SSTR2

56% of Participants on Paltusotine Achieved IGF-1 ≤1.0 xULN vs. 5% on Placebo (p<0.0001) Paltusotine was Generally Well-tolerated with No Serious Adverse Events Positive Topline Results Support Planned NDA Submission to the FDA in 2H 2024 Management Will Host a Conference Call Today at 8:30 a.m. Eastern Time SAN DIEGO, March 19, 2024 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) a clinical stage pharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for endocrine diseases and endocrine-related tumors, today announced positive topline results from PATHFNDR-2, the second of two Phase 3 studies evaluating the efficacy and safety of oral, once-daily investigational paltusotine for the treatment of acromegaly. PATHFNDR-2 (NCT05192382) was a randomized, double-blind, placebo-controlled 24-week treatment period followed by an optional open-label extension study evaluating paltusotine in 111 participants with acromegaly who were not pharmacologically treated. The study met statistical significance (p<0.0001) on the primary endpoint, based on the proportion of participants taking paltusotine (56%) who achieved an insulin-like growth factor 1 (IGF-1) level ≤ 1.0 times the upper limit of normal (xULN) compared to those taking placebo (5%). All secondary endpoints also met statistical significance: Paltusotine (n=54) Placebo (n=57) p-value Primary Endpoint: Proportion of participants who achieved an IGF-1 level ≤ 1.0 xULN, % (n) 56% (30/54) 5% (3/57) <0.0001 Secondary Endpoints: Change from baseline in IGF-1 level (xULN) -0.82 0.09 <0.0001 Proportion of participants who achieved IGF-1 level of <1.3 xULN at EoR* 67% 14% <0.0001 Change from baseline in Acromegaly Symptoms Diary (ASD) total score -2.67 2.75 0.004 Proportion of participants who achieved growth hormone (GH) level of <1.0ng/mL at EoR 57% 18% <0.0001 *EoR: End of Randomized control phase “These positive topline results of PATHFNDR-2 are incredibly exciting for both patients with acromegaly and the healthcare providers who treat them,” stated Monica R. Gadelha, M.D., Ph.D., professor of endocrinology at the Medical School of the Universidade Federal do Rio de Janeiro and a principal investigator in the PATHFNDR program. “This study demonstrates that paltusotine can provide both symptom control as well as biochemical control in patients who are not currently on pharmacologic treatment. If approved, the prospect that paltusotine can offer an innovative, once-daily oral alternative represents a significant step forward in improving the treatment experience for patients.” In PATHFNDR-2, paltusotine was generally well-tolerated and no serious adverse events were reported in participants treated with paltusotine. The frequency of participants with at least one treatment emergent adverse event (TEAE) was comparable in the paltusotine treatment arm and placebo arm. The most commonly reported TEAEs in paltusotine-treated participants included: diarrhea, headache, arthralgia and abdominal pain. The frequency of adverse events considered related to acromegaly was notably lower in paltusotine treated participants compared to placebo treated participants. “Paltusotine continues to exceed expectations. Today, PATHFNDR-2 delivered statistically significant topline results across the board,” said Scott Struthers, Ph.D., founder and chief executive officer of Crinetics. “Building upon the success of PATHFNDR-1, the totality of data underscores the potential of paltusotine to provide an important new treatment option for all people living with acromegaly, if approved. We intend to submit a New Drug Application (NDA) to the U.S. Food and Drug Administration in the second half of 2024, and our team is actively preparing for a potential 2025 launch. We are deeply grateful to all the individuals who participated in this study, the skilled clinical staff who provided exceptional care, and the dedicated Crinetics team from around the globe. This collective endeavor has brought an important new potential acromegaly treatment option closer to becoming a reality.” Data Review Conference Call Crinetics will hold a conference call and live webcast on Tuesday, March 19 at 8:30 a.m. Eastern Time to discuss topline results from the PATHFNDR-2 Phase 3 study. To participate, please dial 1-888-886-7786 (domestic) or 1-416-764-8658 (international), or request a callback here and refer to conference ID 95442954. To access the webcast, click here. A presentation to accompany the webcast can be found here. Following the live event, a replay will be available on the Investors section of the Company’s website. About the PATHFNDR Program The PATHFNDR Program consists of two Phase 3 double-blind, placebo-controlled studies. PATHFNDR-1 (NCT04837040) enrolled a total of 58 adults with acromegaly who entered with an IGF-1 level ≤ 1.0x ULN on octreotide or lanreotide depot monotherapy. The participants were randomized to receive once-daily, oral paltusotine for 36 weeks or placebo. PATHFNDR-2 (NCT05192382) enrolled 111 adults with acromegaly who had elevated IGF-1 levels but were medication naïve or were not being treated with pharmacotherapy (untreated patients). The