Pursuing major unmet
needs with our VLP technology

A robust pipeline targeting multiple respiratory diseases

We are advancing VLP vaccine candidates that have the potential to induce high neutralizing antibody (nAb) titers for more effective protection. These vaccines are intended to help protect the most vulnerable populations, including older adults, against severe disease.

Progressing multiple assets in the clinic

*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.

†FDA Fast Track designation.

‡Icosavax has worldwide nonexclusive rights with exception of South Korea (which is not included in the licensed territory), which will convert to exclusive rights in North America and Europe (including Switzerland and United Kingdom) starting in 2025, with non-exclusivity maintained elsewhere.

All of our development programs target areas where there are important unmet needs. There are no approved vaccines for RSV or hMPV, and there are opportunities to improve protection from flu vaccines. In addition, COVID-19 vaccine options are needed, even as we evolve from pandemic to endemic status.

Top 5 pathogens detected in adults hospitalized with community-acquired pneumonia (EPIC study; pre-COVID-19)1

IVX-A12 RSV/hMPV bivalent program

Our first combination vaccine candidate, IVX-A12, targets BOTH RSV and hMPV, two of the top five causes of pneumonia in adults1

FDA FAST TRACK DESIGNATION

Icosavax is currently conducting a Phase 1 trial for IVX-A12 for the prevention of RSV and hMPV. This trial is on track to announce topline results in Q2 2023, with plans thereafter to initiate a Phase 2 trial in the second half of the year. Positive topline efficacy data for the RSV component of the vaccine, IVX-121, was reported in June 2022. In December 2022, positive IVX-121 durability data for the six-month timepoint was also reported. The FDA has granted Fast Track designation for IVX-A12 in older adults ≥60 years of age.

There are currently no approved vaccines for RSV or hMPV, and we are differentiated as the only company pursuing RSV and hMPV with the VLP modality and the only company with a combination RSV/hMPV candidate in the clinic.

RSV and hMPV are related Pneumoviridae that have overlapping seasonal circulation. Both viruses are common, with high re-infection rates. We estimate RSV causes ~105,000 to ~177,000 hospitalizations/year and ~14,000 deaths/year in US adults 65+. The economic burden in the US for RSV is estimated at $1.5–3B in direct medical costs for ages 60+. We estimate hMPV causes ~88,000 to ~123,000 hospitalizations/year in US adults 65+. Data support similar mortality to that seen with RSV.2-7

In our RSV/hMPV development program, we have focused on developing and advancing VLPs that stimulate high nAb titers. Every log2 improvement in nAb titers is believed to lead to a clinically relevant improvement in disease outcome.

Consistent with the evolution of the field, we are utilizing prefusion stabilized F antigens for display on our VLPs

Both our RSV and hMPV VLPs employ the F protein responsible for viral cell entry. F proteins undergo conformational changes upon fusing to the cell membrane; utilizing prefusion F protein may lead to higher nAb titers.

IVX-121 for RSV: Prefusion RSV-F protein may lead to higher nAb titers

Data support prefusion F antigens including DS-Cav1 for targeting RSV8, and IVX-121—the RSV component of IVX-A12—is a VLP with multivalent display of stabilized prefusion F proteins.

IVX-241 for hMPV:
Prefusion stabilized F
hMPV antigen selected

In hMPV, prefusion F protein has been shown in the mouse model to have ~6X nAb titers compared to postfusion F antigen.11

Clinical development is progressing following positive topline results in RSV

A Phase 1/1b trial involving the RSV component of the combination vaccine, IVX-121, was initiated in September of 2021. Positive topline interim results and six-month immunogenecity data were reported in June and December of 2022, respectively. These data are briefly summarized below.

IVX-121 for RSV: Ph 1/1b trial

Allows comparison to NIH DS-Cav1 Phase 1 data in YA, as representative of stablized prefusion F-based vaccines

Assessment of safety and immonogenicity in OA and potential to counter immunosenescence

Assessment of long-term safety and durability and responses to additional dose of IVX-121 in OA

Positive IVX-121 (RSV VLP) Phase 1/1b topline interim results and six-month immunogenecity update12

Briefly, data show:

  • High RSV-A and RSV-B neutralizing antibody titers seen from the lowest dose tested
  • Similarly robust responses in older vs. young adults
  • Favorable tolerability
  • Suitability for combination (tolerability profile up to maximum dose tested in Phase 1 [250 µg] and immunogenicity down to 25 µg gives room for multivalent combinations)
  • Six-month immunogenicity update showed durability of RSV-A and RSV-B neutralizing antibody titers up to 180 days after vaccination
    • Geometric mean titers (GMT) against RSV-A through Day 180 persisting at 64%–98% of the GMTs at Day 28 in older adults
    • First clinical evidence of potential differentiation on durability with company’s VLP platform technology
    • No safety concerns – IVX-121 continued to be generally well tolerated

Topline immunogenicity data: RSV-A nAb geometric mean titers (in IU/mL)
of unadjuvanted IVX-121 are comparable in young and older adults through Day 180

GMT: geometric mean titer; LLoQ = 9.9; GMFR: geometric mean fold rise (Day 28) from baseline. Assays conducted by Viroclinics.

