Slides
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Corporate Overview December 2024 CHANGING THE LANDSCAPE IN GI Going beyond to advance treatments for patients with acid-related disorders
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This presentation contains forward-looking statements. All statements other than statements of historical facts contained in this presentation, including statements regarding the ultimate decision by the FDA on the action requested in the CP and the timing of any FDA action regarding the CP; and the possible extension of NCE exclusivity to VOQUEZNA tablets; our future results of operations and financial position, anticipated milestones, anticipated cash runway, expectations regarding patent and non-patent regulatory exclusivity, business strategy, prospective products, product approvals, research and development costs, timing and likelihood of success, plans and objectives of management for future operations, and future results of current and anticipated products, are forward-looking statements. 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” or “continue” or the negative of these terms or other similar expressions. These statements involve known and unknown risks, uncertainties 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. These risks, uncertainties and other factors include, without limitation: our ability to successfully commercialize VOQUEZNA, which will depend on a number of factors including coverage and reimbursement levels from governmental authorities and health insurers as well as market acceptance by healthcare providers; estimates of the number of patients with H. pylori and erosive and non-erosive GERD and our estimates on potential market size for VOQUEZNA; the inherent risks of clinical development of vonoprazan; the possibility that the FDA may reject our request to correct the Orange Book listings to reflect the correct expiration date for the NCE exclusivity period on the VOQUEZNA tablets; our dependence on third parties in connection with product manufacturing, research and preclinical and clinical testing; regulatory developments in the United States and foreign countries; unexpected adverse side effects or inadequate efficacy of vonoprazan that may limit its development, regulatory approval and/or commercialization, or may result in recalls or product liability claims; our ability to obtain and maintain intellectual property protection, including patent term extensions, and non-patent regulatory exclusivity for vonoprazan; our ability to comply with our license agreement with Takeda; our ability to achieve and maintain adequate levels of coverage and reimbursement for vonoprazan; the availability of additional funds under our revenue interest financing agreement and term loan agreement; the sufficiency of our capital to fund our operations; our cash and cash equivalents and other anticipated capital may not be sufficient to enable us to reach cashflow positivity; we may face competition earlier than expected if we lose or fail to obtain any of our patent protection or non-patent regulatory exclusivity for VOQUEZNA tablets; and other risks described in our filings with the Securities and Exchange Commission (SEC), including our Annual Report on Form 10-K and any subsequent filings with the SEC. You are cautioned to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and we undertake no obligation to revise or update this presentation to reflect events or circumstances after the date hereof. 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. This presentation also contains estimates and other statistical data made by independent parties and by us relating to market size 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. Phathom, the Phathom logo, and other trademarks or service marks of Phathom appearing in this presentation are the property of Phathom. This presentation also includes trademarks, tradenames and service marks that are the property of other organizations. Solely for convenience, trademarks and tradenames referred to in this prospectus appear without the ® and symbols, but those references are not intended to indicate, in any way, that we will not assert, to the fullest extent under applicable law, our rights or that the applicable owner will not assert its rights, to these trademarks and tradenames. 2 Safe harbor statement
