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Safe Harbor Statement This presentation contains forward-looking
statements. Crinetics Pharmaceuticals, Inc. ("Crinetics," the "company," "we," or "our") cautions you that statements contained in this presentation regarding matters that are not historical facts are
forward-looking statements. These statements are based on the company's current beliefs and expectations. Such forward-looking statements include, but are not limited to, statements regarding: the potential benefits of paltusotine for
acromegaly patients and patients with carcinoid syndrome; the potential for the PATHFNDR program to support registration of paltusotine for all acromegaly patients who require pharmacotherapy; the plans and timelines for clinical development of
paltusotine and CRN04894, including the therapeutic potential and clinical benefits or safety profile thereof; the expected timing of topline data and full results from the PATHFNDR-2 study and the Phase 2 study in patients with carcinoid syndrome
and sharing the results with the FDA to align on and design a Phase 3 program; the expected timing of the submission of a new drug application for paltusotine for the treatment of acromegaly and related open label extension studies, and potential
regulatory approval; 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 benefits of PTH receptor
antagonists for patients with hyperparathyroidism, the potential benefits of TSH antagonist for Graves' Disease or Thyroid eye disease; the potential for any of our ongoing clinical studies to show safety or efficacy; the potential of our
ongoing discovery efforts to target future indications for polycystic kidney disease, or diabetes/obesity, and the expected plans and timing for candidate selection and clinical development of such candidates; our plans to identify and create new
drug candidates for additional diseases; and our expected plans and timing for commercialization of paltusotine and other product candidates pending regulatory approval, including efforts in connection with prescribers, market research, payer
engagement, and distribution channels. 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," "laying the foundation,"
"leading to," "goal," "potential," "aspiring," "target," or the negative of and other similar terms. 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: topline and initial 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, and the FDA and other regulatory authorities may not agree with our interpretation of such results; the risk that preliminary results of preclinical studies or clinical studies do not necessarily predict final results
and that one or more of the clinical outcomes may materially change as patient enrollment continues, following more comprehensive reviews of the data, and as more patient data become available; the possibility of unfavorable new clinical data and
further analyses of existing clinical data; potential delays in the commencement, enrollment and completion of clinical studies and the reporting of data therefrom; the FDA or other regulatory agencies may require additional clinical studies of
paltusotine or suggest changes to our planned Phase 3 clinical studies prior to and in support of the approval of a New Drug Application or applicable foreign regulatory approval; international conflicts may disrupt our business and that of the
third parties on which we depend, including delaying or otherwise disrupting our clinical studies and preclinical studies, manufacturing and supply chain, or impairing employee productivity; our dependence on third parties in connection with product
manufacturing, research and preclinical and clinical testing; the success of our clinical studies, nonclinical studies and preclinical studies for paltusotine, CRN04894, our discovery efforts for hyperparathyroidism, polycystic kidney, Graves'
