Pharvaris N.v. · NASDAQ:PHVS
Pharvaris — Investor Presentation (January 2022)
33 slides from Pharvaris's investor presentation, Jan 10, 2022
Slide 1: Pioneering science for patient choice
Exhibit 99.1 Pioneering science for patient choice January 2022 © 2022 © 2022
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 other than statements of historical factors contained in this Presentation, including statements regarding
Slide 3: Fulfilling an unmet need in the treatment of HAE and other bradykinin-mediated diseases
Pharvaris: Fulfilling an unmet need in the treatment of hereditary angioedema (HAE) and other bradykinin-mediated diseases Competitive product profile Large market opportunity Strong fundamentals Convenient, orally available, small Large global HAE market of $2+ Novel lead series with strong IP (pri
Slide 4: Experienced management with deep expertise in development and rare diseases
Experienced management with deep expertise in development and rare diseases Berndt Modig Anne Lesage, Ph.D. Morgan Conn, Ph.D. Wim Souverijns, Ph.D. Chief Community Engagement Chief Early Development Officer Chief Business Officer Chief Executive Officer and Commercial Officer Includes the leaders b
Slide 5: Hereditary Angioedema (HAE)
Hereditary Angioedema (HAE) © 2022 © 2022
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 patients in the U.S. ‒ At least 8,900 patients in Europe ‒ Globally, under-diagnosed/treated
Slide 7: HAE attacks are unpredictable, debilitating and potentially lethal
HAE attacks are unpredictable, debilitating and potentially lethal § Attacks are unpredictable in Annual attacks (overall) frequency, location, timing, and 40% severity Median: 14 attacks/year •Females: 19 (range: 2-165 attacks/y) •Males: 9 (range: 1-42 attacks/y) ‒ Multiple types of triggers 30% ‒
Slide 8: Swelling of an HAE attack is caused by excess bradykinin
The swelling of an HAE attack is caused by excess levels of bradykinin: PHA121 is designed to block signaling by bradykinin Most genetic causes lead to elevated levels of bradykinin HMWK: high-molecular-weight kininogen; cHMWK: cleaved high-molecular-weight kininogen Busse 2020 J Allergy Clin Immuno
Slide 9: HAE patients actively switch products seeking improvement
HAE patients actively switch products seeking improvement in efficacy, safety/tolerability, and convenience 1 2 3 … but safety & tolerability … while convenience has Efficacy is patient’s are pushing patients to become a key driver for prime concern … explore alternatives … patient preference Patien
Slide 10: HAE is a valuable, growing market
HAE is a valuable, growing market (US approved) On-Demand Prophylaxis § $2B+ market in 2018 growing ~13% annually $772M 2018 open ground B2 receptor § Significant unmet need for an oral solution + generic § Most approved products are injectable § Efficacious, but often with injection-site $251M $253
Slide 11: Product Strategy
Product Strategy © 2022 © 2022 11 CONFIDENTIAL
Slide 12: On-demand and prophylaxis: two oral products utilizing the same active ingredient
On-demand and prophylaxis: Developing two oral products utilizing the same active ingredient PHA121 PHVS416 PHVS719 Softgel capsule formulation Extended-release tablet formulation Aim to maintain compound exposure Potential to provide fast, easy, and to prevent attacks, providing an easy reliable sy
Slide 13: Wholly-owned pipeline focused on bradykinin B2 receptor mechanism
Wholly-owned pipeline focused on bradykinin B2 receptor mechanism Candidate Indication Discovery Preclinical Phase 1 Phase 2 Phase 3 Next Milestone PHA121 Phase 2 topline data PHVS416 in 4Q2022 On-demand HAE (RAPIDe-1 trial) Phase 2 topline data PHVS416 in 4Q2022 HAE Prophylaxis (PoC) (CHAPTER-1 tri
Slide 14: Programs
Programs © 2022 © 2022 CONFIDENTIAL
Slide 15: Pharvaris compounds are potent, orally available competitive inhibitors of the bradykinin 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) Pharvaris Icatibant compound Increasing antagonist concentration Increasing antagonist concentration pA 8.
