Pharvaris N.v. · NASDAQ:PHVS
Pharvaris — Investor Presentation (January 2023)
46 slides from Pharvaris's investor presentation, Jan 9, 2023
Slide 1: Pioneering science for patient choice
Pioneering science for patient choice January 2023 Exhibit 99.2
Slide 2: Disclaimer
Disclaimer This Presentation may contain certain “forward‐looking statements” within the meaning of the federal securities laws that involve substantial risks and uncertainties. All statements contained in this Presentation that do not relate to matters of historical fact should be considered forwar
Slide 3: Pharvaris: Focused on unmet need in HAE and other bradykinin-mediated diseases
Pharvaris: Focused on unmet need in the treatment of hereditary angioedema (HAE) and other bradykinin-mediated diseases 3 Novel lead series with strong IP (primary CoM granted in multiple territories; initial term to 2038); FDA orphan drug designation World-wide operations: the Netherlands, USA, and
Slide 4: Experienced management with deep expertise in development and rare diseases
Experienced management with deep expertise in development and rare diseases 4 Includes the leaders behind the discovery, development, and approval of Firazyr® (icatibant), and a key member of the Takhzyro® (lanadelumab) development team
Slide 5: Hereditary Angioedema (HAE)
Hereditary Angioedema (HAE)
Slide 6: HAE is a rare, life-long condition characterized by attacks of swelling
HAE is a rare, life-long condition characterized by attacks of swelling Rare and potentially life-threatening genetic condition 1:10,000 to 1:50,000 Individuals affected by HAE globally At least 6,600 people living with HAE in the U.S. At least 8,900 people living with HAE in Europe Globally, under-
Slide 7: HAE attacks are unpredictable, debilitating and potentially lethal
HAE attacks are unpredictable, debilitating and potentially lethal Attacks are unpredictable in frequency, location, timing, and severity Multiple types of triggers If untreated, attacks last multiple days Attacks are commonly painful, leading to hospitalization or multiple sick days Half of people
Slide 8: Swelling of an HAE attack is caused by excess bradykinin
HMWK: high-molecular-weight kininogen; cHMWK: cleaved high-molecular-weight kininogen The swelling of an HAE attack is caused by excess levels of bradykinin: PHA121 is designed to block signaling by bradykinin 8 Busse 2020 J Allergy Clin Immunol Pract; Bork et al 2021 J Allergy Clin Immunol Genetic
Slide 9: HAE is a meaningful and growing global market
HAE is a meaningful and growing global market CONFIDENTIAL - board materials 9 est. est. Source: Quarterly filings (NYSE: TAK; NASDAQ: BCRX, PHAR); EvaluatePharma; company research Estimated $2.4B global HAE sales for 2021 Estimated 15% CAGR 2021-2028 SC oral IV est. On-Demand Prophylaxis
Slide 10: Significant global unmet need: potentially up to 100,000 people living with HAE
Significant global unmet need: Potentially up to 100,000 people living with HAE CONFIDENTIAL 10 EU 15-20k US 6-9k LATAM 12-16k JP 2-4k Plus breakthrough attacks ME&A 10-14k Proprietary company research 2022; Maurer et al. Consensus on diagnosis and management of Hereditary Angioedema in the Middle E
Slide 11: People living with HAE actively switch products seeking improvement
People living with HAE actively switch products, seeking improvement in efficacy, safety/tolerability, and convenience 11 People living with HAE desire HAE therapy that can deliver on ALL fronts Proprietary company research 2022
Slide 12: Pharvaris has discovered the first orally bioavailable bradykinin B2 receptor antagonist
Pharvaris has discovered the first orally bioavailable bradykinin B2 receptor antagonist New molecular entity, orally administered Potent inhibition of the bradykinin B2 receptor to compete with bradykinin, the ultimate driver of swelling attacks Results from Phase 1 healthy volunteer studies demons
Slide 13: Product Strategy
Product Strategy 13
Slide 14: On-demand and prophylaxis: two oral products with the same active ingredient
On-demand and prophylaxis: Developing two oral products utilizing the same active ingredient 14 PHVS719 Extended-release tablet formulation Aim to maintain compound exposure to prevent attacks, for convenient and effective control* PHVS416 Softgel capsule formulation Potential to provide rapid, easy
Slide 15: Wholly-owned pipeline focused on bradykinin B2 receptor mechanism
Wholly-owned pipeline focused on bradykinin B2 receptor mechanism 15 * The FDA has placed a clinical hold on the clinical trials of PHA121 in the U.S.; timeline based on studies ongoing outside the U.S.; see slide 16 for an update on our clinical program
Slide 16: Regulatory update
Regulatory update In August 2022, the U.S. Food & Drug Administration (FDA) placed a hold on the clinical trials of PHA121 in the U.S. based on its review of nonclinical data The agency requested that Pharvaris conduct an additional long-term rodent toxicology study and update the Investigator’s Bro
Slide 17: PHVS416/On-Demand
PHVS416/On-Demand Softgel capsule formulation of PHA121
