Crinetics Pharmaceuticals, Inc. (CRNX) Business

Item 1. Business

Business Overview

We are a pharmaceutical company committed to transforming the treatment of endocrine diseases and endocrine-related tumors through science rooted in patient needs. We are focused on discovering, developing, and commercializing novel therapies, with a core expertise in targeting GPCRs with small molecules that have specifically tailored pharmacology and properties.

Our lead product, PALSONIFY (paltusotine), is the first once-daily, oral treatment approved by the FDA for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. Paltusotine is also in clinical development for CS associated with NETs. Our deep pipeline of 10+ disclosed programs includes late-stage investigational candidate atumelnant, which is currently in development for CAH and ADCS, and CRN09682, a NDC candidate that is being developed to treat SST2 expressing NETs and other SST2 expressing solid tumors. Additional discovery programs address a variety of endocrine conditions such as NETs, Graves’ disease (including Graves’ hyperthyroidism and Graves’ orbitopathy, or TED), polycystic kidney disease, hyperparathyroidism, diabetes, obesity, and GPCR-targeted oncology indications.

Approved Product

•On September 25, 2025, the FDA approved PALSONIFY as the first and only once-daily oral somatostatin receptor ligand for the treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option.

Key Pipeline Updates

Paltusotine

•The first patient was enrolled in the Phase 3 study of paltusotine for CS in November 2025.

•In February 2026, the CHMP of the EMA adopted a positive opinion, recommending the marketing authorization of PALSONIFY for the medical treatment of adult patients with acromegaly. The CHMP opinion will be reviewed by the EC, consistent with a timeline for a potential decision in the first half of 2026.

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Atumelnant

•In January 2025, we reported positive results from the first three cohorts of the Phase 2 TouCAHn open-label study of atumelnant in CAH. In January 2026, we provided an update, including data on the fourth cohort of the Phase 2 TouCAHn study and data from the separate OLE study. Participants in all four cohorts were eligible to enroll in the OLE.

•In May 2025, we announced the design of our Phase 3 CALM-CAH study. The first participant in the CALM-CAH study was randomized in December 2025.

•In August 2025, we announced our pediatric trial design in CAH, BALANCE-CAH. BALANCE-CAH is designed as an operationally seamless Phase 2/3 study. The first participant in the BALANCE-CAH study was dosed in January 2026.

•We expect to initiate an operationally seamless Phase 2/3 study of atumelnant in ADCS (EQUILIBRIUM-ADCS) in the first half of 2026.

CRN09682

•In April 2025, we received IND clearance for CRN09682, the first candidate from the NDC platform. In November 2025, the first patient received CRN09682 in the dose escalation phase of a Phase 1/2 study.

Our Strategy

Our mission is to build the world’s leading endocrine company that pioneers new therapeutics to help patients better control their disease and improve their daily lives. To achieve this mission, we are pursuing the following strategy:

•Commercialize our product candidates. PALSONIFY became the first oral nonpeptide SST2-agonist approved by the FDA for the treatment of acromegaly in September 2025 and was commercially available in October 2025 in the U.S. We are establishing a highly specialized and focused commercial organization, including sales, marketing and market access expertise to support the launch of PALSONIFY in the U.S. We continue to execute our launch strategy by educating healthcare providers and patients on the diagnosis and appropriate clinical management of acromegaly and the potential clinical benefits and appropriate use of PALSONIFY.

•We are also activating patients to request PALSONIFY, educating HCPs on PALSONIFY to drive breadth and depth of prescribers and engaging with payers to support patient access to therapy and formulary inclusion of PALSONIFY. We believe PALSONIFY's profile as a once-daily, oral SST2R agonist that is approved to offer biochemical and symptom control and convenience will provide meaningful differentiation in the acromegaly competitive landscape.

•We are building the structure and expertise to commercialize our product candidates in additional markets, including the EU, where we believe we can do this efficiently and effectively, if approved by regulators. In February 2022, we entered into the SKK License pursuant to which SKK has the exclusive right to commercialize paltusotine in Japan. In the future, we may seek relationships with additional global licensing, distribution or other partners for our product candidates where we determine this to be an effective approach.

•Focus on endocrine diseases and endocrine-related tumors with significant unmet medical need. There are numerous endocrine diseases and endocrine-related tumors for which currently available pharmacological therapies (when they exist) have significant limitations in efficacy, safety and/or tolerability. Patients living with these diseases often experience significant morbidity, mortality and/or poor quality of life. We are focused on discovering, developing, and commercializing therapies for multiple indications across endocrinology to advance the standard of care for these patients.

•Rapidly advance multiple product candidates in parallel to clinical proof-of-concept and late-stage development by targeting diseases that employ validated biomarkers as clinical endpoints. Phase 1 clinical trials for endocrine diseases and endocrine-related tumors can often measure predictive biomarkers in healthy volunteers and lower the technical risk by providing a predictive measure of efficacy early in clinical development.

•Continue to expand our therapeutic pipeline for endocrine diseases and endocrine-related tumors by leveraging the capabilities of our experienced discovery team in the area of peptide hormone GPCRs. Our discovery team has significant expertise in understanding and creating product candidates to influence the dynamic behavior of GPCRs and has developed a number of proprietary methods, techniques and tools that we

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believe will enable us to efficiently and reliably evaluate newly synthesized molecules. We employ an iterative strategy where compounds are designed, synthesized, and rapidly characterized for pharmacologic and pharmaceutical properties. This approach has led to our current pipeline, and we will continue to invest in creating additional product candidates acting at this important class of targets. Peptide hormone GPCRs regulate many aspects of physiology and are attractive drug targets for treating a broad range of diseases. There are more than 80 known peptide hormones acting at more than 120 known different receptors. With each of our drug discovery programs, our goal is to specifically tailor a product candidate with pharmacologic and pharmaceutical properties highly optimized for its interaction with its specific GPCR target that we anticipate will translate to downstream benefits in our chosen therapeutic applications. For example, the SST2R ligand in paltusotine is designed to disfavor internalization of SST2R, while the SST2R ligand in CRN09682 is designed to promote internalization.

•Maintain an entrepreneurial, scientifically rigorous, and inclusive corporate culture where employees are fully engaged and strive to bring improved therapeutic options to patients. The patients we seek to treat often have limited treatment options with significant drawbacks and often limited efficacy, safety and/or tolerability. We are passionate about developing new pharmacological therapies to help these patients better control their diseases and to reduce the impact of these diseases on their daily lives. We believe that building a successful and sustainable endocrine company requires not just specific expertise in multiple areas of drug discovery, development, and commercialization, but a team-oriented culture that integrates and harnesses the creative energy, scientific insights and passion of the entire organization.

The Endocrine System

Overview

The endocrine system regulates most of the body’s physiological activities through the actions of hormones, which are chemical and biochemical messengers secreted from different organs that influence growth, gastrointestinal function, maturation and development, reproduction, stress, metabolism and nearly all aspects of homeostasis. Hormonal dysregulation can arise from endocrine organ defects, including injury, inflammation, genetic abnormalities, or the growth of tumors derived from endocrine cells. These insults can result in the under-secretion or over-secretion of one or more hormones, disrupting homeostasis and causing disease. For example, several serious clinical disorders, including acromegaly and Cushing’s disease, result from pituitary tumors secreting excess hormones.

Peptide hormone GPCRs

Various GPCRs are expressed in every type of cell in the body and their function is to transmit signals from outside the cell across the membrane to signaling pathways within the cell, between cells and between organ systems. Because of these critical actions, the GPCR superfamily is the largest and single most important family of drug targets as highlighted by the large number of approved therapeutics targeting this class. However, most currently available GPCR-targeting drugs act as receptors for which the native ligands are small molecules, such as histamine, adrenaline, and neurotransmitters.

Most peptide hormones bind selectively to specific receptors located on the surface of cells in the target tissue. Receptors for peptide hormones are often GPCRs, which play a central role in many biological processes and are linked to a wide range of disease areas. There are more than 80 known peptide hormones acting at more than 120 known different receptors. Historically, it was assumed that small molecules could not replicate or compete with the complex interactions between peptides and their cognate GPCRs. As such, most drugs developed for peptide GPCRs have been and continue to be peptides themselves, which present manufacturing and formulation difficulties and force patients to undergo frequent injections because peptides generally are not orally bioavailable. We believe our approach to developing novel small molecule product candidates that uniquely engage peptide hormone GPCRs will enable us to generate orally bioavailable, and potentially more selective, effective and better tolerated therapeutics for patients.

GPCRs were originally thought to function as simple on-off switches responding to hormones and neurotransmitters but have since been shown to exhibit complex and diverse molecular and cellular behaviors. Many lines of structural and mechanistic research demonstrate that distinct signaling cascades and feedback mechanisms create multi-dimensional pathways with distinct physiological responses. These different responses are based on ligand binding kinetics, receptor regulation and trafficking. Some transduce signals into the cell interior to regulate various cellular functions. Other responses attenuate hormonal signals to prevent overstimulation and include receptor internalization (a removal of the GPCR from the cell surface, which makes it unavailable for external ligands), desensitization and downregulation. We believe our understanding of these different signaling pathways enables us to develop oral, small molecule product candidates that not only are highly selective for specific receptor subtypes but also are further custom-tailored to activate specific GPCR properties and ultimately improve patient outcomes.

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Product Pipeline Summary

All of our product candidates have been discovered and developed internally and we have retained global rights to commercialize our product candidates and have no royalty or licensing obligations, other than the licenses and collaborations discussed under “Our Strategic Collaborations” herein.

The following table summarizes our current product candidate pipeline.

Our Products and Product Candidates

We focus on the discovery and development of nonpeptide therapeutics that target peptide GPCRs with well-understood biological functions, validated biomarkers and the potential to substantially improve the treatment of endocrine diseases and endocrine-related tumors.

