Multiple Hamartoma Syndrome

-Reported positive results from EMERALD-1 phase 2a trial of MORF-057 in ulcerative colitis (UC)- -Enrollment on target in EMERALD-2 phase 2b global randomized trial of MORF-057 in UC- -GARNET phase 2 trial of MORF-057 in Crohn’s disease (CD) expected to begin enrolling in the first half of 2024- -Ended 2023 with $704.3 million in cash and equivalents; cash runway into second half of 2027- WALTHAM, Mass., Feb. 22, 2024 (GLOBE NEWSWIRE) -- Morphic Therapeutic (Nasdaq: MORF), a biopharmaceutical company developing a new generation of oral integrin therapies for the treatment of serious chronic diseases, today reported corporate highlights and financial results for the full year 2023. “Today, our conviction in MORF-057 as a potential oral, well tolerated, and efficacious treatment for inflammatory bowel disease (IBD) is stronger than ever, based on the clear success of the EMERALD-1 trial in UC. Looking forward in 2024, we will work to translate this momentum into further progress with the GARNET phase 2 study in patients with moderately to severely active Crohn’s disease running in parallel with the EMERALD-2 phase 2b study in UC,” commented Praveen Tipirneni, Chief Executive Officer of Morphic. “Further, we are working to expand the pipeline of candidates generated by Morphic’s MInT Platform, most notably with our α5β1 program for pulmonary hypertensive diseases and additional new projects against both integrin and non-integrin targets “On a personal note, I am thankful to return to Morphic after an acute medical event and grateful for the immense support from friends and peers within the biotechnology community and especially the Morphic team,” Tipirneni continued. “This experience has crystallized, for me, that Morphic’s opportunity to fundamentally improve patients’ lives is immense and that there is no time to waste.” 2023 and Recent Corporate Highlights EMERALD-1 Phase 2a trial of MORF-057 in UC: In the EMERALD-1 phase 2a trial of MORF-057 in ulcerative colitis (UC), topline data and additional data presented at UEGW 2023 indicated that in a moderately-to-severely-active UC population with severe disease burden, MORF-057: Was generally well tolerated with no safety signal observedAchieved the study’s primary endpoint with statistical significance in reduction of Robarts Histopathology Index (RHI) Score from baseline to week 12 of 6.4 points (p=0.002)Showed consistent clinical improvement across key measures at week 12, including modified Mayo Clinic Score (mMCS) remission of 25.7% and mMCS response of 45.7%Demonstrated RHI change ≥7 points in 48.6% of patients and RHI remission in 22.9% of patientsLed to clinical improvement in mMCS within the 12-week induction period for 77% of patientsPharmacokinetic and pharmacodynamic results confirmed the results seen in healthy volunteer studies Median α4β7 RO >99% and sustained saturation at week 12α4β1 inhibition below the limit of quantification, in line with the design of MORF-057Predicted lymphocyte subset changes observed, consistent with engagement of α4β7 Demonstrated deepening of clinical effect beyond the 12-week induction period, with symptomatic remission rates continuing to increase out to 44 weeks in both advanced treatment-naïve and advanced treatment-experienced patients Announced completion of enrollment in the exploratory cohort of the EMERALD-1 study comprised of UC patients who have previously failed treatment with vedolizumabContinued the 40-week maintenance phase of the EMERALD-1 study as planned EMERALD-2 Phase 2b trial of MORF-057 in UC: Continued to enroll the EMERALD-2 phase 2b study of MORF-057 in patients with moderately-to-severely active UC EMERALD-2 is a global phase 2b randomized, double-blind, placebo-controlled trial of MORF-057 in patients with moderate-to-severe UCThe primary endpoint of EMERALD-2 is clinical remission rate as measured by mMCS at 12 weeks and is expected to report in the first half of 2025 GARNET Phase 2 trial of MORF-057 in Crohn’s Disease: Announced that launch activities are underway for the randomized placebo-controlled GARNET Phase 2 study of MORF-057 in CD and that the study is anticipated to enroll its first patients in the first half of 2024 The GARNET study will evaluate 210 patients across three cohorts, each comprising 70 patients: 70 patients receiving MORF-057 200 mg BID (twice daily), 70 patients receiving MORF-057 100 mg BID and 70 patients receiving placeboThe primary endpoint of the GARNET study is the proportion of participants in endoscopic response (>=50% reduction) at week 14 as determined using Simple Endoscopic Score for Crohn’s Disease (SES-CD) MORF-057 Preclinical and Phase 1 Studies: Presented new biomarker data at DDW 2023, demonstrating increases in circulating plasmablasts, consistent with