UNITED STATES
SECURITIES AND EXCHANGE COMMISSION
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FORM
CURRENT REPORT
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| Item 7.01 | Regulation FD Disclosure. |
The slides attached as Exhibit 99.1 to this Current Report contain certain additional information related to the clinical data results discussed in Item 8.01 below. Icosavax, Inc. (the Company or Icosavax) intends to present the slides during a conference call and live webcast with the investment community on May 22, 2023, at 5:30 p.m. Eastern Time.
The information contained in this Item 7.01, including in Exhibit 99.1 hereto, is being “furnished” and shall not be deemed “filed” for the purposes of Section 18 of the Securities Exchange Act of 1934, as amended, is not subject to the liabilities of that section and is not deemed incorporated by reference in any filing under the Securities Act of 1933, as amended, or the Securities Exchange Act of 1934, as amended, except as shall be expressly set forth by specific reference in such a filing.
| Item 8.01 | Other Events. |
On May 22, 2023, the Company announced positive topline interim results from its Phase 1 clinical trial of IVX-A12 against respiratory syncytial virus (RSV) and human metapneumovirus (hMPV) in older adults. IVX-A12 is comprised of IVX-121, the Company’s RSV prefusion F protein VLP vaccine candidate, and IVX-241, the Company’s hMPV prefusion F protein VLP vaccine candidate.
IVX-A12 Phase 1 Trial Design
The ongoing Phase 1 clinical trial of IVX-A12 is a randomized, observer-blinded, placebo-controlled, multi-center study designed to evaluate the safety and immunogenicity of varying dosage levels and ratios of RSV and hMPV VLPs in IVX-A12, with and without CSL Seqirus’ proprietary adjuvant MF59®.
The trial enrolled 140 healthy older adults aged 60 to 75 years, of which 123 subjects were evaluable for immunogenicity. Subjects were administered a single dose of IVX-A12, at one of three combination dosage levels below, or placebo:
| • | 150 µg total VLP content (75 µg of IVX-121 (RSV) and 75 µg of IVX-241 (hMPV)), with or without MF59® |
| • | 225 µg total VLP content (75 µg of IVX-121 and 150 µg of IVX-241), with or without MF59® |
| • | 300 µg total VLP content (75 µg of IVX-121 and 225 µg of IVX-241), without MF59® |
The objective of the Phase 1 study of IVX-A12 is to evaluate safety and immunogenicity against both RSV and hMPV, as well as to assess the potential for immunologic interference, with subjects followed through 12 months after vaccination.
Topline Interim Results
Safety:
In this Phase 1 trial, IVX-A12 was generally well-tolerated across all dosage groups as of Day 28.
| • | Solicited local and systemic adverse events (AEs) were generally mild or moderate, without dose-limiting reactogenicity. |
| • | Across the five dosage groups for IVX-A12 with or without adjuvant, the proportion of subjects experiencing any systemic AE within seven days was 25-41%, and similar to 35% for placebo. |
| • | The most common local and systemic AEs were injection site tenderness, headache and myalgia. |
| • | There were no vaccine related serious adverse events (SAEs), clinical events of special interest, or AEs leading to discontinuation. |
Immunogenicity:
In this Phase 1 trial, IVX-A12 induced robust immune responses against both RSV and hMPV at Day 28 in older adults across dosage levels and with and without adjuvant.
| • | There was no evidence of immune interference between RSV and hMPV VLPs when administered in combination. |
| • | Across dosage groups, IVX-A12 induced geometric mean titers (GMTs) in RSV-A neutralizing antibody titers (nAbs) of up to approximately 16,100 IU/mL compared to approximately 2,600 IU/mL for placebo at Day 28. IVX-A12 induced GMTs in RSV-B nAbs of up to approximately 8,300 IU/mL compared to approximately 2,500 IU/mL for placebo at Day 28. |
| • | There were higher Day 28 post-vaccination levels of RSV A and RSV B nAbs (IU/ml) observed in this IVX-A12 study than seen in the previous Phase 1 clinical study of IVX-121 (RSV) alone. |
| • | Across dosage groups, IVX-A12 induced GMTs in hMPV-A nAbs of up to approximately 3,300 assay units/mL compared to approximately 900 assay units/mL for placebo at Day 28. IVX-A12 induced GMTs in hMPV-B nAbs of up to approximately 23,900 assay units/mL compared to approximately 11,500 assay units/mL for placebo at Day 28. No standardized international units exist in the field for hMPV. |
| • | High baseline nAbs to RSV-A and RSV-B were observed, likely reflecting an off-cycle RSV season following the COVID-19 pandemic. |
| • | Geometric mean fold rise (GMFR) at Day 28 was up to 4-fold in RSV-A and 3-fold in RSV-B across all treatment groups. In a pre-specified sub-analysis of data from subjects with the lowest tertile baseline nAbs titers, the corresponding GMFRs for RSV-A and RSV-B were up to 11-fold and 7-fold, respectively. |
| • | GMFR at Day 28 was up to 5-fold in hMPV-A and 4-fold in hMPV-B. In a pre-specified sub-analysis of data from subjects with the lowest tertile baseline nABs titers, the corresponding GMFRs for hMPV-A and hMPV-B were up to 9-fold and 8-fold, respectively. |
Next Steps
Based on these results, Icosavax now plans to initiate a Phase 2 trial for IVX-A12 in RSV and hMPV in mid-2023. The company plans to evaluate two formulations of IVX-A12 in this next clinical trial.