Paltusotine (SST2 Agonist Program)

Acromegaly Disease Background

Acromegaly is a serious chronic endocrine disorder typically caused by a pituitary tumor that secretes excess GH. Pituitary tumors are generally benign adenomas that, in addition to GH secretion, also express membrane receptors for somatostatin. Increased GH secretion results in excess downstream secretion of IGF-1 from the liver. GH and IGF-1 promote tissue growth and have other metabolic effects throughout the body.

The consequences of chronically elevated GH and IGF-1 can be severe, including changes in facial features, enlargement of the hands and feet, and carpal tunnel syndrome. Enlargement of the heart can lead to congestive heart failure and these excess hormones also induce insulin resistance, hypertension, and other negative clinical consequences.

From the perspective of someone living with acromegaly, the physical changes in their appearance, not to mention the sweating and skin changes, can be alarming and socially isolating. Severe headaches, fatigue, joint pain, and peripheral neuropathies can be debilitating. Additional symptoms can include thick, coarse, oily skin, skin tags, excessive sweating and skin odor, fatigue and weakness, headaches, goiter, decreased libido, menstrual abnormalities in women and erectile

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dysfunction in men. As the tumor grows, it can impinge on the nerves in the optic chiasm leading to visual problems and potentially vision loss. Compression of the surrounding normal pituitary tissues can decrease production of other pituitary hormones, resulting in hypopituitarism. Acromegaly patients experience increased mortality rates, principally due to cardiovascular diseases (diabetes, hypertension), respiratory disease and cerebrovascular diseases.

Acromegaly is often suspected when the patient exhibits enlargement of extremities and an alteration of facial features. Pituitary tumors are also often found during clinical workup for severe headaches, vision changes or incidentally on cranial imaging initiated for other reasons. Elevation of serum IGF-1 levels confirms the suspicion of acromegaly, but a formal diagnosis requires lack of suppression of serum GH levels in response to an oral glucose tolerance test. A magnetic resonance imaging (MRI) or computerized tomography (CT) scan of the pituitary is then used to locate the tumor, determine its size and assess the potential for surgical intervention. Unfortunately, for many patients, it can take 5 to 10 years to reach a diagnosis.

Our research suggests that there are approximately 36,000 people living with acromegaly in the U.S., of which 17,000 or more are undiagnosed, 7,500 are not in active follow-up for treatment, and 11,500 are actively managed. Our research further suggests that of the 11,500 actively managed patients in the U.S., 40% are treatment naïve, 25% are on injectable somatostatin receptor ligands, 20% are on other therapies, and 15% have discontinued treatment. Our research also indicates that there are approximately 1,500 newly diagnosed patients per year, 500 of which are candidates to initiate pharmaceutical treatment.

Acromegaly Clinical Development Program

PALSONIFY, is the first once-daily, oral treatment approved by the FDA in the U.S. for the first-line treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. Paltusotine is also in clinical development for CS associated with neuroendocrine tumors.

Paltusotine establishes a new class of oral selective nonpeptide SST2 agonists designed for the treatment of adults with acromegaly and CS due to well-differentiated neuroendocrine tumors. Somatostatin is a neuropeptide hormone that broadly inhibits the secretion of other hormones, including GH from the pituitary gland.

Our Phase 3 development program for paltusotine in acromegaly consisted of two placebo-controlled clinical trials, PATHFNDR-1 and PATHFNDR-2. The PATHFNDR-1 trial was designed as a double-blind, placebo-controlled, nine-month clinical trial of paltusotine in acromegaly patients with average IGF-1 levels less than or equal to 1.0 times the ULN and who had been on stable doses of somatostatin receptor ligand monotherapy (octreotide LAR or lanreotide depot). We also conducted a second study, the PATHFNDR-2 trial, which was designed as a double-blind, placebo-controlled, six-month clinical trial of acromegaly patients who were not on pharmacological treatment and had elevated IGF-1 levels. The primary endpoint of both PATHFNDR studies was the proportion of patients with IGF-1 ≤ 1.0 ×ULN at the end of the treatment period on paltusotine as compared to placebo.

Positive topline data from the randomized controlled portion of the PATHFNDR-1 study was reported in September 2023, where the primary endpoint and all secondary endpoints of the study were achieved. Additionally, in the PATHFNDR-1 study, paltusotine was well tolerated and no serious or severe adverse events were reported in participants treated with paltusotine.

In March 2024, we reported positive topline results from the PATHFNDR-2 study. The study met statistical significance (p0.0001) on the primary endpoint, and all secondary endpoints. Additionally, in PATHFNDR-2, paltusotine was generally well-tolerated and no serious adverse events were reported in participants treated with paltusotine.

The OLE phases of both PATHFNDR trials are ongoing. In July 2025, we presented open-label extension data from both the pivotal PATHFNDR-1 and PATHFNDR-2 trials in two presentations, showing the long-term clinical profile of PALSONIFY in people with acromegaly.

Data from the PATHFNDR-1 OLE demonstrated that mean insulin-like IGF-1 levels remained stable with IGF-1 (mean ± SE) of 0.93 ± 0.22 at OLE baseline and 0.81 ± 0.21 times the ULN at Week 96, demonstrating durable biochemical control over this time span. Symptom control, as measured by the ASD, and GH level also remained stable at Week 96. PALSONIFY was generally well tolerated.

Data from the PATHFNDR-2 OLE demonstrated that patients with placebo during the RC portion of the study and then transitioned to paltusotine experienced sustained reductions in IGF-1, with a mean change from baseline of –0.81 × ULN at Week 84 (n=39). Direct-to-OLE participants (n=9) showed similar reductions (–0.75 × ULN), while those who had been treated with PALSONIFY during the RC phase (n=40) maintained control (mean change –0.01 × ULN). GH, ASD symptom scores and pituitary tumor size were durably controlled over the study period. PALSONIFY was generally well tolerated.

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On September 25, 2025, the FDA approved PALSONIFY for the first-line treatment of adults with acromegaly who had an inadequate response to surgery and/or for whom surgery is not an option. The FDA has granted orphan drug designation for paltusotine for the treatment of acromegaly. We believe that the results of the clinical trials of paltusotine could support marketing applications outside the U.S. for the use of paltusotine for all acromegaly patients who require pharmacotherapy, including untreated patients and those switching from other therapies.

In February 2025, the EMA, granted paltusotine orphan drug designation for the treatment of acromegaly. Designation was given following a positive recommendation from the EMA Committee for Orphan Medicinal Products, highlighting the potential impact of paltusotine for acromegaly patients in the European Union. The EMA validated the MAA in March 2025. The EMA also granted ODD for paltusotine for the treatment of acromegaly, further highlighting the level of unmet need and the potential for paltusotine to offer significant benefit to patients. In February 2026, CHMP of the EMA adopted a positive opinion, recommending the marketing authorization of PALSONIFY for the medical treatment of adult patients with acromegaly. The CHMP opinion will be reviewed by the EC, consistent with a timeline for a potential decision in the first half of 2026. Paltusotine is also in development for acromegaly in Japan through our licensing agreement with SKK.

To date, our clinical trials have shown that paltusotine was generally well tolerated among healthy adults and patients with acromegaly.

CS Disease Background

NENs are comprised of NECs, which are poorly differentiated and highly proliferative, with rapid disease progression; and NETs, which are well differentiated and generally slow-growing. NETs represent 80-90% of NENs and include tumors with a broad range of disease characteristics depending on site, grade and other features. NETs most commonly originate from the gastrointestinal tract, lungs and pancreas, and approximately 75% of NETs express SST2 receptors, with higher rates of expression in well-differentiated NETs.

Many NETs are well differentiated and exhibit indolent growth, frequently remaining asymptomatic for prolonged periods. As a result, a significant proportion of patients are diagnosed at an advanced or metastatic stage, often with liver metastases that can drive morbidity and mortality. A subset of NETs are functional, meaning they secrete hormones or other biologically active substances and are associated with corresponding symptoms. Approximately one-fifth of NETs cases are associated with excess serotonin secretion, leading to CS. The key debilitating symptoms of CS are cutaneous flushing (90% of cases) and chronic diarrhea (60-80% of cases). Patients with CS may also present with related systemic symptoms, including mesenteric fibrosis, abdominal pain, carcinoid heart disease and other symptoms.

We estimate that 28,000-51,000 adults diagnosed with NETs are undergoing medical management. Of these, it is estimated that approximately 18,000-34,000 are candidates for treatment with paltusotine, if it is approved for the treatment of CS.

CS Clinical Development Program

In March 2024, we reported positive topline results from our randomized, open-label, parallel group, multi-center Phase 2 study to assess safety, tolerability, pharmacokinetics, and efficacy of paltusotine in people living with CS. A total of 36 participants were randomized to receive either 40 mg (n=18) or 80 mg (n=18) of paltusotine for eight weeks, with the ability to adjust dose based on tolerability or inadequate control of symptoms during the first four weeks of treatment. Results demonstrated that administration of paltusotine resulted in rapid and sustained reductions in bowel movement frequency and flushing episodes. Paltusotine was generally well-tolerated with a safety profile consistent with prior clinical studies, with no treatment-related severe or serious adverse events.

Patients from the Phase 2 study were eligible to enroll in an open-label extension study of paltusotine in CS. In November 2025, we shared one-year investigator-assessed PFS data from the open-label study, which showed a PFS rate of 74% following one year of treatment.

The Phase 3 CAREFNDR study is designed to evaluate the safety and efficacy of paltusotine in patients with CS. The first patient in the CAREFNDR study was dosed in November 2025 and we continue to activate additional sites. CAREFNDR is designed as a double-blind, placebo-controlled, sixteen-week clinical trial to enroll CS patients (who may or may not be on pharmacological treatment at baseline) and are actively symptomatic. The primary endpoint of the CAREFNDR trial is the percentage change from baseline in the frequency of flushing episodes at week 12. In addition, a key secondary endpoint measures the change from baseline in bowel movement frequency at week 12. The CAREFNDR trial is designed to capture other efficacy endpoints including severity of flushing and urgency of bowel movements. Following the 16-week randomized controlled period, the trial will include a 104-week OLE to evaluate long-term efficacy, safety and additional clinical outcomes. The OLE will include an exploratory assessment of tumor control.