Disease & thyroid eye disease or diabetes/obesity product candidates; regulatory developments or price restrictions 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; and other risks
described under the heading "Risk Factors" in documents we file from time to time with the Securities and Exchange Commission ("SEC"). 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. This presentation also contains estimates and other statistical data made by independent parties and by us relating to addressable patients and addressable market size and growth and
other data about our industry. This data involves a number of assumptions and limitations, and you are cautioned not to give undue weight to such estimates. In addition, projections, assumptions, and estimates of our future performance and the
future performance of the markets in which we operate are necessarily subject to a high degree of uncertainty and risk. 2 2
Building a Premier Fully Integrated Endocrine- focused Pharmaceutical
Company Strategic Approach to Growing Long-term Value 3
Positive Phase 3 Results in Acromegaly for Paltusotine 2023 Laid the
Foundation for a Positive Initial Phase 2 Results in Carcinoid Syndrome for Paltusotine Transformative Completed Enrollment in Second Phase 3 Study for 2024-2025 Acromegaly Initiated Two Phase 2 Studies for Second Clinical Asset (CRN04894) $350M
The Crinetics Way: Endocrinology for Health Deep roots in endocrinology
Purposely crafted Commitment to transforming = people's lives medicines World-class in-house R&D Paltusotine is an investigational drug candidate currently in clinical studies 5 |
Deep Pipeline of Transformative Drug Candidates Discovery Preclinical
Phase 1 Phase 2 Phase 3 Program Anticipated Milestones Acromegaly (PATHFNDR-1) NDA Submission (2H24) Acromegaly (PATHFNDR-2) Paltusotine (SST2 agonist) Topline Results (1Q24) Full Phase 2 Data Release (1H24) Carcinoid syndrome Cushing's
disease Phase 2 Data (1H24) CRN04894 (ACTH antagonist) Phase 2 Data (1H24) Congenital adrenal hyperplasia Hyperparathyroidism Candidate Selection (1H24) PTH antagonist Candidate Selection (1H24) Polycystic kidney disease SST3 agonist (Exploring
global partnership) Expansion into highly prevalent indications Graves' disease & TED Candidate Selection (2024) TSH antagonist Diabetes/Obesity Oral GLP-1 nonpeptide Candidate Selection (2025) Oral GIP nonpeptide Diabetes/Obesity SST:
somatostatin receptor type; ACTH: adrenocorticotropic hormone; PTH: parathyroid hormone; TSH: thyroid-stimulating hormone; 6 6 | TED: thyroid eye disease; GLP-1: glucagon-like peptide-1 receptor agonists; GIP: gastric inhibitory polypeptide
World-class Development Leading to Global Commercialization Paltusotine:
Lead Clinical Asset for Acromegaly and Carcinoid Syndrome PATHFNDR-1 CARCINOID SYNDROME PHASE 3 RESULTS PHASE 2 RESULTS 7
Paltusotine: Designed to Allow People with Acromegaly and Carcinoid
Syndrome to Focus on Living POTENTIAL CURRENT STANDARD BENEFITS OF Reliable, Poor PALTUSOTINE* OF CARE consistent, Symptom and durable Control control 77% report No injection injections, VS site well reactions tolerated Painful, inconsistent
Once-daily and oral tablet inconvenient treatment option *Pending receipt by paltusotine of regulatory approval. Clinical studies to support applications for regulatory approval are ongoing. References 1. Geer EB, Sisco J, Adelman DT, et al. Patient
reported outcome data from acromegaly patients treated with injectable somatostatin receptor ligands (SRLs) in routine clinical practice. BMC Endocr Disord. 2020;20(1):117. doi:10.1186/s12902-020-00595-4; 2. Strasburger CJ, Karavitaki N,
St rmann S, et al. 8 Patient-reported outcomes of parenteral somatostatin analogue injections in 195 patients with acromegaly. Eur J Endocrinol. 2016;174(3):355-62. doi:10.1530/EJE-15-1042; 3. Fleseriu et al. Frontiers in Endocrinology; March
