Pharvaris N.v. · NASDAQ:PHVS
Pharvaris — Investor Presentation (November 2022)
45 slides from Pharvaris's investor presentation, Nov 1, 2022
Slide 1: Pioneering science for patient choice
Pioneering science for patient choice November 2022 EX-99.1
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 Most genetic causes lead to elevated levels of b
Slide 9: People living with HAE actively switch products seeking improvement
People living with HAE actively switch products seeking improvement in efficacy, safety/tolerability, and convenience 9 1 2 3 Efficacy is patients’ prime concern … … but safety & tolerability are pushing patients to explore alternatives … … while convenience has become a key driver for patient prefe
Slide 10: HAE is a meaningful and growing global market
HAE is a meaningful and growing global market CONFIDENTIAL - board materials 10 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 11: Product Strategy
Product Strategy 11
Slide 12: 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 12 PHVS719 Extended-release tablet formulation Aim to maintain compound exposure to prevent attacks, for easy and effective control PHVS416 Softgel capsule formulation Potential to provide fast, easy, and re
Slide 13: Wholly-owned pipeline focused on bradykinin B2 receptor mechanism
Wholly-owned pipeline focused on bradykinin B2 receptor mechanism 13 * 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 14 for an update on our clinical program
Slide 14: Update on clinical programs
Update on clinical programs 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 Investig
Slide 15: Programs
Programs
Slide 16: Pharvaris compounds are potent, orally available competitive inhibitors of the B2 receptor
Pharvaris compounds are potent, orally available competitive inhibitors of the bradykinin B2 receptor Competitive antagonism of bradykinin-induced contraction (human umbilical vein preparation) PHA121 is 25-fold more potent than icatibant at the endogenous human B2 receptor Lesage et al, Frontiers i
Slide 17: PHA121 PK/PD in humans
PHA121 PK/PD in humans
Slide 18: PHA121 was well tolerated in Phase 1 SAD and MAD trials
PHA121 was well tolerated in Phase 1 SAD and MAD trials 18 PHA121 (oral solution) No clinically significant changes were observed for physical exams, vitals, ECG, and safety lab assessments No SAEs or severe AEs were reported with no treatment discontinuations Most AEs observed were of mild severity
Slide 19: Phase 1 pharmacokinetics offer options for on-demand and prophylactic development
Phase 1 pharmacokinetics offer options for on-demand and prophylactic development When dosed BID with food, exposure maintained above target levels, steady state reached within 72 hours Surpasses target exposure (EC85) within 15 minutes under both fasted and fed status https://epostersonline.com/aca
Slide 20: Inhibition of bradykinin-induced hemodynamic effects is a validated surrogate assessment
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 treatment of hereditary angioedema attacks: 10 years of the icatibant outcome survey (EAACI Poster #1118, June 6-8, 2020): https
Slide 21: Oral PHA121 inhibits bradykinin challenge with longer duration than SC icatibant
In preclinical in vivo studies, oral PHA121 inhibits challenge by bradykinin with longer duration and faster onset than SC icatibant 21 https://education.aaaai.org/sites/default/files/L37%20Lesage_1.pdf
Slide 22: Oral PHA121 blocks bradykinin-induced hemodynamic changes in healthy volunteers
In healthy volunteers, oral pre-treatment with PHA121 blocks the effect of bradykinin-induced hemodynamic changes 22 https://epostersonline.com/acaai2020/node/1369; https://doi.org/10.1016/j.jaci.2019.12.094; https://www.accessdata.fda.gov/drugsatfda_docs/nda/2011/022150Orig1s000ClinPharmR.pdf Systo
Slide 23: PHVS416/On-Demand
PHVS416/On-Demand Softgel capsule formulation of PHA121
Slide 24: HAE RAPIDe-1 study design
HAE RAPIDe-1 study: Dose-ranging study for acute treatment of angioedema attacks in patients with hereditary angioedema Phase 2 double-blind placebo-controlled cross-over Patients randomized to one of three doses Each patient receives dosage to treat three attacks, two active and one placebo (2:1 tr
Slide 25: HAE RAPIDe-1 study: Topline data expected Dec 2022
HAE RAPIDe-1 study: Topline data expected Dec 2022 25 Primary topline data expected Dec 2022 based on collected dataset of attacks Continued monitoring of attacks of enrolled patients in countries outside the U.S. in RAPIDe-1 and RAPIDe-2 (open-label extension) Enrollment target achieved 72 HAE pati
Slide 26: RAPIDe-1: Primary and secondary endpoints
