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| Item 8.01 | Other Events |
On June 28, 2022, Icosavax, Inc. (the “Company”) announced positive topline interim data for the Company’s Phase 1/1b clinical trial for its virus-like particle vaccine candidate IVX-121 against Respiratory Syncytial Virus. A description of these topline results is contained in the press release and corporate presentation each dated June 28, 2022, which are attached as Exhibit 99.1 and Exhibit 99.2, respectively, to this current report and are incorporated by reference herein.
| Item 9.01 | Financial Statements and Exhibits. |
(d) Exhibits
| 99.1 | Press Release of Icosavax, Inc. dated June 28, 2022 | |
| 99.2 | Corporate Presentation of Icosavax, Inc. dated June 28, 2022 | |
| 104 | Cover Page Interactive Data File (formatted as Inline XBRL) | |
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: June 28, 2022 | By: | /s/ Tom Russo | ||||
| Tom Russo | ||||||
| Chief Financial Officer | ||||||
Exhibit 99.1
Icosavax Announces Positive Topline Interim Phase 1/1b Results for VLP Vaccine Candidate IVX-121 Against RSV
- IVX-121 demonstrated robust immunologic response to RSV, with comparable Geometric Mean Titer (GMT) levels achieved at Day 28 in both young and older adult groups -
- IVX-121 was generally well tolerated with no vaccine-related SAEs -
- Provides initial indication of a differentiated VLP platform technology -
- Icosavax plans to file an IND submission and initiate a Phase 1 trial for IVX-A12, a combination bivalent RSV + hMPV VLP candidate, in 2H 2022 –
- Company to host conference call/webcast today at 4:30 p.m. ET / 1:30 p.m. PT -
SEATTLE, June 28, 2022 – Icosavax, Inc. (Nasdaq: ICVX), a biopharmaceutical company leveraging its innovative virus-like particle (VLP) platform technology to develop vaccines against infectious diseases, with an initial focus on life-threatening respiratory diseases and a vision of creating pan-respiratory vaccines for older adults, today announced positive topline interim results from its Phase 1/1b clinical trial of IVX-121, a VLP displaying a prefusion stabilized Respiratory Syncytial Virus (RSV) F antigen, in young and older adults.
“I’m delighted to share these topline, interim data from our Phase 1/1b trial in RSV, in which IVX-121 demonstrated a robust immunologic response in both young and older adult groups. Importantly, we believe these Phase 1/1b data provide initial validation of our underlying VLP technology. They also reaffirm our strategy to combine multiple pathogen targets in one vaccine,” said Adam Simpson, Chief Executive Officer of Icosavax. “As planned, Icosavax will now progress development of IVX-121 combined with a human metapneumovirus (hMPV) VLP, as our IVX-A12 bivalent vaccine candidate. We believe IVX-A12 could be unique in providing protection against these two leading causes of pneumonia, each of which currently lack an approved vaccine.”
IVX-121 Phase 1/1b Trial Design
The Phase 1/1b clinical trial of IVX-121 is a randomized, observer-blinded, placebo-controlled, multi-center study designed to evaluate the safety and immunogenicity of three dose levels of IVX-121, with and without aluminum hydroxide adjuvant, in healthy young and older adults.
The Phase 1 part of the trial enrolled 90 healthy young adults aged 18-45 years. The Phase 1b part of the trial enrolled 130 healthy older adults aged 60-75 years. Subjects were administered a single dose of IVX-121 at one of three dose levels (25, 75, 250 µg), with or without aluminum hydroxide adjuvant, or placebo.
The primary outcomes of the study were safety and immunogenicity up to 28 days post-vaccination; neutralizing antibodies to RSV-A and RSV-B were measured in international units (IU/mL) using the WHO international reference standard. The trial was intended to inform the dose of IVX-121 to be evaluated in combination with Icosavax’s hMPV VLP in an upcoming Phase 1 clinical trial of the company’s RSV/hMPV bivalent vaccine candidate IVX-A12.