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High unmet need & attractive commercial dynamics • ~22M+ patients with GERD are diagnosed and treated annually, many of which are unsatisfied with their therapy and seeking innovative treatment options • No branded competition in the space 1st novel treatment in over 30 years • Approved for the treatment of Erosive GERD, Non-Erosive GERD, and H. pylori infection • VOQUEZNA is the first-ever acid suppressant to demonstrate superiority vs. a PPI across multiple indications1 Building upon demonstrated success • Approved in 10+ countries worldwide with >60 million patients treated • Blockbuster in Japan: #1 prescribed acid suppressant2 1 Superiority of vonoprazan demonstrated versus lansoprazole in studies of Erosive GERD and H. pylori infection 2 IQVIA MIDAS as of March 31, 2024, amongst all PPI and PCAB molecules Only FDA-approved treatment of its kind from a new class of acid suppressants called Potassium Competitive Acid Blockers (PCAB) NOW APPROVED for a NEW Indication: Non-Erosive GERD NEW 3 Phathom is focused on building VOQUEZNA® into a blockbuster
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>$850M annual net sales in Japan1 (vonoprazan) PCAB 0% 10% 20% 30% 40% 50% 60% 70% 2015 2016 2017 2018 2019 2020 2021 2022 2023 2024 Generics H2 ANTAGONISTS ~$3.5B peak US sales ANTACIDS Marketed OTC PPIs ~$12.5B peak US sales 25 YEARS No Innovation Japan Revenue-Based Market Share2 Driven predominantly by volumetric gains from generic competitors Majority of vonoprazan sales are in GERD Branded premium price Vonoprazan has been highly successful in Japan 2015 1 US dollars based on conversion rate of 0.0090 dollars to one yen. Annual net sales figure reflects the twelve-months ended Dec. 31, 2021. 2 IQVIA MIDAS as of March 31, 2024, amongst all PPI and PCAB molecules Introduced in Japan 2015 First introduced in 1989 Introduced in 1970s Introduced in 1930s 4 Commercial success of acid suppression treatments
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® Durable Rapid Potent Maintains continuous acid suppression over 24 hours Increased pH within 2-3 hours, reaching pH >4 within 4 hours Achieved strong acid suppression on Day 1, with a mean pH of 4.6 5 VOQUEZNA has a differentiated mechanism of action and is the first and only approved PCAB in the United States
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6 Mechanistic differences between PPIs and PCABs Secretory canaliculus Secretory canaliculus Tubulovesicle Proton pump (H+, K+ -ATPase) Active phase after mealQuiescent phase Active phase after mealQuiescent phase • Short plasma half-life • Acid needed for activation but unstable in presence of acid • Meal required to stimulate pumps PPI: COVALENTL Y BINDING PRODRUG VOQUEZNA: COMPETITIVE ENZYME INHIBITOR Rapid onset of action Potent acid control Durable 24-hr activity Slow onset of action Limited potency Limited duration of activity Tubulovesicle Proton pump (H+, K+ -ATPase) • Long plasma half-life • Stable in acid • High accumulation in canaliculus • Very slow dissociation rate
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Non-Erosive GERDEoE Target indications Phase 11 Phase 21 Phase 3 Positive Phase 2 results Evaluating potential Phase 3 trial timing As Needed treatment of heartburn associated with Non-Erosive GERD Treatment of eosinophilic esophagitis (EoE) for adult & pediatric use Planning to initiate Phase 2 trial in 1H25 Daily dosing treatment of heartburn associated with Non-Erosive GERD 1 Phase 1 and 2 studies supporting applications for Erosive GERD and H. pylori were conducted by Takeda; Phathom has development & commercialization rights to vonoprazan in the US, Europe, & Canada Erosive GERD Healing of Erosive GERD & relief of related heartburn in adults Maintenance of healing of Erosive GERD & relief of related heartburn in adults H. pylori Infection Treatment of H. pylori infection in adults Status 7 Three approved products across three indications