the increased antibody activity expected with anti-inflammatory mechanism of α4β7 inhibition, supporting MORF-057 program in UCPresented preclinical data on rational selection of combination therapy for IBD treatment using an established clinical mode at UEGW 2023 This study explored preclinical combination models in UC and preliminarily examined the potential utility and rationale of combining anti-inflammatory mechanisms with α4β7 integrin inhibition in IBD Pipeline Programs: Announced α5β1 as the integrin target of Morphic’s small molecule integrin inhibitor program in pulmonary hypertensive diseases The inhibition of fibronectin integrins, including α5β1, suppresses pulmonary arterial smooth muscle cell proliferation and data to date indicate that inhibition of α5β1 contributes to improved cardiac output and the reversal of vascular remodeling Initiated discovery efforts that expand the Company’s scope in the immunology space with oral programs targeting the IL-23 and TL1A pathways, among others Financial Results for the Full Year 2023 Net loss for the year ended December 31, 2023, was $152.1 million or $3.59 per share compared to a net loss of $59.0 million or $1.55 per share for the year ended December 31, 2022Revenue was $0.5 million for the year ended December 31, 2023, compared to $70.8 million for the year ended December 31, 2022. The change was primarily due to recognition of revenue due to the conclusion of the AbbVie collaboration in 2022 and to the amounts due at the conclusion of the Janssen collaboration in 2023Research and development expenses were $140.4 million for the year ended December 31, 2023, as compared to $102.1 million for the year ended December 31, 2022. The increase was primarily attributable to higher development costs along with increased clinical trial costs to support phase 2 clinical studies and development activities for MORF-057, as well as other research costs to support early development candidatesGeneral and administrative expenses were $38.8 million for the year ended December 31, 2023, compared to $32.1 million for the year ended December 31, 2022. The increase was due to increased personnel related costs and non-cash equity-based compensation, partially offset by decreases in consulting and insurance expensesMorphic raised approximately $444 million, net, through equity financings in 2023 comprised of approximately $100 million in proceeds from a PIPE offering, approximately $259 million in a public offering and approximately $85 million though use of the ATM facilityAs of December 31, 2023, Morphic had cash, cash equivalents and marketable securities of $704.3 million, compared to $348.2 million as of December 31, 2022. We believe that our cash, cash equivalents and marketable securities of $704.3 million as of December 31, 2023, will enable us to fund our operating expenses and capital expenditure requirements into the second half of 2027 About MORF-057 Morphic is developing MORF-057 as a selective, oral small molecule inhibitor of the α4β7 integrin for patients with inflammatory bowel disease (IBD). α4β7 has been clinically validated as a target for the treatment of IBD by the success of the approved injectable antibody therapeutic vedolizumab. MORF-057, like vedolizumab, is designed to block the interactions between α4β7 on the surface of lymphocytes and the mucosal endothelial cell ligand MAdCAM-1, substantially reducing lymphocyte migration from the bloodstream into intestinal mucosal tissues and avoiding inflammation that is associated with IBD. About the EMERALD-1 Study EMERALD-1 (MORF-057-201) is an open-label multi-center phase 2a trial designed to evaluate the efficacy, safety, and tolerability of MORF-057 in adults with moderate to severe ulcerative colitis. The primary endpoint of EMERALD-1, change in Robarts Histopathology Index (RHI) from baseline at twelve weeks, was achieved with statistical significance. RHI is a validated instrument that measures histological disease activity in ulcerative colitis. Patients were eligible to continue for an additional 40 weeks of maintenance therapy followed by a 52-week assessment as well as an open-label extension period. Secondary and additional outcome measures in the EMERALD-1 study include change in the modified Mayo clinic score, safety, pharmacokinetic parameters and key pharmacodynamic measures including α4β7 receptor occupancy and lymphocyte subset trafficking. About the EMERALD-2 Study EMERALD-2 (MORF-057-202) is a global phase 2b randomized, double-blind, placebo-controlled trial of MORF-057 that is currently enrolling patients with moderate-to-severe ulcerative colitis. The primary endpoint of EMERALD-2 is clinical remission rate as measured by the Modified Mayo Clinic Score (mMCS) at 12 weeks. EMERALD-2 will also measure several