include, among other things, matters relating to employee development, management and engagement, pay equity, and our demographics, diversity and inclusion.

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in October 2018.

Our principal executive offices are located at 1700 Owens Street, Suite 205, San Francisco, California 94158, and our telephone number is (415) 660-5320.

Our principal executive offices are located at 1600 Sierra Point Parkway, Brisbane, California 94005, and our telephone number is (415) 660-5320.

The mark “Nurix” is our registered trademark in Canada, France, Germany, Italy, Japan, Mexico, Spain, the United Kingdom and the United States.

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and our Board Committee Charters.

We will provide any of the foregoing information without charge upon written request to our Corporate Secretary, Nurix Therapeutics, Inc., 1700 Owens Street, Suite 205, San Francisco, California 94158.

We will provide any of the foregoing information without charge upon written request to our Corporate Secretary, Nurix Therapeutics, Inc., 1600 Sierra Point Parkway, Brisbane, California 94005.

We use our Investor Relations website (http://ir.nurixtx.com) as a means of disclosing material non-public information and for complying with our disclosure obligations under Regulation FD promulgated by the SEC.

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Compared sentence by sentence after normalising whitespace, quotation marks, case and digits, so re-formatting and restated figures do not read as changed language. Wording changes appear as one removal and one addition. The current filing and the prior one are authoritative.

What changed 10-K

Item 1. Business