Slide 18: On-demand treatment of HAE attacks: significant unmet need
On-demand treatment of HAE attacks: No new approvals beyond injectable options have left a significant unmet need 18 Treatment today means painful injections … … and often one dose does not suffice … … while finding a place to administer the drug causes an extra burden As a result, people living wit
Slide 19: People living with HAE are hoping for better on-demand therapies
People living with HAE are hoping for better on-demand therapies that offer rapid symptom relief with one single, oral dose 19 Patients want rapid onset of symptom relief … … with single dose durability … … in an oral pill Effectively targeting the bradykinin receptor with a small molecule has the p
Slide 20: HAE RAPIDe-1 study design
HAE RAPIDe-1 study: Phase 2 study of on-demand treatment of angioedema attacks in patients with Type I or II HAE www.hae-rapide.com; https://clinicaltrials.gov/ct2/show/NCT04618211; https://hae-rapide.us/; https://www.clinicaltrialsregister.eu/ctr-search/search?query=2020-003445-11 20 Screening Peri
Slide 21: Positive top-line Phase 2 data from RAPIDe-1
Positive top-line Phase 2 data from RAPIDe-1 study of PHVS416 for the on-demand treatment of HAE attacks A total of 74 patients from 13 countries were enrolled to the study, 62 of them had 147 attacks that were treated with blinded study drug and included in efficacy evaluation The primary endpoint
Slide 22: PK profile in HAE patients
PK profile in HAE patients: Rapid absorption confirmed on oral dosing, consistent with Phase 1 healthy volunteer studies 22 Rapid absorption with mean plasma levels exceeding EC85 (13.8 ng/mL) within 30 min Mean plasma levels maintained >EC85 for approximately 8 h at 10 mg or 20 mg >10 h at 30 mg do
Slide 23: Primary endpoint: PHVS416 significantly reduces attack symptoms by VAS-3 at 4h
†Nominal p-value; VAS assessed every 30 minutes up to 4 hours post-treatment, then at 5, 6, 8, 24, 48 hours; N = The number of attacks in the mITT Analysis Set. Attacks in mITT Analysis Set refer to attacks treated with blinded study drug that had non-missing VAS result at pre-treatment and at least
Slide 24: PHVS416 significantly shortened time to onset of symptom relief
†Nominal p-value; N = The number of attacks in the mITT Analysis Set. Median time based on Kaplan-Meier estimates. p-values based on a marginal Cox proportional hazards model. The combined PHVS416 results are based on post-hoc analyses to provide a reference of the result by pooling all three active
Slide 25: TOS Patient Reported Outcome (PRO)
TOS Patient Reported Outcome (PRO) 25 TOS PRO captures change in five symptom complexes of HAE attacks At each timepoint, the change in attack symptom from pre-treatment is reported by patient PRO – how do you feel now compared to before receiving study drug?
Slide 26: TOS endpoint shows early response to treatment
TOS endpoint shows early response to treatment: Significant at 4h 26 Source: Vernon M, Rentz AM, Wyrwich KW, et al. Qual Life Res.2009; †Nominal p-value; N = The number of attacks in the mITT Analysis Set. TOS = Treatment Outcome Score. Figure is based on descriptive summary of mean and SEM. The lea
Slide 27: PHVS416 significantly reduces time to almost complete or complete symptom relief
PHVS416 significantly reduces time to almost complete or complete symptom relief (all individual VAS ≤ 10) 27 †Nominal p-value; N = The number of attacks in the mITT Analysis Set. Median time based on Kaplan-Meier estimates. p-values based on a marginal Cox proportional hazards model. The combined P
Slide 28: Patients treating with PHVS416 used substantially less rescue medication
Patients treating with PHVS416 used substantially less rescue medication 28 N = The number of attacks in the mITT Analysis Set This presentation includes data for an investigational product not yet approved by regulatory authorities
Slide 29: PHVS416 was well tolerated at all doses
PHVS416 was well tolerated at all doses 29 No treatment-related SAEs or AEs of severe severity No AEs leading to treatment discontinuation No treatment-related AEs of laboratory parameters, vital signs, or ECG parameters Few treatment-related AEs reported within 48 h after administration of study dr
Slide 30: Oral acute therapy would increase likelihood patients treat more attacks, earlier
Both doctors and patients consider an oral acute therapy would increase likelihood that patients would treat more attacks, earlier CONFIDENTIAL 30 Proprietary Pharvaris research, 2022 (representative sample of patients, n = 103, and doctors, n = 100)
Slide 31: Predictive value of the BK challenge surrogate-marker model
Predictive value of our unique in vivo surrogate-marker model, the BK challenge, allows for derisking of our clinical studies 31 https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000ClinPharmR.pdf; Maurer et al 2020: Long-term effectiveness and safety of icatibant for the on-demand
Slide 32: PHVS719/Prophylaxis
PHVS719/Prophylaxis Extended-release tablet formulation of PHA121
Slide 33: HAE CHAPTER-1 study ongoing outside U.S.