To date, our clinical trials have shown that paltusotine was generally well tolerated among healthy adults and patients with CS.

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Atumelnant (ACTH Antagonist)

Atumelnant is our investigational, orally available, nonpeptide product candidate designed to block the action of ACTH on the ACTH receptor. It is intended for the treatment of diseases caused by excess ACTH, including CAH and ADCS, which includes patients with either Cushing's disease or EAS.

We conducted a double-blind, randomized, placebo-controlled Phase 1 study of atumelnant in healthy volunteers to assess the safety and tolerability of single and multiple doses of atumelnant. In addition, the study was designed to measure the effect of atumelnant on suppression of cortisol, cortisol precursors, and adrenal androgens following exogenous ACTH stimulation. In May 2022, we announced positive topline data from the Phase 1 study in healthy volunteers which showed atumelnant was well tolerated and demonstrated dose-dependent increases in atumelnant plasma concentrations. We believe atumelnant demonstrated pharmacologic proof-of-concept, as the Phase 1 results showed dose-dependent reductions of both basal cortisol and elevated cortisol following an ACTH challenge. All adverse events were considered mild to moderate and there were no serious adverse events.

CAH encompasses a set of disorders that are caused by genetic mutations that result in impaired cortisol synthesis. A lack of cortisol leads to a breakdown of feedback mechanisms and results in persistently high levels of ACTH, which, in turn, causes overstimulation of the adrenal cortex. The resulting adrenal hyperplasia and over-secretion of other steroids (particularly androgens) and steroid precursors can lead to a variety of effects from improper gonadal development to life-threatening dysregulation of mineralocorticoids. We estimate that approximately 17,000 patients are potential candidates for treatment with atumelnant, 12,000 of which are adults and 5,000 of which are pediatric.

Cushing’s disease results from a pituitary tumor that secretes excess ACTH, and EAS results from non-pituitary ectopic tumors which secrete ACTH. The excess secretion of ACTH causes the downstream synthesis and over-secretion of cortisol by the adrenal glands. Cortisol is the body’s main stress hormone and excess amounts can cause significant increases in mortality and morbidity. We estimate there are over 11,000 patients with Cushing’s disease in the U.S., of which approximately 5,000 patients are potential candidates for treatment with atumelnant.

CAH Disease Background

CAH encompasses a set of disorders that are caused by genetic mutations that result in impaired cortisol synthesis. This lack of cortisol leads to a breakdown of feedback mechanisms and results in persistently high levels of ACTH, which in turn causes overstimulation of the adrenal cortex. The resulting adrenal hyperplasia and over-secretion of other steroids (particularly androgens) and steroid precursors can lead to a variety of effects from improper gonadal development to life-threatening dysregulation of mineralocorticoids. CAH patients have a two-fold risk of bone fractures compared to the general population and commonly suffer from hypercholesterolemia, insulin resistance, and hypertension. Compared to the general population, CAH patients have a diminished life expectancy of 7 years, and more than 20% of CAH patients will die of a condition complicated by adrenal crisis.

Treatment goals for adults with CAH include:

•Reduce A4 and other androgens to address hyperandrogenism, which can manifest as excessive facial hair, acne and polycythemia;

•Restore normal menstrual cycles and fertility in women;

•Shrink testicular adrenal rest tumors, alleviate pain and restore fertility in men; and

•Eliminate excessive exposure to glucocorticoids to minimize steroid therapy related adverse effects including weight gain, cardiovascular issues, diabetes, and osteoporosis.

CAH is an orphan indication with an estimated prevalence of approximately 17,000 patients in the U.S., of which 12,000 are adult and 5,000 are pediatric.

CAH Clinical Development Program

We conducted the TouCAHn Phase 2 study of atumelnant in adult CAH patients. This open-label study was designed to evaluate the safety, efficacy, and pharmacokinetics of different doses of atumelnant. In addition, biomarkers, including serum A4 and 17 hydroxyprogesterone (17-OHP), were measured to evaluate the potential efficacy of atumelnant. We reported positive initial findings from our Phase 2 study in June 2024 and topline data from 28 patients in January 2025. Atumelnant administration was shown to result in rapid, substantial and sustained statistically significant reduction in A4 levels, the key biomarker for disease control, and demonstrated significant clinical improvements. Atumelnant demonstrated statistically significant reductions of A4 at the first 2-week time point in all dose groups (40 mg, 80 mg, and 120 mg). These effects were sustained through the 12-week prespecified primary endpoint where the degree of suppression

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was dose dependent and statistically significant. The data showed that atumelnant was well-tolerated with no treatment-related severe or serious adverse events.

We have continued progress on the development program for atumelnant across multiple trials. In January 2026, we presented additional data from the Phase 2 study of atumelnant in adults with CAH. The update included data from the fourth cohort (n=10, 12-week study); two participants withdrew consent for administrative reasons. The participants received atumelnant (80 mg) once daily in the morning and underwent GC dose reduction toward physiologic levels (11 mg/m2/day HC or equivalent) in weeks 2 to 10. Treatment with atumelnant resulted in rapid, sustained lowering of A4 (in all 8 patients that completed the fourth cohort). Seven out of these 8 patients continued to maintain lower A4 after glucocorticoid doses were reduced to physiologic levels. Atumelnant was well-tolerated with no serious adverse events and no treatment-related severe adverse events. No participants discontinued due to adverse events. No patients experienced hepatic transaminase adverse events. Participants from this study were given the option to enroll in our open-label extension study.

We have initiated a Phase 3 study (CALM-CAH) in adult CAH patients, with first participant randomized in December 2025. The study has an uncompromising primary endpoint to demonstrate atumelnant’s potential ability to normalize A4 levels while patients are on physiological doses of GC replacement. CALM-CAH is designed as a Phase 3 double-blind, placebo-controlled, thirty two-week clinical trial to enroll patients with CAH. The primary endpoint of the CALM-CAH trial is the proportion of participants with A4 ≤ULN (upper limit of normal) who are on physiologic GC replacement at week 32. The CALM-CAH trial is also designed to evaluate the impact of atumelnant on the clinical signs, symptoms, co-morbidities and outcomes of CAH. The participants in the CALM-CAH can roll into the open-label extension study referenced above.

In January 2026, we presented a data snapshot with limited source data verification from the first 7 patients in the OLE to have completed at least 13 weeks. Those data showed both serum A4 reductions and GC dose reductions that were in line with those seen in Cohort 4. Additionally, investigators have not observed any serious adverse events or any treatment-related severe adverse events, and have not observed any hepatic transaminase adverse events to date with 25 patients enrolled and with 7 participants who have completed over 20 weeks of treatment in the study.

The BALANCE-CAH pediatric study is a seamlessly-operational Phase 2/3 study, and the first patient was dosed in January 2026. The Phase 2 is an open-label, semi-sequential cohort study to evaluate the safety, efficacy, and PK of atumelnant treatment in pediatric participants with classic CAH. The Phase 3 is a double-blind, placebo-controlled confirmatory portion of the study to evaluate the safety and efficacy of atumelnant in pediatric participants with classic CAH. Pediatric participants that completed participation in either Phase 2 or Phase 3 of this study will be eligible to enroll in the OLE, a single-arm, open-label, long-term safety and efficacy study. The primary endpoint in the Phase 2 portion is change from baseline in morning serum A4 at Week 8, and the primary endpoint in the Phase 3 portion is the percent change from baseline in GC daily dose at Week 28 while serum early morning A4 is less than the upper limit of normal.

ACTH-Dependent Cushing's Syndrome Disease Background

Cushing’s syndrome results from a prolonged exposure to elevated levels of glucocorticoids, particularly cortisol. Common signs include growth of fat pads (above the collarbone and on back of the neck), abdominal obesity, facial fat accumulation, excessive sweating, dilation of capillaries, thinning of the skin, muscle weakness, hirsutism, depression/anxiety, hypertension, osteoporosis, insulin resistance and hyperglycemia, heart disease and a range of other metabolic disturbances resulting in high morbidity. While excessive synthetic steroid administration or adrenal tumors can cause ACTH-independent forms of the disease, ACTH dependent Cushing’s syndrome (which includes Cushing’s disease and Ectopic ACTH Syndrome) is the most common form, accounting for 60-80% of all cases. Cushing’s disease is caused by tumors of pituitary corticotroph cells that secrete excess ACTH. EAS is caused by tumors outside the pituitary gland that secrete excess ACTH.

EAS is a rare disorder that results from non-pituitary tumors that secrete excessive amounts of ACTH. The supraphysiological degree of ACTH secretion in EAS can vary with effects that range from cushingoid to acutely life-threatening. Treatment options for EAS are limited, with the first goal being surgical removal of the tumors, if possible. If surgery is not an option, medical therapy may be used to block cortisol production. And in some cases, adrenalectomy is required if the tumor cannot be located and medical therapy does not fully block the cortisol.

Cushing’s disease is an orphan indication with a prevalence of approximately 11,000 patients in the U.S. It presents more commonly in women, and usually between 30 and 50 years of age. Cushing’s disease often takes many years to diagnose and may well be under-diagnosed in the general population as many of its symptoms such as lethargy, depression, obesity, hypertension, hirsutism and menstrual irregularity can be incorrectly attributed to other more common disorders.