Topline Results
Safety:
In this Phase 1/1b study, IVX-121 was generally well-tolerated across all dosage groups.
| • | Solicited local and systemic adverse events (AEs) were generally mild or moderate, without dose-limiting reactogenicity. |
| • | In the older adult target population, across the six dosage groups for IVX-121 with or without adjuvant, the proportion of subjects experiencing any systemic AE within seven days was 11-33%, and similar to 21% for placebo. |
| • | The most common local and systemic AEs were injection site tenderness, headache and fatigue. |
| • | There were no serious AEs related to vaccine, AEs of special interest, or AEs leading to discontinuation. |
Immunogenicity:
In this Phase 1/1b study, IVX-121 induced a robust immune response in both young and older adult groups.
| • | The data indicated a dose-independent response, including at the lowest non-adjuvanted dose (25 µg). |
| • | No additional benefit from the aluminum hydroxide adjuvant was observed at any dosage level in either portion of the study. |
| • | Geometric mean titers for RSV-A and RSV-B were in comparable ranges for both groups. |
Young Adults (Phase 1):
| • | In young adults, across dosage groups, IVX-121 induced Geometric Mean Titers (GMTs) in RSV-A neutralizing antibodies (nAbs) of up to 7,687 IU/mL compared to 1,100 IU/mL for placebo at Day 28. |
| • | These titers corresponded to a Geometric Mean Fold Rise (GMFR) versus baseline up to 10-fold for IVX-121 at Day 28. |
Older Adults (Phase 1b):
| • | GMT responses in IU/mL for older adults were comparable with those for young adults. |
| • | Across dosage groups, IVX-121 induced GMTs in RSV-A nAbs of up to 7,561 IU/mL compared to 1,692 IU/mL for placebo at Day 28. |
| • | GMFR at Day 28 was up to 6-fold, reflecting higher baseline titers in the older adults group. |
“These topline interim data from our Phase 1/1b trial indicate that IVX-121 was generally well tolerated and elicited a strong and consistent response against RSV in healthy young and older adults. These data are particularly encouraging for the vulnerable older adult population with co-morbidities and increased risk for severe disease and hospitalization,” said Niranjan Kanesa-thasan, M.D., Chief Medical Officer of Icosavax. “The immunogenicity of IVX-121, even at very low microgram dosage levels, and its favorable tolerability to the highest dose level, makes it well suited to a combination vaccine approach.”
Icosavax plans to submit an IND for IVX-A12 to the U.S. Food and Drug Administration (FDA) and thereafter initiate a Phase 1 clinical trial in 2H 2022. This study will examine safety and immunogenicity of bivalent (RSV/hMPV) formulations, incorporating a single RSV dosage level and multiple hMPV dosage levels.
Interim data from the Phase 1/1b IVX-121 trial will also support a Phase 1b extension study, in which eligible older adults from the Phase 1b cohort will be followed out to 12 months to assess durability of response.
Conference Call and Webcast
Icosavax will host a conference call and a live webcast at 4:30 p.m. ET / 1:30 p.m. PT on June 28, 2022 to discuss the topline interim Phase 1/1b results for IVX-121. Individuals interested in listening to the conference call may do so by dialing (844) 467-8978 for domestic callers, or (929) 517-0913 for international callers and reference conference ID: 6829745; or from the webcast link in the investor relations section of the company’s website at www.icosavax.com. The webcast will be available in the investor relations section on the company’s website for 30 days following the completion of the call.
About Icosavax
Icosavax is a biopharmaceutical company leveraging its innovative VLP platform technology to develop vaccines against infectious diseases, with an initial focus on life-threatening respiratory diseases and a vision for combination and pan-respiratory vaccines. Icosavax’s VLP platform technology is designed to enable multivalent, particle-based display of complex viral antigens, which it believes will induce broad, robust, and durable protection against the specific viruses
targeted. Icosavax’s pipeline includes vaccine candidates targeting respiratory syncytial virus (RSV), human metapneumovirus (hMPV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), and an emerging program in influenza. Icosavax was formed in 2017 to advance the breakthrough VLP technology from the Institute for Protein Design at the University of Washington with the goal to discover, develop, and commercialize vaccines against infectious diseases. Icosavax is located in Seattle.