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1 El-Serag HB, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastro-oesophageal reflux disease: a systematic review. Gut. 2014;63(6):871-880. doi:10.1136/gutjnl-2012-304269 2 Machicado J.D., Greer J.B., Yadav D. (2020) Epidemiology of Gastrointestinal Diseases. In: Pitchumoni C., Dharmarajan T. (eds) Geriatric Gastroenterology. Springer, Cham. https://doi.org/10.1007/978-3-319-90761-1_7-1 3 IQVIA NPA & Consumer Health Care Data Q1-3 2022; 4 IQVIA Xponent retail & mail-order Rx data (2022) 5 Vaezi MF, Brunton S, Mark Fendrick A, et al. Patient journey in erosive esophagitis: real-world perspectives from US physicians and patients. BMJ Open Gastroenterology 2022 * Company estimates based on its market research. ~15M adults diagnosed & treated with Non-Erosive GERD people with Non- Erosive GERD1,2 ~65M people in the US with GERD1,2 ~45M ~7M adults diagnosed & treated with Erosive GERD* people with Erosive GERD1,2 ~20M Less than 50% of patients are satisfied with their current treatment5 High Dissatisfaction ~85% of the total PPI volume-based market is driven by Rx vs. OTC3 Prescription Based ~110M PPI TRx are written and filled annually (all indications)4 8 GERD represents a large US market with high unmet need VOQUEZNA US potential peak revenue opportunity $3 Billion*
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15M treated Non-Erosive GERD patients 7M treated Erosive GERD patients Planned Launch Sequence 1 Company estimates based on its market research. Goal to Displace PPIs 9 VOQUEZNA vision builds on each indication with the potential to transform the landscape of acid-related disorders and displace PPIs GERD Market Opportunity ~ ~ 22M total treated patients ~ 1 Combined First Launch 4Q 2023 Second Launch 3Q 2024 Increased eradication H. pylori infection (or HP) Lasting symptom control Non-Erosive GERD Daily dosing Improved healing and maintenance Erosive GERD (Erosive Esophagitis / EE) GERD
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FDA-approved for the treatment of heartburn associated with Non-Erosive GERD in adults as well as the healing and maintenance of healing of Erosive GERD in adults and relief of associated heartburn 10 VOQUEZNA’s pharmacologic profile is differentiated compared to existing acid suppression alternatives Satisfied attribute Unsatisfied attribute Rapid effect Potent acid suppression Durability of effect Flexibility of administration PPIs H2R blockers Antacids VOQUEZNA®
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Treatment churn ~35% of patients treated with a prescription PPI switch to a different PPI after ~3 months1 Erosive & Non-Erosive GERD patient journeys are similar; both include multiple lines of PPI therapy 1 Phathom data on file, diagnosed Erosive GERD patients between Jan. 2016 - Feb. 2022 (n=265,717) Source: Visual represents a summary of patient journey qualitative market research, May 2020 Treatment churn Trial of OTCs, including PPIs Erosive GERD Rx PPI Non-Erosive GERD Diagnosis Rx PPI Managed by GI or PCP Progress to GI for endoscopy 11 Visit to PCP and Rx PPI Typical GERD patient journey highlights current dissatisfaction
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HCPs expect to prescribe VOQUEZNA to 42% of their Erosive GERD patients1 Erosive GERD 42% HCPs expect to prescribe VOQUEZNA to 31% of their Non-Erosive GERD patients 2 31% 1 Erosive GERD Demand Study / Jan 2022 / n=301 (151 GI; 100 PCP; 50 APP) 2 Non-Erosive Demand Study / July 2023 / n=252 (101 GIs, 100 PCPs and 51 APPs) Non-Erosive GERD 12 Physician research indicates high intention to prescribe VOQUEZNA
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Communicating clinical superiority vs. a PPI1 and establishing VOQUEZNA as a treatment of choice Driving brand awareness and increasing demand Consumer Building widespread access for patients Payer PhysicianUnique & differentiated profile resonates across all customer segments 13 1 Superiority of vonoprazan demonstrated versus lansoprazole in studies of Erosive GERD and H. pylori infection Executing on three core goals during the early stages of launch
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18% 17% 5% 60% ~52K HCP Targets2 Other PCP Targeting high prescribing physicians who write an average ~1,200 PPI TRx annually2 320 Sales Reps GI APP1 14 1 APPs = advanced practice provider (i.e., nurse practitioners and physician assistants) 2 IQVIA APLD (Nov 2020 – Oct 2022) and IQVIA Xponent (Dec 2020 – Nov2022); Annual PPI prescription metric is based on total prescribing across all indications The VOQUEZNA sales force is targeting high volume PPI prescribers
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High volume HCPs are being reached by salesforce coupled with broad and aggressive communication campaign Online promotion Paid search & Search Engine Optimization (SEO) Targeted social media ads Telehealth ~52K GI, PCP, APPs Patients Consumers are responsive to comprehensive launch activation tactics resulting in high demand for VOQUEZNA 15 1 IQVIA APLD (Nov 2020 – Oct 2022) and IQVIA Xponent (Dec 2020 – Nov2022); Annual PPI prescription metric is based on total prescribing across all indications Promotional plans active across consumer and physician audiences DTC Campaign across Streaming & broadcast TV Digital promotion Mobile alerts Targeted marketing campaigns Scientific education Scientific publications & literature Medical meetings Patient reimbursement assistance Co-pay cards BlinkRx cloud pharmacy 320 sales reps targeting prescribing physicians who write an average ~1,200 PPI TRX annually 1
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LIVE ON BROADCAST TELEVISION! 1616 Full-scale DTC Campaign aims to motivate patients to request VOQUEZNA
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17 1 Per MMIT formulary lookup tool as of 11/1/2024. 2 Eligible, commercially insured patients may pay as little as $25 per prescription fill of VOQUEZNA; Offer not valid for patients enrolled in Medicare, Medicaid, or other federal or state healthcare programs; See VOQUEZNA.com for full program eligibility terms and conditions Widespread commercial coverage with large payers and additional support in place for patients who face access or affordability challenges Broad access with placement on major commercial formularies • Low out-of-pocket cost for eligible patients • Simple patient experience • Prior Authorization support • Free at-home delivery • Available nationwide • Dedicated customer support Patient Co-Pay Assistance2 Enhanced Patient Access commercial coverage1 >80% commercial lives covered1 120M>
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18 1 IQVIA + BlinkRx as of 10/25/24. Q4 2023 Q1 2024 Q2 2024 Q3 2024 ~500 ~9,500 ~35,000 ~69,000 ~100% Quarterly Filled Prescriptions1 Filled Prescriptions Launch-to-Date1 Previously: 60,000+ (as of 7/26/24) 143,000 + Early Non-Erosive GERD launch data fueled continued growth in Q3
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19 1 IQVIA + BlinkRx as of 10/18/24. Quarterly Cumulative Writers1 Cumulative Writers Launch-to-Date1 Previously: 8,200+ (as of 7/19/24) 13,600 + Q4 2023 Q1 2024 Q2 2024 Q3 2024 ~250 ~2,900 ~7,250 ~12,400 ~70% Growth in writers continues to indicate strong adoption
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No Branded Competition No branded competition & share of voice ownership Physician Attractiveness Strong physician interest & concentrated high prescribers High Unmet Needs Large population & high level of dissatisfaction Differentiated Profile Novel MOA & clinical differentiation Goal to displace PPIs and become the #1 selling acid suppressant 20 Significant opportunity and attractive commercial dynamics exist for blockbuster potential
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Based on our current operating plan: We believe our existing cash, cash equivalents, and other anticipated capital3 will be sufficient to enable us to reach cashflow positivity Debt Facility: $300M gross proceeds from August 2024 equity offering1 $175M principal outstanding $125M potentially available2(closed August 20, 2024)(as of September 30, 2024) 21 1 Gross and net proceeds include pre-funded warrants. Net proceeds were approximately $121.7M, which reflects deductions for underwriting discounts and commissions and estimated offering expenses. 2 The remaining $125M of the $300M term loan, is potentially available in three tranches: (1) $25M through December 15, 2024 (2) $50M subject to the achievement of a specified revenue milestone through June 30, 2025 (3) $50M subject to the achievement of a specified revenue milestone through December 31, 2025. 3 Assumes full drawdown and availability of the remaining $125M under the amended term loan and anticipated future product sales, pursuant to the operating plan. Financial highlights Equity Offering: $130M Revenues: $16.4M in Q3 2024 net revenues (as of September 30, 2024) Cash Balance: $334.7M in cash and cash equivalents