Positive Phase 3 Results in Acromegaly Provide Strong Footing for First
Commercial Launch* in 2025 100% 83% (25/30) p<0.0001 80% SECONDARY ENDPOINTS PRIMARY ENDPOINT SAFETY (paltusotine arm vs placebo) 60% 83% of participants Change from baseline in Paltusotine was well- on paltusotine IGF-1 (p < 0.0001) tolerated
with no severe or serious adverse events maintained IGF-1 Change from baseline in 1.0xULN vs 4% on 40% Paltusotine demonstrated Acromegaly Symptoms Diary placebo (p < 0.0001) score (p = 0.02) no new safety signals Proportion of
participants 20% who maintained GH <1.0 4% ng/mL (p = 0.0003) (1/28) 0% Paltusotine is an investigational drug in clinical studies for Paltusotine Placebo the treatment of acromegaly and carcinoid syndrome 9 9 | *Pending NDA Submission and
Regulatory Approval Participants Achieving Primary Endpoint (%)
Paltusotine: Progressing Towards Phase 3 in a Second, More Prevalent
Indication 5-HT + Other Carcinoid Syndrome Lung Factors ~33,000 Patients Diagnosed with Carcinoid Syndrome (US) Facial flushing in a patient with carcinoid syndrome NETs Treatment Goals 1. Reduce frequency and urgency of highly disruptive excess
bowel movements Pancreas 2. Reduce frequency and severity of severe flushing episodes which can be debilitating and potentially dangerous 3. Prevent severe complications from carcinoid heart Courtesy of Stephen E Goldfinger, MD disease (found in up
to 50% of patients) & carcinoid Intestine crisis 4. Eliminate breakthrough of symptoms with injected SRLs and reduce a high burden of care 10 10 | 5-HT = Serotonin; NETs = Neuroendocrine tumors; SRL = somatostatin receptor ligand
Example Carcinoid Syndrome Study Participant: Elimination of Flushing
and Normalization of BMs 10 9 8 Paltusotine 80 mg/day 7 Excess BM 6 >3/d BMs Flushes 5 4 3 No Prior 2 Normal BM Therapy 3/d to 3/w 1 0 -1 -30 -20 -10 0 10 20 30 40 50 60 Study Day 11 BM = bowel movement Frequency (per day)
Paltusotine Reduced the Frequency of Both Key Carcinoid Syndrome Core
Symptoms: Excess BM and Flushing Flushing Frequency Excess Bowel Movement* Frequency For Patients with 1/day at Baseline For Patients with >3/day at Baseline 3.0 p < 0.01 p = 0.05 3.0 N=19 N=11 3.1 2.0 -65% 2.0 -65% 2.3 1.0 1.0 1.1 0.8
0.0 0.0 Baseline Last Visit Baseline Last Visit *Excess bowel movements (BM) were defined as daily bowel movements above the upper limit of normal (3 per day) 12 Exploratory analysis of last visit prior to the preliminary data cut off includes 23
subjects: 15 subjects completed the week 8 visit, 4 subjects completed week 6 visit, 3 subjects completed week 4 visit and 1 subject completed week 2 visit. Excess (>3/day) Daily Frequency (7d avg) Daily Frequency (7d avg)
Paltusotine: Initial Multi-billion Dollar U.S. Market Opportunity in
Acromegaly and Carcinoid Syndrome Acromegaly Carcinoid Syndrome Diagnosed Prevalence 27,000 33,000 (U.S. Patients) Addressable Patients 11,000 33,000 Not cured surgically Candidates for SRL Current Patients 10,000 10,000 On Endocrine Therapy*
Average Annual WAC** $70K $100K For Injectables Current Market $1,000M $700M For Endocrine Therapy (U.S.) Total Addressable Market $800M $3,300M For Endocrine Therapy (U.S.) *Endocrine therapy includes SRLs, dopamine agonists, and growth hormone
antagonists. 13 **WAC: Wholesale acquisition cost; Sources: Company data on file
CONFIDENTIAL Building the Base for Commercial Success in Multiple
Indications for Paltusotine Complete Prescribers Map Market Research 200 HCPs initiating 80% of Backbone of marketing group acromegaly scripts in place 40 overlapping centers for both Market research indicates