Forward Looking Statements
Statements contained in this press release 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 potential for the company’s VLP platform to result in safe and effective vaccines against infectious diseases; the potential for IVX-A12 to serve as a safe and effective combination vaccine and provide protection against RSV and hMPV; and the company’s specific plans and anticipated timing to file an IND submission and initiate a Phase 1 trial for IVX-A12. Actual results or developments may differ from those set forth in this press release due to the risks and uncertainties inherent in the company’s business, including, without limitation: the fact that topline results are based on preliminary analysis of key safety and immunogenicity data, and such data may change following a more comprehensive review of the data related to the clinical trial and such topline data may not accurately reflect the complete results of the clinical trial; the risk that interim results of a clinical trial do not predict final results and that one or more of the outcomes may materially change as follow-up on the outcome of any particular subject continues, as more subject data become available and following more comprehensive reviews of the data; the possibility of unexpected adverse side effects or inadequate immunogenicity or efficacy of IVX-121 or IVX-A12 that may limit development, regulatory approval, and/or commercialization; the possibility of disappointing results in later clinical trials despite promising results in earlier preclinical research or clinical trials; the possibility that cross study comparisons may not prove accurate as clinical data accrue or due to the inherent limitations of cross study comparisons; potential delays or difficulties in submission of an IND and the commencement, enrollment, and completion of the Phase 1b extension study for IVX-121, the planned Phase 1 trial for IVX-A12 and other clinical trials; the company’s approach to the discovery and development of vaccine candidates, which is novel and unproven; competing approaches limiting the commercial value of the company’s vaccine candidates and VLP vaccine technology; regulatory developments in the United States and other countries; potential disruption to the company’s operations and continued conduct of clinical trials from the COVID-19 pandemic or the conflict in Ukraine; 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, 2022 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.
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IVX-121 Phase 1/1b Topline Data June 28, 2022 Exhibit 99.2
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 potential for the company’s VLP platform to result in safe and effective vaccines against infectious diseases; the potential for IVX-A12 to serve as a safe and effective combination vaccine and provide protection against RSV and hMPV; and the company’s specific plans and anticipated timing to file an IND submission and initiate a Phase 1 trial for IVX-A12. Actual results or developments may differ from those set forth in this press release due to the risks and uncertainties inherent in the company’s business, including, without limitation: the fact that topline results are based on preliminary analysis of key safety and immunogenicity data, and such data may change following a more comprehensive review of the data related to the clinical trial and such topline data may not accurately reflect the complete results of the clinical trial; the risk that interim results of a clinical trial do not predict final results and that one or more of the outcomes may materially change as follow-up on the outcome of any particular subject continues, as more subject data become available and following more comprehensive reviews of the data; the possibility of unexpected adverse side effects or inadequate immunogenicity or efficacy of IVX-121 or IVX-A12 that may limit development, regulatory approval, and/or commercialization; the possibility of disappointing results in later clinical trials despite promising results in earlier preclinical research or clinical trials; the possibility