primary endpoint for both studies is the proportion of patients achieving IGF-1 ≤1.0 xULN compared to placebo. Crinetics believes these studies could support registration of paltusotine in the United States and Europe for all acromegaly patients who require pharmacotherapy, including untreated patients and those switching from standard of care. About Acromegaly Acromegaly is a serious rare disease generally caused by a pituitary adenoma, a benign tumor in the pituitary that secretes growth hormone (GH). Excess GH secretion causes excess secretion of IGF-1 from the liver. Prolonged exposure to increased levels of IGF-1 and GH leads to progressive and serious systemic complications, often resulting in bone, joint, cardiovascular, metabolic, cerebrovascular, or respiratory disease. Acromegaly symptoms include headache, joint aches, fatigue, sleep apnea, severe sweating, hyperhidrosis/oily skin, bone and cartilage overgrowth, abnormal growth of hands and feet, enlargement of heart, liver, and other organs and alteration of facial features. Uncontrolled acromegaly results in increased mortality and has a debilitating impact on daily functioning and quality of life. Surgical removal of pituitary adenomas, if possible, is the preferred initial treatment for most acromegaly patients. Pharmacotherapy is used for patients who are not candidates for surgery, or when surgery is unsuccessful in achieving treatment goals. Approximately 50% of patients with acromegaly prove to be candidates for pharmacotherapy. Injectable depot somatostatin analogues are the most common initial pharmacologic treatment; however, these drugs require monthly depot injections with large gauge needles that are commonly associated with pain, injection site reactions, and an increased burden on the lives of patients. About Paltusotine Paltusotine is the first oral, once-daily selectively-targeted somatostatin receptor type 2 (SST2) agonist and is currently in investigational Phase 3 studies for acromegaly and a Phase 2 study for carcinoid syndrome. It was designed by the Crinetics’ discovery team to provide an efficacious and convenient once-daily option for people living with acromegaly and carcinoid syndrome. In Phase 2 studies and the recently completed PATHFNDR-1 Phase 3 study, paltusotine maintained IGF-1 levels in acromegaly patients who switched from monthly injectable medications to paltusotine. IGF-1 is the primary biomarker endocrinologists use to manage acromegaly patients. Results from the Phase 2 study in carcinoid syndrome further support paltusotine’s potential use beyond acromegaly. About Crinetics Pharmaceuticals Crinetics Pharmaceuticals is a clinical stage pharmaceutical company focused on the discovery, development, and commercialization of novel therapeutics for endocrine diseases and endocrine-related tumors. Paltusotine, an investigational, first-in-class, oral somatostatin receptor type 2 (SST2) agonist, is in Phase 3 clinical development for acromegaly and in Phase 2 clinical development for carcinoid syndrome associated with neuroendocrine tumors. Crinetics has demonstrated pharmacologic proof-of-concept in a Phase 1 clinical study for CRN04894, an investigational, first-in-class, oral ACTH antagonist, that is currently in Phase 2 clinical studies for the treatment of congenital adrenal hyperplasia and Cushing’s disease. All of the company’s drug candidates are orally delivered, small molecule new chemical entities resulting from in-house drug discovery efforts, including additional discovery programs addressing a variety of endocrine conditions such as hyperparathyroidism, polycystic kidney disease, Graves’ disease, thyroid eye disease, diabetes and obesity. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts contained in this press release are forward-looking statements, including statements regarding the plans and timelines for the clinical development of paltusotine and CRN04894, including the therapeutic potential and clinical benefits or safety pro plans to submit data from the ongoing Phase 3 clinical studies of paltusotine in acromegaly to regulators in support of applications seeking approval for the use of paltusotine in acromegaly patients and the expected timing of an NDA submission for paltusotine for the treatment for all acromegaly patients who require pharmacotherapy;our expected plans and timing for commercialization of paltusotine and other product candidates pending regulatory approval; the ability for paltusotine to effectively provide symptom control and biochemical control in acromegaly patients; and the commercialization of paltusotine as the first once-daily, oral SRL for the treatment of acromegaly; the commercial acceptance of paltusotine as a new medical treatment for acromegaly with improvements in treatment experience and access to care for patients and medical providers; the potential for our discovery program for endocrine diseases including hyperparathyroidism, polycystic kidney disease, Graves’ disease, thyroid eye disease, diabetes and obesity to progress to drug candidates and show safety or efficacy; and our plans to identify and create new drug