10-K: Nurix Therapeutics Advances Pipeline, Reports Increased Net Loss

Nurix Therapeutics, a clinical-stage biopharmaceutical company, reported a net loss of $264.5 million for fiscal year 2025, while advancing its targeted protein degradation pipeline with key clinical milestones and strategic collaborations.

Summary

• Net loss increased to $264.5 million in fiscal year 2025 from $193.6 million in 2024.
• Accumulated deficit reached $1,003.2 million as of November 30, 2025.
• Total revenue increased to $83.98 million in 2025 from $54.55 million in 2024, driven by license revenue.
• Collaboration revenue slightly decreased to $53.98 million in 2025 from $54.55 million in 2024.
• License revenue was $30.0 million in 2025 (from Sanofi License Extensions), up from $0 in 2024.
• Research and development expenses increased by $95.3 million to $316.9 million in 2025, primarily due to increased clinical trial enrollment, contract manufacturing, and facility costs.
• General and administrative expenses increased by $6.8 million to $52.7 million in 2025.
• Cash, cash equivalents, and marketable securities totaled $592.9 million as of November 30, 2025.
• The company initiated a Phase 2 pivotal trial for bexobrutideg (NX-5948) in relapsed/refractory CLL in October 2025.
• Bexobrutideg received Fast Track designation from the FDA for CLL/SLL (Jan 2024) and WM (Dec 2024), and PRIME designation from the EMA for CLL/SLL (Nov 2024).
• Enrollment for zelebrudomide (NX-2127) Phase 1a/1b trial recommenced in August 2024 after a partial clinical hold resolution.
• NX-1607 Phase 1a/1b dose escalation is ongoing in solid tumors, showing promising clinical activity and a confirmed partial response in MSS CRC.
• Received $482.0 million in non-dilutive financing from collaborations to date, with potential for up to $6.1 billion in future milestones and royalties.
• Sanofi licensed two development candidates in March and May 2025, triggering $30.0 million in license extension fees.
• Pfizer collaboration achieved three preclinical milestones, totaling $15.0 million in payments.
• Raised $234.4 million net from a registered direct offering in October 2025.

Sentiment

Score: 6

Explanation: The company demonstrated significant clinical progress with bexobrutideg entering a pivotal Phase 2 trial and receiving multiple expedited designations, and positive early data for zelebrudomide and NX-1607. Strategic collaborations with major pharmaceutical companies continue to generate non-dilutive funding and future milestone potential. A substantial capital raise in October 2025 strengthened the cash position. However, net losses increased significantly year-over-year, and the accumulated deficit surpassed $1 billion, indicating a high cash burn rate as the company advances its pipeline. The long path to commercialization and profitability, coupled with the need for substantial future funding, presents ongoing financial challenges despite the scientific and clinical advancements.

Positives

• Initiation of Phase 2 pivotal trial for bexobrutideg (NX-5948) in relapsed/refractory CLL, designed for Accelerated Approval.
• Bexobrutideg received Fast Track designation from the FDA for CLL/SLL (January 2024) and Waldenstrom's macroglobulinemia (December 2024).
• Bexobrutideg received Priority Medicine (PRIME) designation from the EMA for CLL/SLL (November 2024).
• Phase 1a clinical findings for bexobrutideg in CLL/SLL showed an 83.0% objective response rate (ORR) across all doses and a median progression-free survival (PFS) of 22.1 months.
• Preliminary Phase 1b data for bexobrutideg showed higher ORR and longer PFS at the 600mg dose compared to 200mg.
• Bexobrutideg Phase 1 trial in Waldenstrom's macroglobulinemia showed a 75.0% ORR (28 evaluable patients) and 82.6% ORR (23 patients with 2+ assessments), with median duration of response not reached.
• Resolution of partial clinical hold for zelebrudomide (NX-2127) in August 2024, allowing recommencement of patient enrollment.
• Zelebrudomide clinical study showed promising clinical activity in NHL (two complete responses, two partial responses) and CLL (40.7% ORR), even in heavily pre-treated patients with BTK mutations.
• NX-1607 demonstrated dose-dependent pharmacologic activity and clinical activity in solid tumors, including a confirmed partial response in micro-satellite stable colorectal cancer (MSS CRC).
• NX-1607 was awarded an Innovation Passport from the UK MHRA to accelerate time to market.
• Received $482.0 million in non-dilutive financing from collaborations (Gilead, Sanofi, Pfizer) to date.
• Eligible to receive up to $6.1 billion in potential future fees and milestone payments, plus royalties from collaborations.
• Gilead extended research term for multiple TPD programs in March 2024, triggering a $15.0 million payment.
• Gilead licensed IRAK4 TPD program in March 2023, triggering a $20.0 million payment.
• FDA cleared IND for GS-6791/NX-0479 (IRAK4 degrader) in April 2025.
• Sanofi extended research term for STAT6 TPD in April 2024.
• Sanofi licensed development candidate NX-3911 in June 2025 and commenced IND enabling studies.
• Sanofi licensed a second undisclosed program in May 2025.
• Achieved three preclinical milestones with Pfizer, totaling $15.0 million in payments.
• Strong cash position with $592.9 million in cash, cash equivalents, and marketable securities as of November 30, 2025.
• Successful capital raise of $234.4 million net from a registered direct offering in October 2025.
• DEL-AI platform is fully AI-integrated, leveraging machine learning for discovery, design, synthesis, and screening, providing a significant advantage.
• Proprietary pan-mutant BRAF program shows potency against various BRAF mutations, sparing wild-type activity, and potential for improved therapeutic window.
• DAC platform combines selective degradation with cell-specific delivery, potentially enhancing safety and efficacy.
• Effective internal control over financial reporting as of November 30, 2025.

