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Forward-Looking Statements This presentation and the accompanying oral
commentary contain forward-looking statements that are based on our management's beliefs and assumptions and on information currently available to our management. Forward-looking statements are inherently subject to risks and uncertainties,
some of which cannot be predicted or quantified. In some cases, you can identify forward-looking statements by terminology such as "may," "will," "should," "could," "expect,"
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nonclinical and clinical development activities, timing and results of nonclinical studies and clinical trials, efficacy and safety profiles of our product candidates, any expectations about safety, efficacy of sebetralstat and our ability to obtain
regulatory approvals for sebetralstat and other candidates in development, the ability of sebetralstat to treat hereditary angioedema (HAE), the potential therapeutic benefits and economic value of our product candidates, potential growth
opportunities, competitive position, industry environment and potential market opportunities, our ability to protect intellectual property and the impact of global business or macroeconomic conditions, including as a result of inflation, rising
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Company Highlights Discovery, development, and commercialization
of oral, small molecule protease inhibitors Lead program Sebetralstat for on-demand treatment of rare disease hereditary angioedema (HAE) Data from Phase 3 KONFIDENT trial announced February 2024; met all primary and secondary
endpoints, with favorable safety profile; NDA expected H1 2024 Sebetralstat would be first oral option in $900 million on-demand HAE market and has potential to transform treatment of the disease and the entire $2.7 billion market
Preclinical oral Factor XIIa program focused on HAE and additional indications All programs internally developed, with full rights and IP protection into the 2040's Funded into 2025 with $103 million at October 31, 2023
Program Portfolio Product Indication Preclinical Phase 1 Phase 2 Phase 3
Status Data reported; Sebetralstat On-Demand HAE KONFIDENT (trial completed) NDA mid-2024 Trial ongoing KONFIDENT-S (Open-Label Extension) Advancing to sNDA Orally Disintegrating Tablets as lifecycle extension Discovery and Oral Factor XIIa HAE
Prophylaxis Optimization Thrombosis, Future opportunities Oral Factor XIIa inflammation under evaluation 4
Hereditary Angioedema (HAE)
Hereditary Angioedema (HAE) Genetic condition causing painful
and pronounced swelling in various parts of the body Primarily caused by defect in C1 inhibitor activity, which leads to uncontrolled plasma kallikrein activation and bradykinin release 1 Orphan disease: incidence 1 in 10,000 to 1 in
50,000 6,500 - 8,000 patients in US; similar in EU Incidence consistent worldwide; patients have average of ~2 attacks per month Approved on-demand therapies are injected or infused - high unmet need for efficacious and
safe oral administration On-demand + prophylaxis is majority share in US, although burden of treatment remains high On-demand only is majority share ex-US 1 www.haei.org 6
On-Demand is $900 Million Market, With Growth Potential At branded
prices, On-demand was $900 Million US on-demand market alone revenue market in 2022 would be $1+ billion Ruconest Global US units 2022 $206 On-demand Berinert Market Ruconest 29,200 Cinryze $288 $147 Berinert 35,400 Haegarda $436 Firazyr Firayzr
10,500 $189 Gx icatibant 49,300 Generic Orladeyo Total units 124,400 $250 icatibant $185 Kalbitor Firazyr WAC/dose: $10,800 $30 Global Prophylaxis Takhzyro Market $1,144 All Data from Evaluate Pharma, public filings and certain Company estimates.
