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S e p t e m b e r 2 5 , 2 0 2 5 PALSONIFY (paltusotine) FDA Approval
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2 Forward Looking Statements This presentation contains forward-looking statements. Crinetics Pharmaceuticals, Inc. (“Crinetics,” the “company,” “we,” “us,” or “our”) cautions you that all statements other than statements of historical facts contained in this presentation are forward-looking statements. Such forward-looking statements include, but are not limited to, statements regarding: the estimates relating to market size, our ability to optimize the launch or ensure broad access to Palsonify or our ability to drive diagnosis and treatment for undiagnosed patients; the plans and timelines regulatory filings or approval of paltusotine outside the US; the expected timing of patient enrollment in the Phase 3 program of paltusotine for carcinoid syndrome; the expected timing of patient enrollment in additional studies of atumelnant in CAH or our plans or timing for a phase 2/3 study of atumelnant in Cushing’s syndrome; the plans and timelines for the clinical development of our drug candidates, including the therapeutic potential and clinical benefits or safety profile thereof; and the expected timing for the initiation of clinical trials or the potential benefits of our development candidates in patients across multiple indications; the expected timing of additional research pipeline updates or the expected timing of the advancement of those programs; and the company’s anticipated cash runway or its operating cash burn guidance. In some cases, you can identify forward-looking statements by terms such as “may,” “believe,” “anticipate,” “could,” “should,” “estimate,” “expect,” “intend,” “plan,” “project,” “will,” “contemplate,” “predict,” “continue,” “forecast,” “aspire,” “lead to,” “designed to,” “goal,” “aim,” “potential,” “target,” or other similar terms or the negatives thereof. These statements speak only as of the date of this presentation, involve known and unknown risks, uncertainties, assumptions, and other important factors that may cause our actual results, performance or achievements to be materially different from any future results, performance or achievements expressed or implied by the forward-looking statements, including, without limitation: estimates relating to market size and growth potential, which involve a number of assumptions and limitations, particularly about any projections, assumptions, and estimates of our future performance; the future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk; the possibility of unfavorable new clinical data and further analyses of existing clinical data; potential delays in the commencement, enrollment and completion of clinical trials and the reporting of data therefrom; our dependence on third parties in connection with product manufacturing, research and preclinical and clinical testing; the success of our clinical trials and nonclinical studies; regulatory developments or political changes, including policies related to pricing and pharmaceutical drug reimbursement in the United States and foreign countries; unexpected adverse side effects or inadequate efficacy of our product candidates that may limit their development, regulatory approval and/or commercialization; our ability to obtain and maintain intellectual property protection for our product candidates; we may use our capital resources sooner than we expect or our cash burn rate may accelerate; and other risks described under the heading “Risk Factors” in documents we file from time to time with the Securities and Exchange Commission. Because forward-looking statements are inherently subject to risks and uncertainties, some of which cannot be predicted or quantified and some of which are beyond our control, you should not rely on these forward-looking statements as predictions of future events. The events and circumstances reflected in our forward-looking statements may not be achieved or occur and actual results could differ materially from those projected in the forward-looking statements. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995 and, except as required by applicable law, we do 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.