Looking to extend this positive data, we are currently conducting a Phase 1 trial for our IVX-A12 RSV/hMPV combination vaccine. The Phase 1 and 2 studies for IVX-A12 will help us to optimize our bivalent formulation and inform clinical endpoints for a potential POC Phase 2b efficacy study.

IVX-A12 Phase 1 and 2 trials will inform bivalent formulation prior to anticipated proof of concept disease prevention efficacy study

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

Dose optimization with expanded safety and immunogenicity in older adults, ahead of a subsequent proof-of-concept efficacy study

Assess longer-term safety and durability of immune response to RSV/hMPV candidate

Flu program

Flu is an important part of our vision

A VLP-based vaccine targeting influenza—potentially deployed as part of a combination vaccine—is being pursued. In relation to this initiative, we also have plans to build a rapid production system capable of supporting seasonal flu, which we expect to also enhance our pandemic response capabilities.

There is an unmet need for a flu vaccine with improved efficacy, particularly in the older adult population. Even though numerous marketed vaccines are available, flu still causes ~380K hospitalizations and ~20K deaths/year in the US—the majority in people over 65.13 In addition, despite their commercial success, existing flu vaccines have historically had suboptimal efficacy (~20%–50% over the last 10 years) and need to be updated every season.13

US flu disease burden, 2019–2020 flu season13

Suboptimal efficacy is seen with currently available flu vaccines13

*2020-2021 flu vaccine effectiveness was not estimated due to low flu virus circulation during the 2020-2021 flu season.
†Interim vaccine effectiveness estimates, as of June 2022.

Preclinical candidate development is in process.

COVID-19 program

Better vaccines for COVID-19 are needed

We believe there will be a need for better vaccines and that a meaningful opportunity could persist beyond the pandemic in COVID-19, and this is an area of interest to the company for its optionality as a potential component of our combination vaccines vision.

Preclinical COVID-19 candidate development is in process, and we are currently focusing on a bivalent strategy for a COVID-19 candidate displaying computationally engineered receptor binding domain (RBD) antigens. The objective is antigen prototypes that improve the stability of the RBD subdomain from the SARS-CoV-2 S protein and could allow for the successful presentation of evolving variants of interest, including omicron and subsequent derivatives.

1. CDC, EPIC study. 2. U.S. Census 2021 population data. 3. Sieling WD et al. Influenza Other Respir Viruses. 2021;15(5):670-677. 4. Widmer K et al. J Infect Dis. 2012; 206(1):56-62. 5. CDC, RSV Trends and Surveillance. 6. Falsey AR et al. N Engl J Med. 2005;352(17):1749-59. 7. Herring WL et al. Vaccine. 2022;40(3):483-493. 8. Ruckwardt TJ et al. Lancet Respir Med. 2021;9(10):1111-1120. 9. Mas V et al. PLoS Pathog. 2016;12(9):e1005859. 10. Battles MB et al. Nat Commun. 2017;8(1):1528. 11. Hsieh C-L et al. Nat Commun. 2022;13(1):1299. 12. Data on file. Icosavax, Inc. 13. CDC, flu seasonal burden and seasonal flu vaccine effectiveness studies.

Early/expanded access policy

Icosavax is committed to the development of vaccines designed to address significant unmet public health and medical needs. Our goal is to ensure access to our investigational vaccines at the appropriate time and in a clinically appropriate manner as determined by your physician.

At this time, Icosavax believes that participation in one of our clinical trials, which are carefully designed to determine the safety and immunogenicity or efficacy of an investigational vaccine, is the best and most appropriate way to access our investigational vaccines. We do not currently provide our investigational vaccines for use through expanded access.

If you are interested in accessing any of our investigational vaccines, please speak with your physician. You may also learn more about ongoing clinical trials by going to clinicaltrials.gov and searching for Icosavax.

Consistent with the 21st Century Cures Act, Icosavax may revise this policy at any time.