that cross study comparisons may not prove accurate as clinical data accrue or due to the inherent limitations of cross study comparisons; potential delays or difficulties in submission of an IND and the commencement, enrollment, and completion of the Phase 1b extension study for IVX-121, the planned Phase 1 trial for IVX-A12 and other clinical trials; the company’s approach to the discovery and development of vaccine candidates, which is novel and unproven; competing approaches limiting the commercial value of the company’s vaccine candidates and VLP vaccine technology; regulatory developments in the United States and other countries; potential disruption to the company’s operations and continued conduct of clinical trials from the COVID-19 pandemic or the conflict in Ukraine; 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, 2022 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 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-121 Phase 1/1b topline interim results Initial indication of the company’s differentiated VLP platform technology High RSV-A and RSV-B neutralizing antibody titers seen even at lowest dose tested Positive topline data from the Phase 1/1b trial of IVX-121 suggest a competitive initial profile in RSV Similarly robust responses in older versus young adults, favorable tolerability, suitability for combination Opportunities to further differentiate RSV profile; durability to be assessed in Phase 1b extension out to 12 months Proceeding to combination with proprietary hMPV VLP in a differentiated bivalent vaccine candidate IVX-A12 (RSV/hMPV) for older adults Tolerability profile at maximum dose tested in Phase 1 (250 µg) and immunogenicity down to 25 µg gives room for multivalent combinations Next step: IVX-A12 (RSV/hMPV) on track for IND submission and anticipated start of Phase 1 trial in 2H’22
VLPs may offer one or more of these potential benefits Magnitude of response When compared to existing modalities, WE BELIEVE OUR VLP TECHNOLOGY HAS THE POTENTIAL TO IMPROVE UPON: Breadth of coverage Durability to counter immunosenescence that can occur in the elderly greater degree of protection against related viral strains and mutations; less customization for variants longer antibody persistence and requiring fewer boosters Tolerability/reactogenicity Manufacturing Combinability lower incidence of side effects and greater acceptability high productivity and scalability with process efficiencies, storage flexibility and stability ability to combine multiple VLPs in one vaccine
Unlike soluble antigens, VLPs mimic the structure of real viruses Natural virus Soluble antigen VLP-based antigen Traditionally manufactured or mRNA-derived
Our VLPs are produced via a proprietary, 2-component, computationally-designed system IVX-121 IVX-241 FLU IVX-411 hMPV RSV SARS-CoV-2 FLU Trimeric protein genetically fused to target antigen Antigen properly folds to display neutralizing epitopes before assembly into VLP New antigen design capabilities allow us to prepare for future threats VLPs Component B (common) Can be used across multiple vaccine candidates Self-assemble when components A and B are combined Icosahedral symmetry and particle size mimics viral properties to potentially enhance immunogenicity VLPs can have one antigen target per VLP or multiple different antigens on a single VLP Component A (antigen-specific)
Graham et al 2015; Ruckwardt et al 2021 IVX-121 for RSV: Prefusion RSV-F protein may lead to higher neutralizing antibody titers Proof of concept Subunit (Ph1) Subunit Recombinant vector or mRNA VLP Companies & Technologies: mRNA DS-Cav1 Adult Neutralizing Titer GMFR ~7-10x Postfusion protein subunit vaccines Prefusion stabilized protein subunit vaccines (e.g., DS-Cav1) VLP with multivalent display of stabilized prefusion proteins Postfusion F protein Prefusion F protein IVX-121 Subunit Particle Older Adults Neutralizing Titer Geometric Fold Rise (GMFR) ~2-4x
