Nurix Therapeutics and Gilead Extend Strategic Collaboration with Over $4.1 Billion in Potential Value to Develop Multiple Targeted Protein Degraders

On April 2, 2024, Nurix Therapeutics ("Nurix") announced that the company has extended its ongoing collaboration with Gilead Sciences ("Gilead"). The collaboration began in 2019.Nurix will continue to leverage its proprietary drug discovery platform to develop multiple targeted protein degraders against various targets, and Gilead will have the option to select additional multiple candidate drugs.；The term has been extended by two years based on the previous agreement.

According to the new agreement, NurixWill receive a $15 million extension fee and is eligible for up to $73.5 million in preclinical milestones and potential future licensing payments, as well as a total of up to $1.7 billion.The potential future development, regulatory and sales milestones, and tiered royalties. The two parties will share the development costs, profits, and losses in the United States on a 50/50 basis, and Nurix will be eligible for royalties outside the United States.

In 2019, Gilead Sciences and Nurix Therapeutics reached a multi-year agreement; according to the terms of the agreement, Gilead will have the option to select drug candidates targeting up to five targets; NurixWill receive a prepayment of 45 million US dollars,And is expected to receive payments based on the achievement of drug development, preclinical, clinical, regulatory, and commercialization milestones.Up to Approximately USD 2.3 BillionAdditional PaymentAnd net sales royalties。As of November 2023, Nurix Therapeutics, Inc. has received an additional $70 million, including R&D milestones, the option exercise payment for IRAK4 degrader GS-6791 (NX-0479), and more.。

Part.1

Platform Advantages

Nurix, founded in 2009, owns the unique DELigase targeted protein modulation platform;The DELigase platform is highly differentiated,Can identify and reduceTargeted Protein Degradation (TPD)Or small molecules that increase (TPE) protein levels, also known as targeted protein modulation (TPM).The process.Based on this platform, Nurix can either utilize E3 ligases to degrade specific target proteins (such as BTK CTM) or inhibit specific ligases to increase substrate protein levels (such as CBL-B inhibitors).

Part.2

Pipeline and Key Drug Introduction

The company focuses on developing drugs in the fields of oncology, immuno-oncology, adoptive cell therapy, and immune diseases, and is advancing three internally discovered and wholly-owned clinical-stage drug candidates aimed at treating patients with hematologic malignancies and solid tumors.

Key drugs of the company include:

1、NX-5948：NX-5948 is an orally available BTK degrader, designed without IMiD activity, and is currently under development for the treatment of certain B-cell malignancies and autoimmune diseases. In addition to oncology indications, NX-5948 has been shown to cross the blood-brain barrier in animal models and demonstrated activity in animal models of autoimmune diseases.

The latest data from the Phase 1a/1b clinical trial show that: (1) NX-5948 exhibits dose-dependent pharmacokinetics (PK) with a half-life of approximately 24 hours, supporting once-daily dosing. (2) Rapid and sustained degradation of BTK protein was observed in all patients at three different dose levels (50, 100, and 200 mg). (3) Rapid and sustained degradation of BTK protein was observed in all patients at three different dose levels (50, 100, and 200 mg). (4) NX-5948 demonstrated good tolerability at all tested doses, with no dose-limiting toxicity (DLT) or treatment-related serious adverse events (SAE), and no treatment-emergent adverse events (TEAE) leading to drug discontinuation. Importantly, no atrial fibrillation or hypertension occurred.

2、NX-2127：It is a novel bifunctional molecule capable of degrading BTK, Ikaros (IKZF1), and Aiolos (IKZF3), formed by linking a BTK inhibitor to a CRBN ligand via a linker. It can degrade both wild-type BTK and the BTK C481S variant, intended for treating patients with relapsed or refractory B-cell malignancies.

In 2023At the ASH meeting, Nurix announced positive clinical data for NX-2127, aiming to evaluate the efficacy and safety of NX-2127 in Phase 1a dose escalation and Phase 1b dose expansion cohorts in patients with relapsed or refractory (r/r) B-cell malignancies (CLL, MCL, and DLBCL).

3、NX-0479：Is a selective oral IRAK4 degrader that targets both the scaffolding and kinase functions of the IRAK4 protein kinase, and is capable of blocking toll-like receptors (TLR) and the pro-inflammatory IL-1 cytokine receptor family (IL1Rs) downstream inflammatory responses, showing potential applications in the treatment of rheumatoid arthritis and other inflammatory diseases.

4、NX-1607：Is the first CBL-B inhibitor to enter the clinical stage and is currently undergoing a human, multi-center, open-label, Phase 1a/1b dose escalation/expansion trial to evaluate the safety, tolerability, pharmacokinetics/pharmacodynamics (PK/PD), and preliminary efficacy of the drug. The company expects to present data from the Phase 1a dose escalation portion of the NX-1607 trial in 2024 and determine the dose for Phase 1b cohort expansion.

In March 2024, the company first disclosed the latest research findings and drug structure of NX-1607 at the 2024 ASC. As a molecular glue targeting the CBL-B protein, NX-1607 locks it in a closed and inactive conformation, thereby lowering the threshold for T-cell activation. While improving molecular properties, the drug increases enzyme efficiency by more than 10,000 times; in various models, monotherapy with NX-1607 induces anti-tumor responses; combining NX-1607 with Anti-PD-1 enhances survival across multiple models; additionally, studies show that NX-1607 has good in vitro safety. Preliminary PK data indicates that NX-1607 exhibits dose-proportional exposure, with an average half-life of 6 to 8 hours within the 5 to 50 mg dose range.

Part.3

Cooperation Status

In terms of transactions, exceptApart from Gilead Sciences, the company has also successively reached collaborations with BMS, Sanofi, Seagen, and others., including:

• In September 2023, a deal with Seagen (now acquired by Pfizer) was signed, featuring an upfront payment of $60 million and total milestones worth $3.4 billion, to jointly develop a new class of drug known as Degradation Activating Conjugates (DAC).

• In January 2020, Sanofi and Nurix Therapeutics entered into a global strategic collaboration with a $55 million upfront payment and $2.5 billion in milestone payments to develop innovative targeted protein degradation drugs for challenging diseases across multiple therapeutic areas.

• In September 2015, Nurix entered into a collaboration and license agreement with Celgene (acquired by BMS) to collaborate on cancer, inflammation, and immunotherapy.

Part.4

Financial Status

As of November 30, 2023, the company's full year (12 months)Revenue of $77 million, representing a 99% year-over-year increase from $38.6 million in 2022.；Mainly due to milestone and license option exercise payments from Sanofi and Gilead Sciences related to product development during this period. Research and development expenses were $189.1 million, representing a 2.5% increase compared to $184.5 million in 2022. General and administrative expenses were $42.9 million, an increase of 12.9% compared to $38.0 million in 2022.

As of November 30, 2023,The company's cash, cash equivalents, and marketable securities totaled $295.3 million.。