A New Class of Cancer Drug Enters the Arena

SAN DIEGO, CA – December 03, 2025 – In the persistent and often challenging fight against cancer, a new therapeutic strategy has officially entered the clinical arena. Crinetics Pharmaceuticals announced today that the first patient has been dosed in a trial for CRN09682, a novel drug designed to combat neuroendocrine tumors and other solid tumors that have proven resistant to standard treatments. This milestone is more than just another step in a drug’s development; it marks the clinical debut of an entirely new class of medicine: the nonpeptide drug conjugate (NDC).

This first-in-human study, known as the BRAVESST2 trial, represents a potential paradigm shift in targeted oncology. It’s a moment of cautious optimism for patients and a significant strategic move for the San Diego-based company, which is leveraging its deep expertise in endocrine science to forge a new path into the competitive world of cancer therapy.

The Science of a Precision Strike

At the heart of this innovation is the unique design of CRN09682. It’s engineered to function like a highly sophisticated guided missile, seeking out and destroying cancer cells while minimizing collateral damage to healthy tissue. The drug targets a specific protein found on the surface of certain tumor cells called the somatostatin receptor type 2 (SST2), which is present in about 80% of neuroendocrine tumors (NETs).

Unlike larger antibody-drug conjugates (ADCs) that use bulky proteins as their guidance system, Crinetics' NDC platform uses a small, nonpeptide molecule to find its target. This smaller size is theorized to allow for better penetration into dense tumor tissues. Once the drug’s ligand binds to the SST2 receptor, the tumor cell internalizes it, pulling the entire complex inside like a Trojan horse. Within the cell, a specialized linker is cleaved by cellular enzymes, releasing a potent cytotoxic payload called monomethyl auristatin E (MMAE). MMAE is a well-understood agent that disrupts the cell's internal scaffolding, leading to its arrest and eventual death.

“We developed CRN09682 to address the need for a more efficacious, safer, and convenient targeted therapy for patients with SST2-expressing tumors,” said Stephen Betz, Ph.D., Chief Scientific Officer and Co-Founder of Crinetics. “Dosing the first patient in the Phase 1/2 study marks a major milestone for CRN09682 and our NDC platform as a whole.”

This approach offers a key manufacturing advantage. NDCs are produced through traditional chemical synthesis, a process that is generally more straightforward and scalable than the complex biological manufacturing required for ADCs or the specialized handling needed for radiopharmaceuticals like Lutathera, a current treatment that also targets SST2 but delivers radiation instead of a chemical toxin.

Hope for Patients with Limited Options

The development of CRN09682 addresses a profound unmet need. Neuroendocrine tumors are a diverse group of cancers that can arise throughout the body, often growing slowly but relentlessly. When the disease becomes metastatic, or spreads to other organs, it is generally considered incurable. Patients often cycle through a series of treatments, from somatostatin analogs that primarily manage symptoms to more aggressive therapies that come with significant side effects.

For those whose disease progresses despite these options, the path forward becomes uncertain. This is the specific patient population the BRAVESST2 trial aims to serve: individuals with metastatic or locally advanced disease who have already undergone standard therapies. The trial’s design specifically requires confirmation of SST2 expression via imaging, ensuring that only patients who are most likely to benefit from this targeted mechanism are enrolled.

By delivering a powerful anti-cancer agent directly into the tumor cells, CRN09682 holds the promise of a more potent effect with fewer systemic toxicities, such as the nausea, fatigue, and hair loss commonly associated with traditional chemotherapy. If successful, it could offer a vital new lifeline, potentially improving not only survival but also the quality of life for those battling these difficult cancers.

A Strategic Expansion into Oncology

For Crinetics Pharmaceuticals, this trial marks a pivotal expansion. The company has built its reputation on treating endocrine diseases, successfully bringing PALSONIFY (paltusotine) to market as the first once-daily oral treatment for acromegaly, a rare hormonal disorder. Its pipeline is rich with candidates for other endocrine conditions like congenital adrenal hyperplasia and Cushing’s syndrome.

The move into oncology, while ambitious, is a logical extension of its core competency. The company’s expertise lies in designing small molecules that precisely target G-protein coupled receptors (GPCRs)—a vast family of receptors involved in countless bodily functions. The SST2 receptor targeted by CRN09682 is a member of this very family. In essence, Crinetics is applying its proven platform for endocrine disorders to the complex challenge of cancer.

This strategic diversification is backed by a strong financial position, with the company holding more cash than debt. While still operating at a loss—a common scenario for biotechs heavily investing in research and development—this financial runway is critical for funding long and expensive clinical programs like the BRAVESST2 trial. Successfully developing its NDC platform could transform Crinetics from a specialized endocrine company into a major player in precision oncology, a move closely watched by investors and the broader pharmaceutical industry.

The Road Ahead: What the BRAVESST2 Trial Seeks to Prove

The journey for any new drug is long, and the BRAVESST2 trial is a critical first step on the clinical path for CRN09682. This Phase 1/2 study is designed to answer fundamental questions. The initial Phase 1 portion will focus on safety, with researchers carefully escalating the dose to find the maximum amount that can be administered without unacceptable side effects.

Once a safe and effective dose is determined, the trial will move into its Phase 2 expansion. In this stage, more patients will be treated at the recommended dose to gather further data on safety and, crucially, to get a preliminary look at the drug's anti-tumor activity. Researchers will measure outcomes like tumor shrinkage, the duration of response, and how long patients live without their disease progressing.

With plans to enroll up to 150 participants across multiple sites, the study is a robust undertaking. Its results will provide the first human data on whether the elegant science behind the NDC platform can translate into a meaningful clinical benefit for patients. While the ultimate outcome remains to be seen, the initiation of this trial represents a tangible step forward, embodying the spirit of innovation in the service of those confronting a formidable disease.