IVX-121 for RSV: Ph 1/1b trial initiated September 2021 Phase 1b revaccination Subset of Ph 1b OA cohort 12 months follow-up Revaccination at 12 months after initial Ph 1b dose Following the Phase 1/1b trial, we plan to combine IVX-121 with IVX-241 (our hMPV candidate) for further clinical development as IVX-A12 combination candidate Phase 1 First-in-human dose escalation Healthy young adults (YA), aged 18–45 yrs 6 treatment groups: 3 dosage levels IVX-121 (25, 75, 250 µg) +/- alum adjuvant N = 90 (dosing complete) Phase 1b Healthy older adults (OA), aged 60–75 yrs 6 treatment groups: 3 dosage levels IVX-121 (25, 75, 250 µg) +/- alum adjuvant N = 130 (dosing complete) Allows comparison to NIH DS-Cav1 Phase 1 data in YA, as representative of stabilized prefusion F-based vaccines Assessment of safety and immunogenicity in OA and potential to counter immunosenescence Assessment of long term safety and durability and responses to additional dose of IVX-121 in OA Preliminary; subject to change
IVX-121 Phase 1/1b Topline Data
Study Design: Phase 1/1b randomized, observer-blinded, placebo-controlled study to evaluate IVX-121 administration in young and older adult subjects Young Adult Subjects (ages 18-45) n=90 PH1 Older Adult Subjects (ages 60-75) n=130 PH1b alum: 500 µg/mL aluminum hydroxide Placebo 25, 75, or 250 µg No Adjuvant 25, 75, or 250 µg + alum 1 DOSE N=6 N=14/grp N=14/grp Placebo 25, 75, or 250 µg No Adjuvant 25, 75, or 250 µg + alum 1 DOSE N=19 N=18-19/grp N=18-19/grp DAY 0 28 DAY 0 28 Topline Data through Day 28 Solicited AEs SAEs, AESIs, MAAEs, Unsolicited AEs Immunogenicity DAYS 0-7 DAYS 0-28 DAYS 0 & 28 RSV-A and RSV-B Live Virus Microneutralization
Summary of safety data No SAEs, AEs of special interest (AESIs) or AEs leading to study withdrawal IVX-121 n (%) Placebo n (%) IVX-121 n (%) Placebo n (%) Any serious adverse event (AE) 0 0 0 0 Any AE of special interest 0 0 0 0 Any AE leading to death or study discontinuation 0 0 0 0 Any grade 4 (life-threatening) AE 0 0 0 0 Any related Medically-Attended AE 0 0 2 (1.8) 0 Any unsolicited adverse event (through day 28) Mild 25 (29.8) 2 (33.3) 27 (24.3) 7 (36.8) Moderate 33 (39.3) 1 (16.7) 21 (18.9) 2 (10.5) Severe 1* (1.2) 0 3* (2.7) 0 Young Adult Subjects (ages 18-45) n=90 PH1 Older Adult Subjects (ages 60-75) n=130 PH1b *None of the severe unsolicited adverse events were vaccine-related
No Adjuvant 25 µg 75 µg 250 µg + alum 25 µg 75 µg 250 µg Placebo Placebo Solicited adverse events within 7 days of single dose, maximal severity Unadjuvanted IVX-121 reactogenicity is mild in older adults with similar tolerability to placebo alum: 500 µg/mL aluminum hydroxide Older Adult Subjects (ages 60-75) n=130 PH1b No Adjuvant 25 µg 75 µg 250 µg + alum 25 µg 75 µg 250 µg Placebo Placebo Mild Moderate Severe Mild Moderate Severe Systemic Adverse Events (Tolerability) Local Adverse Events (Reactogenicity) 19 N 18 18 19 18 19 19 19 N 18 18 19 18 19 19
Topline immunogenicity data: RSV-A nAb (unadjuvanted) GMT expressed in IU/mL – Viroclinics Live nAb Assay Geometric mean titers (in IU/mL) of unadjuvanted IVX-121 are comparable in young and older adults GMT: Geometric mean titer; LLoQ = 9.9; GMFR: Geometric Mean Fold Rise (Day 28) from Baseline. Assays Conducted by Viroclinics Day 0 Day 28 GMT (95% CI) Day 0 and Day 28 Results No Adjuvant PBO GMT (95% CI) 25 µg 75 µg 250 µg Day 0 Day 28 Day 0 and Day 28 Results N= 14 13 14 14 14 13 6 6 GMFR 8- to 10-fold 7.6 1.0 Young Adult Subjects (ages 18-45) n=90 PH1 Older Adult Subjects (ages 60-75) n=130 PH1b No Adjuvant PBO 25 µg 75 µg 250 µg N= 17 19 18 18 18 18 19 19 GMFR 5- to 6-fold 7.6 1.4 Similar responses throughout the dose range RSV-B titers in similar range (GMT up to ~6000 IU/mL) in older adults
Topline immunogenicity data: RSV-A nAb (unadjuvanted vs. adjuvanted) GMT expressed in IU/mL – Viroclinics Live nAb Assay Alum adjuvant had no beneficial effect in young and older adults GMT: Geometric Mean Titer. LLoQ = 9.9. alum: 500 µg/mL aluminum hydroxide. Assays conducted by Viroclinics GMT (95% CI) GMT (95% CI) No Adjuvant + alum PBO 25 µg 75 µg 250 µg 25 µg 75 µg 250 µg Young Adult Subjects (ages 18-45) n=90 PH1 Older Adult Subjects (ages 60-75) n=130 PH1b No Adjuvant + alum PBO 25 µg 75 µg 250 µg 25 µg 75 µg 250 µg Day 0 Day 28 Day 0 and Day 28 Results Day 0 Day 28 Day 0 and Day 28 Results
