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Indicate by check mark whether the registrant is an emerging growth company as defined in Rule 405 of the Securities Act of 1933 (§ 230.405 of this chapter) or Rule 12b-2 of the Securities Exchange Act of 1934 (§ 240.12b-2 of this chapter).
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Explanatory Note
Item 8.01 Other Events.
On February 15, 2022, the Company is hosting an Investor Day. A copy of the investor presentation is filed as Exhibit 99.1 to this Current Report on Form 8-K and is incorporated herein by reference.
Item 9.01 Financial Statements and Exhibits.
(d) Exhibits
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99.1 |
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SIGNATURES
Pursuant to the requirements of the Securities Exchange Act of 1934, the registrant has duly caused this report to be signed on its behalf by the undersigned thereunto duly authorized.
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Allakos Inc. |
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February 15, 2022 |
By: |
/s/ H. Baird Radford, III |
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H. Baird Radford, III |
Corporate Update February 15, 2022 Exhibit 99.1
Disclaimer This presentation contains forward-looking statements. All statements other than statements of historical fact contained in this presentation, including statements regarding the financial position of Allakos Inc. (“Allakos,” the “Company,” “we” or “our”); the generation of future value; business strategy; plans and objectives for future operations; our expectations regarding the potential benefits, activity, effectiveness and safety of our product candidates; our expectations with regard to the initiation, design, timing and results of our clinical studies, preclinical studies and research and development programs, including the timing and availability of data from such studies; our preclinical, clinical and regulatory development plans for our product candidates, including the timing or likelihood of regulatory filings and approvals for our product candidates; the size of the market opportunity for our product candidates in the diseases we are targeting; and our expectations with regard to our ability to acquire, discover and develop additional product candidates and advance such product candidates into, and successfully complete, clinical studies, are forward-looking statements. Allakos has based these forward-looking statements on its estimates and assumptions and its current expectations and projections about future events. The words ‘‘anticipate,’’ ‘‘believe,’’ ‘‘continue,’’ ‘‘could,’’ ‘‘estimate,’’ ‘‘expect,’’ ‘‘intend,’’ ‘‘may,’’ ‘‘plan,’’ ‘‘potential,’’ ‘‘predict,’’ ‘‘project,’’ ‘‘target,’’ ‘‘should,’’ ‘‘would,’’ and similar expressions are intended to identify forward-looking statements, although not all forward-looking statements contain these identifying words. The Company may not actually achieve the plans, intentions, or expectations disclosed in these forward-looking statements, and you should not place undue reliance on these forward-looking statements. The forward-looking statements included in this presentation speak only as of the date of this presentation and are subject to a number of risks, uncertainties, and assumptions, including, but not limited to: the Company’s stages of clinical drug development; the Company’s ability to timely complete clinical trials for, and if approved, commercialize lirentelimab (AK002), its lead compound; the Company’s ability to obtain required regulatory approvals for its product candidates; uncertainties related to the enrollment of patients in its clinical trials; the Company’s ability to demonstrate sufficient safety and efficacy of its product candidates in its clinical trials; uncertainties related to the success of later-stage clinical trials, regardless of the outcomes of preclinical testing and early-stage trials; market acceptance of the Company’s product candidates; uncertainties related to the projections of the size of patient populations suffering from some of the diseases the Company is targeting; the Company’s ability to advance additional product candidates beyond AK002; the Company’s ability to obtain additional capital to finance its operations; and other risks described in the “Risk Factors” section included in our periodic filings that we have made and will make with the Securities and Exchange Commission (“SEC”). In addition, Allakos operates in a very competitive and rapidly changing environment. New risks emerge from time to time. It is not possible for Allakos’s management to predict all risks, nor can Allakos assess the impact of all factors on its business or the extent to which any factor, or combination of factors, may cause actual results to differ materially from those contained in any forward-looking statements that Allakos may make. In light of these risks, uncertainties and assumptions, the forward-looking events and circumstances discussed in this presentation are inherently uncertain and may not occur, and actual results could differ materially and adversely from those anticipated or implied in the forward-looking statements. Accordingly, you should not rely upon forward-looking statements as predictions of future events. Allakos does not undertake any obligation to update or revise any forward-looking statements, to conform these statements to actual results or to make changes in Allakos’ expectations, except as required by law. Accuracy of Data: This presentation contains statistical data based on independent industry publications or other publicly available information, as well as other information based on Allakos’s internal sources. We have not independently verified the accuracy or completeness of the data contained in these industry publications and other publicly available information. Accordingly, Allakos makes no representations as to the accuracy or completeness of that data. Additional Information: The Company has filed and will file Current Reports on Form 8-K, Quarterly Reports on Form 10-Q, and Annual Reports on Form 10-K, and other documents with the SEC. You should read these documents for more complete information about the Company. You may get these documents for free by visiting EDGAR on the SEC website at www.sec.gov. This presentation concerns products that are under clinical investigation and which have not yet been approved for marketing by the U.S. Food and Drug Administration. It is currently limited by federal law to investigational use, and no representation is made as to its safety or effectiveness for the purposes for which it is being investigated.
Robert Alexander, PhD Introductions Craig A. Paterson, MD Review of KRYPTOS and ENIGMA 2 Clinical Studies Evan S. Dellon, MD, MPH Physician Perspective Robert Alexander, PhD Atopic Dermatitis and Chronic Spontaneous Urticaria Marcus Maurer, MD Physician Perspective Brad A. Youngblood, PhD Pipeline Strategy & Update Closing Remarks Q&A Allakos Investor Day Agenda
Review of KRYPTOS (EoE) and ENIGMA2 (EG/EoD) Clinical Studies Craig A. Paterson, MD CMO – Allakos Inc.