Pending results from the planned Phase 2 trial, Icosavax intends to conduct an IVX-A12 hMPV human challenge clinical trial, which Icosavax considers the most relevant proof-of-concept model for evaluating disease prevention for its bivalent vaccine candidate incorporating stabilized prefusion F proteins for each of RSV and hMPV. This hMPV human challenge model is currently in development and builds on an established precedent in the RSV field.
The IVX-121 (RSV) component of IVX-A12 (RSV/hMPV) previously demonstrated positive immunogenicity and tolerability results in a Phase 1/1b study, and a subset of these Phase 1b older adult subjects continue to be followed. In December 2022, Icosavax reported positive durability data at the six-month timepoint, with twelve-month immunogenicity data expected in mid-2023.
Forward-Looking Statements
Statements contained in this report regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on the company’s current beliefs and expectations and include, but are not limited to: the company’s expectation regarding the opportunities for, and the prophylactic and commercial potential of, its vaccine candidates and technology platform; and the company’s planned development activities, including clinical trials and data readouts, and the timing thereof. Actual results may differ from those set forth in this report due to the risks and uncertainties inherent in the company’s business, including, without limitation: the early stage of the company’s development efforts; the risk that results of a clinical trial at a particular time point may not predict final results and that an outcome may materially change as follow-up of subjects continues and following more comprehensive reviews of the data; the company’s approach to the development of vaccine candidates, including its development of a combination bivalent RSV/hMPV VLP vaccine candidate, which is a novel and unproven approach; potential delays in the development process including without limitation in the commencement, enrollment, conduct of, and receipt of data from, clinical trials; difficulties in developing an hMPV challenge model and the risk that the planned challenge study may produce negative or inconclusive results based on such model or otherwise; unexpected
adverse side effects or inadequate immunogenicity or efficacy of the company’s vaccine candidates that may limit their development, regulatory approval, and/or commercialization; the company’s dependence on third parties in connection with manufacturing, research, and clinical testing; the risk that recent and expected regulatory approval of third party RSV vaccines may make conducting clinical trials more difficult and costly and otherwise adversely affect the company’s ability to successfully develop, obtain regulatory approval of and commercialize its vaccine candidates; the potential for challenges encountered in the manufacturing and scale up process, including without limitation challenges that reduce drug product stability or potency; competing approaches limiting the commercial value of the company’s vaccine candidates; regulatory developments in the United States and other countries; the risk that the company may use its capital resources sooner than it expects; and other risks described in the company’s prior filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in the company’s quarterly report on Form 10-Q for the quarter ended March 31, 2023 and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and the company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.
| Item 9.01. | Financial Statements and Exhibits. |
(d) Exhibits
| Exhibit No. |
Description | |
| 99.1 | Slide Presentation | |
| 104 | Cover Page Interactive Data File (embedded within the Inline XBRL document). | |
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 hereunto duly authorized.