Clinical study met primary safety and immunogenicity objectives Generally well tolerated with no serious or dose limiting adverse events in adults, including older adults Mild reactogenicity associated with unadjuvanted IVX-121 in older adults Systemic adverse events comparable to placebo for older adults Immunogenicity data show substantial induction of neutralizing antibodies to RSV-A and RSV-B Geometric mean titers (in IU/mL) were comparable in young and older adults Robust antibody responses seen at lowest (25 µg) unadjuvanted IVX-121 dose and across range of doses Despite high baseline titers, age dependent geometric mean fold rises up to 10 fold at Day 28 No beneficial adjuvant effect from formulation with alum in either adult cohort Supports planned combination with hMPV antigen The immunogenicity of IVX-121, even at the lowest dose, and its tolerability to the highest dose level, makes it well suited to a combination vaccine approach Key takeaways from IVX-121 Phase 1/1b topline interim results IVX-121 showed favorable safety and immunogenicity in older adults, even at very low dosages; supports moving ahead with combination vaccine strategy
Wrap-up
Favorable IVX-121 tolerability data in Phase 1/1b study RSV vaccines – OA Shingles vaccine Quadrivalent influenza vaccines – OA1 RSVpreF3 (w/ AS01) Ad26.RSV. preF + preF RSVpreF2 mRNA-1345 Shingrix (w/ AS01) Fluzone Flublok Afluria mRNA-10103 IVX-121 25-250 µg - OA N=111 (GSK) (Janssen) (Pfizer) (Moderna) (GSK) (Sanofi) (Sanofi) (Sequirus) (Moderna) Solicited systemic AEs – 41% 49% 50 - 79%6 66% 25% 25% 20% 48% - 77% 11-33% Grade 3+ solicited systemic AEs ‘Grade 3 AE rates were generally low’ 2% 0 - 7%4 – 11% 0.4% 1% – 0% - 16% 0% SAEs ‘Low reporting of SAEs’ 5% 5 - 19% 3% 1% 0% 3% 2%7 0% 0% Vaccine-related SAEs 0% 0% 0% 0% 0% 0% 0% 0%7 0% 0% Vaccine-related deaths 0% 0% 0% – 0% 0% 0% 0%7 – 0% Age Group 65-80 65+ 65-85 65-79 50+ 65+ 50+ 65+ 65+ 60-75 Study Phase 1/2 2b 1/2 1 3 3 3 3 2 1 **Data shown side by side for illustrative purposes only; not a head-to-head comparison and there could be assay and laboratory differences across trials** Data are based on: IDWeek2020 (GSK), ReSViNET 2021 (Janssen), Falsey et al 2021 (Pfizer), Jordan et al 2020 (Bavarian Nordic), Moderna Vaccines day 2022 (Moderna), Lal et al, 2015 (Shingrix), Treanor et al 2017 (Afluria), FDA influenza package inserts (Shingrix, Fluzone, Flublok, Afluria); 1 Non-exhaustive, representative set of quadrivalent flu vaccines recommended for 2021-2022 flu season; 2 Ranges represents 60 µg – 240 µg doses +/- alum; 3 Ranges represent 25 µg - 100 µg doses; 4‘Solicited severe systemic events’ interpreted as Grade 3+ AEs; 6 Range represents data post 1 dose (12.5 µg - 200 µg); 7Data available only for combined safety population (YA and OA), 65+ population represents ~50% of Afluria cohort IVX-121 Phase 1/1b safety data support advancement of multivalent vaccine vision
At comparable or lower antigen dose equivalents, IVX-121 elicits high RSV-A NAb titers relative to those previously shown for DS-Cav1 antigen DS-Cav1 soluble protein (NIH)2 YA immunogenicity, ~1 month post dose (unadjuvanted): RSV-A neutralization assays (IU/mL)1 IVX-121 VLP YA (18-50) YA (18-45) **Data shown side by side for illustrative purposes only; not a head-to-head comparison and there could be assay and laboratory differences across trials** 1 NAb assays conducted at different labs, using the World Health Organization (WHO) International Standard for antiserum to RSV-A (NIBSC code: 16/284), for conversions to WHO International Units/mL (IU/mL); 2 DS-Cav1 doses range from 50-500 µg (Ruckwardt et al 2021), doses comparable to IVX-121 are shown Robust initial immunogenicity at lower dose levels of VLP enables advancement of multivalent vaccine vision
