Pheiron Presents AI-Derived Evidence Supporting Dual Modulation of Lipoprotein(a) and PCSK9 to Further Reduce ASCVD Risk

Oral Spotlight at AHA Scientific Sessions 2025 highlights genetic evidence suggesting additive risk reduction from jointly targeting Lp(a) and PCSK9

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Published November 10, 2025

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New Orleans, USA — November 10, 2025. Pheiron, an AI-native techbio company, presented new findings at the American Heart Association (AHA) Scientific Sessions 2025 demonstrating genetic evidence that simultaneous reduction of lipoprotein(a) [Lp(a)] and PCSK9 may deliver additive risk reduction in atherosclerotic cardiovascular disease (ASCVD) beyond modulation of either pathway alone. The analysis integrates large-scale human genetics with AI-driven phenotyping across population-scale biobanks.

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PCSK9 inhibition has reduced cardiovascular events in large outcomes trials when added to statins, including FOURIER (evolocumab) and ODYSSEY OUTCOMES (alirocumab)^1,2. By contrast, while multiple investigational agents can robustly lower Lp(a), definitive cardiovascular outcomes data are still pending. The pivotal Lp(a)HORIZON trial of pelacarsen is ongoing, with results expected to clarify whether lowering Lp(a) translates into fewer major adverse cardiovascular events. Mid-stage studies of additional agents (e.g., siRNA and oral small molecules) have shown large and durable Lp(a) reductions^3,4.

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Using Pheiron’s AI platform, we combined rare and common variant analyses to estimate the causal impact of lowering LPA and PCSK9 levels jointly. Across multiple strings of evidence, our models support an additive benefit from concurrent pathway modulation. These results provide human genetic evidence to inform the design of dual-pathway therapeutic strategies and patient-selection approaches.

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“Multi-omic data from millions of individuals gives us the opportunity to look at these two targets and how inhibition affects their disease trajectories. Our analysis indicates that lowering Lp(a) and PCSK9 together could yield additive risk reduction in ASCVD. We see immediate applications in biomarker-guided development and patient stratification for dual-pathway approaches,” said Jakob Steinfeldt, MD, Chief Scientific Officer at Pheiron.

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Pheiron will extend this work by developing translational biomarkers and patient-selection strategies tailored to dual LPA/PCSK9 modulation and by exploring siRNA-based and other combination approaches in collaboration with partners.

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About Pheiron

Pheiron is an AI-native techbio company building PheironGPS, an AI-driven human evidence platform that integrates multi-omic data and AI phenotyping to pinpoint causal biology and de-risk therapeutic development. The platform supports target identification, indication prioritization, and precision patient stratification for partners across pharma and biotech.

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Media Contact

press@pheiron.com

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References

1. Sabatine MS, Giugliano RP, Keech AC, et al. Evolocumab and clinical outcomes in patients with cardiovascular disease. N Engl J Med. 2017;376(18):1713-1722. doi:10.1056/NEJMoa1615664.
2. Bittner V; Kumbhani DJ; Eagle KA. Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab (ODYSSEY OUTCOMES). American College of Cardiology. Updated May 16, 2023. