Paltusotine

Novel Nonpeptide Drug Conjugate Platform to be Debuted, Featuring Preclinical Profile of Lead Candidate CRN09682 Targeting SST2-Expressing Tumors, which is on Track for IND Submission Early 2025 Data From Phase 2 Trial of Paltusotine in Carcinoid Syndrome to be Highlighted in Crinetics Symposium and Two Presentations SAN DIEGO, Nov. 14, 2024 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) today announced two abstracts from its transformative, in-house discovery and development programs will be presented at the upcoming North American Neuroendocrine Tumor Society Multidisciplinary NET Medical Symposium (NANETS 2024), taking place November 21-23, 2024, in Chicago. “We are eager to share our latest pipeline progress at NANETS 2024. Crinetics is committed to the neuroendocrine tumor community, and we are now utilizing our world class drug discovery and development capabilities to support people living with both functional and non-functional NETs,” said Scott Struthers, Ph.D., Founder and Chief Executive Officer of Crinetics. “We are excited to present preclinical data from our groundbreaking nonpeptide drug conjugate platform for our lead candidate CRN09682, an investigational anti-tumor therapy targeting SST2-expressing tumors, including NETs. We will also present data from the Phase 2 clinical study of our investigational drug candidate paltusotine, highlighting its ability to reduce the frequency and severity of carcinoid syndrome symptoms in patients with functional NETs.” CRN09682, is a first-in-class, somatostatin receptor 2 (SST2) targeted, nonpeptide drug conjugate (NDC). Built upon the well-validated concept of antibody-drug conjugates, Crinetics’ NDCs use a highly optimized small molecule G protein coupled receptor (GPCR) ligand, instead of an antibody, to deliver a potent anti-cancer agent to tumor cells with high selectivity and efficiency. CRN09682 was designed to provide enhanced tumor penetration, selectively bind to SST2 expressing tumor cells, induce internalization, and intracellularly release a potent anti-tumor agent, while minimizing systemic exposure and associated toxicities. In addition, CRN09682 is manufactured by traditional chemical synthesis methods, avoiding the complex and heterogeneous manufacturing methods required for antibody drug conjugates. Preclinical data to be presented at NANETS 2024 demonstrate the potent and selective anti-tumor activity of CRN09682, potentially providing a novel alternative for the treatment of NETs and other SST2-expressing tumors. Another abstract will be featured as both an oral and poster presentation, which includes follow-up from an open-label Phase 2 carcinoid syndrome study of investigational candidate paltusotine, a once-daily, oral, nonpeptide, selective SST2 agonist being developed for the treatment of acromegaly and carcinoid syndrome. The NANETS presentation includes findings from all 36 trial participants, with new analyses that show paltusotine reduced the frequency and severity of carcinoid syndrome symptoms and was well tolerated, justifying further clinical development. Data for paltusotine and CRN09682, along with additional information on NDCs, will also be featured in a Crinetics-sponsored symposium titled “Paltusotine and CRN09682: Novel Nonpeptide Approaches to Treating Carcinoid Syndrome and Neuroendocrine Tumors” at the conference on Thursday, November 21, from 12:15-1:15 p.m. CT. Featured speakers include Scott Struthers and Dr. Aman Chauhan, leader of Neuroendocrine Oncology and Co-Leader Radiopharmaceutical Drug Development at Sylvester Comprehensive Cancer Center, University of Miami Health System. Details on the abstracts to be presented at NANETS are shown below: Title: A Novel Nonpeptide Drug Conjugate (NDC) for the Treatment of Somatostatin Receptor 2-Expressing TumorsDate/Time: Poster: November 21, 5:15 pm CT Title: Once-daily Oral Paltusotine in the Treatment of Patients With Carcinoid Syndrome: Results From a Phase 2, Randomized, Parallel-Group StudyDate/Time: Oral: November 22 from 3:10 – 3:22 pm CT Poster: November 21, 5:15 pm CT The poster presentations will be made available on the Crinetics website at the time of presentation in accordance with the NANETS embargo policy. ABOUT CRN09682CRN09682 is an investigational, potentially first-in-class, non-radioactive, nonpeptide drug conjugate (NDC) linking a somatostatin receptor 2 (SST2) agonist with the cytotoxic drug monomethyl auristatin E (MMAE) via a spacer and a cleavable linker for the treatment of neuroendocrine tumors (NETs) and potentially for use in other solid tumors that express SST2. The SST2 ligand on the NDC molecule binds to SST2 on the tumor cell surface and is internalized in the cell whereby enzymes cleave the MMAE and release it within the cell. MMAE is known to cause microtubule disruption leading to cell arrest and death. The NDC approach is intended to enhance tumor penetration, selectively bind to specific GPCR expressing tumor cells, induce internalization, and intracellularly release a potent anti-tumor agent, while minimizing systemic exposure and associated