KRYPTOS Phase 2/3 EoE Study Design Multi-center, randomized, DB, placebo-controlled Active moderate to severe symptoms Dysphagia Symptom Questionnaire (DSQ) ≥12 Biopsy confirmed EoE Esophagus: ≥15 eos/high power field (hpf) in 1 hpf 276 patients dosed (1:1:1 randomization) High dose lirentelimab 1 + 3 + 3 + 3 + 3 + 3 mg/kg (n=91) Low dose lirentelimab 1 + 1 + 1 + 1 + 1 + 1 mg/kg (n=93) Placebo (n=92) 6 monthly doses Includes adolescents age 12-17 Open-label extension Histologic Co-Primary Endpoint Proportion of tissue eosinophil responders: Esophagus: ≤6 eos/hpf in peak hpf Symptom Co-Primary Endpoint Absolute change in Dysphagia Symptom Questionnaire (DSQ) score Secondary Endpoints Percent change in DSQ from baseline Other Analyses of Interest Activity in adolescents Open-label extension Study Design Endpoints
Histology Co-primary Endpoint: Eosinophil Responders * Difference from placebo p-values <0.0001 derived using Fisher’s Exact Test 1 ITT: Missing data was treated as non-responders High Dose * (80/91) (86/93) Low Dose Lirentelimab * Placebo (10/92) * (80/80) (86/87) * (10/88) Proportion of EoE Eosinophil Responders (≤6 eos/hpf at Week 24) Primary Analysis1 Analysis with Observed Data High Dose Low Dose Placebo Lirentelimab % of Patients % of Patients
Complete Histologic Responders * Difference from placebo p-values <0.0001 derived using Fisher’s Exact Test 1 Observed data Secondary Endpoint: Complete Histologic Remission at Week 241 * (77/80) (82/87) * (4/88) High Dose Low Dose Placebo Lirentelimab % of Patients Achieved Peak Esophageal Eos ≤1 Eos/hpf at Week 24
Symptom Co-primary Endpoint: Change in DSQ * LS Means and HD lirentelimab from placebo p-values derived from ANCOVA model Absolute Change LS Mean Change from BL 35.2 34.2 36.4 BL DSQ = Change in DSQ at Weeks 23-24 Percent Change Mean % Change from BL High Dose (n=82) Low Dose (n=88) Placebo (n=89) High Dose (n=82) Low Dose (n=88) Placebo (n=89) Lirentelimab Lirentelimab *p=0.2372 *p=0.0511
Baseline Demographics and Patient Characteristics 1 Asthma, allergic rhinitis, atopic dermatitis and/or food allergy Patient Characteristics HD Lirentelimab (n=91) LD Lirentelimab (n=93) Placebo (n=92) Age, median years (range) 29 (12 - 69) 34 (12 - 67) 32 (12 - 70) Female sex, % (n) 29% (26) 43% (40) 40% (37) History of EoE, % (n) 89% (81) 90% (84) 93% (86) Duration of EoE, median years (range) 4 (0 - 38) 5 (0 - 56) 4 (0 - 18) History of proton pump inhibitor use for EoE, % (n) 23% (21) 23% (21) 23% (21) History of swallowed topical steroid for EoE, % (n) 20% (18) 17% (16) 21% (19) History of esophageal dilatations, % (n) 4% (4) 6% (6) 8% (7) Number of prior esophageal dilatations, mean ± SD 2.3 ± 1.3 2.3 ± 1.5 1.4 ± 0.5 History of atopy1, % (n) 76% (69) 71% (66) 79% (73) Peak esophageal eosinophil counts/hpf, mean ± SD 59 ± 33 61 ± 35 59 ± 33 Peripheral blood eosinophils cells/µL, median (IQR) 300 (230 - 470) 270 (180 - 440) 350 (200 - 435) Serum IgE, kU/L, median (IQR) 103 (53 - 349) 99 (39 - 283) 90 (29 - 241) Baseline DSQ [0-84], mean ± SD 34 ± 12 36 ± 12 35 ± 12
Eosinophilic Threshold for Establishing Moderate-Severe EoE Fig 1. Rothenberg ME. J Allergy Clin Immunol 2001;108:891-4. Primary EoE
Baseline Demographics and Patient Characteristics: By Peak Esophageal Eosinophils SOURCE: Stein ML, Collins MH, et al. J Allergy Clin Immunol 2006;118:1312-3219; Noel RJ, Putnam PE, Rothenberg ME. N Engl J Med 2004;351:940-941. Rothenberg ME, J Allergy Clin Immunol 2001 Patient Characteristics Peak Esophageal Eosinophil Counts ≤24/hpf Peak Esophageal Eosinophil Counts >24/hpf Patient Characteristics HD Lirentelimab (n=14) LD Lirentelimab (n=18) Placebo (n=16) HD Lirentelimab (n=77) LD Lirentelimab (n=75) Placebo (n=76) Age, median years (range) 35.5 (15 - 67) 33.5 (15 - 67) 43.5 (20 - 68) 29 (12 - 69) 34 (12 - 67) 30 (12 - 70) Female sex, % (n) 43% (6) 44% (8) 38% (6) 26% (20) 43% (32) 41% (31) History of EoE, % (n) 79% (11) 83% (15) 94% (15) 91% (70) 92% (69) 93% (71) Duration of EoE, median years (range) [mean] 4 (1 - 19) [6.5] 4 (0 - 11) [5.0] 4 (0 - 12) [4.9] 4 (0 - 38) [6.3] 5 (0 - 56) [7.7] 5 (0 - 18) [5.2] History of proton pump inhibitor use for EoE, % (n) 21% (3) 11% (2) 0% 23% (18) 25% (19) 28% (21) History of swallowed topical steroid for EoE, % (n) 7% (1) 22% (4) 6% (1) 22% (17) 16% (12) 24% (18) History of esophageal dilatations, n (%) 14% (2) 17% (3) 6% (1) 3% (2) 4% (3) 8% (6) Number of prior esophageal dilatations, mean ± SD 3 ± 1 3 ± 1 2 ± 0 2 ± 1 2 ± 1 1 ± 1 History of atopy, % (n) 79% (11) 