secondary and exploratory endpoints based on the mMCS as well as histologic, pharmacokinetic and pharmacodynamic measures, and safety parameters. Patients in the EMERALD-2 study will be randomized to receive either 200 mg BID (twice daily) MORF-057, 100 mg BID MORF-057, a QD (once daily) dose of MORF-057, or a placebo dose. Following the 12-week induction phase, all patients will receive MORF-057 for 40 weeks of maintenance dosing. For more information about the EMERALD clinical trials of MORF-057, please click here. About the GARNET StudyGARNET (MORF-057-203) is a global Phase 2b randomized, double-blind, placebo-controlled trial of MORF-057 in Crohn’s disease. The primary endpoint of GARNET is the proportion of participants in endoscopic response (>=50% reduction) at week 14 as determined using Simple Endoscopic Score for Crohn’s Disease, or SES-CD. The secondary endpoints will include the change in Crohn’s Disease Activity Index, or CDAI, measures, as well as safety parameters. Patients enrolled in the GARNET study will be randomized to receive one of two active doses or a placebo: 200 mg BID (twice daily), 100 mg BID or a placebo that will cross over to MORF-057 after the 14-week induction phase. Following the 14-week induction phase, patients will move to a 38-week maintenance phase. About Morphic TherapeuticMorphic Therapeutic is a biopharmaceutical company developing a portfolio of oral integrin therapies for the treatment of serious chronic diseases, including autoimmune, cardiovascular, and metabolic diseases, fibrosis, and cancer. Morphic is also advancing its pipeline and discovery activities in collaboration with Schrödinger using its proprietary MInT technology platform which leverages the Company’s unique understanding of integrin structure and biology. For more information, visit www.morphictx.com. Cautionary Note Regarding Forward-Looking StatementsThis press release contains “forward-looking” statements within the meaning of the Securities Act of 1933, as amended, the Securities Exchange Act of 1934, as amended, and of the “safe harbor” provisions of the Private Securities Litigation Reform Act of 1995, including, but not limited to: the MInT Platform’s ability to discover drug candidates; our plans to develop and commercialize oral small-molecule integrin therapeutics and any proposed timing thereof; the initiation, execution and completion of clinical trials of MORF-057; any expectations about safety, efficacy, timing and ability to commence or complete clinical and pre-clinical studies and/or trials and to obtain regulatory approvals for MORF-057 and other candidates in development; the timing of further data presentation; and the ability of MORF-057 to treat inflammatory bowel disease, including UC, CD, and other indications. Statements including words such as “believe,” “plan,” “continue,” “expect,” “will be,” “develop,” “signal,” “potential,” “anticipate” or “ongoing” and statements in the future tense are forward-looking statements. These forward-looking statements involve risks and uncertainties, as well as assumptions, which, if they do not fully materialize or prove incorrect, could cause our results to differ materially from those expressed or implied by such forward-looking statements. Forward-looking statements are subject to risks and uncertainties that may cause our actual activities or results to differ significantly from those expressed in any forward-looking statement, including risks and uncertainties in this press release and other risks set forth in our filings with the Securities and Exchange Commission, including, among others, our or a partner’s ability to complete a current or future clinical trial of any of our current or future product candidates, our ability to develop or obtain regulatory approval for or commercialize any product candidate, our ability to protect our intellectual property, and the sufficiency of our cash, cash equivalents and investments to fund our operations. These forward-looking statements speak only as of the date hereof and we specifically disclaim any obligation to update these forward-looking statements or reasons why actual results might differ, whether as a result of new information, future events or otherwise, except as required by law. Morphic Holding, Inc.Condensed Consolidated Statements of Operations(unaudited)(in thousands, except share and per share data)​Year Ended December 31,​ 2023 2022 Collaboration revenue$521 $70,808 Operating expenses: Research and development 140,384 102,062 General and administrative 38,823 32,142 Total operating expenses 179,207 134,204 Loss from operations (178,686) (63,396)Other income: Interest income, net 26,969 4,567 Other income (expense), net 2 (145)Total other income, net 26,971 4,422 Loss before provision for income taxes (151,715) (58,974)Provision for income taxes (380) (67)Net loss$(152,095) $(59,041)Net loss per share, basic and diluted$(3.59) $(1.55)Weighted average common shares outstanding, basic and diluted 42,390,554 38,112,498 Morphic Holding, Inc.Condensed Consolidated Balance Sheets (unaudited)(in thousands) December 31, 2023 December 31, 2022Assets Cash, cash equivalents and marketable securities$704,349 $348,248Other current assets 12,579 13,934Total current assets 716,928 362,182Other assets 5,586 6,407Total assets$722,514 $368,589 Liabilities and Stockholders' Equity Current liabilities$24,776 $17,126Long-term liabilities 716 2,344Total liabilities 25,492 19,470Total stockholders' equity 697,022 349,119Total liabilities and stockholders' equity$722,514 $368,589 ContactsMorphic TherapeuticChris Erdmanchris.erdman@morphictx.com617.686.1718

XHANCE significantly reduced both symptoms and sinus opacification in participants with chronic sinusitis (chronic rhinosinusitis) in two randomized controlled Phase 3 Clinical Trials (ReOpen1 and ReOpen2) FDA Supplemental New Drug Application Filed with Prescription Drug User Fee Act Target Goal Date of March 16, 2024 YARDLEY, Pa., Jan. 18, 2024 (GLOBE NEWSWIRE) -- Optinose (NASDAQ:OPTN), a pharmaceutical company focused on patients treated by ear, nose and throat (ENT) and allergy specialists, today announced peer-reviewed publication of results from both ReOpen1 and ReOpen2 in the Journal of Allergy and Clinical Immunology: In Practice1. The ReOpen program evaluated XHANCE for treatment of adults with chronic sinusitis (chronic rhinosinusitis). A drug-device combination product, XHANCE® (fluticasone propionate) nasal spray uniquely combines a widely used nasal anti-inflammatory drug with the Exhalation Delivery System™, an innovative delivery system designed to deliver the medication high and deep into difficult-to-access sinuses and sinonasal drainage tracts. “Patients with chronic sinusitis often suffer for years and may use multiple over-the-counter treatments in a search for ways to alleviate their symptoms. The burden of chronic sinusitis has been measured and is serious, with a degree of impaired quality of life and functioning comparable to other serious chronic conditions such as chronic heart failure, sciatica, or migraine. Chronic sinusitis is also common: data suggests it is one of the top diagnoses in adult outpatient physician visits. Although surgery is available, there has never been a medication approved by the FDA as safe and effective for this disease,” said Ramy Mahmoud, MD, MPH, CEO of Optinose. “Having a proven effective medication would finally allow doctors to have confidence that they can offer some relief to tens of millions of people suffering from this burdensome inflammatory condition.” As detailed in the new scientific publication Efficacy of EDS-FLU for Chronic Rhinosinusitis: Two Randomized Controlled Trials (ReOpen1 and ReOpen2), both trials showed statistically significant improvement in symptoms, and in inflammation inside the sinuses, in patients with chronic sinusitis (chronic rhinosinusitis) treated with XHANCE compared to patients receiving a vehicle combined with the Exhalation Delivery System (EDS-placebo). The primary endpoints include a composite symptom score (congestion, facial pain or pressure, and nasal discharge) and CT scans of the sinuses to objectively measure change in inflammation inside the sinus cavities. In additional statistically well-controlled measures, these trials also showed that XHANCE reduced the incidence of acute disease exacerbations by more than half and that treatment significantly reduced symptoms even for patients who entered the trials with symptoms despite using a standard-delivery nasal spray steroid, which are now generally available at prescription strength as over-the-counter treatments. The safety profile and tolerability of XHANCE for patients in the ReOpen trials was generally consistent with its currently labeled safety profile. The most common adverse reactions (incidence ≥ 3%) in the ReOpen program were epistaxis, headache, and nasopharyngitis. “With the help of patients and doctors in many countries, after years of effort, we are thrilled to see that results from these two pivotal trials are now available in a peer reviewed publication. Not only do these data support the sNDA we filed with FDA in 2023,” stated John Messina, PharmD, Senior Vice President of Clinical Research and Medical Affairs, “but they represent the first body of large, controlled trial evidence we are aware of showing that any nasal medication can produce improvement in symptoms and can reduce inflammation inside the sinus cavities of patients suffering from chronic sinusitis either with or without concurrent nasal polyps. Our team is proud of this breakthrough