toxicities. Additionally, NDCs are manufactured by traditional chemical synthesis methods, avoiding the limitations of fermentation, bioconjugation, and heterogeneous manufacturing methods required by most ADCs. NETs are generally incurable when metastatic, regardless of tumor grade. Overall survival rates vary significantly by stage, grade, age at diagnosis, primary site, and time period of diagnosis. ABOUT PALTUSOTINECrinetics’ lead development candidate, paltusotine, is the first investigational once-daily, oral, selective somatostatin receptor type 2 (SST2) nonpeptide agonist that has completed Phase 3 clinical development for acromegaly and is in Phase 2 clinical development for carcinoid syndrome associated with neuroendocrine tumors. It was designed by Crinetics with the goal of providing a once-daily, oral option for reliable and consistent control of acromegaly and carcinoid syndrome. In Phase 3 studies, once-daily, oral paltusotine maintained IGF-1 levels and symptom control in patients with acromegaly who were switched from monthly injectable medications (PATHFNDR-1) and rapidly decreased IGF-1 levels and symptom burden in medically untreated acromegaly patients (PATHFNDR-2). IGF-1 is the primary biomarker endocrinologists use to manage acromegaly patients. Results from the Phase 2 study in carcinoid syndrome provide supporting data and rationale for paltusotine to initiate a Phase 3 trial for another important indication related to the treatment of carcinoid syndrome in patients with neuroendocrine tumors. ABOUT CRINETICS PHARMACEUTICALSCrinetics Pharmaceuticals is a clinical stage pharmaceutical company focused on the discovery, development, and commercialization of novel therapeutics for endocrine diseases and endocrine-related tumors. Crinetics’ lead development candidate, paltusotine, is the first investigational once-daily, oral, selective somatostatin receptor type 2 (SST2) nonpeptide agonist that has completed Phase 3 clinical development for acromegaly and is in Phase 2 clinical development for carcinoid syndrome associated with neuroendocrine tumors. Crinetics is also developing atumelnant (CRN04894), an investigational, first-in-class, oral ACTH antagonist, that is currently completing 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 (including thyroid eye disease), diabetes, obesity and GPCR -targeted oncology indications. 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 CRN09682, including the therapeutic potential and clinical benefits or safety profile thereof; and IND-enabling studies for CRN09682; plans to develop CRN09682; and preclinical studies may not proceed at the time or in the manner expected, or at all; the timing and outcome of research, development and regulatory review is uncertain, and Crinetics’ drug candidates may not advance in development. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplates,” “believes,” “estimates,” “predicts,” “potential,” “upcoming,” or “continue” or the negative of these terms or other similar expressions . 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, initial or topline data 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 U.S. Food and Drug Administration and other regulatory authorities may not agree with our interpretation of such results; we may not be able to obtain, maintain and enforce our patents and other intellectual property rights, and it may be prohibitively difficult or costly to protect such rights; geopolitical events may disrupt Crinetics’ business and that of the third parties on which it depends, including delaying or otherwise disrupting its clinical studies and preclinical studies, manufacturing and supply chain, or impairing employee productivity, unexpected adverse side effects or inadequate efficacy of the company’s product candidates that may limit their development, regulatory approval and/or commercialization; the company’s dependence on third parties in connection with product manufacturing, research and preclinical and clinical testing; the success of Crinetics’ clinical and nonclinical studies; regulatory developments in the United States and foreign countries; clinical studies and preclinical studies may not proceed at the time or in the manner expected, or at all; the timing and outcome of research, development and regulatory review is uncertain, and Crinetics’ drug candidates may not advance in development or be approved for marketing; Crinetics may use its capital resources sooner than expected; any future impacts to our business resulting from geopolitical developments outside our control; 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 and its Quarterly reports on Form 10-Q for the quarters ended March 31, 2024, June 30, 2024 and September 30, 2024. You are cautioned not to place undue reliance on these forward-looking statements. 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: Investors:Gayathri DiwakarHead of Investor Relationsgdiwakar@crinetics.com(858) 345-6340 Media: Natalie BadilloHead of Corporate Communicationsnbadillo@crinetics.com(858) 345-6075