Slide 16: PHA121 PK/PD in humans
PHA121 PK/PD in humans © 2022 © 2022 CONFIDENTIAL
Slide 17: PHA121 was well tolerated in Phase 1 SAD and MAD trials
PHA121 was well tolerated in Phase 1 SAD and MAD trials PHA121 (oral solution) has completed SAD and MAD All doses were well tolerated in Phase 1 studies SAD, SADext, and MAD studies (oral solution) § Single ascending dose: 1-50 mg; double-blind, placebo-controlled § No SAEs or severe AEs were repor
Slide 18: PHA121 demonstrates a dose-proportional PK profile
PHA121 demonstrates a well-behaved dose-proportional PK profile 1 mg PHA-022121 fasted 250 22 mg PHA121 1000 250 (fasted) 2 mg PHA-022121 fasted 200 22 mg PHA121 4.5 mg PHA-022121 fasted 200 100 (HCHF meal) 150 12 mg PHA-022121 fasted 22 mg PHA121 100 22 mg PHA-022121 fasted 150 10 (standard meal) 4
Slide 19: BID doses of PHA121 maintain exposure above predicted efficacious levels
In multiple-dose studies, when dosed with food, BID doses of PHA121 solution maintain exposure above predicted efficacious levels C (mean) on Day 10 Exposure following last dose (Day 10) trough prior to final dose 250 200 150 EC 85 100 50 EC85 0 12 mg 22 mg 33 mg 55 mg BID BID BID BID Steady state r
Slide 20: Inhibition of bradykinin-induced hemodynamic effects is a validated surrogate assessment
Inhibition of bradykinin-induced hemodynamic effects is a validated surrogate assessment § In healthy volunteers, pre-dosing a bradykinin-B2-receptor antagonist blocks the Bradykinin (BK) hemodynamic effects of bradykinin • Bradykinin effects restored as single-dose eliminated BP HR § Used to select
Slide 21: Preclinical: oral PHA121 inhibits bradykinin challenge with longer duration than icatibant
In preclinical in vivo studies, oral PHA121 inhibits challenge by bradykinin with longer duration and faster onset than SC icatibant https://education.aaaai.org/sites/default/files/L37%20Lesage_1.pdf © 2022 21
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 PHA121 or placebo (po) Bradykinin BK BK BK BK BK (BK) Human BK challenge PHA121 +12 0 +1 +4 +8 hours +24 Predose EC (ng/mL) 2.4 50 EC (ng/mL) 13.8 85 Predose +1 h after dose Systolic BP
Slide 23: Single PHA121 dose predicted to match two icatibant injections
A single PHA121 dose predicted to provide similar pharmacodynamic effect as two injections of icatibant Estimated duration of effect (icatibant versus PHA121) PK (exposure) Icatibant PHA121 PHA121 Response 30 mg SC 12 mg PO 22 mg PO Time (h) plasma level above EC at 50% confidence level 85 DBP 5.5 7
Slide 24: PHVS416/On-Demand Softgel capsule formulation of PHA121
PHVS416/On-Demand Softgel capsule formulation of PHA121 © 2022 © 2022 CONFIDENTIAL
Slide 25: HAE RAPIDe-1 study underway: on-demand treatment of acute attacks
HAE RAPIDe-1 study underway: On-demand treatment of acute attacks in Type 1 or 2 HAE patients Study Site Home Treatment§ Primary objective: to evaluate angioedema Non-attack Attack 1 Attack 2 Attack 3 symptom relief within four hours in acute PHVS416 PHVS416 placebo attacks of patients with HAE type
Slide 26: On-Demand: PHVS416 aims to provide clear differentiation
On-Demand: PHVS416 aims to provide clear differentiation for efficacy and convenience Clinical data PHVS416 Icatibant KVD900 berotralstat BERINERT® RUCONEST® KALBITOR® FDA Approval (Phase 2) 2011 (end of Phase 2) (EOP2, dropped) 2009 2014 2009 Mechanism B2R B2R pKi pKi C1INH C1INH pKi Dose ≤30 mg 30
Slide 27: PHVS719/Prophylaxis Extended-release tablet formulation of PHA121
PHVS719/Prophylaxis Extended-release tablet formulation of PHA121 © 2022 © 2022
Slide 28: Prophylactic proof-of-concept study underway with PHVS416
Prophylactic proof-of-concept study underway with PHVS416 Candidate Phase 1 Phase 2 Phase 3 Indication Utilizing the food effect observed in Phase 1, PK/PD modeling PHVS416 Data 4Q22 suggests that PHA121 can maintain exposure >EC 85 Prophylaxis HAE with twice-daily dosing of PHVS416 PHVS719 Data 1Q2
Slide 29: HAE CHAPTER-1 study recruiting: prevention of attacks
HAE CHAPTER-1 study recruiting: Prevention of attacks in HAE patients § Primary objective: assessing safety and efficacy of 12 WEEKS PHA121 in preventing HAE attacks in patients with HAE type 1 or type 2 Placebo 2 placebo capsules § Placebo-controlled, 3 parallel arms, two doses § Primary endpoint:
Slide 30: PHVS719 PK study underway: assessing QD potential
PHVS719 PK study underway: Assessing QD potential § Open-label, crossover comparison in 8 adult § Primary objective to assess PK under male healthy volunteers fasting conditions • Secondary objectives to assess food effect; § Sequential dosing (random order) of: compare exposure to PHVS416; evaluate
Slide 31: Prophylaxis: PHVS719 compared to approved therapies and oral pipeline
Prophylaxis: PHVS719 aims to combine efficacy and convenience compared to approved therapies and oral pipeline PHVS719 KVD824 ORLADEYO® TAKHZYRO® HAEGARDA® CINRYZE® FDA Approval (Phase 1/2) (Phase 2) 2020 2018 2017 2008 Mechanism B2R pKi pKi pK mAb C1INH C1INH Dose ≤40 mg 300-900 mg 150 mg, 110 mg 3
Slide 32: Pharvaris poised for multiple milestones in 2022
Pharvaris poised for multiple milestones in 2022 HAE On-Demand HAE Prophylaxis (type 1 and type 2) (type 1 and type 2) RAPIDe-1 Ph2 topline data CHAPTER-1 Ph2 topline data PHVS416 soft capsule (anticipated 4Q22) (anticipated 4Q22) Ph1 topline PK data PHVS719 XR tablet not applicable (anticipated 1Q2
Slide 33: © 2022 © 2022
Nasdaq: PHVS © 2022 © 2022