Negatives

• Net loss increased to $264.5 million in fiscal year 2025 from $193.6 million in 2024.
• Accumulated deficit reached $1,003.2 million as of November 30, 2025.
• Collaboration revenue decreased slightly by $0.6 million in 2025, primarily due to conclusion of initial research terms for some Sanofi and Gilead targets.
• Significant increase in research and development expenses ($95.3 million increase) and general and administrative expenses ($6.8 million increase).
• Zelebrudomide Phase 1a/1b enrollment was paused in 2023 due to a partial clinical hold stemming from a manufacturing change.

Risks

• Significant losses since inception and expectation to incur losses for at least the next several years, potentially never achieving profitability.
• Need for substantial additional funding; inability to raise capital could delay, limit, reduce, or terminate research/development or commercialization efforts.
• Early stage of development for lead drug candidates (bexobrutideg, zelebrudomide, NX-1607) with high risk of failure.
• Unproven nature of targeted protein degradation as a treatment modality, making development time, cost, and success likelihood difficult to predict.
• Potential for serious adverse events, undesirable side effects, or unexpected characteristics during development, requiring abandonment or limitation of clinical development.
• Results of preclinical studies and early-stage clinical trials may not be predictive of future results; initial success is not indicative of later-stage success.
• Delays or difficulties in enrolling patients in clinical trials could delay or prevent marketing approvals.
• Risk of expending limited resources on drug candidates or indications that prove less profitable or successful.
• Substantial competition in a rapidly changing technological environment, potentially leading to others commercializing products more successfully.
• Reliance on third-party contract manufacturing organizations (CMOs) for drug substance and finished drug product, increasing risk of insufficient quantities, unacceptable cost/quality, or supply disruption.
• Inability to obtain and maintain patent protection for technology and drug candidates, or insufficient breadth of protection, allowing competitors to commercialize similar products.
• Risk of not identifying relevant third-party patents or incorrectly interpreting their scope, leading to infringement allegations and legal proceedings.
• Unfavorable global economic conditions (inflation, interest rates, market volatility, geopolitical conflicts, banking instability) could adversely affect business, financial condition, and stock price.
• Failure to attract and retain management and other key personnel could impede successful development and business plan implementation.
• Even if commercialized, products may face unfavorable pricing regulations, third-party reimbursement practices, or healthcare reform initiatives, or fail to secure positive health technology assessments.
• Product liability lawsuits could incur substantial liabilities and limit commercialization.
• Uncertainties and changes in patent law could diminish patent value.
• Limited life of patent protection, allowing generic/biosimilar competition.
• Need to license intellectual property from third parties, which may not be available or on reasonable terms.
• Claims by third parties of misappropriation of trade secrets or ownership of intellectual property.
• Involvement in lawsuits to protect or enforce intellectual property, which are expensive and time-consuming.
• Inability to protect intellectual property rights in all foreign jurisdictions.
• Regulatory approval process is lengthy, time-consuming, and unpredictable; failure to obtain approval would substantially harm business.
• Fast Track/PRIME designations do not guarantee faster development or approval.
• Potential failure to obtain approval via Accelerated Approval pathway or withdrawal of such approval if confirmatory trials fail.
• Limited company experience in regulatory approval, pivotal trials, manufacturing, and quality assurance.
• Failure to obtain marketing approval in foreign jurisdictions.
• Post-marketing restrictions or withdrawal from market if issues arise or regulations are not complied with.