Sebetralstat: HAE On-Demand Therapy
Welcome to the New Era of HAE Positive topline results from the largest
clinical trial conducted in HAE We believe SEBETRALSTAT offers the promise to be the foundational HAE treatment Adults and On-demand with or Any attack location adolescents without prophylaxis or severity 9
Unmet Need In HAE Is Underappreciated The goal of treatment is to
minimize compromises in lifestyle, but attacks still cause anxiety and impact quality of life 96% of people on People typically delay Anxiety and ~50% of people People living with HAE prophylaxis feel they injectable treatment depression are taking
prophylaxis prefer to treat at home to must change their for hours and studies common in people continue to plans for the day avoid treating attacks in show more than 40% living with HAE experience HAE public when an attack of attacks aren't 3
attacks occurs 1,2,4 treated at all 1 2 Maurer M, et al. Hereditary Angioedema Attacks Resolve Faster and Are Shorter after Early Icatibant Treatment. PLoS ONE. 2013;8(2):e53773. Longhurst H J et al. Real-world 3 outcomes in hereditary angioedema:
first experience from the Icatibant Outcome Survey in the United Kingdom Allergy Asthma Clin Immunol. 2018;14: 28. Remaining Burden of Hereditary Angioedema (HAE) Attacks Despite Modern Long-term Prophylaxis Stephen Betschel, Sally van Kooten,
Markus Heckmann, Sherry Danese, Ledia Goga,Teresa 10 4 Caballero; EAACI 2023 Hybrid Congress. Banerji A, et al. Allergy Asthma Proc. 2015;36(3):213-7. doi: 10.2500/aap.2015.36.3824
Patients on LTP Still Have Attacks Proportion of patients that
experienced attacks on approved LTP in placebo-controlled trials 1 2 3 Treatment C1-INH (SC) 60 IU/kg Lanadelumab 300 mg Q2W Berotralstat 125 mg Randomized, double- Randomized, placebo- Randomized, double-blind, parallel-group, placebo- blind,
parallel-group, Trial design controlled crossover controlled phase 3 trial (26 weeks) dose-response phase 2 phase 3 trial (16 weeks) 4 trial (28 days) Proportion of C1-INH (SC) Lanadelumab Berotralstat patients 60 IU/kg (N=45) 300 mg Q2W (N=27) 125
mg (N=14) experiencing attacks during observed 23% period 57% 60% 56% Entire 28-day treatment Entire 16-day Entire 26-week Steady state period treatment period treatment period (days 70-182) Although LTP reduces attack frequency, many patients
continue to have attacks and require ready access to effective on-demand treatment References: 1. Longhurst H, et al. N Engl J Med. 2017;376(12):1131-1140. 2. Banerji A, et al. JAMA. 2018;320(20): 2108-2121. 3. Ayg ren-P rs n E, et
al. N Engl J Med. 2018;379:352-362. 4.Not reported in 11 phase 3 trial.
The Sebetralstat Treatment Vision 100% ALL ATTACKS EASE OF USE EARLY
Patients empowered to treat Patients able to treat all Sebetralstat dosing is simple with early - at first recognition of attacks, since it is impossible easy-to-take tablets attack to predict which ones will Patients
can easily carry, store escalate in severity or migrate Halt progression of swelling at and access anytime, anywhere to other anatomic locations, earliest stages including the larynx Quick-dissolving oral disintegrating tablet (ODT),
a Current barriers to treatment potential future advancement are removed including pain and inconvenience associated with parenteral therapies 12
Topline Data from Phase 3 KONFIDENT Trial
Sebetralstat Phase 3 Trial Design Double blind crossover trial
assessing 300 mg and 600 mg sebetralstat versus placebo Primary endpoint: Time to beginning of symptom relief using PGI-C At least 90% powered to detect treatment differences vs placebo Each patient treats up to 3 attacks