| ICOSAVAX, INC. | ||||||
| Date: May 22, 2023 | By: | /s/ Thomas Russo | ||||
| Thomas Russo | ||||||
| Chief Financial Officer | ||||||
The world needs better vaccines. We’re striving to create them. IVX-A12 Phase 1 Topline Interim Data | MAY 22, 2023 Exhibit 99.1
Forward looking statements Statements contained in this presentation regarding matters that are not historical facts are forward-looking statements. The forward-looking statements are based on the company’s current beliefs and expectations and include, but are not limited to: the company’s expectation regarding the opportunities for, and the prophylactic and commercial potential of, its vaccine candidates and technology platform; and the company’s planned development activities, including clinical trials and data readouts, and the timing thereof. Actual results may differ from those set forth in this presentation due to the risks and uncertainties inherent in the company’s business, including, without limitation: the early stage of the company’s development efforts; the risk that results of a clinical trial at a particular time point may not predict final results and that an outcome may materially change as follow-up of subjects continues and following more comprehensive reviews of the data; the company’s approach to the development of vaccine candidates, including its development of a combination bivalent RSV/hMPV VLP vaccine candidate, which is a novel and unproven approach; potential delays in the development process including without limitation in the commencement, enrollment, conduct of, and receipt of data from, clinical trials; difficulties in developing an hMPV challenge model and the risk that the planned challenge study may produce negative or inconclusive results based on such model or otherwise; unexpected adverse side effects or inadequate immunogenicity or efficacy of the company’s vaccine candidates that may limit their development, regulatory approval, and/or commercialization; the company’s dependence on third parties in connection with manufacturing, research, and clinical testing; the risk that recent and expected regulatory approval of third party RSV vaccines may make conducting clinical trials more difficult and costly and otherwise adversely affect the company’s ability to successfully develop, obtain regulatory approval of and commercialize its vaccine candidates; the potential for challenges encountered in the manufacturing and scale up process, including without limitation challenges that reduce drug product stability or potency; competing approaches limiting the commercial value of the company’s vaccine candidates; regulatory developments in the United States and other countries; the risk that the company may use its capital resources sooner than it expects; and other risks described in the company’s prior filings with the Securities and Exchange Commission (SEC), including under the heading “Risk Factors” in the company’s quarterly report on Form 10-Q for the quarter ended March 31, 2023 and any subsequent filings with the SEC. You are cautioned not to place undue reliance on these forward-looking statements, which speak only as of the date hereof, and the company undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date hereof. All forward-looking statements are qualified in their entirety by this cautionary statement, which is made under the safe harbor provisions of the Private Securities Litigation Reform Act of 1995.
Agenda Introduction and Key Takeaways Adam Simpson Chief Executive Officer Topline Interim Data Niranjan Kanesa-thasan, M.D. Chief Medical Officer Wrap-up and Q&A Adam Simpson Chief Executive Officer Niranjan Kanesa-thasan, M.D. Chief Medical Officer Tom Russo Chief Financial Officer
Positive IVX-A12 Phase 1 topline interim data* readout Potential first-in-class combination vaccine candidate displaying prefusion F antigens for both RSV and hMPV Robust immune responses to both RSV and hMPV in this clinical trial of older adult subjects First demonstration of hMPV vaccine immunogenicity in an older adult population for the field Applies similar approaches to stabilized prefusion F antigen design of RSV, to hMPV Tolerability up to highest dose tested provides a potential competitive advantage and allows for a full range of formulations in Phase 2 Systemic adverse events comparable to placebo; mild reactogenicity across formulations tested No evidence of immune interference between RSV & hMPV observed in this trial Higher post-vaccination levels of RSV A & B antibody titers (nAbs) (IU/ml) in this IVX-A12 study than historically seen with IVX-121 (RSV) alone Trial run in context of an atypical RSV epidemic following Covid-19 disruptions, potentially driving high baseline titers Prespecified sub-analysis showed particularly strong responses in those with the lowest baseline titers - GMFRs for RSV-A and RSV-B were up to 11-fold and 7-fold, respectively; GMFRs for hMPV-A and hMPV-B were up to 9-fold and 8-fold, respectively Supports progression to Phase 2 safety and immunogenicity trial in larger older adult population to select final formulation for subsequent disease prevention proof of concept study Next step: Plan to advance IVX-A12 (RSV/hMPV) to Phase 2 in mid 2023, followed by hMPV human challenge as key proof-of-concept efficacy study *As of post-vaccination D28