IVX-121 neutralizing antibody titers are in the estimated range of a leading RSV candidate in Phase 3 for older adults RSVpreF soluble protein (Pfizer; estimated titers) IVX-121 VLP (Older Adults) Ph 2 Young adults (YA) human challenge3 Ph 1/2 Older Adults2 dose recently demonstrated ~87% efficacy in a YA human challenge study4 **Data shown side by side for illustrative purposes only; not a head-to-head comparison and there could be assay and laboratory differences across trials** 1 NAb assays conducted at different labs, using the World Health Organization (WHO) International Standard for antiserum to RSV/A (NIBSC code: 16/284), for conversions to WHO International Units/mL (IU/mL); 2 Based on Ph 1/2 OA expanded cohort in Falsey et al 2021, data are approximate estimates derived from reported graphs and IU/mL conversion factors; 3 Beate Schmoele-Thoma et al 2022; 4 Final RSVpreF formulation selected for OA (120 µg no adj, Baber et al 2022) Immunogenicity, ~1 month post dose (unadjuvanted): RSV-A neutralization assays (IU/mL)1 **RSV-B estimated titers ~6,500-7,000 GMT IU/mL for 120 µg dose across the two Pfizer studies shown IVX-121 durability profile to be assessed in Phase 1b extension out to 12 months RSV-B titers up to ~6,000 GMT IU/mL in older adults for IVX-121
VLPs may offer one or more of these potential benefits Magnitude of response When compared to existing modalities, WE BELIEVE OUR VLP TECHNOLOGY HAS THE POTENTIAL TO IMPROVE UPON: Breadth of coverage Durability to counter immunosenescence that can occur in the elderly greater degree of protection against related viral strains and mutations; less customization for variants longer antibody persistence and requiring fewer boosters Will be assessed in Phase 1b extension study Tolerability/reactogenicity Manufacturing Combinability lower incidence of side effects and greater acceptability high productivity and scalability with process efficiencies, storage flexibility and stability ability to combine multiple VLPs in one vaccine Will be assessed in IVX-A12 RSV/hMPV combination study Based on early clinical data and a limited number of subjects, to be assessed further in subsequent clinical studies
Our first combination vaccine candidate—IVX-A12—targets both RSV and hMPV 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 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 Clinical precedent for use of VLPs for combination vaccines targeting related pathogens (e.g., human papillomavirus, norovirus) Icosavax utilizing prefusion stabilized F antigens for display on VLP IVX-121 RSV IVX-241 hMPV + RSV and hMPV are related Pneumoviridae and have overlapping seasonal circulation Both viruses are common with high re-infection rates The goal for both is to target the F protein (responsible for viral cell entry) Jain et al 2015; Widmer et al 2012; Walsh et al 2008; T Shi et al 2019 RSV hMPV IVX-A12 RSV/hMPV bivalent vaccine candidate Next step: IVX-A12 (RSV/hMPV) on track for IND submission and start of Phase 1 trial in 2H’22
Q&A
Appendix
Demographics of trial participants Young Adult Subjects (ages 18-45) n=90 PH1 Older Adult Subjects (ages 60-75) n=130 PH1b IVX-121 N=84 Placebo N=6 Gender Male (%) 31.0 66.7 Female (%) 69.0 33.3 Age Average Age (min, max) 30.1 (18, 44) 33.3 (21, 41) Race White or Caucasian (%) 97.6 100 BMI (kg/m2) Mean 24.26 24.17 IVX-121 N=111 Placebo N=19 Gender Male (%) 49.5 68.4 Female (%) 50.5 31.6 Age Average Age (min, max) 65.7 (60, 76) 66.1 (59, 75) Race White or Caucasian (%) 100 100 BMI (kg/m2) Mean 26.32 24.41
GMT ranges for RSV-A and RSV-B in older adults Older Adult Subjects (ages 60-75) PH1b RSV-A 25 µg 75 µg 250 µg GMT (95% CI) Day 28 Results (Unadjuvanted) N= 19 18 18 Pattern of RSV-B responses show immunogenicity even at lowest dosage level and comparable ranges to those of RSV-A RSV-B Day 28 Results (Unadjuvanted) 25 µg 75 µg 250 µg GMT (95% CI) N= 19 18 18 Similar responses throughout the dose range
Icosavax is the only company pursuing RSV and hMPV with the VLP modality PRECLINICAL PHASE 1 PHASE 2 PHASE 3 VLP Subunit / Soluble Antigen Recombinant Vector GSK Prefusion RSV-F + AS01 Pfizer Prefusion RSV-F Janssen Adenovirus + soluble RSV-F Bavarian Nordic MVA RSV-F Live-Attenuated Meissa RSV Most technologically competitive w/ Icosavax Nucleic Acid Moderna RSV-F Meissa hMPV RSV monovalent hMPV monovalent RSV-hMPV bivalent RSV+hMPV Prefusion RSV-F+alum Other RSV Combo Sanofi: RSV Sanofi: RSV+hMPV Moderna: RSV+COVID-19+Flu RSV-F = RSV F (fusion) protein antigen Older Adult RSV and / or hMPV Pipeline Candidates