anytime, anywhere One with each treatment in a randomized, blinded sequence Patients take up to two doses per attack Primary endpoint: Time to beginning of symptom relief (PGI-C) Screening Randomization Treat 3 Attacks Key
secondary endpoints: Time to improvement (PGI-S) Time to resolution (PGI-S) 14
Key Differences in Design Between the Sebetralstat Phase 2 and Phase 3
KONFIDENT Trials Phase 2 Trial Phase 3 KONFIDENT Trial PGI-C: TOSR defined as at least "a little better" Time to use of conventional attack treatment Primary endpoint ( 2 time points in a row) within 12 hours after study drug
administration within 12 hours after study drug administration Adults ( 18 years of age) Adolescents and adults ( 12 years of age) Population with HAE type 1 or 2 with HAE type 1 or 2 Stable LTP eligible to participate LTP No LTP allowed
(excluding androgens and tranexamic acid) Attack locations Peripheral, abdominal All attack locations Attack severity Mild to moderate Mild to very severe Patient required to notify trial physician to confirm Patient not required to call physician
to confirm Attack eligibility attack eligibility before dosing attack eligibility before dosing Single dose of study drug with minimum 48-hour Up to 2 doses of study drug permitted as treatment Treatment washout between attacks for a single attack
Enrollment and Demographics Total (N=110) Randomized Age (years)
(N=136) Mean (SD) 37.7 (15.0) Median (min, max) 39.5 (13, 74) Age (category), n (%) Patients who treated 18+ 97 (88.2) 1 attack (N=110) 12-17 13 (11.8) Sex, n (%) Female 66 (60.0) 300 mg sebetralstat 600 mg sebetralstat Placebo (n=87 attacks)
(n=93 attacks) (n=84 attacks) Male 44 (40.0) 2 BMI (kg/m ) Mean (SD) 27.4 (6.3) Median (min, max) 26.2 (18.2, 45.6) 10 patients discontinued from the trial Geography, n (%) No patients withdrew due to an AE Europe 58 (52.7) US 34
(30.9) a Asia/Pacific 18 (16.4) Data on file 16
Comparable Attack Severity in Patients Using LTP 1 60 Attacks in
patients using on-demand treatment only (n=206) 1 Attacks in patients using on-demand treatment + LTP (n=58) 50 46.6 41.7 Total 38.8 37.9 40 (N=110) Current treatment regimen, n (%) 30 On-demand only 86 (78.2) On-demand + LTP 24 (21.8) 20
Berotralstat 11 (10.0) 15.0 12.1 Lanadelumab 8 (7.3) 10 C1INH 5 (4.5) 2.9 1.7 1.0 0.0 0 None Mild Moderate Severe Very severe Baseline attack severity (PGI-S) 1. Baseline severity for 1 attack in each group not reported. Data on file. 17 Proportion
Primary Endpoint: Time to Beginning of Symptom Relief 100 Time
to beginning of symptom relief was statistically significantly faster vs placebo for 75 300 mg (p<0.0001) 600 mg (p=0.0013) 50 Median time (95% CI) to beginning of symptom relief was 25 1.61 h (1.28, 2.27) for 300
mg Sebetralstat 300 mg Sebetralstat 600 mg 1.79 h (1.33, 2.27) for 600 mg Placebo 0 0 1 2 3 4 5 6 7 8 9 10 11 12 6.72 h (2.33, >12) for placebo Time from first study drug administration (hours) Data on file 18 Proportion of
Primary Endpoint: Consistent Treatment Effect Across Subgroups
Trial was not powered to statistically test treatment effect within subgroups Treatment effect with sebetralstat was consistent across subgroups including Sex, race, age, geographic region, HAE subtype, time to treatment, attack
location, attack severity Importantly, consistent treatment effect was also observed in subgroups not previously studied with sebetralstat Time to beginning of symptom relief Sebetralstat 300 mg Sebetralstat 600 mg Subgroup n Median (95% CI)
n Median (95% CI) On-demand with LTP 19 1.85 (0.79, 3.47) 21 2.03 (0.78, 3.41) Adolescent 10 2.27 (0.28, 9.36) 11 2.16 (0.33, 9.53) Severe/very severe 14 1.40 (0.78, 2.78) 18 1.50 (0.79, 2.27) Data on file 19
Key Secondary: Time to Reduction in Attack Severity 100 Time to