Novel Nonpeptide Drug Conjugate Platform to be Debuted, Featuring Preclinical Profile of Lead Candidate CRN09682 Targeting SST2-Expressing Tumors, which is on Track for IND Submission Early 2025 Data From Phase 2 Trial of Paltusotine in Carcinoid Syndrome to be Highlighted in Crinetics Symposium and Two Presentations SAN DIEGO, Nov. 12, 2024 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) today announced two abstracts from its transformative, in-house discovery and development programs will be presented at the upcoming North American Neuroendocrine Tumor Society Multidisciplinary NET Medical Symposium (NANETS 2024), taking place November 21-23, 2024, in Chicago. “We are eager to share our latest pipeline progress at NANETS 2024. Crinetics is committed to the neuroendocrine tumor community, and we are now utilizing our world class drug discovery and development capabilities to support people living with both functional and non-functional NETs,” said Scott Struthers, Ph.D., Founder and Chief Executive Officer of Crinetics. “We are excited to present preclinical data from our groundbreaking nonpeptide drug conjugate platform for our lead candidate CRN09682, an investigational anti-tumor therapy targeting SST2-expressing tumors, including NETs. We will also present data from the Phase 2 clinical study of our investigational drug candidate paltusotine, highlighting its ability to reduce the frequency and severity of carcinoid syndrome symptoms in patients with functional NETs.” CRN09682, is a first-in-class, somatostatin receptor 2 (SST2) targeted, nonpeptide drug conjugate (NDC). Built upon the well-validated concept of antibody-drug conjugates, Crinetics’ NDCs use a highly optimized small molecule G protein coupled receptor (GPCR) ligand, instead of an antibody, to deliver a potent anti-cancer agent to tumor cells with high selectivity and efficiency. CRN09682 was designed to provide enhanced tumor penetration, selectively bind to SST2 expressing tumor cells, induce internalization, and intracellularly release a potent anti-tumor agent, while minimizing systemic exposure and associated toxicities. In addition, CRN09682 is manufactured by traditional chemical synthesis methods, avoiding the complex and heterogeneous manufacturing methods required for antibody drug conjugates. Preclinical data to be presented at NANETS 2024 demonstrate the potent and selective anti-tumor activity of CRN09682, potentially providing a novel alternative for the treatment of NETs and other SST2-expressing tumors. Another abstract will be featured as both an oral and poster presentation, which includes follow-up from an open-label Phase 2 carcinoid syndrome study of investigational candidate paltusotine, a once-daily, oral, nonpeptide, selective SST2 agonist being developed for the treatment of acromegaly and carcinoid syndrome. The NANETS presentation includes findings from all 36 trial participants, with new analyses that show paltusotine reduced the frequency and severity of carcinoid syndrome symptoms and was well tolerated, justifying further clinical development. Data for paltusotine and CRN09682, along with additional information on NDCs, will also be featured in a Crinetics-sponsored symposium titled “Paltusotine and CRN09682: Novel Nonpeptide Approaches to Treating Carcinoid Syndrome and Neuroendocrine Tumors” at the conference on Thursday, November 21, from 12:15-1:15 p.m. CT. Featured speakers include Scott Struthers and Dr. Aman Chauhan, leader of Neuroendocrine Oncology and Co-Leader Radiopharmaceutical Drug Development at Sylvester Comprehensive Cancer Center, University of Miami Health System. Details on the abstracts to be presented at NANETS are shown below: Title:A Novel Nonpeptide Drug Conjugate (NDC) for the Treatment of Somatostatin Receptor 2-Expressing TumorsDate/Time:Poster: November 22 from 5:15 – 6:30 pm CT Title:Once-daily Oral Paltusotine in the Treatment of Patients With Carcinoid Syndrome: Results From a Phase 2, Randomized, Parallel-Group StudyDate/Time: Oral: November 22 from 3:10 – 3:22 pm CTPoster: November 22 from 5:15 – 6:30 pm CT The poster presentations will be made available on the Crinetics website at the time of presentation in accordance with the NANETS embargo policy. ABOUT CRN09682CRN09682 is an investigational, potentially first-in-class, non-radioactive, nonpeptide drug conjugate (NDC) linking a somatostatin receptor 2 (SST2) agonist with the cytotoxic drug monomethyl auristatin E (MMAE) via a spacer and a cleavable linker for the treatment of neuroendocrine tumors (NETs) and potentially for use in other solid tumors that express SST2. The SST2 ligand on the NDC molecule binds to SST2 on the tumor cell surface and is internalized in the cell whereby enzymes cleave the MMAE and release it within the cell. MMAE is known to cause microtubule disruption leading to cell arrest and death. The NDC approach is intended to enhance tumor penetration, selectively bind to specific GPCR expressing tumor cells, induce internalization, and intracellularly release a potent anti-tumor agent, while minimizing systemic exposure and associated toxicities. Additionally, NDCs are manufactured by traditional chemical