67% (12) 56% (9) 75% (58) 72% (54) 84% (64) Peak esophageal eosinophil counts/hpf, mean ± SD 20 ± 3 19 ± 3 20 ± 3 66 ± 31 71 ± 32 67 ± 30 Peak esophageal eos/hpf in distal location, mean ± SD 15 ± 7 17 ± 4 17 ± 7 54 ± 32 59 ± 31 55 ± 29 Peak esophageal eos/hpf in proximal/mid location, mean ± SD 13 ± 9 7 ± 9 10 ± 9 48 ± 29 54 ± 37 46 ± 35 Peripheral blood eosinophils cells/µL, median (IQR) 310 (213 - 430) 175 (143 - 245) 220 (98 - 400) 300 (240 - 470) 300 (210 - 500) 380 (240 - 455) Serum IgE, kU/L, median (IQR) 83 (33 - 348) 64 (21 - 168) 65 (24 - 140) 105 (54 - 349) 117 (46 - 314) 98 (33 - 255) Baseline DSQ [0-84], mean ± SD 34 ± 10 38 ± 11 36 ± 10 34 ± 12 36 ± 12 35 ± 13
DSQ Response in Patients by Baseline Peak Eosinophil Count Baseline Eos ≤24/hpf Mean Change from BL Lirentelimab 36.1 34.2 37.9 BL DSQ = * LS Means and HD lirentelimab from placebo p-values derived from MMRM model Baseline Eos >24 /hpf Lirentelimab 35.0 34.2 36.1 BL DSQ = * Change in DSQ by Baseline Eosinophil Count Levels at Weeks 23-24 Mean Change from BL Placebo (n=15) High Dose (n=12) Low Dose (n=17) Placebo (n=76) High Dose (n=73) Low Dose (n=73) *p=0.0222
DSQ Response in Patients by Baseline Peak Eosinophil Count Baseline Eos >24 /hpf Baseline Eos ≤24/hpf Lirentelimab Lirentelimab * LS Means and HD lirentelimab from placebo p-values derived from MMRM model * Mean % Change from BL % Change in DSQ by Baseline Peak Esophageal Eos Level at Week 23-24 Placebo (n=15) High Dose (n=12) Low Dose (n=17) Placebo (n=76) High Dose (n=73) Low Dose (n=73) *p=0.0019 Mean % Change from BL
Study Results in Adolescents Age 12 - 17 years
Baseline Demographics and Patient Characteristics: Adolescents 1 Asthma, allergic rhinitis, atopic dermatitis and/or food allergy Patient Characteristics HD Lirentelimab (n=17) LD Lirentelimab (n=17) Placebo (n=17) Age, median years (range) 14 (12 - 17) 15 (12 - 17) 14 (12 - 17) Female sex, % (n) 12% (2) 29% (5) 24% (4) History of EoE, % (n) 94% (16) 100% (17) 94% (16) Duration of EoE, median years (range) 4 (2 - 10) 5 (0 - 13) 6 (1 - 15) History of proton pump inhibitor use for EoE, % (n) 29% (5) 53% (9) 41% (7) History of swallowed topical steroid for EoE, % (n) 18% (3) 24% (4) 53% (9) History of atopy1, % (n) 88% (15) 88% (15) 88% (15) Peak esophageal eosinophil counts/hpf, mean ± SD 66 ± 32 84 ± 32 55 ± 26 Peak esophageal eos/hpf in distal location, mean ± SD 61 ± 32 69 ± 39 48 ± 25 Peak esophageal eos/hpf in proximal/mid location, mean ± SD 45 ± 31 67 ± 28 33 ± 28 Peripheral blood eosinophils cells/µL, median (IQR) 295 (225 - 400) 625 (285 - 770) 420 (380 - 675) Serum IgE, kU/L, median (IQR) 237 (140 - 806) 304 (74 - 402) 185 (85 - 374) Baseline DSQ [0-84], mean ± SD 35 ± 14 35 ± 13 34 ± 12
Histologic Response in Adolescents * Difference from placebo p-values <0.0001 derived using Fisher’s Exact Test 1 Observed data * * Lirentelimab Placebo High Dose Low Dose Proportion of Eosinophil Responders in Adolescents1 Achieved Peak Esophageal Eos ≤6 Eos/hpf at Week 24 % of Patients
DSQ Response in Adolescents * LS Means and HD lirentelimab from placebo p-values derived from ANCOVA model 1 Observed data Mean % Change from BL Mean Change from BL Percent Change Absolute Change Change in DSQ1 at Weeks 23-24 in Adolescents *p=0.1316 *p=0.0474 Lirentelimab 33.2 34.6 35.2 BL DSQ = Placebo (n=16) High Dose (n=15) Low Dose (n=16) Lirentelimab Placebo (n=16) High Dose (n=15) Low Dose (n=16) *
Safety Summary
KRYPTOS Safety Summary n (%) of Patients HD Lirentelimab (n=91) LD Lirentelimab (n=93) Placebo (n=92) ≥1 Treatment-Emergent Adverse Event (TEAE) 61 (67.0%) 65 (69.9%) 53 (57.6%) Infusion related reaction 35 (38.5%) 24 (25.8%) 11 (12.0%) Headache 6 (6.6%) 8 (8.6%) 6 (6.5%) Drug-related Serious AEs: 2 patients on HD lirentelimab, 1 patient on Placebo Safety risk profile overall was consistent with previously reported safety profile in ENIGMA1 and other lirentelimab studies to date Treatment-Emergent AEs in ≥5% of Patients
Open-Label Extension
Durability of Effect in Open-Label Extension * LS Means and p-values derived from MMRM model Baseline DSQ Score, mean ± SD Placebo: 35.0±12.5; LD Lirentelimab: 36.1±12.3; HD Lirentelimab: 34.2±12.2 Absolute Change Absolute Change Mean (SE) / Mean (SD) Change in DSQ from Baseline: Patients with BL Esophageal Eos >24/hpf Percent Change 76 n= -12.5 Weeks 23-24 Weeks 43-44 (OLE) 73 73 -12.7 -17.6 27 -20.7 26 26 -18.7 -20.5 76 n= -29.4% Weeks 23-24 Weeks 43-44 (OLE) 73 73 -37.6% -55.8% 27 -67.3% 26 26 -65.4% -65.8% % Change Mean (SE) / Mean(SD) *p=0.0222 *p=0.0019 Placebo LD Lirentelimab HD Lirentelimab Placebo/Lirentelimab LD/Lirentelimab HD/Lirentelimab