• Risk of generic versions of drug candidates being approved or failure to obtain appropriate data/market exclusivity.
• Failure to obtain regulatory data protection or extensions if drug candidates are not considered new active substances or pediatric studies are not completed.
• Subject to anti-kickback, fraud and abuse, and other healthcare laws, leading to penalties for non-compliance.
• Disruptions at the FDA (e.g., government shutdowns, staffing changes) could slow review/approval.
• Current and future legislation (e.g., IRA) may increase difficulty and cost of approval and commercialization, affecting prices.
• Strict price controls in foreign governments could adversely affect revenues.
• Difficulties in managing organizational growth.
• Misconduct by employees, contractors, or consultants.
• Dependence on information technology systems; security breaches, cyber-attacks, or data loss could harm business.
• Use of artificial intelligence (AI) carries risks of inaccuracy, bias, cybersecurity incidents, and evolving regulation.
• U.S. federal income tax reform and changes in other tax laws could adversely affect the company.
• Ability to utilize net operating loss carryforwards may be limited.
• Future acquisitions, joint ventures, spin outs or strategic alliances or transactions could disrupt business.
• Subject to anti-corruption laws, export control laws, customs laws, sanctions laws and other laws governing operations.
• Failure to comply with environmental, health and safety laws and regulations.
• Exposure to foreign exchange risk.
• Current operations in the San Francisco Bay Area are susceptible to earthquakes or other natural disasters.
• Quarterly results of operations may fluctuate significantly or fall below expectations.
• Stock price may be volatile and investors could lose all or part of their investment.
• Sale of a substantial number of shares of common stock may cause the price to decline.
• If securities or industry analysts do not publish research or reports, or issue adverse opinions, stock price and trading volume could decline.
• Future sale and issuance of equity or convertible debt securities will dilute share capital.
• Anti-takeover provisions in charter documents and under Delaware law could make an acquisition more difficult.
• Exclusive forum provisions for certain claims could limit stockholders' ability to obtain a favorable judicial forum.
• Significant costs incurred as a public company, with management devoting substantial time to compliance.
• Failure to maintain effective internal control over financial reporting could impair ability to produce accurate and timely financial statements.
• No anticipation of paying cash dividends on capital stock in the foreseeable future, making capital appreciation the sole source of gain.
• Subject to securities litigation, which is expensive and could divert management attention.

Future Outlook

The company expects to incur significant expenses and increasing operating losses for at least the next several years, with operating expenses and capital expenditure requirements anticipated to increase substantially as clinical trials advance, IND submissions occur, manufacturing scales up, the DEL-AI platform expands, and commercialization efforts begin. It intends to commence additional pivotal trials for bexobrutideg in 2026 and may explore its use in autoimmune diseases. Doses for Phase 1b cohort expansions for zelebrudomide and NX-1607 are expected to be defined in 2026. The company anticipates earning multiple additional preclinical and clinical milestones from its partnerships in 2026 and subsequent years. It plans to continue investing in its DEL-AI research engine and aims to become a fully integrated biopharmaceutical company with its own sales force in the U.S. and potentially other countries, while also pursuing selective collaborations. Existing cash, cash equivalents, and marketable securities are projected to fund operations for at least the next 12 months, but substantial additional funding will be required thereafter. Domestic research and experimental costs will no longer require capitalization under Section 174 of the Internal Revenue Code starting with the tax year ending November 30, 2026.