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INTRODUCTORY REMARKS Scott Struthers, Ph.D. Founder & Chief Executive Officer CRINETICS PHARMACEUTICALS | 3
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CRINETICS PHARMACEUTICALS | 4 Our Mission: To be the world’s leading endocrine company that consistently pioneers new therapeutics to help patients better control their disease and improve their daily lives Acromegaly Congenital Adrenal Hyperplasia ACTH-Dependent Cushing’s Syndrome NETs and SST2-Expressing Solid Tumors Graves’ Disease Hyperparathyroidism ADPKD Obesity Carcinoid Syndrome Stacey Tony Ellen Dee Wendy Matthew Claire
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Acromegaly Symptoms Take a Toll on Patients GHRH = growth hormone-releasing hormone; IGF-1 = insulin-like growth factor 1. 1. Colao A, et al. Nat Rev Dis Primers. 2019;5(1):20. 2. Gomes-Porras M, et al. Int J Mol Sci. 2020;21(5):1682. Figure adapted with permission from Colao A, et al. Nat Rev Dis Primers. 2019;5(1):20. 3. Fleseriu M, et al. Lancet Diabetes Endocrinol. 2022;10(11):804-826. 4. Slagboom TNA, et al. Pituitary. 2023;23(4):319-332. Acromegaly is a rare chronic disease caused by a pituitary adenoma that secretes excess GH, resulting in hypersecretion of IGF-I1,2 Skin changes: oily skin, thickened skin, excessive sweating Joint pain, vertebral fractures Patient Symptoms3-4 Enlarged hands, feet, lips, nose, tongue, and jaw Headaches, which may be frequent and/or severe Peripheral neuropathy, carpal tunnel syndrome CRINETICS PHARMACEUTICALS | 5 Effects of Prolonged Exposure to IGF-I and GH1,2 LOCAL TUMOR EFFECTS Headache | Visual impairments Hyperprolactinemia | Hypopituitarism CARDIOVASCULAR Hypertension Congestive heart failure Cardiac hypertrophy RESPIRATORY Upper airway obstruction Sleep apnea SKELETAL Bone and cartilage overgrowth | Abnormal growth of hands and feet Arthritis | Vertebral fractures PHYSICAL CHANGES Alteration in facial features Hyperhidrosis/oily skin Tall stature/gigantism Carpal tunnel syndrome GASTROINTESTINAL Colonic polyps METABOLIC Impaired Glucose tolerance Diabetes mellitus REPRODUCTIVE Menstrual disturbance Erectile dysfunction
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- Dave, living with acromegaly Acromegaly is a cage... I've been dealing with this a long time. And there are medicines out there that will let you live life somewhat...I'm not symptom-free…If I was better controlled, I wouldn’t have to take that 30-minute nap when I get home or feel like my head is dragging. Because of acromegaly, I stopped singing and playing music… I have hope to actually get parts of my life back that I had thought I'd lost…I hope everyone living with acromegaly can get their song back. “ ”
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CRINETICS PHARMACEUTICALS | 7 NOW FDA APPROVED A New Era in Acromegaly Treatment
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CLINICAL DATA REVIEW Dana Pizzuti, M.D. Chief Medical Officer CRINETICS PHARMACEUTICALS | 8
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Highlights of Prescribing Information PALSONIFY’s Broad Label Supported by Robust Clinical Database CRINETICS PHARMACEUTICALS | 9Prescribing Information and Instructions for Use of PALSONIFY are available here
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In Phase 3 Studies, PALSONIFY Achieved Rapid, Reliable and Consistent Biochemical Control in Switch Patients *Last observation carried forward for patients who received rescue medication or discontinued from the study. EOT=end of treatment (week 36 or last assessment before rescue) 83% 4% PALSONIFY Placebo Patients Switching From Standard-of-Care p<0.0001 PALSONIFY Treatment Maintained IGF-1 Control in Patients who Switched from SRL Injections Maintained IGF-1 ≤ 1.0xULN Only 1 patient taking PALSONIFY in PATHFNDR-1 had an IGF-1 above 1.1x ULN at EOT* 0.0 0.5 1.0 1.5 2.0 0 4 8 12 16 20 24 28 32 36 Mean (±SE) IGF-I (× ULN) Paltusotine (n=30) Placebo (n=28) CRINETICS PHARMACEUTICALS | 10 PRIMARY ENDPOINT
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Week 4 8 16 2420122 220 6 -50 -40 -30 -20 -10 0 10 PALSONIFY (N=54) Placebo (N=57) 93% of participants ↓IGF-1 Rapid ↓IGF-1 (2-4 weeks) Durable ↓IGF-1 -0.82 xULN p<0.0001 In Phase 3 Studies, PALSONIFY Achieved Rapid, Reliable and Consistent Biochemical Control in Naïve Patients IGF-1 values measured prior to rescue or discontinuation are carried forward Percent Change from Baseline in IGF-1 Level by Visit IGF-1 Mean Percent Change from Baseline (± SE) 56% 5% PALSONIFY Placebo Non-Pharmacologically- Treated Patients PRIMARY ENDPOINT Achieved IGF-1 ≤ 1.0xULN p<0.0001 CRINETICS PHARMACEUTICALS | 11