A vaccine able to prevent both RSV and hMPV could have a significant public health impact in older adults U.S. health and economic burden (older adults) RSV hMPV hospitalizations ~105,000 – 177,000 deaths ~14,000 Economic burden: Estimated at $1.5-3B in direct medical costs for ages 60+ Annual estimates, older adults 65+ Data support similar mortality to that seen with RSV hospitalizations ~88,000 – 123,000 Annual estimates, older adults 65+ Economic burden: TBD – likely in same range as RSV given similar morbidity and mortality estimates A vaccine targeting both RSV and hMPV has potential to almost double the health and economic impact of a vaccine targeting RSV alone – assuming similar efficacy against both pathogens RSV and hMPV hospitalization estimates based on U.S. Census 2021 population data and: Sieling et al 2021, Influenza Other Respiratory Viruses, Widmer et al 2012, J Inf Dis; Falsey et al, 2005, NEJM; Herring et al 2022, Vaccine
The transition to prefusion F protein was a game changer in RSV vaccine development; IVX-A12 incorporates stabilized prefusion F proteins for each of RSV and hMPV IVX-241 hMPV Prefusion stabilized F protein (PreF) also found to be important antigen with hMPV Development of the hMPV PreF antigen in IVX-241 was an extension of the structural biology efforts underlying RSV preF Postfusion F protein Postfusion protein subunit vaccines that were unsuccessful Particle Subunit Companies & Technologies: Prefusion F protein Prefusion stabilized protein subunit vaccines; recently validated by clinical efficacy data and initial regulatory approvals Proof-of-concept Subunit (Ph1 only) Subunit DS-Cav1 Pre-F RSV Pre-F RSV RSV-LRTI efficacy: ~67-86% Pre-F RSV + AS01E LRTD efficacy: ~83% IVX-121 RSV VLP with multivalent display of stabilized prefusion F proteins IVX-A12 Did not meet pre-specified objectives in efficacy trial Pre-F RSV + Pre-F hMPV Combination of 2 VLPs RSV RSV + hMPV Graham et al 2015; Falloon et al 2017; Novavax press release 2016; Ruckwardt et al 2021; GSK and Pfizer VRBPAC presentations, Feb 28 & Mar 1 ’23; Hsieh et al 2022 Did not prevent RSV disease in efficacy trial
IVX-A12 Phase 1 Topline Interim Data
Interim Data through Day 28 Solicited AEs SAEs, AESIs, MAAEs, Unsolicited AEs Immunogenicity DAYS 0-7 DAYS 0-28 DAYS 0 & 28 RSV-A, RSV-B, hMPV-A, & hMPV-B Virus Microneutralization assay Trial Design: Phase 1 randomized, observer-blinded, placebo-controlled trial to evaluate IVX-A12 administration in older adult subjects MF59®: Seqirus Inc.’s proprietary adjuvant. IVX-A12 Total VLP Content IVX-121 (RSV) VLP IVX-241 (hMPV) VLP 150 µg 75 µg 75 µg 225 µg 75 µg 150 µg 300 µg 75 µg 225 µg Note: 75 µg IVX-121 VLP = 42 µg RSV antigen; 75, 150, 225 µg hMPV VLP = 41, 82, 124 µg hMPV antigen 1 DOSE DAY 0 28 Placebo (N=23; 21) Total VLP Content - 150 µg + MF59 (N=29; 23) Total VLP Content - 225 µg + MF59 (N=20; 20) Total VLP Content - 150 µg No Adjuvant (N=20; 20) Total VLP Content - 225 µg No Adjuvant (N=29; 20) Total VLP Content - 300 µg No Adjuvant (N=19; 19) Older Adult Subjects (60-75 years of age) N=140 (safety analysis set); 123 (per protocol analysis set)
Summary of overall interim safety results Older Adult Subjects (60-75 years of age) IVX-A12 N=117 n (%) Placebo N=23 n (%) Any serious adverse event (AE) 0 0 Any clinical event of special interest (CESI) 0 0 Any AE leading to death or study discontinuation 0 0 Any grade 4 (life-threatening) AE 0 0 Any related medically-attended AE 0 0 Any unsolicited adverse event 27 (23.1) 6 (26.1) Mild 18 (15.4) 2 (8.7) Moderate 8 (6.8) 4 (17.4) Severe 1* (0.9) 0 No related SAEs, clinical events of special interest, or AEs leading to study withdrawal. * Severe unsolicited AE (unrelated) of hypertension on Day 28 in subject with prior medical history, resolved Unsolicited AEs are collected to Day 28. Other AEs are collected to Day 180. Safety analysis set.
Solicited adverse events within 7 days of single dose, maximal severity IVX-A12 was generally well tolerated – solicited adverse events included mild reactogenicity with systemic AEs similar to placebo. No severe solicited AEs. No Adjuvant 150 µg 225 µg 300 µg + MF59 150 µg 225 µg Placebo Placebo No Adjuvant 150 µg 225 µg 300 µg + MF59 150 µg 225 µg Placebo Placebo Mild Moderate Severe Local Adverse Events (Reactogenicity) Mild Moderate Severe N 20 29 19 29 20 23 N 20 29 19 29 20 23 Systemic Adverse Events (Tolerability) IVX-A12 Total VLP IVX-121 VLP (RSV) IVX-241 VLP (hMPV) 150 µg 75 µg 75 µg 225 µg 75 µg 150 µg 300 µg 75 µg 225 µg MF59®: Seqirus Inc.’s proprietary adjuvant. Safety analysis set.