synthesis methods, avoiding the limitations of fermentation, bioconjugation, and heterogeneous manufacturing methods required by most ADCs. NETs are generally incurable when metastatic, regardless of tumor grade. Overall survival rates vary significantly by stage, grade, age at diagnosis, primary site, and time period of diagnosis. ABOUT PALTUSOTINECrinetics’ lead development candidate, paltusotine, is the first investigational once-daily, oral, selective somatostatin receptor type 2 (SST2) nonpeptide agonist that has completed Phase 3 clinical development for acromegaly and is in Phase 2 clinical development for carcinoid syndrome associated with neuroendocrine tumors. It was designed by Crinetics with the goal of providing a once-daily, oral option for reliable and consistent control of acromegaly and carcinoid syndrome. In Phase 3 studies, once-daily, oral paltusotine maintained IGF-1 levels and symptom control in patients with acromegaly who were switched from monthly injectable medications (PATHFNDR-1) and rapidly decreased IGF-1 levels and symptom burden in medically untreated acromegaly patients (PATHFNDR-2). IGF-1 is the primary biomarker endocrinologists use to manage acromegaly patients. Results from the Phase 2 study in carcinoid syndrome provide supporting data and rationale for paltusotine to initiate a Phase 3 trial for another important indication related to the treatment of carcinoid syndrome in patients with neuroendocrine tumors. ABOUT CRINETICS PHARMACEUTICALSCrinetics Pharmaceuticals is a clinical stage pharmaceutical company focused on the discovery, development, and commercialization of novel therapeutics for endocrine diseases and endocrine-related tumors. Crinetics’ lead development candidate, paltusotine, is the first investigational once-daily, oral, selective somatostatin receptor type 2 (SST2) nonpeptide agonist that has completed Phase 3 clinical development for acromegaly and is in Phase 2 clinical development for carcinoid syndrome associated with neuroendocrine tumors. Crinetics is also developing atumelnant (CRN04894), an investigational, first-in-class, oral ACTH antagonist, that is currently completing 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 (including thyroid eye disease), diabetes, obesity and GPCR -targeted oncology indications. 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 CRN09682, including the therapeutic potential and clinical benefits or safety profile thereof; and IND-enabling studies for CRN09682; plans to develop CRN09682; and preclinical studies may not proceed at the time or in the manner expected, or at all; the timing and outcome of research, development and regulatory review is uncertain, and Crinetics’ drug candidates may not advance in development. In some cases, you can identify forward-looking statements by terms such as “may,” “will,” “should,” “expect,” “plan,” “anticipate,” “could,” “intend,” “target,” “project,” “contemplates,” “believes,” “estimates,” “predicts,” “potential,” “upcoming,” or “continue” or the negative of these terms or other similar expressions . 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, initial or topline data 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 U.S. Food and Drug Administration and other regulatory authorities may not agree with our interpretation of such results; we may not be able to obtain, maintain and enforce our patents and other intellectual property rights, and it may be prohibitively difficult or costly to protect such rights; geopolitical events may disrupt Crinetics’ business and that of the third parties on which it depends, including delaying or otherwise disrupting its clinical studies and preclinical studies, manufacturing and supply chain, or impairing employee productivity, unexpected adverse side effects or inadequate efficacy of the company’s product candidates that may limit their development, regulatory approval and/or commercialization; the company’s dependence on third parties in connection with product manufacturing, research and preclinical and clinical testing; the success of Crinetics’ clinical and nonclinical studies; regulatory developments in the United States and foreign countries; clinical studies and preclinical studies may not proceed at the time or in the manner expected, or at all; the timing and outcome of research, development and regulatory review is uncertain, and Crinetics’ drug candidates may not advance in development or be approved for marketing; Crinetics may use its capital resources sooner than expected; any future impacts to our business resulting from geopolitical developments outside our control; 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 and its Quarterly reports on Form 10-Q for the quarters ended March 31, 2024, June 30, 2024 and September 30, 2024. You are cautioned not to place undue reliance on these forward-looking statements. 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: Investors:Gayathri DiwakarHead of Investor Relationsgdiwakar@crinetics.com(858) 345-6340 Media: Natalie BadilloHead of Corporate Communicationsnbadillo@crinetics.com(858) 345-6075