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PALSONIFY Treatment Results in Long-Term, Stable Biochemical Control Across a Range of Acromegaly Patients CRINETICS PHARMACEUTICALS | 12 ULN 9 months PATHFNDR-2 OLE Median IGF-I ± IQR 114 BL 113 W2 113 W12 108 W24 88 W36 N IGF-I (x ULN) 0.0 0.5 1.0 1.5 2.0 14 months PATHFNDR-1 OLE Median IGF-I ± IQR 53 BL 51 W3 52 W12 52 W24 50 W48 50 W60 51 W36 N ULN IGF-I (x ULN) 0.0 0.5 1.0 1.5 2.0 LA- SRL Wash -out Evolve/ Edge IGF-I (x ULN) ACROBAT Advance Median IGF-I ± IQR ULN 4343 43 W3 42 W15 39 W39 40 W51 37 W103 20 W207 33 W155 35 W129 28 W181 37 W77 N 4 years 0.0 1.0 2.0 3.0
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In Phase 3 Studies, PALSONIFY Achieved Consistent Control of Symptoms and Reduced Frequency of Symptom Exacerbations CRINETICS PHARMACEUTICALS | 13Data on File. iSRL : injectable somatostatin receptor ligands; ASD: Acromegaly Symptom Diary. 0 5 10 15 20 25 30 35 Online Survey Paltusotine Screening Paltusotine 0-3 month Paltusotine 3-6 month Paltusotine 6-9 month Symptom Exacerbation Rate (%) Prior SRL (Screening) PALSONIFY 0-3 Months PALSONIFY 3-6 Months PALSONIFY 6-9 Months Online Symptom Survey (n=31 on iSRLs) (Exploratory Analysis n=22, Exploratory post hoc analysis; should not be interpreted as establishing clinical significance) Exploratory Post-Hoc Analyses with Acromegaly Symptom Diary (ASD) Symptom exacerbation frequency continued to decline throughout the 9-month study Label includes reduced severity of 7 key symptoms in both randomized trials CRINETICS PHARMACEUTICALS | 13
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CRINETICS PHARMACEUTICALS | 14 PALSONIFY was Well-Tolerated with No Severe or Serious Adverse Events Key safety outcomes from the randomized control period of Phase 3 studies • No serious adverse events None occurred with PALSONIFY vs 2.4% with placebo • GI AEs resolved Most GI AEs occurred within the first 2 months (median duration of 6 to 18 days), were generally mild to moderate and resolved without discontinuing PALSONIFY • Low discontinuation rate <4% of patients taking PALSONIFY discontinued due to AEs • Stability or reduction in size of pituitary tumors No patients receiving PALSONIFY had clinically significant increases in tumor volume; clinically significant decreases were observed in 4 patients taking PALSONIFY but not in any patients taking placebo Adverse Reaction PALSONIFY N=30 n(%) Placebo N=28 n(%) Diarrhea 7 (23) 3 (11) Nausea 4 (13) 1 (4) Decreased appetite 3 (10) 0 Palpitation 2 (7) 0 Gastroenteritis 2 (7) 0 Adverse Reaction PALSONIFY N=54 n(%) Placebo N=57 n(%) Diarrhea 18 (33) 8 (14) Abdominal pain 10 (19) 3 (5) Nausea 5 (9) 1 (2) Sinus bradycardia 4 (7) 0 (0) Hyperglycemia 4 (7) 1 (2) CRINETICS PHARMACEUTICALS | 14GI: Gastrointestinal; AEs: Adverse Events.
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COMMERCIAL LAUNCH STRATEGY Isabel Kalofonos Chief Commercial Officer CRINETICS PHARMACEUTICALS | 15
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Four Pillars to Optimize the Launch of PALSONIFY A C T I V A T E A D O P T A C C E S S A D H E R E W I N O N E F F I C A C Y Switch and naïve patients deserve a therapy that works fast, lasts and controls symptoms E N S UR E A C C E S S Removing friction to help more patients get the therapy that is right for them D R I V E A D H E R E NC E With the right support, patients stay on therapy longer and see better outcomes Success isn’t just about IGF-1 control, it’s about helping patients feel better and live better S H I F T T H E M I N D S E T CRINETICS PHARMACEUTICALS | 16
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Experienced Team in Place with Comprehensive Engagement Plan CRINETICS PHARMACEUTICALS | 17 14 Medical Science Liaisons 5 Nurse Educators 6 CrinetiCARE Specialists 4 Field Reimbursement Liaisons 4 Payer National Account Directors in pharma/biotech19.7 years in rare disease9.2 years in endocrinology8.7 years 60% of patients are treated in the community 36 Sales Team Sales Talent Metrics Mean years of experience ~3,600 Community HCP Targets 45 Core Pituitary Treatment Centers ~1,800 PTC + Academic HCP Targets
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CRINETICS PHARMACEUTICALS | 18 17,000+ Undiagnosed 11,500 Actively Managed 7,500 No Active Follow-up 1,500/yr diagnosed 15% Treatment Discontinued 20% Other Therapies 25% Injectable SRL 40% Treatment Naïve Acromegaly Patient Reach 500/yr initiating pharmacotherapy 11,500 Actively Managed and Addressable in Short-Term 36,000 People Living with Acromegaly in the US Note: Prevalence and incidence are estimates. Sources: Crisafulli S, et al. European Journal of Endocrinology. 2021;185(2):251 -263. Komodo Claims Data Analysis and Symphony D ata.