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Vonoprazan Species US Patent 7,977,488 expires Aug. 11, 2028 Expiration date with expected patent term extension: April 2030**** Vonoprazan Fumarate Formulation US Patent 9,186,411 expires Aug. 11, 2030 Patent Exclusivity*** Key Considerations ● GAIN Act NCE exclusivity tied to the active moiety, vonoprazan, with potential to apply to all Phathom products containing vonoprazan, regardless of indication ● First ANDA seeking approval of a generic vonoprazan cannot be filed until expiration of regulatory exclusivity ● Subsequent generic launch timing subject to FDA review and approval 5 years NCE exclusivity + 5 years GAIN Act NCE* exclusivity + 6 months pediatric exclusivity** = November 2032 Potential Regulatory Exclusivity 22 Vonoprazan Species Vonoprazan Fumarate * On December 11, 2024 we submitted a Citizen Petition seeking correction of our VOQUEZNA Orange Book listings to reflect the full 10 years of NCE exclusivity ** Subject to timely completion of pediatric studies and reports *** All patent terms will be extended by 6 months if pediatric exclusivity is granted, subject to timely completion of pediatric studies and reports **** Subject to grant of patent term extension by USPTO Regulatory exclusivity potentially through November 2032
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RAPID POTENT DURABLE 23
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Appendix: Phathom’s Clinical Trial Results 24
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Phase 3 trial for H. pylori infection PHALCON-HP 25
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Patients with H. pylori infection (n = 992) vonoprazan dual therapy (n = 324) vonoprazan triple therapy (n = 338) lansoprazole triple therapy (n = 330) 14 Day Treatment Period 4 Weeks Post-Treatment Primary Endpoint: non-inferiority eradication rate, excluding subjects with infection resistant to clarithromycin and amoxicillin Secondary Endpoint #1: superiority eradication rate in subjects with clarithromycin resistant strains Secondary Endpoint #2: superiority eradication rate in all subjects PHALCON-HP Phase 3 study design Diagnosis of infection and test of cure confirmed by 13C-urea breath test Vonoprazan dual therapy = vonoprazan 20 mg BID + amoxicillin 1 g TID Vonoprazan triple therapy = vonoprazan 20 mg BID + amoxicillin 1 g BID + clarithromycin 500 mg BID Lansoprazole triple therapy = lansoprazole 30 mg BID + amoxicillin 1 g BID + clarithromycin 500 mg BID 26
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90.40% 81.20% 82.10% vonoprazan 20mgvonoprazan 20mg lansoprazole 30mg 84.70% 60% 70% 80% 90% 100% lansoprazole 30mg Eradication Rate vonoprazan 20mg 78.50% vonoprazan 20mg 78.80% mITT population Per-protocol population p < 0.00011 vonoprazan triple therapy lansoprazole triple therapy vonoprazan dual therapy p = 0.0073 p = 0.01551 Eradication rates (%) among patients without clarithromycin- or amoxicillin-resistant strains PHALCON-HP met primary endpoints 1 Not adjusted for multiple comparisons p < 0.0001 27
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Both vonoprazan-based therapies met superiority for secondary endpoints Vonoprazan triple therapy subjects with clarithromycin resistant strains all subjects Vonoprazan dual therapy mITT population Per-protocol population mITT population Per-protocol population Δ 12.3% Δ 15.7% Δ 33.9% Δ 38.2% mITT population Per-protocol population Δ 8.7% Δ 11.1% mITT population Per-protocol population Δ 37.7% Δ 50.5% 1 Not adjusted for multiple comparisons 80.80% 85.70% 70.00% 60% 70% 80% 90% 100% Eradication Rate vonoprazan 20mg lansoprazole 30mglansoprazole 30mg 68.50% vonoprazan 20mg 31.90% 29.00% 20% 30% 40% 50% 60% 70% 80% 90% 100% Eradication Rate lansoprazole 30mgvonoprazan 20mg vonoprazan 20mg 67.20% lansoprazole 30mg 65.80% 81.10% 70.00% vonoprazan 20mg lansoprazole 30mglansoprazole 30mg vonoprazan 20mg 77.20% 68.50% 69.60% 31.90% 79.50% 29.00% vonoprazan 20mg lansoprazole 30mg vonoprazan 20mg lansoprazole 30mg p = 0.0003 p < 0.00011 p = 0.0127 p = 0.00271 p < 0.0001 p < 0.00011 p < 0.0001 p < 0.00011 28
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% (n) with adverse event Vonoprazan triple therapy (n=346) Vonoprazan dual therapy (n=348) Lansoprazole triple therapy (n=345) Diarrhea 4.0% (14) 5.2% (18) 9.6% (33) Nausea 1.7% (6) 1.7% (6) 2.6% (9) Dysgeusia 4.3% (15) 0.6% (2) 6.1% (21) Headache 2.6% (9) 1.4% (5) 1.4% (5) Vaginal infection 2.3% (8) 0.9% (3) 0.3% (1) Safety Set: All subjects who received at least one dose of study medication Most frequent (>2.0%) adverse events in PHALCON-HP subjects Safety profile Vonoprazan-based regimens generally well tolerated; comparable to lansoprazole triple therapy 29