candidates for additional diseases. These forward-looking statements speak only as of the date of this press release and are subject to a number of known and unknown risks, uncertainties and assumptions, including, without limitation, topline results that we report may change following a more comprehensive review of the data related to the clinical studies and such data may not accurately reflect the complete results of a clinical study, the possibility of unfavorable new clinical data and further analyses of existing clinical data, and the FDA and other regulatory authorities may not agree with our interpretation of such results; and the other risks and uncertainties described in the company’s periodic filings with the Securities and Exchange Commission (SEC). The events and circumstances reflected in the company’s forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Additional information on risks facing Crinetics can be found under the heading “Risk Factors” in Crinetics’ periodic filings with the SEC, including its annual report on Form 10-K for the year ended December 31, 2023. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Except as required by applicable law, Crinetics does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Contact: Corey Davis LifeSci Advisors cdavis@lifesciadvisors.com (212) 915-2577 Media: Natalie Badillo Head of Corporate Communications nbadillo@crinetics.com (858) 345-6075

Carcinoid syndrome occurs in around 20% of patients with neuroendocrine tumors, a rare, slow-growing cancer that usually originates in the digestive tract. As Crinetics prepares to make a tilt for FDA approval in a rare growth disorder later this year, a topline readout from a phase 2 study suggests the same drug also has the potential to treat symptoms associated with a neuroendocrine tumor. The phase 2 study enrolled 36 patients with carcinoid syndrome who initially received either 40 mg or 80 mg daily doses of the oral somatostatin receptor type 2 (SST2) agonist, paltusotine, for eight weeks. Thirty patients completed the randomized treatment phase, with one participant from the 40 mg cohort and five from the 80 mg group discontinuing treatment. The trial showed “rapid and sustained reductions in flushing episodes and bowel movement,” Crinetics said in a March 12 release. This included a 63% reduction from baseline in mean flushing frequency for the 24 patients with more than one bowel movement (BM) a day. For the 16 patients experiencing more than three BMs a day—considered the upper limit of normal—there was a 60% mean reduction in mean excess frequency, the company added. Across all the patients, there was a 61% reduction in flushing severity and a 64% reduction in BM urgency. Reductions in the frequency and severity of symptoms were observed from less than two weeks of the treatment beginning and were sustained through the eight-week regimen in both treatment naïve patients and those who had switched over from injectable somatostatin receptor ligand (SRL) therapy, which is the current mainstay treatment for carcinoid syndrome. No treatment-related severe or serious adverse events (AEs) were reported, with diarrhea, abdominal pain, nausea and headache being the most commonly reported AEs across both dose cohorts. Crinetics CEO Scott Struthers, Ph.D., said the latest results “confirm our decision to move expeditiously toward phase 3.” “These results highlight the potential of paltusotine to deliver significant benefits to patients living with the debilitating symptoms of carcinoid syndrome,” Struthers added. “We plan to engage with the FDA to align on a phase 3 study design and have begun preparations to enable the initiation of a phase 3 program by the end of the year.” Carcinoid syndrome occurs in around 20% of patients with neuroendocrine tumors, a rare, slow-growing cancer that usually originates in the digestive tract. If the cancer metastasizes to the liver it can cause carcinoid syndrome, which is typically associated with diarrhea and flushing. While injectable SRL therapies are currently used to treat the condition, these injections are “associated with considerable treatment burden and offer inadequate relief of carcinoid syndrome symptoms for many patients,” according to Crinetics. Paltusotine is also being developed for acromegaly, a rare hormone disorder that causes abnormal growth and swelling in adults. A phase 3 study suggested patients were able to switch over “seamlessly” to the new treatment from their usual treatment of injectable depot somatostatin drugs. The September 2023 data showed that insulin-like growth factor 1 (IGF-1) levels were maintained in 83% of patients taking the drug, compared to just 4% on placebo, which was the main goal of the study. Results from another phase 3 trial in acromegaly are expected by the end of the month, ahead of a planned approval submission to the FDA in the growth disorder indication in the second half of the year. To help bankroll these plans, Crinetics announced a private placement financing two weeks ago that brought in around $350 million. The biotech expects these funds to provide a cash runway through 2028.