Summary & Conclusions KRYPTOS Phase 2/3 study included patients with questionable EoE diagnosis Clear activity observed in moderate-to-severe EoE patients Clear activity in adolescents Durability of effect observed in interim analysis of open-label extension Lirentelimab was well-tolerated in both adults and adolescents with EoE
Review of ENIGMA2 Phase 3 EG/EoD Study
ENIGMA2 Phase 3 EG/EoD Study Design Multi-center, randomized, DB, placebo-controlled Active moderate to severe symptoms Biopsy confirmed EG and/or EoD Stomach: ≥30 eos/high powered field (hpf) in 5 hpfs Duodenum: ≥30 eos/hpf in 3 hpfs 180 adult patients (1:1 randomization) Lirentelimab 1 + 3 + 3 + 3 + 3 + 3 mg/kg (n = 91) Placebo (n = 89) 6 monthly doses Open-label extension Histologic Co-Primary Endpoint Proportion of tissue histologic responders: Stomach: ≤4 eos/hpf in 5 hpfs, and/or Duodenum: ≤15 eos/hpf in 3 hpfs Symptom Co-Primary Endpoint Absolute change in patient reported TSS-6 Key Secondary Endpoints Percent change in TSS-6 from baseline Proportion of patients achieving ≥50% and ≥70% improvement in TSS-6 Study Design Endpoints
Histology Co-Primary Endpoint: Eosinophil Responders * Difference from placebo p-values <0.0001 derived using Fisher’s Exact Test 1 Eosinophil response criteria: ≤4 eos/hpf in top 5 gastric hpfs and/or ≤15 eos/hpf in top 3 duodenal hpfs 2 ITT: Missing data was treated as non-responders 98% mean reduction of eosinophils on lirentelimab vs 24% in the placebo group Primary Analysis2 Lirentelimab Placebo * (77/91) (4/89) (77/83) (4/83) * Lirentelimab Placebo Proportion of Patients Achieving EG/EoD Histologic Response1 at Week 24 % of Patients % of Patients Analysis with Observed Data
Symptom Co-Primary Endpoint: TSS6 1 TSS6 Symptoms: abdominal pain, nausea, early satiety, loss of appetite, bloating, abdominal cramping Absolute Change LS Mean Change from BL Change in Total Symptom Score1 Percent Change Lirentelimab (n=75) Placebo (n=75) 27.7 29.5 BL TSS = Lirentelimab (n=75) Placebo (n=75) LS Mean % Change from BL
Responder Analysis Suggests Clinical Activity Secondary Endpoint: Proportion of Patients Achieving TSS Thresholds at Weeks 23-241 Lirentelimab (n=75) Placebo (n=75) ≥30% Reduction % (n) of Patients ≥50% Reduction ≥70% Reduction ≥90% Reduction (42) (45) (36) (29) (26) (18) (11) (6) 1 Observed data
Baseline Demographics & Patient Characteristics: ENIGMA1 and ENIGMA2 Patient Characteristics Ph2 ENIGMA1 (E1) Ph3 ENIGMA2 Patient Characteristics n=65 AK002 n=91 Placebo n=89 Age, median years (range) 40 (18-74) 43 (17-77) 41 (18-78) Female sex, % (n) 62% (40) 62% (56) 69% (61) History of EoE, % (n) 54% (35) 23% (21) 24% (21) History of EG or EoD, % (n) 80% (52) 32% (29) 29% (26) History of IBS, % (n) 3% (2) 40% (36) 37% (33) History and background corticosteroid use, % (n) 42% (27) 41% (37) 31% (28) Baseline use of physician prescribed diet regimen, % (n) 17% (11) 8% (7) 10% (9) Gastric/duodenal eos/hpf in top 5/3 hpfs, mean ± SD 84 ± 52 65 ± 51 52 ± 25 Screening blood eos cells/µL, median (IQR) 330 (160-720) 200 (133-463) 230 (113-340) Screening IgE kU/L, median (IQR) 141 (44-361) 59 (18-167) 61 (25-165) Baseline Total Symptom Score (TSS) [0-60], mean ± SD 28 ± 12 29 ± 11 28 ± 11
Baseline Demographics & Patient Characteristics: Site Comparison Patient Characteristics Ph2 ENIGMA1 (E1) Ph3 ENIGMA2 Patient Characteristics n=65 E1 Sites n=81 Non-E1 Sites n=99 Age, median years (range) 40 (18-74) 45 (18-77) 40 (17-78) Female sex, % (n) 62% (40) 59% (48) 70% (69) History of EoE, % (n) 54% (35) 27% (22) 20% (20) History of EG or EoD, % (n) 80% (52) 47% (38) 17% (17) History of IBS, % (n) 3% (2) 31% (25) 44% (44) History and background corticosteroid use, % (n) 42% (27) 43% (35) 30% (30) Baseline use of physician prescribed diet regimen, % (n) 17% (11) 14% (11) 5% (5) Gastric/duodenal eos/hpf in top 5/3 hpfs, mean ± SD 84 ± 52 70 ± 53 50 ± 25 Screening blood eos cells/µL, median (IQR) 330 (160-720) 250 (170-665) 180 (110-290) Screening IgE kU/L, median (IQR) 141 (44-361) 72 (29-166) 58 (17-165) Baseline Total Symptom Score (TSS) [0-60], mean ± SD 28 ± 12 29 ± 12 29 ± 11
Consistent Effects Observed in ENIGMA1 Site Patients Mean Change in TSS6 from Baseline at End of Treatment1 * LS Means and p-values derived from ANCOVA/MMRM models 1 ENIGMA1: mean TSS6 change from BL to Weeks 13-14; ENIGMA2: mean TSS6 change from BL to Weeks 23-24 Mean TSS6 Change from BL Placebo (n=20) Lirentelimab (n=20) Placebo (n=34) Lirentelimab (n=38) Phase 2 ENIGMA (E1) Phase 3 ENIGMA2: E1 Site Pts *p<0.05 *p<0.05 29.7 BL TSS6 = 28.1 29.4 27.8 * *