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Phase 3 trial for Erosive GERD PHALCON-EE 30
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Part 1: Healing Phase Part 2: Maintenance Phase Patients with Erosive GERD (n = 1,0241) 2 to 8 week Treatment Period vonoprazan 20 mg QD (n = 514) % of patients who maintain complete healing Re- randomize healed patients (n = 8781) vonoprazan 10 mg QD (n= 293) vonoprazan 20 mg QD (n = 291) lansoprazole 15 mg QD (n =294) 24 week Treatment Period lansoprazole 30 mg QD (n = 510) % of patients with healed Erosive GERD PHALCON-EE Phase 3 study design US/Europe study in Erosive GERD 1 Represents modified intent to treat (mITT) population 31
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All Erosive GERD Patients LA Grades C/D (Moderate-to-Severe) Erosive GERD Patients 74% 93% 68% 85% Patients with healed Erosive GERD (%) Week 2 Week 8 70% 92% 53% 72% Week 2 Week 8 n=514 n=510 n=514 n=510 n=177 n=174 n=177 n=174 Primary Endpoint100% 90% 80% 70% 60% 50% 40% p<0.0001* p=0.0348^ p<0.0001^ p=0.0008# PHALCON-EE Phase 3 met primary and key secondary healing endpoints ^ nominal p-value presented, superiority comparison, not formally tested based on pre-specified testing hierarchy * p-value for both primary non-inferiority endpoint and unadjusted p-value for exploratory superiority comparison # p-value for pre-specified secondary endpoint superiority comparison lansoprazole 30 mg vonoprazan 20 mg 32
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Patients with maintained healing Erosive GERD (%) vonoprazan 10 mg lansoprazole 15 mg vonoprazan 20 mg 77% 75% 61% 81% 79% 72% n=291 n=293 n=294 n=92 n=95 n=96 100% 90% 80% 70% 60% 50% Primary Endpoint p<0.0001* p=0.0136# p<0.0001* p=0.0436# p=0.0196# p=0.0490# PHALCON-EE Phase 3 met all maintenance of healing endpoints * p-value for primary endpoint non-inferiority comparison # p-value for pre-specified secondary endpoint superiority comparison All Erosive GERD Patients LA Grades C/D (Moderate-to-Severe) Erosive GERD Patients 33
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Overall, the safety results observed in PHALCON-EE were consistent with those observed in prior clinical studies of vonoprazan % (n) Vonoprazan 20 mg Lansoprazole 30 mg Diarrhea 2.1% (11) 2.5% (13) % (n) Vonoprazan 20 mg Vonoprazan 10 mg Lansoprazole 15 mg Abdominal Pain 5.4% (16) 4.1% (12) 2.4% (7) Gastritis 2.7% (8) 6.4% (19) 2.7% (8) COVID-19 10.1% (30) 6.1% (18) 6.7% (20) Most Common Adverse Events Healing Phase Maintenance Phase Serious Adverse Events (>1 patient) Most Common Adverse Events (≥ 5%) Vonoprazan 20 mg Vonoprazan 10 mg Lansoprazole 15 mg COVID-191 (n) 5 2 0 Both Phases Summary of PHALCON-EE Phase 3 safety data 1 No COVID-19 SAEs were deemed related to the study drug by the investigator | Safety Set: All subjects who received at least one dose of study medication34
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Primary endpointHealing Phase Maintenance Phase Denotes primary endpoints tested for noninferiority; endpoints were also tested for superiority PHALCON-EE Phase 3 met primary and key secondary endpoints * Healing phase primary endpoint, exploratory superiority comparison, nominal p<0.0001 ^ Maintenance phase primary endpoint, prespecified secondary superiority comparison: vonoprazan 20 mg: p=0.0136; vonoprazan 10 mg p=0.0436 # Sustained resolution of heartburn is defined as seven (7) consecutive days without heartburn symptoms. For this test to be satisfied a patient must commence the seven consecutive day period on either day 1, 2 or 3 and last, respectively, up to day 7, day 8 or day 9. Noninferiority: % of subjects with complete healing of Erosive GERD by Week 8 p<0.0001* Noninferiority: % of 24-hour heartburn-free days over the Healing Period 95%CI: (-1.60,7.03) Superiority: % of Grades C/D subjects who have healing at Week 2 p=0.0008 Superiority: % of subjects with onset of sustained resolution of heartburn by Day 3# p=0.4392 Superiority: % of Grades C/D subjects who have healing by Week 8 not tested in hierarchy p<0.0001 (nominal) Superiority: % of subjects (All Grades) who have healing at Week 2 not tested in hierarchy p=0.0348 (nominal) Vonoprazan 20 mg Vonoprazan 20 mg Vonoprazan 10 mg Noninferiority: % of subjects who maintained healing through Week 24 p<0.0001^ p<0.0001^ Superiority: % Grades C/D maintain healing through Week 24 p=0.0196 p=0.0490 Superiority: % all Grades maintain healing through Week 24 p=0.0136 p=0.0436 Noninferiority % of 24-hour heartburn-free days through Week 24 95%CI: (-2.63, 6.72) 95%CI: (-2.27, 6.84) 35