Management Comments

• We are a clinical stage biopharmaceutical company focused on the discovery, development and commercialization of targeted protein degradation medicines, the next frontier in innovative drug design aimed at improving treatment options for patients with cancer and inflammatory diseases.
• Powered by a fully artificial intelligence (AI)-integrated discovery engine capable of tackling any protein class, and coupled with leading ligase expertise, Nurix has built a significant advantage in translating the science of protein degradation into clinical advancements with the aim of establishing degrader-based treatments at the forefront of patient care.
• 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.
• 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.
• We believe our degraders will be clinically advantageous over existing therapies based on in vivo preclinical models that show improved potency against clinically relevant BRAF mutations and superior efficacy compared to other clinical and preclinical BRAF and RAF agents.
• We believe that a pan-mutant BRAF degrader will provide more sustained MAPK pathway suppression through its catalytic mechanism of action with the potential to target relapsed and refractory BRAF-mutant positive class I patient populations as well as class II and III BRAF patients for which there exists no approved BRAF therapies.
• We believe DACs, formed by conjugating a diseaseor cell-type-selective antibody to a targeted protein degrader, can overcome the limitations of traditional ADCs.
• We believe we are uniquely positioned to identify novel chemical starting points to undruggable proteins and ligases.
• 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.
• We intend to become a fully integrated biopharmaceutical company by building a targeted sales force in the United States and potentially other countries to support the commercialization of our approved drug candidates.
• Management believes that its cash, cash equivalents and short-term marketable securities are sufficient to continue operating activities for at least 12 months following the issuance date of these financial statements.

Industry Context

The biopharmaceutical industry is characterized by rapidly advancing technologies, intense competition, and a strong emphasis on intellectual property. Targeted protein degradation is emerging as a significant new therapeutic modality, with many companies, including Nurix, focusing on this area. The market for BTK inhibitors was estimated at $10.6 billion in 2024, and immunomodulatory drugs peaked at $16.2 billion in 2021, indicating substantial market opportunities in oncology and immune-mediated diseases. Nurix faces competition from both protein degradation specialists and companies utilizing traditional therapeutic modalities. The industry is also subject to extensive and evolving regulatory frameworks, including new EU health technology regulations and U.S. drug pricing reforms like the Inflation Reduction Act, which could impact future revenues and market access. The development of Degrader Antibody Conjugates (DACs) represents an innovative advancement in targeted therapy, building on existing antibody-drug conjugate technology.

Comparison to Industry Standards

• Bexobrutideg and zelebrudomide are designed with the goal to be first-in-class or best-in-class therapeutics, aiming to surpass existing treatments.
• Bexobrutideg is believed to offer unique advantages over currently available BTK inhibitors by addressing both the enzymatic and scaffold activities of BTK, which are key to its function.
• Preclinical models of Nurix's BRAF degraders show improved potency against clinically relevant BRAF mutations and superior efficacy compared to other clinical and preclinical BRAF and RAF agents.
• Nurix's BRAF degraders are expected to provide a greater therapeutic window compared to existing BRAF agents by avoiding paradoxical pathway activation while preserving normal wild-type BRAF function.
• The company's Degrader Antibody Conjugates (DACs) are positioned as the next generation of antibody drug conjugate technology, designed to achieve enhanced safety and improved efficacy compared to traditional ADCs.
• Nurix's DEL-AI discovery engine is described as providing a significant advantage in translating protein degradation science into clinical advancements, suggesting a leading position in this innovative drug design space.
• The company has amassed one of the industry's largest datasets specifically generated from experiments relevant to targeted protein degradation, indicating a strong data-driven approach compared to peers.
• NX-1607 demonstrated on-target peripheral immune activation, suggesting a unique mechanism of action distinct from established PD-1/PD-L1 therapies in immuno-oncology.

Legal Proceedings

• Not presently a party to any material legal proceedings that, in the opinion of management, would have a material adverse effect on the business or financial statements.
• In January 2019, the California Franchise Tax Board (FTB) initiated an examination of California tax returns for tax years ending in 2015, 2016, 2017, and 2018. The company challenged proposed audit assessments related to revenue sourcing and R&D credits. In May 2025, new information from the FTB led to a remeasurement of the unrecognized tax benefit, resulting in discrete tax expense. Settlement procedures with the FTB were initiated in September 2025.

Related Party Transactions

• The company's Chief Financial Officer is a trustee for a multiple employer welfare association that facilitates the acquisition and administration of the company's healthcare plans. Expenses related to these healthcare plan premiums were $6.3 million in 2025, $4.3 million in 2024, and $4.4 million in 2023.