GMT (95% CI) No Adjuvant + MF59 75 µg IVX-121 150 µg 225 µg 300 µg 150 µg PBO 225 µg GMT (95% CI) No Adjuvant + MF59 75 µg IVX-121 150 µg 225 µg 300 µg 150 µg PBO 225 µg Day 0 and Day 28 Results Day 28 Day 0 RSV-B Interim immunogenicity data: RSV-A and RSV-B NAb GMT expressed in IU/mL – Viroclinics Live NAb Assay Day 0 and Day 28 Results Day 28 Day 0 RSV-A N= 20 18 20 18 19 19 23 23 20 20 21 20 17 17 GMFR - 2 - 2 - 4 - 3 - 4 - 1 - 4 N= 20 18 20 18 19 19 23 23 20 20 21 20 17 17 GMFR - 1 - 2 - 3 - 3 - 3 - 1 - 3 IVX-A12 Total VLP IVX-121 VLP (RSV) IVX-241 VLP (hMPV) 150 µg 75 µg 75 µg 225 µg 75 µg 150 µg 300 µg 75 µg 225 µg No interference from increasing hMPV dosage levels. IVX-A12 induced NAb titers of up to ~16,100 IU/mL for RSV-A and ~8,300 IU/mL for RSV-B. Per-protocol analysis set. RSV-A LLoQ = 9.4. RSV-B LLoQ = 8.0. MF59®: Seqirus Inc.’s proprietary adjuvant. 75 µg IVX-121: IVX-121 Ph 1 reference sera panel from OA subjects receiving unadjuvanted 75 μg IVX-121. GMFR: Geometric Mean Fold Rise from Baseline. Assays Conducted by Viroclinics.
GMT (95% CI) No Adjuvant + MF59 150 µg 225 µg 300 µg 150 µg PBO 225 µg GMT (95% CI) No Adjuvant + MF59 150 µg 225 µg 300 µg 150 µg PBO 225 µg Interim immunogenicity data: hMPV-A and hMPV-B NAb GMT expressed in assay units/mL – Viroclinics Live NAb Assay Day 0 and Day 28 Results Day 28 Day 0 hMPV-B Day 0 and Day 28 Results Day 28 Day 0 hMPV-A First demonstration of hMPV vaccine immunogenicity in older adult population; similar pattern of response as seen with RSV. Clinical samples from this trial will be used to explore potential to protect against hMPV infection in a preclinical passive transfer model. N= 20 18 20 18 19 19 23 23 20 20 21 21 GMFR - 1 - 3 - 5 - 3 - 3 - 1 N= 20 18 20 18 19 19 23 23 20 20 21 20 GMFR - 2 - 2 - 4 - 3 - 3 - 1 IVX-A12 Total VLP IVX-121 VLP (RSV) IVX-241 VLP (hMPV) 150 µg 75 µg 75 µg 225 µg 75 µg 150 µg 300 µg 75 µg 225 µg Per-protocol analysis set. hMPV-A and hMPV-B LLoQ = 4.0 log 2. MF59®: Seqirus Inc.’s proprietary adjuvant. GMFR: Geometric Mean Fold Rise from Baseline. Assays Conducted by Viroclinics.
IVX-A12 Trial Sites Subjects Enrolled (%)4 Florida 104 (85%) Other 19 (15%) ~Mar-May ’22: RSV Epidemic Onset3 IVX-A12 Ph 1 trial was run during an atypical RSV epidemic following COVID-19 disruptions, with off-cycle RSV circulation potentially contributing to the high baseline titers Florida RSV Positive PCR Detections (n), 2022-20232 IVX-A12 Ph 1 subjects were enrolled during a historically high RSV season with ~2X higher hospitalizations than pre-pandemic years. Ph 2a trial is timed to complete enrollment mid-year ’23, ahead of more typical RSV seasonal patterns. RSV Seasonality Sept 26 ‘22: First patient dosed, IVX-A12 U.S. RSV-Associated Hospitalizations, ages ≥651 Season Rate per 100,000 2022-2023 66.4 2021-2022 24.5 2020-2021 0.3 2019-2020 45.1 2018-2019 38.7 Florida, where the majority of IVX-A12 Ph 1 subjects were enrolled, experienced an off-cycle peak shortly before trial start The ’22-’23 RSV season was the most severe seen in a 5 year period – evidenced by RSV-associated hospitalization rates 1 Max cumulative hospitalization rate for 2018-2023 seasons in ages ≥65, MMWR Week 16 (April), RSV-NET Interactive Dashboard; 2 Florida RSV detections, by 5 week average, CDC NREVSS, State Trends; 3 Florida ’22-’23 RSV Onset Month, RS10, 10FB, and 3% test positivity methods, Hamid et al, MMWR Apr 7 ’23, Vol. 72/No. 14; 4 Share of Per Protocol Analysis Set (total 140 subjects enrolled, including 123 in Per Protocol analysis set)
150 µg 225 µg GMT (95% CI) PBO 300 µg 150 µg 225 µg GMT (95% CI) PBO 300 µg RSV-A and RSV-B NAb pre-specified sub-analysis, 1st baseline tertile GMT expressed in IU/mL; pooled by dose – Viroclinics Live NAb Assay RSV-A First Pooled* Baseline Tertile Subjects with lowest baseline titers (1st tertile) showed GMFR of up to ~11-fold and 7-fold for RSV-A and RSV-B, respectively. RSV-B First Pooled Baseline Tertile N= 16 16 10 9 5 5 10 10 GMFR 5- to 11-Fold 5 - 5 - 11 - 2 N= 14 14 14 13 6 6 7 7 GMFR 3- to 7-Fold 6 - 3 - 7 - 1 Day 28 Day 0 Day 28 Day 0 IVX-A12 Total VLP IVX-121 VLP (RSV) IVX-241 VLP (hMPV) 150 µg 75 µg 75 µg 225 µg 75 µg 150 µg 300 µg 75 µg 225 µg * Data pooled across adjuvanted and non-adjuvanted groups within a dose. Per-protocol analysis set. RSV-A LLoQ = 9.4. RSV-B LLoQ = 8.0. MF59®: Seqirus Inc.’s proprietary adjuvant. GMFR: Geometric Mean Fold Rise from Baseline. Assays Conducted by Viroclinics.