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ACTH-Dependent Cushing’s Syndrome Clinical Development Program

Atumelnant is currently being studied in patients with ADCS, including those with Cushing's disease and Ectopic ACTH Syndrome, in an open-label, multiple-ascending dose Phase 1b/2a trial. This single-center, in-patient study is in collaboration with the NIDDK of the NIH. The ten-day study is designed to evaluate safety, tolerability, and pharmacokinetics of different doses of atumelnant in patients with ADCS as well as to measure 24-hour urinary-free cortisol and serum cortisol as indicators of efficacy. We reported positive initial findings from the study in June 2024, and the study remains ongoing. We expect to initiate an operationally seamless Phase 2/3 study of atumelnant in ADCS (EQUILIBRIUM-ADCS) in the first half of 2026. The Phase 2 is a double-blind, placebo-controlled study, and will inform dose selection for the Phase 3 double-blind placebo-controlled part of the study. Participants that participate in either the Phase 2 or Phase 3 portion will be eligible to enroll in the OLE, a single-arm, open-label, long-term safety and efficacy part of the study.

CRN09682 (non-peptide drug conjugate for SST2 positive solid tumors)

We have developed a first-in-class, non-peptide, non-radioactive NDC linking an SST2 agonist with the cytotoxic drug MMAE, via a spacer and a cleavable linker for the treatment of NETs and potentially for use in other solid tumors that express SST2, or SST2+ tumors. CRN09682 is designed to selectively deliver MMAE to SST2-expressing tumor cells, such that the delivery of MMAE is directed to the SST2 expressing tumors to drive antitumor activity, while minimizing the uptake of the conjugate in other tissues that do not express or express low levels of SST2.

Measurement of CRN09682 and MMAE levels in tumor tissues from mice bearing small-cell lung cancer (NCI-H524 SCLC CDX) demonstrated high tumor uptake for CRN09682 and prolonged MMAE tumor exposure, relative to MMAE in plasma and CRN09682 in plasma. These in vitro data suggest that CRN09682 inhibits cancer cell proliferation upon selective SST2 activation and internalization of CRN09682.

SST2-Positive Solid Tumor Disease Background

NENs arise across multiple organs and vary widely in behavior, with treatment guided by tumor grade and differentiation. Disease severity ranges from well‑differentiated, indolent NETs to poorly differentiated, highly aggressive NECs, including SCLC. Well‑differentiated tumors generally exhibit higher SST2 expression and are often associated with better outcomes. Approximately 75% of NET patients express SST2, with higher, more consistent expression in well-differentiated, low-grade, and GEP-NETs. Poorly differentiated NECs typically exhibit lower SST2 expression and are linked to more aggressive disease and poorer prognoses.

NENs often present at advanced, incurable stages, with more than half of cases metastatic, typically to the liver. They are classified as functional or nonfunctional based on symptoms or hormone hypersecretion; for example, CS results from excess serotonin production.

Patients with locoregional and resectable tumors often undergo surgery as a first step. Those with metastatic or unresectable tumors may undergo medical management for symptom and/or tumor control. Medical management may commonly include SSAs, PRRT, chemotherapy, or kinase / mTOR inhibitors.

We estimate that 28,000 to 51,000 patients with NENs receive medical management, of which an estimated 11,000 to 21,000 seek treatment for tumor control and represent the initial addressable population for CRN09682. Additional SST2‑expressing tumors—such as SCLC, meningioma, head and neck cancer, and breast cancer—may further expand the number of patients who could benefit from CRN09682.

SST2-Positive Solid Tumors Clinical Development Program

We received IND clearance for CRN09682, the first candidate from our NDC platform, along with a “Study May Proceed” letter authorizing initiation of a Phase 1/2 study in metastatic or locally advanced SST2‑positive neuroendocrine tumors and other SST2‑expressing solid tumors. In November 2025, the first patient was dosed in our BRAVESST2 Phase 1/2 study.

During the Phase 1 dose‑escalation stage, we plan to enroll 3–6 patients per ascending dose cohort until the maximum tolerated dose is established. Results from this stage will guide selection of the recommended expansion dose for Phase 2 and determine the tumor sub‑types to include in the expansion cohorts. Across both phases, we expect to enroll up to 150 participants.

Early Stage Product Pipeline Summary

In addition to our clinical stage pipeline, we have several preclinical candidates in development. We may provide updates on these molecules from time to time or if and when they have received IND clearance.

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Research Discovery

Patients with many other debilitating endocrine diseases and endocrine related tumors await new therapeutic options, and we continuously evaluate and prioritize where to deploy our drug discovery efforts. We plan to continue to expand our drug discovery efforts and leverage our expertise in the evaluation of additional unmet medical needs. Our drug discovery and development efforts are focused on endocrine, metabolism, and targeted therapies.

Endocrine: Our deep understanding of endocrine systems and patient needs have produced a robust pipeline of transformative novel molecules that are purposefully designed to meet the needs of patients. We focus on developing innovative nonpeptide drug candidates with unique methods of action, targeting particular endocrine pathways, including non-traditional ones, where modulating irregular hormone secretion can lead to improving conditions that significantly impact patients’ lives.

Metabolism: Metabolic disorders including diabetes, obesity, and others impact the lives of hundreds of millions of people across the world and their effects on patients are significant and varied. Many of these disorders are a result of the dysregulation of key metabolic hormones, including insulin, glucagon, glucagon-like peptide-1, gastric inhibitory polypeptide, and others. Crinetics’ understanding of these hormonal pathways and the GPCRs that control them coupled with our expertise in developing nonpeptides with specific pharmacologies allows us to create new molecules with the chance to improve the lives of patients with metabolic diseases.

Targeted Therapies: Our efforts in precision oncology began with developing nonpeptide, GPCR-targeted radioligands for the imaging and treatment of a broad range of endocrine receptor-driven cancers, ultimately leading to the formation of Radionetics in 2021. Our continued dedication to this concept has led to our latest novel development program that is exploring a new modality known as NDCs, a unique therapeutic approach that leverages endocrine receptors for highly selective targeting of anti-tumor agents.

Product Competition for Clinical Stage Candidates

The commercialization of new drugs is competitive, and we could face competition from a number of pharmaceutical or biotechnology companies around the world. Our commercial opportunity could be reduced or eliminated if our competitors develop and commercialize products that are safer, more effective, have fewer or less severe side effects or are more convenient than any products that we may develop. Our competitors also may obtain FDA or other regulatory approval for their products more rapidly than we do. The key competitive factors affecting the success of all of our programs are likely to be their efficacy, safety and convenience. See "Risk Factors – Risks related to commercialization of PALSONIFY and our product candidates."

Acromegaly

The major goals of treatment are to reduce serum GH and normalize IGF-1 levels, ameliorate symptoms, and reduce or stabilize the pituitary tumors that cause acromegaly. Surgical removal of the pituitary tumor is usually the first treatment and can result in long-term remission if the tumor is fully resected. For those for whom surgery is not an option and those whose tumors are not able to be completely removed, standard pharmacotherapy has historically consisted of peptide somatostatin receptor ligands, a GH receptor antagonist, and off-label use of dopamine agonists.

There are three injected somatostatin analogs approved for the treatment of acromegaly: octreotide (marketed by Novartis AG), lanreotide (marketed by Ipsen Biopharmaceuticals, Inc.) and pasireotide (marketed by Recordati Rare Diseases Inc.). Oral octreotide (marketed by Chiesi Farmaceutici) is approved in the U.S. for long-term maintenance treatment in acromegaly patients who have responded to and tolerated treatment with octreotide or lanreotide. Pegvisomant (marketed by Pfizer Inc.) is a daily injectable GHRA and is generally used in patients not fully controlled on somatostatin analogs. Orally administered dopamine agonists, such as bromocriptine and cabergoline, are also used. In December 2021, the FDA approved a biosimilar of lanreotide injection, followed by the approval of a generic lanreotide injection in May 2024 for the treatment of acromegaly, CS, and GEP-NETs. Both products are manufactured by Cipla Ltd. Additionally, in December 2023, the FDA approved an octreotide acetate injectable suspension for treating acromegaly and CS. Other products in clinical development include new formulations of peptide somatostatin agonists (Camurus AB), GH receptor antagonists (Alexion Pharmaceuticals, Inc./AstraZeneca PLC) and anti-GHRA monoclonal antibodies (Marea Therapeutics).

NETs/CS

Long-acting injectable formulations of peptide SSAs are also routinely used in the treatment of NETs to control symptoms associated with hormone hypersecretion and to slow tumor growth in patients with well-differentiated disease. For adults with CS whose symptoms are inadequately controlled by somatostatin therapy alone, telotristat ethyl (marketed by TerSera Therapeutics, Inc.) is available as an orally administered add-on therapy to reduce serotonin-mediated symptoms.

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For patients with advanced or metastatic NETs, additional systemic treatment options include peptide receptor radionuclide therapy (PRRT), cytotoxic chemotherapy, and targeted therapies such as mTOR inhibitors and tyrosine kinase inhibitors. However, there is no established consensus regarding optimal treatment sequencing. PRRT is constrained by a limited number of lifetime treatment cycles and is associated with manufacturing, logistical, and administration complexities. Chemotherapy agents lack tumor specificity and generally produce transient responses with cumulative toxicity. Targeted therapies typically provide modest and largely cytostatic clinical benefit, with limited durability of response and the development of treatment resistance during chronic administration.

More recent approvals for the treatment of NETs include FDA approval of Novartis’ Lutathera for the treatment of somatostatin receptor-positive GEP-NETs in 2018, and Exelexis’ Cabometyx for the treatment of previously treated NETs in 2025. Other companies developing NETs therapeutics that target somatostatin receptors include Oranomed/RadioMedix, ASCIL Biopharm, RayzeBio, Molecular Targeting Technologies Inc., Perspective Therapeutics, and Immunwork Inc. Camurus, Chiesi Farmaceutici, POINT Biopharma Global Inc., RayzeBio, and ITM Isotopen Technologien Munchen are currently engaged in Phase 3 trials of new compounds for use in the treatment of NETs.