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Education and Engagement Required to Empower Patients to Demand More CRINETICS PHARMACEUTICALS | 19 PATIENT ACTIVATION PATIENT ADVOCACY CrinetiCARE ACROMEGALY REALITY Strengthening patient engagement through events, surveys and toolkits designed to elevate the patient voice and build community Comprehensive patient support services to assist with access, adherence and personalized care throughout the treatment journey Disease education campaign to raise awareness of the lived realities of acromegaly and support earlier recognition and diagnosis Omnichannel Approach to Support Patients with an Acromegaly Diagnosis
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Pre-Launch Engagement with Payers to Facilitate Post-Launch Formulary Access CRINETICS PHARMACEUTICALS | 20 Unprecedented Safety and Efficacy Ability to achieve rapid biochemical and symptom control based on Phase 3 data Optimize Treatment Paradigm Ensure patients getting intended clinical benefit Maintain Control Limit patient and societal burden of uncontrolled acromegaly Improve Patient Adherence and Outcomes Once-daily oral dosing Strong value proposition to payers includes: 60% Commercial 30% Medicare 10% Medicaid Note: Payer mix is an estimate
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*All CrinetiCARE programs are subject to eligibility requirements and changes. Criteria above do not represent all criteria for each program. Must be U.S. resident or U.S. territory resident. Restrictions apply. Patient Insurance Support Commercial Payer Co-pay Program Patient Assistance Program (Long-term) Supporting Patients at Every Step of Their Journey CRINETICS PHARMACEUTICALS | 21 MD Finder Quickstart Program (Short-term) Customized Adherence and Compliance Program Live Nurse Support Patient Support Center
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Palsonify is here to transform acromegaly care ” Broad Label and Strong Data Patient Focus Experienced Team A New Era in Acromegaly Has Started Tony, living with acromegaly
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CLOSING REMARKS Scott Struthers, Ph.D. Founder & Chief Executive Officer CRINETICS PHARMACEUTICALS | 23
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Palsonify is Just the Beginning: Building the Foundation for Our Pipeline SST: somatostatin receptor type; ACTH: adrenocorticotropic hormone; NETs: Neuroendocrine tumors; TSH: thyroid-stimulating hormone; TED: thyroid eye disease; ADPKD: Autosomal dominant polycystic kidney disease; PTH: parathyroid hormone; GLP-1: glucagon-like peptide-1 receptor agonists; GIP: gastric inhibitory polypeptide; IND: Investigational New Drug Application; PDUFA: Prescription Drug User Fee Act; CHMP: Committee for Medicinal Products for Human Use. Acromegaly (US) Acromegaly (EU) Hyperparathyroidism ADPKD ACTH dependent Cushing’s syndrome Congenital adrenal hyperplasia (pediatric) Obesity Obesity Graves’ disease (hyperthyroidism and TED) NETs and SST2-expressing solid tumors Partners Congenital adrenal hyperplasia (adult) Carcinoid syndrome Japan Development and Commercialization Partner for Paltusotine Licensee of targeted, nonpeptide radiopharmaceuticals Licensee of CRN01941 for veterinary use Program Discovery IND- Enabling Phase 1 Phase 2 Phase 3 Registration Approved Paltusotine (SST2 agonist) Atumelnant (ACTH antagonist) Nonpeptide drug conjugate (CRN09682) TSH antagonist SST3 agonist PTH antagonist Oral GLP-1 nonpeptide Oral GIP nonpeptide CRINETICS PHARMACEUTICALS | 24
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THANK YOU Q&A