150 µg 225 µg GMT (95% CI) PBO 300 µg 150 µg 225 µg GMT (95% CI) PBO 300 µg hMPV-A and hMPV-B NAb pre-specified sub-analysis, 1st baseline tertile GMT expressed in assay units/mL; pooled by dose – Viroclinics Live NAb Assay hMPV-A First Pooled* Baseline Tertile Subjects with lowest baseline titers (1st tertile) showed GMFR of up to 9-fold and 8-fold for hMPV-A and hMPV-B, respectively. hMPV-B First Pooled Baseline Tertile N= 11 11 12 12 10 10 8 8 GMFR 5- to 9-Fold 5 - 5 - 11 - 1 N= 17 16 12 11 8 8 4 4 GMFR 7- to 8-Fold 6 - 3 - 7 - 1 Day 28 Day 0 Day 28 Day 0 * Data pooled across adjuvanted and non-adjuvanted groups within a dose. Per-protocol analysis set. hMPV-A and hMPV-B LLoQ = 4.0 log 2. MF59®: Seqirus Inc.’s proprietary adjuvant. GMFR: Geometric Mean Fold Rise from Baseline. Assays Conducted by Viroclinics. IVX-A12 Total VLP IVX-121 VLP (RSV) IVX-241 VLP (hMPV) 150 µg 75 µg 75 µg 225 µg 75 µg 150 µg 300 µg 75 µg 225 µg
Wrap-up
Applies similar approaches to stabilized prefusion F antigen design of RSV to hMPV Robust D28 immunogenicity against two leading causes of viral pneumonia, RSV and hMPV – demonstrated in Phase 1 trial, supporting advancement to Phase 2 Potential to further reduce hospitalizations and deaths in older adults compared with vaccines targeting RSV alone – driving a substantial differentiation and commercial opportunity Potential for further differentiation based on durability suggested based on results observed with monovalent RSV candidate IVX-A12: Potential first-in-class combination vaccine candidate for RSV/hMPV advancing to Phase 2 Phase 2 safety and immunogenicity trial in larger older adult population anticipated to initiate mid-2023 hMPV passive transfer study planned to be run in parallel with Phase 2 trial hMPV human challenge model in development with clinical trial intended to be conducted thereafter, as proof-of-concept efficacy study VLPs mimic the structure of viruses to enhance the immune response Potentially driving magnitude of response, breadth of coverage, durability, favorable tolerability, highly-productive manufacturing, and combinability Moving forward rapidly with IVX-A12; next steps: Unique VLP platform may offer one or more potential benefits IVX-A12 is the only RSV/hMPV combination candidate in the clinic for older adults
Q&A
Appendix
Data suggest correlation between hMPV titer levels and symptomatic infection MNA titer: <1024 1024-1448 1449-2353 >2353 1 Left panel – Falsey AR et al., 2010: Evaluation of pre-illness baseline titers of subjects with RT-PCR positive hMPV illness and age and group matched controls with no hMPV illness or sero-response. MNA titer: antilog of Log2 MNA titers; 2 Right panel – Falsey AR et al., 2010: Evaluation of rise in endpoint titers immediately (3-4d) following symptom onset vs. 4-6 weeks following confirmed hMPV (hMPV RT-PCR and / or a >4-fold rise in hMPV specific IgG). Infection considered severe in subjects hospitalized and mild in subjects managed as outpatients. ** Fold-rise in endpoint titers determined by calculating the fold difference in antilog of Log2 values 2 fold* Log2 MNA titer: Fold-rise in titers seen in symptomatic infections2 Probability of infection by baseline antibody titer1 The lower the baseline titers, the greater the probability of infection * Prospective study saw a statistically significant 2-fold decrease in probability of infection with increased titers For subjects who had confirmed infection, a 3-5 fold-rise in endpoint titers observed following infection Fold rise in endpoint titers** between acute to convalescent sera in subjects with confirmed symptomatic infection Fold rise in endpoint titers** Mild infection (symptomatic but not hospitalized) ~3.7 Severe infection (hospitalized) ~5.2 % Infected
Icosavax has exclusively licensed rights to the prefusion stabilized F antigen incorporated into IVX-241 (except for one mRNA license that can be granted) IVX-241 for hMPV: Prefusion stabilized F hMPV antigen Prefusion F Protein Postfusion F Protein Battles et al., 2017 Mas et al., 2016 Similar to RSV, the hMPV F protein undergoes a conformational change from the prefusion to the postfusion structure to enable entry into the host cell Prefusion F protein has been shown in the mouse model to have ~6X neutralizing antibody titers against hMPV compared to postfusion F antigen Mas et al 2016, PLOS Pathogens; Battles et al 2017, Nat Commun; Hsieh et al 2022, Nat Commun