CAH

The current treatment algorithm for CAH consists of lifelong daily glucocorticoid supplementation which attempts to address the body's inability to synthesize cortisol as well as its over-production of androgens that results from misregulated steroidogenesis. The inability to precisely dose glucocorticoids can often lead to enduring cycles of over- or under-treatment. Under-treatment can result in adrenal crisis and intramuscular stress doses of glucocorticoid for acute illness are common.

In December 2024, the FDA approved an oral CRF1 receptor antagonist, crinecerfont (marketed by Neurocrine Biosciences) as an adjunctive treatment of classic congenital adrenal hyperplasia. Neurocrine Biosciences is also developing a peptide CRF receptor antagonist for CAH. Other companies developing products for potential use in CAH include Lundbeck Pharmaceuticals, and OMass Therapeutics.

ACTH-Dependent Cushing's Syndrome

As with acromegaly, first-line therapy for Cushing’s disease is surgery to remove the pituitary tumor if possible. The use of adrenal enzyme inhibitors (metyrapone, ketoconazole and more recently levoketoconazole which gained FDA approval in December 2021 and is marketed by Xeris Pharmaceuticals) prevent the synthesis of cortisol and can improve symptoms. Mifepristone (marketed by Corcept Therapeutics, Inc.), a glucocorticoid receptor antagonist, is approved for control of hyperglycemia in Cushing’s syndrome. A generic form of mifepristone has been approved for the treatment of endogenous Cushing’s syndrome. Osilodrostat (marketed by Recordati Rare Diseases Inc.), a cortisol synthesis inhibitor, is approved for the treatment of endogenous Cushing’s syndrome. The somatostatin agonist pasireotide is also approved for Cushing’s disease. Other companies developing products for potential use in Cushing’s disease include Corcept Therapeutics, Inc., Sparrow Pharmaceuticals, and Lundbeck Pharmaceuticals.

Earlier Stage Clinical Programs

There may be other earlier-stage clinical programs that, if approved, would compete with our products. Many of our competitors have substantially greater financial, technical and human resources than we have. Additional mergers and acquisitions in the pharmaceutical industry may result in even more resources being concentrated on our competitors. Competition may increase further as a result of advances made in the commercial applicability of technologies and greater availability of capital for investment in these fields. Our success will be based in part on our ability to build and actively manage a portfolio of drugs that address unmet medical needs and create value in patient therapy.

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Our Strategic Collaborations

Radionetics Oncology, Inc.

We formed Radionetics in October 2021, together with other investors. Radionetics aims to develop a deep pipeline of novel, targeted, nonpeptide radiopharmaceuticals for the treatment of a broad range of oncology indications. In connection with the formation of Radionetics, we entered into the Radionetics License, granting Radionetics an exclusive world-wide license to certain targets for the development of radiotherapeutics and related radio-imaging agents. As of December 31, 2025, we had an approximate 25% ownership stake in Radionetics consisting of common and preferred stock.

Sanwa Kagaku Kenkyusho Co., Ltd.

In February 2022, we and SKK entered into the SKK License, pursuant to which we granted SKK an exclusive license to develop and commercialize paltusotine in Japan.

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On June 14, 2022, we and SKK entered into the SKK Clinical Supply Agreement, whereby we are responsible for manufacturing and supplying certain materials to SKK for specified activities under the SKK License.

Loyal License Agreement

On March 24, 2023, we and Loyal entered into the Loyal License, pursuant to which we granted Loyal an exclusive license to develop and commercialize CRN01941, a somatostatin receptor type 2 agonist, for veterinary use.

Intellectual Property

We actively protect our commercially important proprietary technology by, among other methods, obtaining, maintaining, and defending our patent rights. Issued patents can provide protection for varying periods of time, depending upon the date of filing of the patent application, the date of patent issuance and the legal term of patents in the countries in which they are obtained. In general, patents issued for applications filed in the U.S. can provide exclusionary rights for 20 years from the earliest effective non-provisional filing date. In addition, in certain instances, the term of an issued U.S. patent that covers or claims an FDA approved product can be extended to recapture a portion of the term effectively lost as a result of the FDA regulatory review period, which is called patent term extension. The period of patent term extension in the U.S. cannot be longer than five years and the total patent term, including the extension period, must not exceed 14 years following FDA approval of the product. The term of patents outside of the U.S. varies in accordance with the laws of the foreign jurisdiction, but typically is also 20 years from the earliest effective non-provisional filing date. However, the actual protection afforded by a patent varies on a product-by-product basis, from country-to-country, and depends upon many factors, including the type of patent, the scope of its coverage, the availability of regulatory-related extensions, the availability of legal remedies in a particular country and the validity and enforceability of the patent. Some countries also provide mechanisms to recapture a portion of the patent term lost during regulatory review, similar to patent term extension in the U.S.. The amount of patent term that can be recaptured depends on the laws of the relevant jurisdictions. There is no guarantee that the applicable authorities, including the USPTO in the U.S., will agree with our assessment of whether such extensions should be granted, and if granted, the length of such extensions. For more information regarding the risks related to our intellectual property, see “Risk Factors – Risks related to our intellectual property.”

We have filed numerous patent applications covering our internally developed product candidates in the U.S. and in jurisdictions outside of the U.S., resulting in multiple issued patents. We file patent applications geographically broadly, in multiple pharmaceutical markets and in alignment with our commercial strategy. We pursue patent protection for inventions and improvements throughout development, including, when possible, compositions of matter, methods of use, dosage regimens, formulations, crystalline forms (polymorphs), manufacturing processes, and others.

We own multiple issued patents and pending patent applications relating to PALSONIFY (paltusotine). Issued patents claiming the compound paltusotine as composition-of-matter have been obtained in the U.S., Europe, China, Japan, and

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Brazil, among other jurisdictions, and are estimated to expire in 2037, not including any available patent term adjustments or extensions. We own issued patents and pending patent applications relating to PALSONIFY (paltusotine) methods of use, dosage regimens, formulations, and crystalline forms (polymorphs), which, when issued, are estimated to expire between 2039 and 2046, not including any available patent term adjustments or extensions.

We own multiple issued patents and pending patent applications relating to our ACTH antagonist product candidate atumelnant. Issued patents claiming the compound atumelnant as composition-of-matter have been obtained in the U.S., China, and Japan, among other jurisdictions, and are estimated to expire in 2039, not including any available patent term adjustments or extensions. We own additional pending patent applications relating to our product candidate atumelnant, its methods of use, dosage regimens, and crystalline forms (polymorphs), which, when issued, are estimated to expire between 2042 and 2046, not including any available patent term adjustments or extensions.

We own one U.S. patent and multiple pending patent applications relating to our NDC platform, including as compositions of matter as well as methods of use and dosage regimens, which expire or are estimated to expire between 2043 and 2046, not including any available patent term adjustments or extensions.

We own a variety of other issued patents and pending patent applications related to various compounds, pharmaceutical compositions and methods of use. The issued patents, and any patents that may issue from the pending patent applications, are estimated to expire between 2036 and 2046, not including any available patent term adjustments or extensions.

We also possess substantial know-how and trade secrets relating to the development and commercialization of our product candidates, including related manufacturing processes and technology, which strengthen and maintain our proprietary position in the field of endocrinology. We own registered trademarks and have pending registration applications protecting our corporate marks and product marks, including PALSONIFYTM, in the U.S. and in jurisdictions outside of the U.S., in multiple pharmaceutical markets and in alignment with our commercial strategy. We also plan to rely on data exclusivities and market exclusivities, when available, to provide additional protection for our products.

Certain intellectual property rights, including for our lead programs, have been generated through the use of U.S. government funding provided from our SBIR Grants awarded to us by the National Institute of Diabetes and Digestive and Kidney Diseases of the National Institutes of Health, and are therefore subject to certain federal regulations. As a result, the U.S. government may have certain rights to intellectual property embodied in our current or future product candidates pursuant to the Bayh-Dole Act of 1980.

Manufacturing and Supply

We do not own or operate manufacturing facilities for the production of PALSONIFY or our other product candidates and do not currently plan to develop internal manufacturing operations for commercial products or clinical materials.

We rely on third-party CMOs and suppliers for the manufacture of raw materials, drug substance, and finished drug product used in our preclinical research, clinical trials, and commercial activities, and we expect to continue relying on third-party manufacturers for the commercial supply of our products. We oversee these CMOs through a combination of internal personnel and third-party consultants.

Currently, the drug substance for paltusotine is synthesized in India, undergoes a bioavailability optimization step in Portugal, and is then tableted into finished drug product in the U.S.

Sales, Marketing and Distribution

We are a commercial-stage company following the U.S. regulatory approval and commercial launch of PALSONIFY in the fourth quarter of 2025. We market and sell PALSONIFY in the U.S. through a targeted organization focused on specialty physicians treating rare diseases.

Our product support infrastructure includes medical affairs personnel and commercial teams, including a specialty sales force supported by internal marketing, market access, sales operations, and distribution resources. We distribute PALSONIFY in the U.S. through a third-party distributor and manage sales, marketing, and distribution through a combination of internal resources and third-party relationships.

We may elect in the future to utilize additional strategic partners, distributors, or contract sales organizations to support the commercialization of our product candidates.

For more information regarding the risks related to commercialization, see “Risk Factors – Risks related to commercialization of PALSONIFY and our product candidates.”

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U.S. Government Regulation

Government authorities in the U.S., at the federal, state and local level, and other countries extensively regulate, among other things, the research, development, testing, manufacture, quality control, approval, labeling, packaging, storage, record-keeping, promotion, advertising, distribution, marketing and export and import of products such as those we are developing. A new drug must be approved by the FDA through the NDA process before it may be legally marketed in the U.S. The process of complying with the extensive regulations and obtaining these approvals and, if approved, the subsequent compliance with applicable federal, state and local statutes and regulations require the expenditure of substantial management and financial resources.