in the treatment of chronic sinusitis, and we sincerely thank the healthcare professionals who advised us along the way as well as those at our research sites and all the patients whose participation made this program possible.” About the ReOpen ProgramThe ReOpen program comprised two global, randomized, double-blind, placebo-controlled Phase 3 trials that evaluated the efficacy and safety of one or two sprays of XHANCE in each nostril twice daily, over 24 weeks, in patients suffering from chronic sinusitis. In ReOpen1, the first of the two trials, 332 chronic sinusitis patients either with or without concurrent nasal polyps were treated. In ReOpen2, 222 chronic sinusitis patients who did not have polyps in the nasal cavity were treated. The co-primary endpoints were change from baseline in symptoms, as measured by composite symptom score (nasal congestion, facial pain or pressure, and nasal discharge) at the end of week 4, and change in inflammation inside the sinus cavities, as measured by CT scans (change in the average of the percentages of volume occupied by disease in the ethmoid and maxillary sinuses) at week 24. The ReOpen trial program is a landmark research program that included the first ever large, controlled trials we are aware of to demonstrate that any nasal medication produces significant improvement in both symptoms and inflammation inside the sinuses for patients with chronic sinusitis, regardless of whether or not nasal polyps are present, and to demonstrate significant reduction in the number of acute exacerbations. About Chronic Sinusitis Chronic sinusitis (CS), also called “chronic rhinosinusitis”, has been cited as the second most common chronic disease of adults in the U.S.2 It is a serious chronic inflammatory disease affecting as many as 30 million adults in the U.S. and burdens the U.S. economy with over $30 billion in direct and indirect costs every year.3 CS is characterized by chronic inflammation affecting the paranasal sinuses and the nasal cavity, where the openings from the sinuses normally ventilate and drain. Chronic sinusitis is associated with symptoms that persist for at least 12 weeks, with many patients suffering for years. In addition, the condition is often associated with multiple acute exacerbations that require medical care and result in substantial use of antibiotics. In some patients, chronic sino-nasal inflammation is accompanied by development of polyps in the nasal cavities, referred to as nasal polyposis. Today, there are no FDA-approved drug treatments for the majority of chronic sinusitis patients, those who do not have polyps in the nasal cavity, although there are medications, including XHANCE, that have been approved by FDA for treatment of the smaller population of chronic rhinosinusitis patients who also have nasal polyps. The term “chronic rhinosinusitis” is sometimes used instead of “chronic sinusitis” to acknowledge that inflammation inside the sinuses is typically accompanied by inflammation in the nasal cavity. About OptinoseOptinose is a global specialty pharmaceutical company focused on serving the needs of patients cared for by ear, nose and throat (ENT) and allergy specialists. To learn more, please visit www.optinose.com or follow us on X and LinkedIn. About XHANCEXHANCE® is a drug-device combination product that uses the Exhalation Delivery System™ (also referred to as the EDS®) designed to deliver a topical anti-inflammatory to the high and deep regions of the nasal cavity where sinuses ventilate and drain. XHANCE is approved by the U.S. Food and Drug Administration for the treatment of chronic rhinosinusitis with nasal polyps in patients 18 years of age or older and has been studied for treatment of chronic sinusitis (notably including patients without polyps in the nasal cavity) in two phase 3 trials, ReOpen1 and ReOpen2. These trials are the first ever that we are aware of that show improvement in both symptoms and inflammation inside the sinuses, and reduction in acute exacerbations of disease, with a nasal therapy for chronic sinusitis patients, including patients with or without nasal polyps. If approved, XHANCE may be the first drug ever FDA-approved for treatment of chronic rhinosinusitis either with or without nasal polyps. Important Safety Information CONTRAINDICATIONS: Hypersensitivity to any ingredient in XHANCE. WARNINGS AND PRECAUTIONS: Local Nasal Adverse Reactions: epistaxis, erosion, ulceration, septal perforation, Candida albicans infection, and impaired wound healing. Monitor patients periodically for signs of possible changes on the nasal mucosa. Avoid use in patients with recent nasal ulcerations, nasal surgery, or nasal trauma until healing has occurred.Close monitoring for glaucoma and cataracts is warranted.Hypersensitivity reactions (e.g., anaphylaxis, angioedema, urticaria, contact dermatitis, rash, hypotension, and bronchospasm) have been reported after administration of fluticasone propionate. Discontinue XHANCE if such reactions occur.Immunosuppression and Risk of Infection: potential increased susceptibility to or worsening of infections (e.g., existing tuberculosis; fungal, bacterial, viral, or parasitic infection; ocular herpes simplex). Use with caution in patients with these infections. More serious or even fatal course of chickenpox or measles can occur in susceptible patients.Hypercorticism and adrenal suppression may occur with very high dosages or at the regular dosage in susceptible individuals. If such changes occur, discontinue XHANCE slowly.Patients with major risk factors for decreased bone mineral content should be monitored and treated with established standards of care. ADVERSE REACTIONS: The most common adverse reactions (incidence ≥ 3%) are epistaxis, nasal septal ulceration, nasopharyngitis, nasal mucosal erythema, nasal mucosal ulcerations, nasal congestion, acute sinusitis, nasal septal erythema, headache, and pharyngitis. DRUG INTERACTIONS: Strong cytochrome P450 3A4 inhibitors (e.g., ritonavir, ketoconazole): Use not recommended. May increase risk of systemic corticosteroid effects. USE IN SPECIFIC POPULATIONS: Hepatic impairment. Monitor patients for signs of increased drug exposure. Please see full Prescribing Information, including Instructions for Use References James N. Palmer, Nithin D. Adappa, Rakesh K. Chandra, Greg E. Davis, Mahboobeh Mahdavinia, John Messina, Randall A. Ow, Zara M. Patel, Anju T. Peters, Harry Sacks, Rodney J. Schlosser, Raj Sindwani, Zachary M. Soler, Andrew A. White, Sarah K. Wise, Ramy A. Mahmoud, Efficacy of EDS-FLU for Chronic Rhinosinusitis: Two Randomized Controlled Trials (ReOpen1 and ReOpen2), The Journal of Allergy and Clinical Immunology: In Practice, 2024,, ISSN 2213-2198, https://doi.org/10.1016/j.jaip.2023.12.016. (https://www.sciencedirect.com/science/article/pii/S221321982301365X)Hamilos DL. Chronic rhinosinusitis: epidemiology and medical management. J Allergy Clin Immunol. 2011 Oct;128(4):693-707; quiz 708-9. doi: 10.1016/j.jaci.2011.08.004. Epub 2011 Sep 3. PMID: 21890184.Palmer JN, Messina JC, Biletch R, Grosel K, Mahmoud RA. A cross-sectional, population-based survey of U.S. adults with symptoms of chronic rhinosinusitis. Allergy Asthma Proc. 2019 Jan 14;40(1):48-56. doi: 10.2500/aap.2019.40.4182. PMID: 30582496. Cautionary Note on Forward-Looking Statements This press release contains forward-looking statements within the meaning of the U.S. Private Securities Litigation Reform Act of 1995. All statements that are not historical facts are hereby identified as forward-looking statements for this purpose and include, among others, statements relating to the potential for XHANCE to be the first FDA approved drug product for chronic rhinosinusitis and the potential benefits of such label expansion; and other statements regarding the Company's future operations, prospects, objectives, and other future events. Forward-looking statements are based upon management’s current expectations and assumptions and are subject to a number of risks, uncertainties and other factors that could cause actual results and events to differ materially and adversely from those indicated by such forward-looking statements including, among others: physician and patient acceptance of XHANCE for its current and any potential future indication; potential for varying interpretation of clinical trial results of XHANCE for the treatment of chronic rhinosinusitis; potential that the FDA does not meet the PDUFA target goal date; risks and uncertainties relating to FDA approval of XHANCE for the treatment of chronic rhinosinusitis; the prevalence of chronic sinusitis and market opportunities for XHANCE may be smaller than the Company expects; and the risks, uncertainties and other factors discussed under the caption "Item 1A. Risk Factors" and elsewhere in our most recent Form 10-K and Form 10-Q filings with the Securities and Exchange Commission - which are available at www.sec.gov. As a result, you are cautioned not to place undue reliance on any forward-looking statements. Any forward-looking statements made in this press release speak only as of the date of this press release, and we undertake no obligation to update such forward-looking statements, whether as a result of new information, future developments or otherwise. Optinose Investor ContactJonathan Neelyjonathan.neely@optinose.com267.521.0531