≥30% Reduction % (n) of Patients ≥50% Reduction ≥70% Reduction ≥90% Reduction Lirentelimab (n=20) Placebo (n=20) ≥30% Reduction ≥50% Reduction ≥70% Reduction ≥90% Reduction Lirentelimab (n=38) Placebo (n=34) Similar Results Seen in ENIGMA1 Site Patients Proportion of Patients Achieving TSS6 Thresholds at End of Treatment1 1 ENIGMA1 end of treatment: Weeks 13-14 ENIGMA2 end of treatment: Weeks 23-24 Phase 2 ENIGMA (E1) Phase 3 ENIGMA2: E1 Site Pts
ENIGMA2: Non-ENIGMA1 Site Patients Mean Change in TSS6 from Baseline at End of Treatment Placebo (n=43) Lirentelimab (n=42) ENIGMA2: Non-E1 Site Pts 29.5 27.7 BL TSS6 = Mean TSS6 Change from BL
ENIGMA2: Non-ENIGMA1 Site Patients Proportion of Patients Achieving TSS6 Thresholds at Weeks 23-24: Non-E1 Site Pts ≥30% Reduction % (n) of Patients ≥50% Reduction ≥70% Reduction ≥90% Reduction Lirentelimab (n=42) Placebo (n=43)
Safety Summary
ENIGMA2 Safety Summary No drug-related Serious AEs Safety risk profile overall was consistent with previously reported safety profile in ENIGMA1 and other lirentelimab studies to date n (%) of Patients Lirentelimab (n=91) Placebo (n=89) ≥1 Treatment-Emergent Adverse Event (TEAE) 65 (71.4%) 57 (64.0%) Infusion related reaction 31 (34.1%) 12 (13.5%) Fatigue 5 (5.5%) 1 (1.1%) Treatment-Emergent AEs in ≥5% of Patients
Open Label Extension
Durability of Effect in Open-Label Extension (E1 Site Patients) * LS Means and p-values derived from MMRM model Baseline TSS6 Score, mean ± SD Placebo: 27.8±12.1; Lirentelimab: 29.4±11.4 Absolute Change Absolute Change from BL Mean (SE) / Mean (SD) Change in TSS6 from Baseline: E1 Site Patients 34 -8.0 Weeks 23-24 Weeks 45-46 (OLE) 38 -14.2 15 -12.8 20 -17.4 Percent Change % Change from BL Mean (SE) / Mean (SD) 34 -28.9% Weeks 23-24 Weeks 45-46 (OLE) 38 -47.8% 15 -46.3% 20 -54.1% n= n= *p= 0.0370 *p= 0.0385 Placebo Lirentelimab Placebo/Lirentelimab Lirentelimab/Lirentelimab
Summary of ENIGMA2 ENIGMA2 patients with similar characteristics to those included in Phase 2 reproduced original study results Key patient characteristics identified include: Higher tissue eos counts Higher peripheral blood eos counts Higher IgE levels Durability of effect observed in interim analysis of open-label extension Lirentelimab was well-tolerated in patients with EG and/or EoD
Phase 3 EoD Study
EoD Phase 3 Study Design Multi-center, randomized, double-blind, placebo-controlled study in EoD Active moderate to severe symptoms Biopsy confirmed EoD ± colonic involvement Duodenum: ≥30 eos/hpf in 3 hpfs Stomach: <30 eos/high powered field (hpf) in 5 hpfs (Do NOT have EG) Colonic involvement assessed by colonoscopy: biopsies collected from terminal ileum, colon (ascending, transverse, descending, sigmoid) and rectum 93 adult patients – 2 arms 3.0, 3.0, 3.0, 3.0, 3.0, 3.0 mg/kg lirentelimab Placebo 6 monthly i.v. doses Histologic Co-Primary Endpoint Proportion of responders: Duodenum: ≤ 15 eos/hpf in 3 hpfs Symptom Co-Primary Endpoint Absolute change in patient reported TSS-6 Key Secondary Endpoints Percent change in tissue eosinophil counts Treatment responders: patients who achieve tissue eosinophil thresholds AND >30% improvement in TSS Exploratory: change in colonic eosinophil counts Study Design Endpoints
Phase 3 EoD Study Update Fully enrolled (N=93) Study will complete mid-2022 Population enrolled is similar to ENIGMA2 population Data from EoD study will inform correspondence with the FDA
Next Steps in EGIDs EoE End of Phase 2 meeting Update market post FDA meeting EG/EoD Await and incorporate 021 EoD study data Plan to meet with FDA to discuss data and findings Update the market post the FDA meeting
Professor Evan S. Dellon, MD MPH TITLE: Professor of Medicine, Gastroenterology & Epidemiology Director, Center for Esophageal Diseases and Swallowing Director, CGIBD Biostatistics and Clinical Research Core INSTITUTION: University of North Carolina School of Medicine SPECIALTY: Gastroenterology FOCUS: Epidemiology, pathogenesis, diagnosis, treatment, and outcomes of Eosinophilic Gastrointestinal Disorders Investigator and member of NIH-funded Consortium of Eosinophilic Gastrointestinal Disease Researchers (CEGIR) Editorial Board: Clinical Gastroenterology and Hepatology Author/Co-Author: >300 peer-reviewed publications Investigator for multiple EGID studies including EoE