RAPIDe-1: Primary and secondary endpoints Primary Change of VAS-3 from pre-treatment to 4h post-treatment Secondary Time to onset of symptom relief (VAS-3; ≥30% reduction from pre-treatment score) Time to almost complete and complete symptom relief (VAS; all three components <10 mm) Time to a ≥50% r
Slide 27: RAPIDe-1: Other secondary endpoints
RAPIDe-1: Other secondary endpoints include: Time to onset of primary symptom relief (leading component of VAS) Proportion of IMP-treated attacks requiring the use of HAE rescue medication Time to the first use of HAE rescue medication Safety PK, dose-effect relationship, and concentration-effect re
Slide 28: VAS-3 is a measure of HAE attack severity
VAS-3 is a measure of HAE attack severity, used in past registrational studies 28 Used in approval of two most recently approved on-demand therapies FIRAZYR® icatibant and RUCONEST® C1 esterase inhibitor [recombinant] VAS, MCSC, TOS are only endpoints listed for attacks in FDA compendium of clinical
Slide 29: Clinical practice: Earlier treatment reduces time to resolution
Clinical practice: Earlier treatment reduces time to resolution HAE attacks should be treated early (US, Canada, WHO guidelines) Associated with shorter time to resolution and total attack duration 29 Maurer et al 2022 Allergy; Busse et al 2021 J. Allergy Clin Immunol Pract; Betschel et al 2019 Alle
Slide 30: Prior studies showed higher baseline and changes in VAS-3 with clinic treatment
Prior studies showed higher baseline and changes in VAS-3 scores, with treatment at clinic 30 rC1-INH (Ph2): Travel to clinic <5 hours after symptoms become moderate (high baseline VAS-3) icatibant (FAST-3 Ph3): Travel to clinic <6 hours after symptoms become moderate (high baseline VAS-3) Lumry et
Slide 31: Recent on-demand trials treat sooner at home with smaller changes in VAS-3
Recent on-demand HAE trials treat sooner in home setting, with lower baseline and smaller absolute changes in VAS-3 at 4 hours 31 BCRX poster #110 AAAAI 2019-02-23 https://ir.biocryst.com/static-files/2b3e13b9-ad24-432c-9ac5-15711d954d88; KALV presentation 2021-02-09 ΔKVD900 approx. -10 Δplacebo: ap
Slide 32: Initial relief: Relative change in VAS-3 may depend on baseline
Initial relief: Relative change in VAS-3 may depend on baseline 32 Lumry et al 2011 Ann Allergy Asthma Immunol; Riedl et al 2014 Ann Allergy Asthma Immunol; RUCONEST prescribing information; KALV presentation 2021-02-09 icatibant (FAST-3 Ph3) 2.0 h (VAS-3, 50% reduction) 1.5 h (VAS-3, 30% reduction)
Slide 33: On-Demand: PHVS416 aims to provide clear differentiation
On-Demand: PHVS416 aims to provide clear differentiation for efficacy and convenience Source: Firazyr, Ruconest, Kalbitor prescribing information; Pharming release 2018-12-07; BioCryst release 2018-09-04; Kalvista corporate presentation 2021-02-09; https://www.clinicaltrials.gov/ct2/show/NCT05259917
Slide 34: PHVS719/Prophylaxis
PHVS719/Prophylaxis Extended-release tablet formulation of PHA121
Slide 35: Data from prophylactic proof-of-concept study and PHVS719 PK to inform Phase 3
Data from prophylactic proof-of-concept study (PHVS416) and PHVS719 tablet PK to inform Phase 3 development 35 Utilizing the food effect observed in Phase 1, PK/PD modeling suggests that twice-daily dosing of PHVS416 can maintain PHA121 exposure >EC85 * The FDA has placed a hold on the clinical tria
Slide 36: 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 37: PHVS719 single-dose PK study demonstrates QD potential
PHVS719 single-dose PK study demonstrates QD potential 37 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 and without food Similar AUC24h a
Slide 38: Prophylaxis: PHVS719 aims to combine efficacy and convenience
Prophylaxis: PHVS719 aims to combine efficacy and convenience compared to approved therapies and oral pipeline Source: Takhzyro, Haegarda, Cinryze, Orladeyo prescribing information; Aygoren-Pursun 2018. NEJM 379(4), 352-62; ICER 2018 Final Evidence Report – Long-Term Prophylaxis in HAE; Kalvista cor
Slide 39: Corporate Summary and Milestones
Corporate Summary and Milestones 39 Financially strong: ~€198 million cash (Sep 30, 2022) provides runway through 1Q24
Slide 40: Pharvaris
PHARVARiS Nasdaq: PHVS
Slide 41: PHVS719 single-dose PK study demonstrates QD potential
PHVS719 single-dose PK study demonstrates QD potential 41 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 and without food Similar AUC24h a
Slide 42: PHVS719 single-dose PK study demonstrates QD potential
PHVS719 single-dose PK study demonstrates QD potential 42
Slide 43: PHVS719 single-dose PK study demonstrates QD potential
PHVS719 single-dose PK study demonstrates QD potential 43
Slide 44: PHA121 plasma concentration
PHA121 plasma conc. target plasma level 12 Time (h)
Slide 45: PHVS719 single-dose PK study demonstrates QD potential
PHVS719 single-dose PK study demonstrates QD potential 45