Our business is subject to extensive regulation in the U.S., including the FDA as noted above, and by foreign regulatory authorities, including the EMA. We are required in the U.S. and in the other regions and countries we may intend to commercialize our drug products to obtain approval from regulatory authorities before we manufacture, market and sell our products. If our products obtain regulatory approval, they are subject to U.S. and ex-U.S. regulatory agency authority which may require additional testing and reporting, inspections, or changes to product labeling.

U.S. drug development process

In the U.S., the FDA regulates drugs under the FDCA and its implementing regulations. Failure to comply with the applicable U.S. requirements at any time during the product development process, approval process or after approval may subject an applicant to administrative or judicial sanctions. These sanctions could include the FDA’s refusal to approve pending applications, withdrawal of an approval, a clinical hold, warning letters, product recalls, product seizures, total or partial suspension of production or distribution, injunctions, fines, refusals of government contracts, restitution, disgorgement or civil or criminal penalties. Any agency or judicial enforcement action could have a material adverse effect on us.

The process required by the FDA before a drug may be marketed in the U.S. generally involves the following:

•completion of preclinical laboratory tests, animal studies and formulation studies in accordance with good laboratory practice regulations and other applicable regulations;

•submission to the FDA of an IND, which must become effective before human clinical trials may begin;

•performance of adequate and well-controlled human clinical trials in accordance with GCP requirements to establish the safety and efficacy of the proposed drug for its intended use;

•submission to the FDA of an NDA after completion of all pivotal trials;

•satisfactory completion of an FDA pre-approval inspection of the drug product's manufacturing facility or facilities to assess compliance with cGMP requirements; and

•FDA review and approval of the NDA.

Once a product candidate is identified for development, it enters the preclinical testing stage. Preclinical tests include laboratory evaluations of product chemistry, toxicity and formulation, as well as animal studies. The IND automatically becomes effective 30 days after receipt by the FDA, unless the FDA, within the 30-day time period, places the clinical trial on a clinical hold. In such a case, the IND sponsor and the FDA must resolve any outstanding concerns before the clinical trial can begin. Clinical holds also may be imposed by the FDA at any time before or during clinical trials due to safety concerns about on-going or proposed clinical trials or non-compliance with specific FDA requirements, and the trials may not begin or continue until the FDA notifies the sponsor that the hold has been lifted.

Clinical trials involve the administration of the investigational product to healthy volunteers or to patients, under the supervision of qualified principal investigators. Each clinical study at each clinical site must be reviewed and approved by an independent institutional review board, prior to the recruitment of subjects. Numerous requirements apply including, but not limited to, GCP regulations, privacy regulations, and requirements related to the protection of human subjects, such as informed consent.

Clinical trials are typically conducted in three sequential phases, but the phases may overlap, and different trials may be initiated with the same product candidate within the same phase of development in similar or differing patient populations.

•Phase 1 studies may be conducted in a limited number of patients but are usually conducted in healthy volunteer subjects. The product candidate is usually tested for safety and, as appropriate, for absorption, metabolism, distribution, excretion, pharmacodynamics and pharmacokinetics.

•Phase 2 usually involves studies in a larger, but still limited, patient population to evaluate preliminarily the efficacy of the product candidate for specific, targeted indications; to determine dosage tolerance and optimal dosage; and to identify possible short-term adverse effects and safety risks.

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•Phase 3 trials are undertaken to further evaluate clinical efficacy of a specific endpoint and to test further for safety within an expanded patient population at geographically dispersed clinical study sites.

Post-approval trials, sometimes referred to as Phase 4 studies, may be conducted after initial marketing approval. These trials are used to gain additional experience from the treatment of patients in the intended therapeutic indication. In certain instances, the FDA may mandate the performance of Phase 4 clinical trials as a condition of approval of an NDA.

U.S. review and approval process

The results of product development, preclinical and other non-clinical studies and clinical trials, along with descriptions of the manufacturing process, analytical tests conducted on the chemistry of the drug, proposed labeling and other relevant information are submitted to the FDA as part of an NDA requesting approval to market the product. The submission of an NDA is subject to the payment of substantial user fees; a waiver of such fees may be obtained under certain limited circumstances.

The FDA conducts a preliminary review of all NDAs within the first 60 days after submission, before accepting them for filing, to determine whether they are sufficiently complete to permit substantive review. The FDA may request additional information rather than accept an NDA for filing. In this event, the NDA must be resubmitted with the additional information. The resubmitted application also is subject to review before the FDA accepts it for filing. Once filed, the FDA reviews an NDA to determine, among other things, whether a product is safe and effective for its intended use and whether its manufacturing is cGMP-compliant to assure and preserve the product’s identity, strength, quality and purity. Under the PDUFA, guidelines that are currently in effect, the FDA has a goal of ten months from the date of “filing” of a standard NDA for a new molecular entity to review and act on the submission. This review typically takes twelve months from the date the NDA is submitted to FDA because the FDA has approximately two months to make a “filing” decision after it the application is submitted.

The FDA may refer an application for a novel drug to an advisory committee. An advisory committee is a panel of independent experts, including clinicians and other scientific experts, that reviews, evaluates and provides a recommendation as to whether the application should be approved and under what conditions. The FDA is not bound by the recommendations of an advisory committee, but it considers such recommendations carefully when making decisions. Before approving an NDA, the FDA will inspect the facility or facilities where the product is manufactured. Additionally, before approving an NDA, the FDA may inspect one or more clinical trial sites to assure compliance with GCP requirements.

After the FDA evaluates an NDA and conducts inspections of manufacturing facilities where the investigational product and/or its drug substance will be produced, the FDA may issue an approval letter or a CRL. An approval letter authorizes commercial marketing of the drug with prescribing information for specific indications. A CRL indicates that the review cycle of the application is complete, and the application will not be approved in its present form. A CRL usually describes the specific deficiencies in the NDA identified by the FDA and may require additional clinical data, such as an additional clinical trial or other significant and time-consuming requirements related to clinical trials, nonclinical studies or manufacturing. If a CRL is issued, the sponsor must resubmit the NDA or, addressing all of the deficiencies identified in the letter, or withdraw the application. Even if such data and information are submitted, the FDA may decide that the NDA does not satisfy the criteria for approval.

If a product receives regulatory approval, the approval may be significantly limited to specific diseases and dosages or the indications for use may otherwise be limited, which could restrict the commercial value of the product. In addition, the FDA may require a sponsor to conduct Phase 4 testing, which involves clinical trials designed to further assess a drug’s safety and effectiveness after NDA approval, and may require testing and surveillance programs to monitor the safety of approved products which have been commercialized. The FDA may also place other conditions on approval including the requirement for a REMS to assure the safe use of the drug. If the FDA concludes a REMS is needed, the sponsor of the NDA must submit a proposed REMS. The FDA will not approve the NDA without an approved REMS, if required. A REMS could include medication guides, physician communication plans or elements to assure safe use, such as restricted distribution methods, patient registries and other risk minimization tools. Any of these limitations on approval or marketing could restrict the commercial promotion, distribution, prescription or dispensing of products.

In addition, the PREA requires a sponsor to conduct pediatric clinical trials for most drugs, for a new active ingredient, new indication, new dosage form, new dosing regimen or new route of administration. Under PREA, original NDAs and supplements must contain a pediatric assessment unless the sponsor has received a deferral or waiver. The required assessment must evaluate the safety and effectiveness of the product for the claimed indications in all relevant pediatric subpopulations and support dosing and administration for each pediatric subpopulation for which the product is safe and effective. The sponsor or FDA may request a deferral of pediatric clinical trials for some or all of the pediatric subpopulations. A deferral may be granted for several reasons, including a finding that the drug is ready for approval for

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use in adults before pediatric clinical trials are complete or that additional safety or effectiveness data needs to be collected before the pediatric clinical trials begin. The FDA must send a non-compliance letter to any sponsor that fails to submit the required assessment, keep a deferral current or fails to submit a request for approval of a pediatric formulation.

Orphan drug designation

Under the Orphan Drug Act, the FDA may grant orphan designation to a drug intended to treat a rare disease or condition, which is a disease or condition that affects fewer than 200,000 individuals in the U.S. or, if it affects more than 200,000 individuals in the U.S., there is no reasonable expectation that the cost of developing and making a drug product available in the U.S. for this type of disease or condition will be recovered from sales of the product. Orphan designation must be requested before submitting an NDA. After the FDA grants orphan designation, the identity of the therapeutic agent and its potential orphan use are disclosed publicly by the FDA. Orphan designation does not convey any advantage in or shorten the duration of the regulatory review and approval process.

If a product that has orphan designation subsequently receives the first FDA approval for the disease or condition for which it has such designation, the product is entitled to orphan product exclusivity, which means that the FDA may not approve any other applications to market the same drug for the same disease or condition for seven years, except in limited circumstances, such as a showing of clinical superiority to the product with orphan exclusivity or inability to manufacture the product in sufficient quantities. The designation of such drug also entitles a party to financial incentives such as opportunities for grant funding towards clinical trial costs, tax advantages and user-fee waivers. However, competitors, may receive approval of different products for the indication for which the orphan product has exclusivity or obtain approval for the same product but for a different indication for which the orphan product has exclusivity. Orphan exclusivity also could block the approval of a competing product for seven years if a competitor obtains approval of the same drug as defined by the FDA or if a product candidate is determined to be contained within the competitor’s product for the same disease or condition. In addition, if an orphan designated product receives marketing approval for an indication broader than what is designated, it may not be entitled to orphan exclusivity.