Lirentelimab for Inflammatory Skin Diseases Robert Alexander, PhD CEO
Strong Scientific Rationale for Targeting Mast Cells and Eosinophils in Chronic Inflammatory Skin Diseases Atopic dermatitis (AD) and chronic spontaneous urticaria (CSU) are characterized by inflamed itchy skin Improvements observed in patients with concomitant atopic dermatitis and chronic urticaria in lirentelimab studies Crosstalk between eosinophils, mast cells, and sensory neurons has been shown to drive inflammation and chronic itch in AD and CSU via IgE, IL-4, IL-13, IL-33, and MRGPRX2 Eosinophils and mast cells are found in lesional skin in atopic dermatitis and chronic urticaria Mast cells are drivers of disease processes in atopic dermatitis and chronic spontaneous urticaria
AK002 Mast Cell Inhibition
Lirentelimab Broadly Inhibits Mast Cell Activation Lirentelimab targets multiple disease-driving pathways through mast cell inhibition Mast Cell Inhibition
Lirentelimab Inhibits IL-33-Mediated Mast Cell Activation Transcriptome of IL-33-Activated Mast Cells Resting MCs Isotype Control+ IL-33 Anti-S8 + IL-33 SOURCE: Schanin, J et al. Mucosal Immunology 2020; Korver, W et al. Frontiers in Immunology 2022
Lirentelimab Inhibits IgE-Mediated Mast Cell Activation Phospho-Proteome of IgE-Activated Mast Cells Resting MCs Isotype Control + IgE Anti-S8 + IgE Syk: Y519 Ship1: S1090 Gab2: Y632 Syk: Y520 PKCd: Y311 Dapp1: S141 Ship1: S1130 Ahnak: S699 Dapp1: Y139 SOURCE: Schanin, J et al. Mucosal Immunology 2020; Korver, W et al. Frontiers in Immunology 2022
Lirentelimab Inhibits MRGPRX2-Mediated Mast Cell Activation Lirentelimab inhibits key driver of mast cell activation in chronic disease Mouse Model of MRGPRX2-mediated Inflammation Mast Cell-Derived Inflammatory Cytokines 0h Substance P IP Injection 4h 1h Isotype or lirentelimab Evaluate Inflammation CD63 Expression Mast Cell Activation CCL3 / MIP-1 CCL4 / MIP-1 SOURCE: Gebremeskel S et al. EAACI 2020.
Lirentelimab Reduces TLR-mediated Inflammation In Vivo Day 1 Intranasal TLR3 agonist (Poly (I:C)) Day 3 Isotype or Anti-S8 Evaluate Inflammation Vehicle ISO + poly (I:C) Anti-S8 + poly (I:C) Lirentelimab treatment significantly reduces TLR-mediated airway inflammation, including IL-6, TNF, CCL2/MCP1, IP-10, and IL-1β cytokine and chemokine production SOURCE: Gebremeskel, S et al Frontiers in Immunology 2021; *** p<0.001; **** p<0.0001 (n=5-6 mice/group)
Lirentelimab for Atopic Dermatitis
AD Lesional Biopsies Show Evidence of MC and Eosinophil Activity Immune Cell Numbers Disease Biomarkers Mast Cell Activation Lirentelimab reduces levels of CPA3, CCL17/TARC and CCL26/Eotaxin-3 CCL26 / Eotaxin-3 CCL17 / TARC CPA3 Eosinophils Mast Cells SOURCE: Youngblood, BA et al JCI Insights 2019; Schanin, J et al Mucosal Immunology 2020
Reduction in Clinically-Relevant Cytokines SOURCE: Data on file. Manuscript submitted Ocular Inflammation via Tear Cytokines (Ph1b Severe Allergic Conjunctivitis) Last Dose Last Dose Last Dose Last Dose IL-4 IL-13 CCL26 / Eotaxin-3 CCL3 / MIP-1
Improvement in Concomitant Atopic Dermatitis SOURCE: ENIGMA2 data on file. SAC manuscript submitted Median % Change from BL Weeks 21-22 Placebo (n=4) Lirentelimab (n=5) Atopic Dermatitis (Open-Label SAC Study) Lirentelimab (n=11) Atopic Dermatitis (ENIGMA2)
Phase 2 AD Study Design Multi-center, randomized, DB, placebo-controlled Chronic disease that has been present ≥3 years EASI score ≥16 Involvement of ≥10% of body surface area IGA score ≥3 Inadequate control by topical treatments Dupilumab, tralikinumab, and JAK naïve 120 adult patients (1:1 randomization) 300 mg Q2W subcutaneous lirentelimab (n=60) Placebo (n=60) Open-label extension Primary Endpoint Proportion of patients who achieve eczema area and severity index (EASI)-75 at week 14 Key Secondary Endpoints Percent change in EASI from baseline to week 14 Proportion of patients who achieve an IGA score of 0 or 1 AND a ≥2-point improvement in Investigator Global Assessment (IGA) at week 14 Study Design Endpoints
Chronic Spontaneous Urticaria
Phase 2a Chronic Urticaria Study Open-label in Chronic Urticaria Uncontrolled CU (UCT<12) Diagnosis of CU for at least 3 months, refractory to antihistamine treatment in single or 4-fold dosage 45 patients – 4 arms Omalizumab-naïve CSU Omalizumab-refractory CSU Cholinergic urticaria Symptomatic dermographism 6 monthly doses 0.3 mg/kg starting lirentelimab dose; increased to 1.0 mg/kg (dose 2 and 3); if UCT <12, increased to 3.0 mg/kg (dose 4, 5, and 6) Primary Endpoint Change in Urticaria Control Test (UCT) from Baseline to Week 22 Key Secondary Endpoints Change in disease activity by UAS7 Safety and tolerability Study Design Endpoints