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Phase 3 trial for Non-Erosive GERD PHALCON-NERD-301 36
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vonoprazan 20 mg vonoprazan 10 mg Non-Erosive GERD patients (n=772)1 vonoprazan 20 mg (n=257) vonoprazan 10 mg (n=257) placebo (n=258) 4-week double blind treatment Week 4 Primary Endpoint vonoprazan 10 mg Week 24 End of Treatment 20-week long-term double-blind safety and efficacy evaluation period vonoprazan 20 mg Blinded extension period for further safety and long-term efficacy evaluation Mean % 24-hr heartburn-free days through week 4 Daily dosing x 4 week Controlled Daily dosing efficacy data through 6 months PHALCON-NERD-301 Phase 3 Daily dosing trial design Vonoprazan 10 mg dose was submitted in sNDA for treatment of Non-Erosive GERD 1 A total of 772 patients with Non-Erosive GERD were randomized and dosed37
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27.7% 44.8% 44.4% 0.0% 10.0% 20.0% 30.0% 40.0% 50.0% Placebo (n= 258)1 Vonoprazan 10 mg (n= 257)1 Vonoprazan 20 mg (n= 257)1 Mean percentage (%) of 24-hour heartburn free days over 4-week period p<0.00012 p<0.00012 PHALCON-NERD-301 met the primary endpoint for both doses 1 Intent-to-Treat Set: All subjects who received at least one dose of study medication, randomized treatment 2 p-values from general linear model with treatment group as a factor and severity and frequency of heartburn at baseline as covariates38
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% of 24-hr heartburn free days Placebo (n=258)1 Vonoprazan 10 mg (n=257)1 Vonoprazan 20 mg (n=257)1 Mean 27.7% 44.8% 44.4% P-value vs. Placebo2 -- p<0.0001 p<0.0001 Median 16.7% 48.1% 46.4% Summary of 4-week placebo-controlled period of PHALCON-NERD-301 Primary endpoint: mean percentage of 24-hour heartburn free days 1 Intent-to-Treat Set: All subjects who received at least one dose of study medication, randomized treatment 2 p-values from general linear model with treatment group as a factor and severity and frequency of heartburn at baseline as covariates39
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PHALCON-NERD-301 percentage of subjects without heartburn Over both treatment periods: Intent-To-Treat Set1 1 Intent-to-Treat Set: All subjects who received at least one dose of study medication, randomized treatment 2 The 20-week extension period was not placebo-controlled; descriptive analysis only; no statistical comparisons were conducted 0 10 20 30 40 50 60 70 80 Study Day Percentage of Subjects w/o Daytime or Nighttime Heartburn 1 7 14 21 28 35 42 49 56 63 70 77 84 91 98 105 112 119 126 133 140 147 154 161 168 Vonoprazan 20 mg QD Vonoprazan 10 mg QD Placebo --> Vonoprazan 20 mg QD Placebo --> Vonoprazan 10 mg QD placebo-controlled 4-week period Exploratory 20-Week Extension Period (Not Placebo-Controlled): Mean % of 24-hr Heartburn Free Days2 Placebo Vonoprazan 10 mg Placebo Vonoprazan 20 mg Vonoprazan 10 mg Vonoprazan 20 mg 61.9% 62.9% 62.6% 60.7% All patients were switched to VOQUEZNA for the extension period 40
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4-week placebo-controlled period % (n) Placebo (n=256) Vonoprazan 10 mg (n=259) Vonoprazan 20 mg (n=257) Abdominal Pain 0.8% (2) 1.5% (4) 2.3% (6) Constipation 0.8% (2) 2.3% (6) 0.8% (2) Diarrhea 1.2% (3) 2.3% (6) 0.4% (1) Nausea 0.4% (1) 2.3% (6) 3.1% (8) Serious Adverse Events1 from the Safety Set2 (n): • Placebo: n/a (--) • Vonoprazan 10 mg: viral pericarditis (1) • Vonoprazan 20 mg: salivary gland calculus (1), fibula/tibia fracture (1) Overall, the safety results observed in PHALCON-NERD-301 were consistent with those observed in prior clinical studies of vonoprazan Summary of PHALCON-NERD-301 safety data Most Common Adverse Events1 (≥ 2%), Safety Set2 1 Summary results only include adverse events that are treatment emergent (i.e., started after treatment) 2 Among all subjects who received at least one dose of study medication, actual treatment received % (n) Placebo Vonoprazan 10 mg (n = 118) Placebo Vonoprazan 20 mg (n = 121) Vonoprazan 10 mg (n = 248) Vonoprazan 20 mg (n = 236) Upper Respiratory Tract Infection 1.7% (2) 0.8% (1) 4.8% (12) 2.1% (5) Sinusitis 1.7% (2) 1.7% (2) 3.2% (8) 1.3% (3) Influenza 3.4% (4) 1.7% (2) 2.0% (5) 1.3% (3) Urinary Tract Infection 1.7% (2) -- 2.0% (5) 2.5% (6) Nasopharyngitis 1.7% (2) -- -- 2.1% (5) Gastroenteritis 1.7% (2) 0.8% (1) 0.4% (1) 2.1% (5) Nausea 0.8% (1) 0.8% (1) 1.2% (3) 2.1% (%) 20-week extension period 41