Stakeholder Impact

• Shareholders face potential dilution from future equity offerings, stock price volatility, and no anticipated cash dividends, but also potential long-term value creation if drug candidates are successful.
• Employees benefit from competitive pay, benefits, stock options, RSUs, and development programs, but face competition for qualified personnel.
• Patients may benefit from the development of targeted protein degradation medicines aimed at improving treatment options for cancer and inflammatory diseases, with the potential for first-in-class or best-in-class therapeutics.
• Collaborators (Gilead, Sanofi, Pfizer) are engaged in ongoing partnerships, with potential for future milestone payments and royalties, and co-development/co-commercialization options, but also face risks of discretion and potential termination.
• Suppliers and Contract Manufacturing Organizations (CMOs) are critical for manufacturing, but reliance on them carries risks of supply disruptions, increased costs, and quality issues.
• Regulatory Authorities (FDA, EMA, MHRA) are involved in the approval process, with ongoing engagement for clinical trials, designations, and marketing approvals, subject to evolving regulations.

Next Steps

• Increase enrollment in and further develop bexobrutideg, zelebrudomide, and NX-1607 through Phase 1 and Phase 2 clinical trials.
• Submit investigational new drug applications (INDs) and initiate clinical trials for other drug candidates.
• Enter advanced clinical development and scale up external manufacturing capabilities to supply clinical trials.
• Expand the capabilities of the DEL-AI platform and apply it to advance additional drug candidates.
• Conduct process development for manufacturing of drug candidates.
• Seek marketing approvals for drug candidates that successfully complete clinical trials.
• Prepare for negotiations with pricing authorities and submission to health technology appraisal (HTA) bodies.
• Ultimately establish a sales, marketing, and distribution infrastructure and scale up external manufacturing capabilities to commercialize approved drug candidates.
• Expand, maintain, and protect the intellectual property portfolio.
• Hire additional clinical, regulatory, manufacturing, quality assurance, and scientific personnel.
• Add operational, financial, and management information systems and personnel.
• Commence enrollment of a suite of additional trials in 2026 designed to support potential future registration of bexobrutideg in multiple regulatory jurisdictions.
• May further explore the utility of bexobrutideg in autoimmune and inflammatory diseases with a separate clinical program in 2026, requiring a new IND.
• Expects to define doses to enable a Phase 1b cohort expansion for zelebrudomide in 2026.
• Expects to define doses and potential indications to enable a Phase 1b cohort expansion for NX-1607 in 2026.
• Expects to earn multiple additional preclinical and clinical milestones across three active partnerships in 2026.
• Advance proprietary preclinical programs toward additional INDs, including the pan-mutant BRAF program.
• Continue to invest in and leverage the DEL-AI research engine.
• Explore additional strategic collaborations.

Key Dates

Recommendation

Nurix Therapeutics is making notable scientific and clinical advancements, particularly with bexobrutideg entering a pivotal Phase 2 trial and receiving multiple expedited regulatory designations. The company's DEL-AI platform and strategic collaborations with major pharmaceutical partners like Gilead, Sanofi, and Pfizer are strong assets, providing non-dilutive funding and significant future milestone potential. However, the company's financial performance shows increasing net losses and a growing accumulated deficit, reflecting a high cash burn rate inherent in early-stage biopharmaceutical development. While the recent $234.4 million capital raise provides liquidity for the next 12 months, substantial additional funding will be required for full development and commercialization. The inherent risks of drug development, intense competition, and regulatory uncertainties mean that profitability is still many years away, if ever. Therefore, a 'Hold' recommendation is appropriate, acknowledging the promising pipeline and strategic positioning while recognizing the significant financial and execution risks that temper immediate strong buy sentiment.

Keywords

Targeted Protein Degradation, DEL-AI platform, Bexobrutideg (NX-5948), Zelebrudomide (NX-2127), NX-1607, BTK degrader, CBL-B inhibitor, Degrader Antibody Conjugates (DACs), Oncology, Inflammation, Autoimmune diseases, CLL (Chronic Lymphocytic Leukemia), Waldenstrom's Macroglobulinemia (WM), DLBCL (Diffuse Large B-cell Lymphoma), MCL (Mantle Cell Lymphoma), Solid tumors, Gilead Sciences, Sanofi S.A., Pfizer Inc., Clinical trials, Biopharmaceutical, Drug discovery, Orphan Drug Designation, Fast Track Designation, PRIME Designation, Intellectual Property, SEC filing, 10-K