HAE CHAPTER-1 study ongoing outside U.S.: Prevention of attacks in HAE (proof of concept with PHVS416 softgel capsule) Primary objective: assessing safety and efficacy of PHA121 in preventing HAE attacks in patients with HAE type 1 or type 2 Placebo-controlled, 3 parallel arms, two doses Includes op
Slide 34: Phase 1 pharmacokinetics support softgel capsule as proof-of-concept in prophylaxis
Phase 1 pharmacokinetics offer options to use softgel capsule as proof-of-concept in prophylactic development https://ir.pharvaris.com/static-files/0361cd85-6000-490b-932b-d305e1f3ca1b; https://ir.pharvaris.com/static-files/81a9499d-0769-4b89-8ecd-8ace5ca521d3 34 When dosed BID with food, exposure m
Slide 35: PHVS719 single-dose PK study demonstrates QD potential
PHVS719 single-dose PK study demonstrates QD potential; target for Phase 3 dosage form 35 PHVS416 and PHVS719 well tolerated No SAEs or severe TEAEs PHVS416 rapid exposure confirmed Exceeding EC85 within 15 minutes PHVS719 extended release demonstrated: maintained exposure above EC85 for >24h with a
Slide 36: Corporate summary and milestones
Corporate summary and milestones 36 Financially strong: Cash runway into 4Q24
Slide 37: PHARVARiS
PHARVARiS Nasdaq: PHVS
Slide 38: Appendix: Additional RAPIDe-1 top-line clinical data
Appendix Additional RAPIDe-1 top-line clinical data
Slide 39: RAPIDe-1: Primary, key secondary and other endpoints
RAPIDe-1: Primary, key secondary and other endpoints Primary Endpoint Change in VAS-3 score from pre-treatment to 4h post-treatment Key Secondary Endpoints Time to onset of symptom relief (VAS-3; ≥30% reduction from the pre-treatment score) Time to a ≥50% reduction in VAS-3 score from the pre-treatm
Slide 40: Results summary of primary efficacy endpoint
Results summary of primary efficacy endpoint 40 This presentation includes data for an investigational product not yet approved by regulatory authorities
Slide 41: VAS-3 is a measure of HAE attack severity
VAS-3 is a measure of HAE attack severity, based electronically captured numerically assisted visual scale 41 Used in approval of two most recently approved on-demand therapies FIRAZYR® icatibant and RUCONEST® C1 esterase inhibitor [recombinant] VAS, MSCS, TOS are only endpoints listed for attacks i
Slide 42: Results summary of key secondary efficacy endpoints
Results summary of key secondary efficacy endpoints 42 This presentation includes data for an investigational product not yet approved by regulatory authorities
Slide 43: PHVS416 significantly reduces time to 50% reduction in VAS-3
PHVS416 significantly reduces time to 50% reduction in VAS-3 43 †Nominal p-value; VAS assessed every 30 minutes up to 4 hours post-treatment, then at 5, 6, 8, 24, 48 hours; N = The number of attacks in the mITT Analysis Set. Median time based on Kaplan-Meier estimates. p-values based on a marginal C
Slide 44: MSCS and TOS: definitions
MSCS and TOS: definitions 44 Validated patient-reported outcome measures to comprehensively capture symptom severity and change of HAE attacks MSCS (Mean Symptom Complex Severity) score is a point-in-time measure of symptom severity: Patients rated the severity of each affected symptom on a categori
Slide 45: Greater improvement in MSCS and TOS with PHVS416 than placebo
Greater improvement in MSCS and TOS with PHVS416 than placebo 45 †Nominal p-value; MSCS = Mean Symptom Complex Severity, TOS = Treatment Outcome Score, CI = confidence interval, LSMD = least-squares mean difference; least-squares mean, LSMD, CIs, and p-values for MSCS change from pre-treatment/TOS c
Slide 46: Time to symptom relief by TOS PRO demonstrated consistent efficacy at all doses
Time to symptom relief by TOS PRO demonstrated consistent efficacy at all doses 46 TOS = Treatment Outcome Score. PRO = Patient Reported Outcome. SC = Symptom Complex. KM = Kaplan-Meier. NE = Not Estimable * Within 48 hours assessments This presentation includes data for an investigational product n