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Phase 2 trial for Non-Erosive GERD PHALCON-NERD-201 42
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PHALCON-NERD-201 phase 2 trial design (completed) 1 Dosing initiated at onset of a heartburn episode; rescue antacid medication allowed after 3 hours of taking test medication 2 Patients must meet study drug and diary completion compliance requirements 3 Primary endpoint for NERD phase 2 trial is complete heartburn relief at 3 hours that is sustained for 24 hours. Primary endpoint for phase 3 trial will be based on NERD phase 2 results and subsequent FDA discussions Daily dosing treatment phase 4-week daily dosing open label run-in Primary endpoint Proportion of heartburn episodes with complete relief at 3 hours and sustained for 24 hours3 On-demand treatment phase1 vonoprazan 20 mg (n=52) vonoprazan 10 mg (n=52) Placebo (n=52) 6-week on-demand treatment period vonoprazan 40 mg (n=51) vonoprazan 20 mg (n=458) Patients with last 7 days of sustained relief of heartburn and those who meet compliance requirements progress to on-demand treatment phase2 43
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5.7% 11.9% 18.1% 21.9% 27.3% 8.6% 28.1%* 42.1%* 50.7%* 56.0%* 5.2% 19.3%# 31.5%* 46.2%* 60.6%* 2.8% 22.9%# 43.0%* 57.9%* 70.0%* 0.0% 10.0% 20.0% 30.0% 40.0% 50.0% 60.0% 70.0% 30 minutes 1 hour 1.5 hours 2 hours 3 hours Placebo Vonoprazan 10 mg Vonoprazan 20 mg Vonoprazan 40 mg (n=370) (n=359) (n=327) (n=323) Primary Endpoint % of evaluable episodes^ with complete and sustained heartburn relief^^ PHALCON-NERD-201 met the primary endpoint for all doses and demonstrated significance over placebo for all doses as early as 1-hour * Denotes p < 0.0001 statistically significant difference from placebo # Denotes p < 0.01 statistically significant difference from placebo ^ Evaluable episode: heartburn episode for which subject completes a minimum of one timed assessment ^^ Complete relief: Full symptom relief with no rescue antacid taken (must be achieved within 3 hours of study drug); Sustained relief: No further episodes recorded within following 24 hours 44
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27.3% 56.0% 60.6% 70.0% 20.0% 30.0% 40.0% 50.0% 60.0% 70.0% % of episodes relieved by 3 hr + sustained Placebo (n=370) Vonoprazan 10 mg (n=359) Vonoprazan 20 mg (n=327) Vonoprazan 40 mg (n=323) PHALCON-NERD-201 met the primary endpoint for all doses * Evaluable episode: heartburn episode for which subject completes a minimum of one timed assessment ^ Complete relief: Full symptom relief with no rescue antacid taken (must be achieved within 3 hours of study drug); Sustained relief: No further episodes recorded within following 24 hours % of evaluable episodes* with complete and sustained heartburn relief within 3 hours^ p < 0.0001 p < 0.0001 p < 0.0001 45
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41.9% 72.1% 65.7% 79.6% 0.0% 10.0% 20.0% 30.0% 40.0% 50.0% 60.0% 70.0% 80.0% % of episodes p < 0.0001 p < 0.0001 p < 0.0001 % of evaluable episodes* with complete heartburn relief within 3 hours^ (with or without 24-hour sustained relief) PHALCON-NERD-201 met the key secondary endpoint with all doses resulting in more complete relief of heartburn episodes vs. placebo * Evaluable episode: heartburn episode for which subject completes a minimum of one timed assessment ^ Complete relief: Full symptom relief with no rescue antacid taken (must be achieved within 3 hours of study drug) Placebo (n=370) Vonoprazan 10 mg (n=359) Vonoprazan 20 mg (n=327) Vonoprazan 40 mg (n=323) 46
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Placebo (n=52) Vonoprazan 10 mg (n=52) Vonoprazan 20 mg (n=52) Vonoprazan 40 mg (n=51) % (n) of subjects with at least 1 AE 21.3% (10) 16.3% (8) 18.4% (9) 16.7% (8) • No individual AE was reported by more than one subject in a treatment group • No SAEs Daily dosing treatment phase Vonoprazan 20 mg QD As Needed treatment phase • Most commonly reported events (> 1% of subjects) • Abdominal distension 1.3% • Diarrhea 1.5% • Nausea 1.3% • 4 SAEs • 1 study drug related SAE (anaphylactic reaction) The safety data for all vonoprazan arms were comparable to placebo and consistent with what was reported in previous studies PHALCON-NERD-201 safety data 47