The 2022-2023 RSV season was more severe and had an earlier onset than pre-pandemic RSV seasons Cumulative U.S. RSV-Associated hospitalizations, ages ≥652 Season Rate per 100,000 2022-2023 66.4 2021-2022 24.5 2020-2021 0.3 2019-2020 45.1 2018-2019 38.7 U.S. Rates of RSV-Associated Hospitalizations, ≥65 years of age1 Weekly Hospitalization rate per 100,000 IVX-A12 Ph 1 trial ran during a historically severe and off-cycle RSV season. Data suggest RSV circulation is reverting to pre-pandemic seasonality patterns (~Oct-Apr). 1 RSV-NET Interactive Dashboard (2018-2023 seasons; weekly rates; age group ≥65 years; data updated as of 5/10/2023); 2 Max cumulative hospitalization rate for 2018-2023 seasons in ages ≥65, MMWR Week 16 (April), RSV-NET Interactive Dashboard
Our lead candidate IVX-A12 targets two common causes of pneumonia in adults: RSV and hMPV Bacterial Viral Challenging to vaccinate (100s of strains) Approved vaccines exist ~$8B in sales Approved vaccines exist ~$7B in sales Icosavax lead candidate IVX-A12 Respiratory vaccines are an emerging market: There is unmet need for an RSV and hMPV combination, and opportunities to improve protection from flu vaccines RSV/ hMPV A vaccine against RSV is expected to be recommended by policy makers such as ACIP, particularly in older adults, which could drive rapid coverage and uptake and faster growth to peak sales Analysts project an RSV vaccine market opportunity of ~$10 billion by 2030; we believe hMPV has similar vaccine market potential Other Opportunities: FLU Despite their commercial success, existing vaccines have historically shown suboptimal efficacy (~20%-50% year to year over the last 10 years) COVID-19 Optionality for ICVX; multiple industry sources have estimated that a meaningful commercial opportunity could persist in the SARS-CoV-2 endemic stage Top 5 pathogens detected in adults hospitalized with community-acquired pneumonia (EPIC Study; pre-COVID-19) No approved vaccines Jain S et al 2017, Clin Chest Med; GBD 2015 LRI Collaborators; Lancet Infect Dis 2017; Walsh et al 2008, Arch Internal Med; World Heath Organization; Global Vaccine Market Report 2022, World Health Organization
We are targeting RSV and hMPV in a combination vaccine candidate with VLPs incorporating prefusion-stabilized F proteins from RSV and hMPV viruses RSV Found in 11% of US adults hospitalized for pneumonia where pathogen detected 17% likelihood of ICU admission, 4% likelihood of death Symptoms: Cough, wheezing, dyspnea, congestion, fatigue hMPV IVX-A12 is a potential first in class RSV/hMPV combination vaccine candidate, with Phase 2 start anticipated mid 2023 IVX-121 RSV IVX-241 hMPV + RSV and hMPV are related Pneumoviridae with similar epidemiological and clinical characteristics Both viruses are common with high re-infection rates and overlapping seasonal circulation Our goal for both is to target the prefusion F protein, responsible for viral cell entry RSV hMPV IVX-A12 RSV/hMPV bivalent vaccine candidate Found in 8% of US adults hospitalized for pneumonia where pathogen detected 16% likelihood of ICU admission, 5% likelihood of death Symptoms: Cough, fatigue, dyspnea, congestion, wheezing, fever Jain et al 2015; Widmer et al 2012; Walsh et al 2008; T Shi et al 2019; Sieling et al 2021; Cattoir et al 2019, Acta Clinica Belgica
IVX-A12: Preclinical proof of concept of protection achieved against BOTH viral causes of pneumonia Control (challenge) IVX-A12 Control (no challenge) IVX-121 IVX-A12 IVX-241 Control (challenge) IVX-A12 Control (no challenge) IVX-241 IVX-A12 IVX-121 RSV/A hMPV/A RSV/A hMPV/A Lung viral titers Neutralizing antibody titers Preclinical study showed strong nAb titers induced against both RSV and hMPV, without immune interference In a live virus challenge model, cotton rats were administered two doses of adjuvanted IVX-121, IVX-241, or IVX-A12 and subsequently challenged with RSV/A or hMPV/A* Monovalent and bivalent formulations similarly blocked viral replication post challenge In lung tissue, both monovalent (IVX-121, IVX-241) and bivalent (IVX-A12) formulations reduced viral titers to below the lower limit of quantitation** In preclinical studies, RSV and hMPV two-component VLPs were combined in effort to generate a bivalent immunogen with robust nAb response and blocking of viral replication * Two doses of IVX-121, IVX-241, or IVX-A12 (1 ug of each VLP) formulated with Addavax (oil-in-water adjuvant) were administered on day 0 and day 21, with RSV/A or hMPV/A challenge two weeks post 2nd administration; ** Lung tissue samples tested 5 days post challenge