Significant Reductions in Frequency and Intensity of Both Bowel Movements and Flushing Episodes Were Observed Paltusotine was Well-Tolerated with an Overall Pharmacokinetic Pro was Consistent with Prior Studies Phase 2 Study Enrollment is Complete (N=36), and Topline Results Expected in 1H 2024 Management to Host a Conference Call Today at 5:00 p.m. Eastern Time SAN DIEGO, Dec. 18, 2023 (GLOBE NEWSWIRE) -- Crinetics Pharmaceuticals, Inc. (Nasdaq: CRNX) today announced positive initial findings from its ongoing open-label Phase 2 carcinoid syndrome (CS) study of paltusotine, an oral, once-daily investigational compound being developed for the treatment of acromegaly and CS. “We are very encouraged by these strong initial findings in our Phase 2 study of paltusotine in people with carcinoid syndrome,” said Scott Struthers, Ph.D., founder and chief executive officer of Crinetics. “These initial results show the potential of paltusotine to significantly reduce both frequency and intensity of bowel movements and flushing, the key carcinoid syndrome symptoms. Further, paltusotine was well-tolerated and the overall pharmacokinetic pro consistent with prior studies. After completing this Phase 2 study next quarter, we anticipate sharing the results with the FDA to align on the design of a Phase 3 program.” Key Highlights from Ongoing Open-label Phase 2 Study of Paltusotine in Carcinoid Syndrome: 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. Participants were randomized to receive either 40 mg or 80 mg of paltusotine, with the ability to dose titrate based on tolerability or inadequate control of symptoms during the first four weeks of treatment. At the time of this initial data snapshot, safety data were available for 27 participants, 23 of whom had completed at least two weeks of the randomized treatment period and 15 of whom had completed the full 8-week randomized treatment period. Thirteen of the 15 participants (87%) who completed the randomized treatment phase enrolled in the long-term extension phase of the study. The initial findings indicate that: Administration of paltusotine resulted in rapid and sustained reductions in bowel movement (BM) frequency and flushing episodes: 65% reduction of excess bowel movements (defined as daily bowel movements above the upper limit of normal, 3/day) for patients with >3/day at baseline 65% reduction of flushing frequency for patients with >1/day at baseline Exposure of paltusotine in people with carcinoid syndrome was consistent with prior clinical studies Paltusotine was generally well-tolerated with a safety pro with prior clinical studies There were no treatment-related severe or serious adverse events (AEs), with the majority of treatment-related AEs being mild-to-moderate. The most frequently reported AEs included diarrhea, headache, and abdominal pain. Enrollment in the study is complete, with a total of 36 participants enrolled. Topline data from the complete study is expected in the first half of 2024. Data Review Conference Call Crinetics will hold a conference call and live webcast on Monday, December 18 at 5:00 p.m. Eastern Time to discuss the initial findings from the Phase 2 study. To participate, please dial 1-877-451-6152 (domestic), 1-201-389-0879 (international), or request a callback here and refer to conference ID 13742964. 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. Enrollment in the study is complete, and 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. The treatment phase of the study is expected to be completed in the first quarter of 2024. 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 neuroendocrine tumors. 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. Initial findings from an ongoing Phase 2 study in carcinoid syndrome further support paltusotine’s potential 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 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, a first-in-class, investigational, oral ACTH antagonist, that is currently in Phase 2 clinical studies for the treatment of Cushing’s disease and congenital adrenal hyperplasia. 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, hyperinsulinism, 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 the expected timing of topline data from the ongoing Phase 2 study of paltusotine in carcinoid syndrome;plans and timing for the full results of the Phase 2 study of paltusotine in carcinoid syndrome and sharing the results 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 Cushing’s disease or Congenital Adrenal Hyperplasia 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, hyperinsulinism, 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, initial findings and 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, 2022. 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: Chas Schultz VP, Investor Relations cschultz@crinetics.com (858) 450-6464 Investors: Corey Davis LifeSci Advisors cdavis@lifesciadvisors.com (212) 915-2577 Media: Natalie Badillo Head of Corporate Communications nbadillo@crinetics.com