reduction in attack severity was statistically significantly faster vs placebo for 75 300 mg (p=0.0036) 600 mg (p=0.0032) 50 Median time (95% CI) to reduction in attack severity was: 25 9.27 h (4.08, >12) for 300
mg Sebetralstat 300 mg Sebetralstat 600 mg 7.75 h (3.27, >12) for 600 mg Placebo 0 0 1 2 3 4 5 6 7 8 9 10 11 12 >12 h (>12, >12) for placebo Time from first study drug administration (hours) Data on file 20 Proportion of
Key Secondary: Time to Complete Attack Resolution 100 Time to
complete attack resolution was statistically significantly faster vs placebo for 75 300 mg (p=0.0022) 600 mg (p<0.0001) 50 Proportion achieving complete attack resolution within 24 hours 25 was: Sebetralstat 300 mg
Sebetralstat 600 mg 44.0% for 300 mg Placebo 0 51.7% for 600 mg 0 2 4 6 8 10 12 14 16 18 20 22 24 Time from first study drug administration 28.4% for placebo 21 (hours) Data on file 21 Proportion of attacks (%)
On-treatment Related Adverse Events Sebetralstat Sebetralstat Placebo
System organ class preferred term, n (%) E 300 mg 600 mg (n=86) (n=93) (n=83) Gastrointestinal disorders 1 (1.2) 1 1 (1.1) 1 1 (1.2) 1 Dyspepsia 1 (1.2) 1 0 0 Nausea 0 1 (1.1) 1 1 (1.2) 1 General disorders and administration site conditions 1 (1.2)
1 0 0 Fatigue 1 (1.2) 1 0 0 Nervous system disorders 0 1 (1.1) 1 2 (2.4) 2 Headache 0 1 (1.1) 1 1 (1.2) 1 Dysgeusia 0 0 1 (1.2) 1 Reproductive system and breast disorders 0 0 1 (1.2) 1 Menstruation irregular 0 0 1 (1.2) 1 Skin and subcutaneous
tissue disorders 0 0 1 (1.2) 1 Rash 0 0 1 (1.2) 1 E, number of events; TEAE, treatment-emergent adverse events. On-treatment AEs were defined as TEAEs that start within 3 days of administering the final dose of study drug for an attack. At each
level of patient summarization, a patient is counted once if the patient reported one or more events. Adverse events were coded using MedDRA, Version 26.0. 22 See Table 14.3.1.3.2 - Safety Set. Data on file.
Results in the Sebetralstat Phase 2 Trial and the Phase 3 KONFIDENT
Trial Phase 2 Trial Phase 3 KONFIDENT Trial Population Adults 100% | adolescents 0% Adults 88.2% | adolescents 11.8% On-demand only: 100% On-demand only: 78.2% LTP On-demand + LTP: Not allowed On-demand + LTP: 21.8% Attack Peripheral 68.1% 56.1%
locations Abdominal 26.5% 43.2% Mild 50.4% 42.8% Attack Moderate 45.1% 38.6% severity Severe Not allowed 14.4% Very severe Not allowed 2.7% Sebetralstat Sebetralstat Sebetralstat Dose Placebo Placebo 600 mg 300 mg 600 mg Time to administration 30
minutes 41 minutes Median time to beginning of 1.6 h 9.0 h 1.61 h 1.79 h 6.72 h symptom relief Second dose Not allowed Not allowed 38.4% 41.1% 55.4% Use of conventional treatment 15.1% 30.2% 13.8% 8.6% 25.0% within 12 h Data on file 23
Update: KONFIDENT-S Open-Label Extension Trial to evaluate the
long-term safety of sebetralstat As of February 2, 2024 More than 110 patients enrolled More than 640 attacks treated Median time to treatment: 10 minutes All attack locations well represented, including 14
laryngeal attacks treated to date 24
Sebetralstat Halts the Attack When Today's Patients are Still
Deciding Whether to Treat Current on-demand 5+ HOURS 2 1 3.8 hours 2 to 2.3 hours Time to Treatment Halt the attack Attack Recognition 41-min 96 minutes Treatment Success Is Time to Halt the attack Measured in Minutes Treatment (KONFIDENT) Not Hours
137 MINUTES Sebetralstat 25 1. Firazyr (icatibant). Package insert. Lexington, MA: Shire Orphan Therapies, Inc; 2011. 2. Data on file.
Sebetralstat Can Become the Foundational HAE Therapy Low Patient HAE
Disease Burden High Current treatment paradigm Injectable Injectable on-demand + on-demand prophylaxis Future with sebetralstat Oral on-demand Sebetralstat + with sebetralstat prophylaxis 26