Paltusotine Treatment Demonstrated Rapid and Sustained Reductions in Frequency and Severity of Flushing Episodes and Bowel Movements Paltusotine was Generally Well-Tolerated and Showed an Overall PK Pro with Prior Studies Results Confirm Initial Positive Data Previously Reported Management to Host a Conference Call Today at 4:30 p.m. Eastern Time SAN DIEGO, March 12, 2024 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) a clinical stage pharmaceutical company focused on the discovery, development and commercialization of novel therapeutics for endocrine diseases and endocrine-related tumors, today announced positive topline results from its open-label Phase 2 carcinoid syndrome study of paltusotine, an oral, once-daily investigational compound being developed for the treatment of acromegaly and carcinoid syndrome. “We are very pleased that these results from our Phase 2 study of paltusotine in carcinoid syndrome confirm our decision to move expeditiously toward Phase 3,” said Scott Struthers, Ph.D., founder and chief executive officer of Crinetics. “These results highlight the potential of paltusotine to deliver significant benefits to patients living with the debilitating symptoms of carcinoid syndrome. We plan to engage with the FDA to align on a Phase 3 study design and have begun preparations to enable the initiation of a Phase 3 program by the end of the year.” Key Highlights from the Phase 2 Study: The Phase 2 trial was a randomized, open-label, parallel group, multi-center study evaluating the safety, tolerability, pharmacokinetics, and efficacy of paltusotine in people living with carcinoid syndrome. A total of 36 participants were randomized to receive either 40 mg (n=18) or 80 mg (n=18) of paltusotine for 8 weeks, with the ability to dose titrate based on tolerability or inadequate control of symptoms during the first four weeks of treatment. Six participants in the 40 mg group increased their dose to 80 mg, and 3 participants in the 80 mg group increased to 120 mg. Thirty patients completed the randomized treatment phase, with 1 patient from the 40 mg group and 5 patients from the 80 mg group discontinuing treatment. Twenty-six of the 30 participants who completed the randomized treatment phase enrolled in the long-term extension phase of the study. Results demonstrated: Rapid and sustained reductions in flushing episodes and bowel movement (BM) 63% reduction in mean flushing frequency for patients with >1/day at baseline (n=24; p<0.0001) 60% reduction in mean excess BM frequency (defined as daily bowel movements above the upper limit of normal, 3/day) in patients with >3/day at baseline (n=16; p=0.02) 61% reduction in mean flushing severity (n=31; p<0.0001) and 64% reduction in mean BM urgency (n=31; p<0.0001) Reductions in frequency and severity of symptoms were observed within 2 weeks of paltusotine treatment and sustained through 8 weeks in both naïve/untreated patients and those switching from prior somatostatin receptor ligand (SRL) therapy Overall pharmacokinetic pro paltusotine in patients with carcinoid syndrome was consistent with expectations from healthy volunteers Paltusotine was generally well-tolerated with a safety pro with prior clinical studies: There were no treatment related severe or serious adverse events (AEs) The most frequently reported AEs included diarrhea, abdominal pain, nausea and headache AE findings were similar across 40 mg and 80 mg dosing groups Levels of biomarkers serotonin and 5HIAA provide additional evidence of paltusotine activity in carcinoid syndrome “I am excited about the clinical improvements that paltusotine demonstrated for patients with carcinoid syndrome in this study,” said Aman Chauhan, M.D., Sylvester Comprehensive Cancer Center, University of Miami and an investigator on the study. “There is a critical need for better treatment options for patients with neuroendocrine tumors who experience carcinoid syndrome. The results from this study of paltusotine are highly encouraging and I look forward to the next stage in its development.” Data Review Conference Call Crinetics will hold a conference call and live webcast today, Tuesday, March 12 at 4:30 p.m. Eastern Time to discuss the results from the Phase 2 study. To participate, please dial 1-888-886-7786 (domestic), 1-416-764-8658 (international), or request a callback here and refer to conference ID 02300008. To access the webcast, click here. Following the live event, a replay will be available on the Investors section of the Company’s website. About the Phase 2 Study The Phase 2 study is a randomized, open-label, parallel group, multi-center study evaluating the safety, tolerability, pharmacokinetics and efficacy of paltusotine in people living with carcinoid syndrome. This study consists of a randomized treatment phase followed by a long-term extension phase. A total of 36 patients with documented carcinoid syndrome requiring medical therapy were randomized to receive either 40 mg or 80 mg of daily oral paltusotine for 8 weeks. For additional information, please visit clinicaltrials.gov (NCT05361668). About Carcinoid Syndrome Carcinoid syndrome is found in approximately 20% of patients with neuroendocrine tumors (NETs). NETs are a rare, slow-growing