Phase 2a Chronic Urticaria Study – Results in CSU Omalizumab Naïve CSU Patients (n=13) Baseline Week 22 Omalizumab Refractory CSU Patients Receiving All 6 Doses (n=7) SOURCE: Altrichter S, Staubach P, Pasha M, et al. J Allergy Clin Immunol 2022 (In Press) UAS7 Mean Score ±95% CI Baseline Week 22 *** -75% ** -61% UAS7 Mean Score ±95% CI
Phase 2b Chronic Spontaneous Urticaria Study Multi-center, randomized, DB, placebo-controlled Active moderate-to-severe symptoms CSU diagnosis with onset ≥6 months prior to screening Diagnosis of CSU refractory to antihistamines Presence of itch and hives despite current use of antihistamines UAS7 score ≥16 and HSS7 score ≥8 at baseline Omalizumab, dupilumab, and benralizumab naïve 100 adult patients – 2 arms 300 mg Q2W subcutaneous lirentelimab (n=50) Placebo (n=50) Primary Endpoint Change from baseline in UAS7 at week 12 Key Secondary Endpoints Absolute change in ISS7 Absolute change in HSS7 Proportion of patients with UAS7=0 Study Design Endpoints
Lirentelimab for Inflammatory Skin Diseases Mast cells and eosinophils are key drivers of inflammatory skin diseases Lirentelimab has demonstrated broad inhibition of mast cell and eosinophil activity in vivo and ex vivo studies Clinical proof of concept in patients with CSU and concomitant AD
Professor Marcus Maurer, MD TITLE: Professor of Dermatology and Allergy Director of Research - Allergie Centrum Charité INSTITUTION: Charité Universitätsmedizin Berlin SPECIALTY: Dermatology, Allergy and Immunology FOCUS: Urticaria, Mastocytosis, Angioedema, Pruritus, Skin Infections, Allergic Diseases Organizing and Scientific Committee Member: GA2LEN/ UCARE, Multi-National Urticaria Centers of Excellence Editorial Board: Advances in Dermatology and Allergology Author/Co-Author: >500 peer-reviewed publications, 40 books and book chapters
Pipeline Strategy & Update Bradford A. Youngblood, PhD Head of Research & Preclinical Development – Allakos Inc.
Pipeline Strategy Focused on Targeting Siglecs Current Landscape is Mediator Focused Inhibitory Receptors on Key Pathogenic Cells Most molecules in development for inflammation target individual cytokines implicated in disease While effective, most mediators are produced by a small number of pathogenic immune cells that could be targeted directly Siglecs are inhibitory receptors selectively expressed on key disease driving cells Ability to selectively suppress immune cell activation via agonistic mAbs to reduce chronic inflammation (ie lirentelimab) Opportunity to selectively activate immune cells through neutralization to increase anti-tumor immunity Anti-TSLPR Anti-IgE Anti-IL-4R Anti-TNF Anti-IL-6 Neutrophil Macrophage Eosinophil B Cell T Cell Siglec-3 (CD33) Siglec-5 Siglec-6 Siglec-7 Siglec-8 Siglec-9 Siglec-10 Siglec-11 Siglec-15
Antibody Program Indication Discovery Preclinical Phase 1 Phase 2 Phase 3 Registration Milestone Lirentelimab (Anti-Siglec-8) Eosinophilic Gastritis (EG) and/or EoD Topline data announced Dec 2021 Eosinophilic Duodenitis (EoD) Topline data expected Q3 2022 Eosinophilic Esophagitis (EoE) Topline data announced Dec 2021 Chronic Urticaria Initiation expected mid-2022 Atopic Dermatitis Initiated Q4 2021 Severe Allergic Conjunctivitis Completed 2019 Mast Cell Gastrointestinal Disease Completed 2019 Indolent Systemic Mastocytosis Completed 2019 AK006 (Anti-Siglec-6) Inflammatory Diseases IND expected 1H 2023 AK007 (Undisclosed Target) Inflammation Ongoing Immuno-Oncology Ongoing Allakos Pipeline
AK006 Program
Mast Cells are Pathogenic Cells that are Non-Selectively Targeted Mast cells express numerous activating receptors on their cell surface that contribute to disease Siglec-6 is an inhibitory receptor selectively expressed on mast cells that has unique immunomodulatory activity Siglecs represent attractive targets for broadly regulating mast cell function Molecules Targeting Mast Cell Receptors Currently, none of these molecules selectively target or broadly inhibit mast cells, resulting in incomplete mast cell inhibition or off target effects Multiple molecules in development target single activating receptors on the mast cell surface or mast cell-derived mediators
Siglec-6 Is Selectively Expressed on Human Tissue Mast Cells Gating Strategy for Immune Cells in Human Tissue Siglec-6 Expression Profile Siglec-6 represents a selective mast cell inhibitory receptor n=15 human donors