Expedited development and review programs

The FDA has a fast track designation program that is intended to expedite or facilitate the process for reviewing new drug products that meet certain criteria. Specifically, new drugs are eligible for fast track designation if they are intended to treat a serious or life-threatening disease or condition and demonstrate the potential to address unmet medical needs for the disease or condition. The sponsor of a fast track product candidate has opportunities for more frequent interactions with the applicable FDA review team during product development and, once an NDA is submitted, the product candidate may be eligible for priority review. With regard to a fast track product candidate, the FDA may consider for review sections of the NDA on a rolling basis before the complete application is submitted, if the sponsor provides a schedule for the submission of the sections of the NDA, the FDA agrees to accept sections of the NDA and determines that the schedule is acceptable, and the sponsor pays any required user fees upon submission of the first section of the NDA.

A product candidate intended to treat a serious or life-threatening disease or condition may also be eligible for breakthrough therapy designation to expedite its development and review. A product candidate can receive breakthrough therapy designation if preliminary clinical evidence indicates that the product candidate, alone or in combination with one or more other drugs or biologics, may demonstrate substantial improvement over existing therapies on one or more clinically significant endpoints, such as substantial treatment effects observed early in clinical development. The designation includes all of the fast track program features, as well as more intensive FDA interaction and guidance beginning as early as Phase 1 and an organizational commitment to expedite the development and review of the product candidate, including involvement of senior managers.

Any product candidate submitted to the FDA for approval, including a product candidate with a fast track designation or breakthrough designation, may also be eligible for other types of FDA programs intended to expedite development and review, such as priority review and accelerated approval. An NDA is eligible for priority review if the product candidate is designed to treat a serious condition, and if approved, would provide a significant improvement in safety or efficacy compared to marketed products. The FDA will attempt to direct additional resources to the evaluation of an application for a new drug designated for priority review in an effort to facilitate the review. The FDA endeavors to review applications with priority review designations within six months of the filing date as compared to ten months for review of new molecular entity NDAs under its current PDUFA review goals.

In addition, a product candidate may be eligible for accelerated approval. Drug products intended to treat serious or life-threatening diseases or conditions may be eligible for accelerated approval upon a determination that the product candidate has an effect on a surrogate endpoint that is reasonably likely to predict clinical benefit, or on a clinical endpoint that can be measured earlier than irreversible morbidity or mortality, that is reasonably likely to predict an effect on irreversible morbidity or mortality or other clinical benefit, taking into account the severity, rarity, or prevalence of the condition and

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the availability or lack of alternative treatments. As a condition of approval, the FDA generally requires that a sponsor of a drug receiving accelerated approval perform adequate and well-controlled confirmatory clinical trials. Drugs receiving accelerated approval may be subject to expedited withdrawal procedures if the sponsor fails to conduct the required confirmatory trials in a timely manner or if such trials fail to verify the predicted clinical benefit. In addition, the FDA currently requires as a condition for accelerated approval pre-approval of promotional materials, which could adversely impact the timing of the commercial launch of the product.

Fast track designation, priority review and breakthrough therapy designation do not change the standards for approval but may expedite the development or approval process. Even if a product candidate qualifies for one or more of these programs, the FDA may later decide that the product no longer meets the conditions for qualification or decide that the time period for FDA review or approval will not be shortened.

Post-approval requirements

Any products manufactured or distributed pursuant to FDA approvals are subject to pervasive and continuing regulation by the FDA, including, among other things, requirements relating to record-keeping, reporting of adverse experiences, periodic reporting, product sampling and distribution, and advertising and promotion of the product. After approval, most changes to the approved product, such as adding new indications, certain manufacturing changes and additional labeling claims, are subject to further FDA review and approval. Drug manufacturers and other entities involved in the manufacture and distribution of approved drugs are required to register their establishments with the FDA and certain state agencies and are subject to periodic unannounced inspections by the FDA and certain state agencies for compliance with cGMP regulations and other laws and regulations. Changes to the manufacturing process are strictly regulated, and, depending on the significance of the change, may require prior FDA approval before being implemented. Accordingly, manufacturers must continue to expend time, money and effort in the area of production and quality control to maintain compliance with cGMP and other aspects of regulatory compliance.

The FDA may withdraw approval if compliance with regulatory requirements and standards is not maintained or if problems occur after the product reaches the market. Later discovery of previously unknown problems with a product, including adverse events of unanticipated severity or frequency, or with manufacturing processes, or failure to comply with regulatory requirements, may result in revisions to the approved labeling to add new safety information; imposition of post-market studies or clinical studies to assess new safety risks; or imposition of distribution restrictions or other restrictions under a REMS program. Other potential consequences include, among other things:

•restrictions on the marketing or manufacturing of the product, complete withdrawal of the product from the market or product recalls;

•fines, warning letters, or untitled letters;

•clinical holds on clinical studies;

•refusal of the FDA to approve pending applications or supplements to approved applications, or suspension or revocation of product approvals;

•product seizure or detention, or refusal to permit the import or export of products;

•consent decrees, corporate integrity agreements, debarment or exclusion from federal healthcare programs;

•mandated modification of promotional materials and labeling and the issuance of corrective information;

•the issuance of safety alerts, Dear Healthcare Provider letters, press releases and other communications containing warnings or other safety information about the product; or

•injunctions or the imposition of civil or criminal penalties.

In addition, the FDA closely regulates the marketing, labeling, advertising and promotion of drug products. A company can make only those claims relating to safety and efficacy, purity and potency that are approved by the FDA and in accordance with the provisions of the approved label. The FDA and other agencies actively enforce the laws and regulations prohibiting the promotion of off-label uses. Failure to comply with these requirements can result in, among other things, adverse publicity, warning letters, corrective advertising and potential civil and criminal penalties. Physicians may prescribe legally available products for uses that are not described in the product’s labeling and that differ from those tested by us and approved by the FDA. Such off-label uses are common across medical specialties. Physicians may believe that such off-label uses are the best treatment for many patients in varied circumstances. The FDA does not regulate the behavior of physicians in their choice of treatments. The FDA does, however, restrict manufacturer’s communications on the subject of off-label use of their products.

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Marketing exclusivity

Market exclusivity provisions under the FDCA can delay the submission or the approval of certain marketing applications. The FDCA provides a five-year period of non-patent data exclusivity within the U.S. to the first applicant to obtain approval of an NDA for a new chemical entity. A drug is a new chemical entity if the FDA has not previously approved any other new drug containing the same pharmaceutical ingredient, or API, which is the molecule or ion responsible for the action of the drug substance. During the exclusivity period, the FDA may not approve or even accept for review an ANDA or an NDA submitted under Section 505(b)(2), or 505(b)(2) NDA, submitted by another company for another drug based on the same API, regardless of whether the drug is intended for the same indication as the original innovative drug or for another indication, where the applicant does not own or have a legal right of reference to all of the data required for approval. However, an application may be submitted after four years if it contains a certification of patent invalidity or non-infringement to one of the patents listed with the FDA by the innovator NDA holder. PALSONIFY is a new chemical entity.

The FDCA alternatively provides three years of marketing exclusivity for an NDA, or supplement to an existing NDA if new clinical investigations, other than bioavailability studies, that were conducted or sponsored by the applicant are deemed by the FDA to be essential to the approval of the application, for example new indications or dosages of an existing drug. This three-year exclusivity covers only the modification for which the drug received approval on the basis of the new clinical investigations and does not prohibit the FDA from approving ANDAs or 505(b)(2) NDAs for drugs containing the API for the original indication or condition of use. Five-year and three-year exclusivity will not delay the submission or approval of a full NDA. However, an applicant submitting a full NDA would be required to conduct or obtain a right of reference to all of the preclinical studies and adequate and well-controlled clinical trials necessary to demonstrate safety and effectiveness.

Pediatric exclusivity is another type of marketing exclusivity available in the U.S. Pediatric exclusivity provides for an additional six months of marketing exclusivity attached to another period of exclusivity if a sponsor conducts clinical trials in children in response to a written request from the FDA. The issuance of a written request does not require the sponsor to undertake the described clinical trials.

U.S. coverage and reimbursement

Significant uncertainty exists as to the coverage and reimbursement status of pharmaceutical products. Patients in the U.S. generally rely on third-party payors to reimburse part or all of the costs associated with their prescription drugs. Sales in the U.S. will depend in part on the coverage and reimbursement levels set by governmental authorities, private health insurers, and other third-party payors. As a threshold for coverage and reimbursement, third-party payors generally require that drug products have been approved for marketing by the FDA. Third-party payors also are increasingly challenging the effectiveness of and prices charged for medical products and services.

The process for determining whether a payor will provide coverage for a product is typically separate from the process for setting the reimbursement rate that the payor will pay for the product. A payor’s decision to provide coverage for a product does not imply that an adequate reimbursement rate will be available. No uniform policy for coverage and reimbursement for products exists among third-party payors in the U.S.; therefore, coverage and reimbursement for products can differ significantly from payor to payor. Further, coverage under certain government programs, such as Medicare and Medicaid, may not be available for certain pharmaceutical products. CMS decides whether and to what extent a new product will be covered and reimbursed under Medicare, and private third-party payors often follow CMS’s decisions regarding coverage and reimbursement to a substantial degree. However, one third-party payor’s determination to provide coverage for a pharmaceutical product does not assure that other payors will also provide coverage for the pharmaceutical product. As a result, the coverage determination process will likely be a time-consuming and costly process, with no assurance that coverage and adequate reimbursement will be applied consistently or obtained in the first instance. Further, coverage policies and third-party reimbursement rates may change at any time.

Third-party payors are increasingly challenging the price and examining the medical necessity and cost-effectiveness of medical products and services, in addition to their safety and efficacy. In order to obtain coverage and reimbursement for any future products that might be approved for marketing, we may need to conduct expensive studies in order to demonstrate the medical necessity and cost-effectiveness of any products, which would be in addition to the costs expended to obtain regulatory approvals. Third-party payors may not consider certain pharmaceutical products to be medically necessary or cost-effective compared to other available therapies, or the rebate percentages required to secure favorable coverage may not yield an adequate margin over cost or may not enable us to maintain price levels sufficient to realize an appropriate return on our investment in drug development. These payors may limit coverage through formulary placement, prior authorization, or other utilization management requirements, and they may reduce payment amounts or refuse to cover our products altogether. Changes in laws, regulations, or payor policies could adversely affect coverage, reimbursement levels, and the commercial success of PALSONIFY and any products we may commercialize in the future.