type of cancer that arise most often in the digestive tract. When these tumors metastasize to the liver, carcinoid syndrome can occur and is most commonly characterized by diarrhea and flushing. While injectable depot somatostatin receptor ligand (SRL) therapies are mainstay treatments for carcinoid syndrome, these injections are associated with considerable treatment burden and offer inadequate relief of carcinoid syndrome symptoms for many patients. About Paltusotine Paltusotine is the first oral, once-daily selectively-targeted somatostatin receptor type 2 (SST2) agonist and is currently in investigational Phase 3 studies for acromegaly and a Phase 2 study for carcinoid syndrome. It was designed by the Crinetics’ discovery team to provide an efficacious and convenient once-daily option for people living with acromegaly and carcinoid syndrome. In Phase 2 studies and the recently completed PATHFNDR-1 Phase 3 study, paltusotine maintained IGF-1 levels in acromegaly patients who switched from monthly injectable medications to paltusotine. IGF-1 is the primary biomarker endocrinologists use to manage acromegaly patients. Results from the Phase 2 study in carcinoid syndrome further support paltusotine’s potential use beyond acromegaly. About Crinetics Pharmaceuticals Crinetics Pharmaceuticals is a clinical stage pharmaceutical company focused on the discovery, development, and commercialization of novel therapeutics for endocrine diseases and endocrine-related tumors. Paltusotine, an investigational, first-in-class, oral somatostatin receptor type 2 (SST2) agonist, is in Phase 3 clinical development for acromegaly and in Phase 2 clinical development for carcinoid syndrome associated with neuroendocrine tumors. Crinetics has demonstrated pharmacologic proof-of-concept in a Phase 1 clinical study for CRN04894, an investigational, first-in-class, oral ACTH antagonist, that is currently in Phase 2 clinical studies for the treatment of congenital adrenal hyperplasia and Cushing’s disease. All of the company’s drug candidates are orally delivered, small molecule new chemical entities resulting from in-house drug discovery efforts, including additional discovery programs addressing a variety of endocrine conditions such as hyperparathyroidism, polycystic kidney disease, Graves’ disease, thyroid eye disease, diabetes and obesity. Forward-Looking Statements This press release contains forward-looking statements within the meaning of Section 27A of the Securities Act of 1933, as amended, and Section 21E of the Securities Exchange Act of 1934, as amended. All statements other than statements of historical facts contained in this press release are forward-looking statements, including statements regarding the plans and timelines for the clinical development of paltusotine and CRN04894, including the therapeutic potential and clinical benefits or safety pro plans and timing for sharing the full results of the Phase 2 study of paltusotine in carcinoid syndrome with the FDA to align on and design a Phase 3 program; plans and timing to further develop paltusotine in carcinoid syndrome or to conduct Phase 3 studies of paltusotine in carcinoid syndrome; the potential benefits of CRN04894 in patients with Congenital Adrenal Hyperplasia or Cushing’s disease and the expected plans and timing for data from ongoing clinical studies; the potential for any of our ongoing clinical studies to show safety or efficacy; the potential for our discovery program for endocrine diseases including hyperparathyroidism, polycystic kidney disease, Graves’ disease, thyroid eye disease, diabetes and obesity to progress to drug candidates and show safety or efficacy and our plans to identify and create new drug candidates for additional diseases. These forward-looking statements speak only as of the date of this press release and are subject to a number of known and unknown risks, uncertainties and assumptions, including, without limitation, topline results that we report may change following a more comprehensive review of the data related to the clinical studies and such data may not accurately reflect the complete results of a clinical study, the possibility of unfavorable new clinical data and further analyses of existing clinical data, and the FDA and other regulatory authorities may not agree with our interpretation of such results; and the other risks and uncertainties described in the company’s periodic filings with the SEC. The events and circumstances reflected in the company’s forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. Additional information on risks facing Crinetics can be found under the heading “Risk Factors” in Crinetics’ periodic filings with the SEC, including its annual report on Form 10-K for the year ended December 31, 2023. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof. Except as required by applicable law, Crinetics does not plan to publicly update or revise any forward-looking statements contained herein, whether as a result of any new information, future events, changed circumstances or otherwise. Contact: Corey Davis LifeSci Advisors cdavis@lifesciadvisors.com (212) 915-2577 Media: Natalie Badillo Head of Corporate Communications nbadillo@crinetics.com (858) 345-6075