RSV / hMPV seasonality patterns suggest additional potential benefit of a durable combination vaccine RSV / hMPV seasonality RSV hMPV In most regions, RSV and hMPV show high but not completely overlapping seasonality Data shown for Belgium; other regions (e.g., U.S.) show similar trends RSV tends to precede hMPV; may be prolonged by early and late seasons hMPV season can last >6 months in multiple countries Suggests durability could be particularly important for combination vaccines, like IVX-A12 (RSV/hMPV) Initial data on durability of Icosavax monovalent RSV candidate may bode well for combination RSV / hMPV vaccine given patterns in seasonality – and may further enable pan-respiratory vaccine vision Annual distribution of RSV & hMPV positive samples in Belgium (ages <1 to >65), Cattoir et al 2019, Acta Clinica Belgica
Safety and immunogenicity of bivalent (RSV/hMPV) formulations Healthy older adults (N = 140) Constant RSV dosage (75 µg) + multiple hMPV dosage levels (75, 150, 225 µg) Single dose +/- adjuvant (MF59®) Duration follow-up planned to one year Phase 2b hMPV Human challenge Phase 1 (in progress) Phase 2 (planned mid-2023) IVX-A12 Ph 1 and 2 trials designed to inform bivalent formulation prior to anticipated proof of concept disease-prevention efficacy study Preliminary trial designs; subject to change Safety and immunogenicity; dosage and formulation selection Healthy older adults with wider age range and comorbidities (N ≈ up to 500) Planning for two RSV and hMPV bivalent formulations (may include MF59® adjuvant) Planning for long-term safety and duration of immunogenicity (multi-year) from selected formulation(s) Safety, immunogenicity and protection against hMPV infectious challenge Healthy adults Single formulation based on Phase 2 interim data hMPV challenge model development in-progress Assess safety and immunologic non-interference with varying ratios of RSV/hMPV VLPs Allows assessment of immune responses to hMPV and RSV with and without adjuvant Conduct further dose optimization with expanded safety and immunogenicity evaluation in older adults; assess longer-term safety and durability of immune response Assessment of efficacy potential in hMPV; build understanding of symptom profile to inform Phase 3
IVX-A12 is a potential first in class vaccine targeting both RSV and hMPV in the same formulation PRECLINICAL PHASE 1 PHASE 2 PHASE 3 / REGISTRATION VLP Recombinant Vector Bavarian Nordic MVA RSV-F Most technologically competitive w/ Icosavax Nucleic Acid RSV-F + hMPV RSV-F* Protein / Subunit / Soluble Antigen GSK RSV-F + AS01 Pfizer RSV-F ViceBio: RSV Moderna RSV-F Sanofi: RSV + hMPV Sanofi: RSV Moderna: RSV + Covid + Flu Moderna: RSV + Flu RSV monovalent hMPV monovalent RSV-hMPV bivalent Other RSV Combo RSV-F = RSV F (fusion) protein antigen Older Adult RSV and/or hMPV Pipeline Candidates *Icosavax does not plan to pursue the IVX-121 RSV monovalent candidate as a standalone candidate for RSV in older adults, and is transitioning development to the IVX-A12 bivalent RSV/hMPV candidate following Phase 1/1b
Novel VLP technology with multiple near-term value inflection points Candidate Indication IVX-A12 RSV/hMPV hMPV candidate selection IND submission Phase 1 initiation FDA Fast Track designation Phase 1 topline interim data Phase 2 initiation [mid ’23] IVX-121 RSV Ph 1/1b topline interim data Phase 1/1b, 6 mo. durability data Advanced to IVX-A12 bivalent RSV/hMPV candidate Phase 1b extension, 12 mo. data [mid ’23] Flu candidate Influenza Exercised option for patent license from UW Executed patent license to neuraminidase antigens from UW Candidate selection [2023] SARS-CoV-2 candidate Covid-19 Transitioned to bivalent RBD strategy Bivalent candidate selection [2023] Achieved Milestones UPCOMING Milestones