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Healthcare reform

In the U.S. and some foreign jurisdictions, several legislative and regulatory changes and proposed changes have occurred that could prevent or delay marketing approval of drug product candidates, restrict or regulate post-approval activities, and affect the profitable sale of drug product candidates.

In the U.S., the pharmaceutical industry has been significantly affected by major legislative initiatives, including the 2010 Patient Protection and Affordable Care Act, as subsequently amended by the Health Care and Education Reconciliation Act (collectively the “ACA”), which: (1) increased the minimum Medicaid rebates owed by manufacturers under the Medicaid Drug Rebate Program and extended the rebate program to individuals enrolled in Medicaid managed care organizations; (2) established an annual fee on any entity that manufactures or imports certain specified branded prescription drugs and biologic agents; (3) expanded the 340B drug pricing program by adding new entities to the program; (4) created a new Patient-Centered Outcomes Research Institute to oversee, identify priorities in, and conduct comparative clinical effectiveness research; (5) created a new Medicare Part D coverage gap discount program, in which manufacturers must agree to offer 70% point-of-sale discounts off negotiated prices of applicable brand drugs to eligible beneficiaries during their coverage gap period, as a condition for the manufacturer’s outpatient drugs to be covered under Medicare Part D; and (8) established a Center for Medicare and Medicaid Innovation at the CMS to test innovative payment and service delivery models to lower Medicare and Medicaid spending, potentially including prescription drugs.

Since its enactment, there have been many challenges to the ACA. On June 17, 2021, the U.S. Supreme Court dismissed the most recent judicial challenge to the ACA without specifically ruling on the constitutionality of the ACA.

Other legislative changes have been proposed and adopted since the ACA was enacted, including aggregate reductions of Medicare payments to providers. In addition, the American Rescue Plan Act of 2021, which went into effect on January 1, 2024, eliminated the statutory Medicaid drug rebate cap, previously set at 100% of a drug’s AMP. Moreover, there has been heightened governmental scrutiny of how manufacturers set prices for their marketed products. Several federal and state legislative efforts were designed to bring more transparency to product pricing and reform government program reimbursement methodologies for drug products. The IRA requires manufacturers of certain drugs to engage in price negotiations with Medicare (beginning in 2026); imposes rebates under Medicare Part B and Medicare Part D to penalize price increases that outpace inflation; and replaces the Part D coverage gap discount program with a new discounting program (which began in 2025). However, because the IRA permits the Department of Health and Human Services (HHS) to implement many of these provisions through guidance, as opposed to regulation, for the initial years, it is currently unclear how the IRA will be effectuated. At the state level, legislatures have increasingly passed legislation and implemented regulations designed to control pharmaceutical 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, designed to encourage importation from other countries and bulk purchasing.

U.S. healthcare fraud and abuse laws and compliance requirements

Federal and state healthcare laws and regulations govern business practices in the biopharmaceutical industry. These laws include legal authority pertaining to reducing fraud and abuse, increasing transparency, and addressing drug pricing and payments.

The various federal and state laws designed to curb healthcare fraud and abuse include the federal Anti-Kickback Statute, civil and criminal false claims laws, and data privacy and security laws, such as HIPAA. The federal Anti-Kickback Statute prohibits individuals or entities from knowingly and willfully offering, paying, soliciting or receiving any form of remuneration, directly or indirectly, to induce or in return for of the generation of business involving any item or service reimbursable under Medicare, Medicaid or other federal healthcare programs. No actual knowledge or specific intent to violate the statute is necessary in order to have committed a violation.

The civil False Claims Act, prohibits any individual or entity from knowingly presenting, or causing to be presented, a false claim for payment to the federal government or knowingly making, using or causing to be made or used a false record or statement material to a false claim to the federal government. A claim including items or services resulting from a violation of the federal Anti-Kickback Statute can constitute a false claim for purposes of the civil False Claims Act.

HIPAA created additional federal civil and criminal statutes that prohibit knowingly and willfully executing a scheme to defraud any healthcare benefit program. Similar to the federal Anti-Kickback Statute, a person or entity does not need to have actual knowledge or specific intent to violate the statute to commit a violation. Similar state anti-kickback and false claims laws may apply to business practices, including but not limited to, research, distribution, sales and marketing arrangements and claims involving healthcare items or services reimbursed by non-governmental third-party payors, including private insurers, or by patients themselves. Other state laws restrict payments that may be made to healthcare providers and other potential referral sources.

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Designed to increase transparency, the federal Physician Payments Sunshine Act requires certain manufacturers of drugs, devices, biologics and medical supplies for which payment is available under Medicare, Medicaid or the Children’s Health Insurance Program, to annual report payments and transfers of value to physicians, certain non-physician practitioners, and teaching hospitals, plus physician ownership, to CMS.

Certain state laws also require drug manufacturers to file reports relating to pricing and marketing information which requires tracking gifts and other remuneration and items of value provided to physicians, other healthcare providers and entities, or require the registration of pharmaceutical sales representatives. Other state laws require pharmaceutical companies to comply with the pharmaceutical industry’s voluntary compliance guidelines and the relevant compliance guidance promulgated by the federal government.

Efforts to ensure compliance with applicable healthcare laws and regulations can involve substantial costs. Violations of healthcare laws can result in significant civil, criminal and administrative penalties, including monetary fines, imprisonment, exclusion from participation in federal healthcare programs, integrity oversight and reporting obligations, contractual damages, reputational harm, diminished profits and future earnings, and curtailment or restructuring of operations.

Data Privacy and Security

Numerous state, federal and foreign laws, including consumer protection laws and regulations, govern the collection, dissemination, use, access to, confidentiality and security of personal information, including health-related information. In the U.S., numerous federal and state laws and regulations, including data breach notification laws, health information privacy laws, and consumer protection laws and regulations (e.g., Section 5 of the FTC Act), that govern the collection, use, disclosure, and protection of health-related and other personal information could apply to our operations or the operations of our partners.

For example, California enacted the CCPA effective January 1, 2020, which gives California residents expanded rights to access, correct, and delete their personal information, opt out of certain personal information sharing and disclosure, and receive detailed information about how their personal information is used. The CCPA provides for civil penalties for violations, as well as a private right of action for data breaches that has increased the likelihood of, and risks associated with, data breach litigation. The CCPA may increase our compliance costs and potential liability. Further, the CPRA, generally went into effect on January 1, 2023, and significantly amends the CCPA. The CPRA imposes additional data protection obligations on covered businesses, including additional consumer rights processes, limitations on data uses, new audit requirements for higher risk data, and opt outs for certain uses of sensitive data. It also creates a new California data protection agency authorized to issue substantive regulations and could result in increased privacy and information security enforcement, and additional compliance investment and potential business process changes may be required. Similar laws have passed or been proposed in other states and at the federal level.

In addition, certain foreign laws govern the privacy and security of personal data, including health-related data. Privacy and security laws, regulations, and other obligations are constantly evolving, may conflict with each other to complicate compliance efforts, and can result in investigations, proceedings, or actions that lead to significant civil and/or criminal penalties and restrictions on data processing. See “Risk Factors – Risks related to our business operations and industry” for additional information about the risks to our business associated with a breach or compromise to our information technology systems.

Cybersecurity

In the normal course of business, we may collect and store personal information and certain sensitive company information, including proprietary and confidential business information, trade secrets, intellectual property, information regarding trial participants in connection with clinical trials, sensitive third-party information and employee information. To protect this information, we have implemented a cybersecurity program, described under Item 1C, “Cybersecurity” below. Nonetheless, our security measures cannot guarantee that a significant cyberattack will not occur. A successful attack on our information technology systems could have significant consequences to the business. See “Risk Factors – General Risk Factors” for additional information about the risks to our business associated with a breach or compromise to our information technology systems.

Employees and Human Capital Resources

As of February 13, 2026, we had 594 full-time employees, 150 of whom have a Ph.D. or M.D. None of our employees are represented by labor unions or covered by collective bargaining agreements. We consider our relationship with our employees to be good. In addition, we rely on a number of consultants to assist us.

Our human capital strategy centers on attracting, developing, and retaining top talent to drive organizational success and deliver long-term shareholder value. We achieve this through a holistic approach that combines competitive compensation

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offerings with HR best practices. These include robust leadership, management, and individual development opportunities, recognition programs, and engagement activities. Our compensation philosophy complements these programs by offering competitive base pay, equity incentives, and bonuses designed to motivate and reward performance aligned with company objectives.

Insurance

We maintain limited product liability insurance coverage for our clinical trials in the amount of $10 million per occurrence and $10 million in the aggregate. However, insurance coverage is becoming increasingly expensive, and we may not be able to obtain or maintain insurance coverage at a reasonable cost or in sufficient amounts to protect us against losses due to liability.

About Crinetics

We were incorporated in Delaware on November 18, 2008 and commenced operations in 2010.

Our principal executive offices are located at 6055 Lusk Blvd. San Diego, CA 92121, and our telephone number is (858) 450-6464.

Available Information

We make available, free of charge through our website, our annual report on Form 10-K, quarterly reports on Form 10-Q, current reports on Form 8-K, proxy statements, and any amendments to those reports, filed or furnished pursuant to Sections 13(a) or Section 15(d) of the Exchange Act, as soon as reasonably practicable after they have been electronically filed with or furnished to the SEC at www.sec.gov. Our website address is www.crinetics.com. We use our website as a means of disclosing material non-public information and for complying with our disclosure obligations under Regulation FD. Information contained on or accessible through these websites is not incorporated by reference nor otherwise included in this Report, and any references to these websites are intended to be inactive textual references only.