pituitary and NCCN burden of care is key to Ad boards with top prescribers overcome inertia Expanding Med Affairs team Compelling PATHFNDR-1 data is strengthening awareness Distribution Channel Payer Engagement
Finalized third party logistics vendor contract Medicaid Medicare Part B Negotiating specialty pharmacy network contracts 9.8% Backbone of market access team 1.1% Building Crinetics' Provider & Patient Services Hub
in place. Engaged 50% of top US payers Payers appreciate value of oral ~50 top option payers Branded Services HUB Third Party Specialty Healthcare Commercial Medicare Part D Pharmacies Practitioners 30.9% 57.9% Patients NCCN:
National Comprehensive Cancer Network 14 Source: Crinetics interviews & market research
World-class Discovery to Grow the Clinical Pipeline World-class
Discovery to Grow the Clinical Pipeline Following the Crinetics way to create medicines to help increasingly larger numbers of people 15
CRN04894: Second Clinical Asset In Late-Stage Development Skillfully
Crafted to Help Patients Reach Their Treatment Goals Stress Hypothalamus Lead Indication: Congenital Adrenal Hyperplasia (CAH) Circadian ~27,000 Patients Prevalent/Diagnosed with Classical CAH (US) CRF CRF Clock AVP AVP Treatment Goals:
Glucocorticoids 1. Normalize/eliminate adrenal androgen production Pituitary CRF 2. Restore normal menstrual cycles and fertility in women Antagonists 3. Shrink testicular adrenal rest tumors, alleviate pain, restore fertility in
men CRN04894 (ACTH Antagonist) 4. Prevent consequences of excess androgens in children: ACTH atypical genitalia, precocious puberty, short stature, hirsutism 5. Avoid complications of glucocorticoid excess (weight gain, A4 hypertension, bone
disease ) and enable physiologic 17-OHP Adrenal Gland replacement levels AVP: arginine vasopressin, CRF: corticotropin releasing factor; A4: androstenedione; 16 16 | 17-OHP: 17-hydroxyprogesterone, ACTH: Adrenocorticotropic hormone
CRN04894: Targeting Mechanism Designed to Provide Maximum A4
Suppression. Initial Data Expected 2Q24 A4 suppression and steroid sparing expectations for different mechanisms of action in CAH Patients 700 on Glucocorticoids 600 Mean CRF 500 Dependent A4 Expected ACTH 400 Patients GC dose reduction Dependent On
GC + CRF A4 antagonist* 300 200 CRN04894 100 (Target Profile) Normal Range 0 0 5 10 15 20 2 GC dose (hydrocortisone equivalent) (mg/m /day) 17 | CRF: corticotropin releasing factor; GC: glucocorticoid; A4: androstenedione 17 | CONFIDENTIAL
Androstenedione Level (A4) (ng/dL)
Two New Programs Anticipated to Begin First-in-human Enabling Studies
in 2024 PTH Antagonist for Hyperparathyroidism TSH Antagonist for Graves' Disease and TED* Vehicle Vehicle Vehicle or or or Antagonist Antagonist Antagonist PO PO PO 2.0 1.8 Vehicle 3 mg/kg antagonist M22 Vehicle agonist 10 mg/kg antagonist
antibody 1.6 10 mg/kg antagonist 30 mg/kg antagonist 30 mg/kg antagonist 1.4 PTH infusion 1.2 Continuous SC 10 g/kg/day PTH(1-34) 0 -24 -12 0 12 24 36 48 60 Time (h) Preclinical efficacy data for potential lead candidate Preclinical efficacy
data for potential candidate 18 18 | PTH: parathyroid hormone; TSH: thyroid stimulating hormone; TED: thyroid eye disease Ionized Calcium (mmol/L)
Building a Premier Fully Integrated Endocrine-focused Pharmaceutical
Company 1H Commence CAH Phase 3 2H Paltusotine acromegaly ** ** PDUFA and launch Human POC from new drug 2H File Acromegaly NDA candidates 2Q Initial Phase 2 data New drug candidates enter readouts in
CAH and Multiple additional 2026 - development (obesity) ** Cushings 2030 commercial launches 2H Start Carcinoid Revenues from product * Syndrome Phase 3 sales to support growth New drug candidates enter
Continuous stream of development (PTH, TSH) clinical catalysts 2025 New assets emerging from discovery into development Strategic Approach to 2024 Growing Long-term Value * Pending alignment with FDA 19 ** Pending NDA submission and