AK006: Siglec-6 mAb That Selectively Targets Mast Cells AK006 is a humanized IgG1 agonistic Siglec-6 mAb that selectively targets mast cells High affinity mAb selected for potent Siglec-6 agonism Broad mast cell inhibition via Siglec-6 ITIM agonism Reduction of mast cells via Fc-dependent mechanism Unique MOA that differentiates from other mast cell-targeting molecules Mast Cell Inhibition Opportunity to selectively and completely target mast cells in mast cell-driven diseases
AK006 Inhibits Mast Cell Activation in Human Tissues IgE-Activated Human Tissue Mast Cells AK006 potently inhibits IgE-mediated mast cell activation Human Tissue Mast Cell Activation Assay n=3 human donors
AK006 Completely Protects Against Systemic Anaphylaxis in Humanized Mice Active Tryptase Mast Cell-Specific Mediators Histamine Systemic Anaphylaxis AK006 inhibits IgE-mediated mast cell activation in vivo Humanized Mouse Model of Anaphylaxis Chymase * p < 0.01; n=7 mice/group
AK006 Inhibits KIT-mediated Mast Cell Activation in Siglec-6 Transgenic Mice Mast Cell Activation AK006 inhibits KIT- and IgE-mediated mast cell activation SCF, stem cell factor; * p < 0.01; n=7-8 mice/group Cytokines and Chemokines CD63 IL-6 TNF CXCL1 / GRO- CCL2 / MCP-1
AK006 Inhibits Allergic Contact Dermatitis in Siglec-6 Transgenic Mice Skin Inflammation AK006 reduces skin inflammation via mast cell inhibition * p < 0.01; n=6-7 mice/group DNFB, 2,4-dinitrofluorobenzene Cytokines in Ex Vivo-Cultured Ears Epicutaneous sensitization with DNFB Day 0 ISO or AK006 Day 7 Ear swelling and local mediator production in ears Challenge with DNFB on ear Model of Contact Dermatitis
AK006 Reduces Human Tissue Mast Cells Dosing Study in Humanized Mice AK006 inhibits mast cells and reduces mast cell numbers Ex Vivo Human Tissue Mast Cells Day 0 Day 15 Dosed with AK006 or AK002 or ISO Control MC numbers Day 5 Day 10 Peritoneal Mast Cells Mast Cells in Tissue * p < 0.01; (left) n=3 human donors; (right) n=8-10 mice/group
Summary AK006 is a humanized IgG1 agonistic Siglec-6 mAb that selectively inhibits mast cells and reduces their numbers Represents the first mast cell-specific molecule in development Avoids off-target effects of non-selective mast cell molecules Unique MOA that differentiates from other mast cell-targeting molecules Inhibition of both IgE-dependent and independent mast cell activation Reduces mast cell numbers in tissue First-in-human study planned 1H 2023
Closing Remarks Baird Radford & Robert Alexander, PhD CFO and CEO – Allakos Inc.
Expected Cash Runway into Early Q1 2024 Cash and Investments Balance as of Dec 31, 2020 $659 Million Full Year 2021 Cash Used $235 Million Balance as of Dec 31, 2021 $424 Million Realigned operating and expense structures to enable our lirentelimab and AK006 development plans Completed a 35% reduction in our workforce Negotiated one-time settlements to exit future manufacturing and other contractual obligations with vendors as well as employee severance arrangements totaling approximately $150 million Adjusting Cost Structure
Development Timeline Program 2021 2022 2023 2024 4Q 1Q 2Q 3Q 4Q 1Q 2Q 3Q 4Q 1Q 2Q Eosinophilic Esophagitis (EoE) Eosinophilic Gastritis (EG) and/or EoD Atopic Dermatitis (AD) Chronic Spontaneous Urticaria (CSU) IV SC Ph 3 EG/EoD Study Ph 3 EoD Study Ph 3 EoE Study (SC) – expected initiation Ph 2/3 EoE Study Ph 2 AD Study (SC) Ph 2 CSU Study (SC) AK002 AK002 AK006 Phase 1 SAD & MAD Ph 3 EG/EoD Study (SC) – expected initiation
Q&A
Thank You
References Rothenberg ME, Mishra A, Collins MH, et al. Pathogenesis and clinical features of eosinophilic esophagitis. J Allergy Clin Immunol. 2001 Dec;108(6):891-4. Straumann A, Spichtin HP, Grize L, et al. Natural history of primary eosinophilic esophagitis: A follow-up of 30 adult patients for up to 11.5 years. Gastroenterology 2003;125:1660–9. Stein ML, Collins MH, Villanueva JM, et al. Anti-IL-5 (mepolizumab) therapy for eosinophilic esophagitis. J Allergy Clin Immunol 2006;118:1312–3219. Pentiuk SP, Miller CK, Kaul A. Eosinophilic esophagitis in infants and toddlers. Dysphagia 2007;22:44–48. Straumann A, Conus S, Grzonka P, et al. Anti-interleukin-5 antibody treatment (mepolizumab) in active eosinophilic oesophagitis: a randomised, placebo-controlled, double-blind trial. Gut. 2010 Jan;59(1):21-30. Schaefer ET, Fitzgerald JF, Molleston JP, et al. Comparison of oral prednisone and topical fluticasone in the treatment of eosinophilic esophagitis: a randomized trial in children. Clin Gastroenterol Hepatol. 2008 Feb;6(2):165-73.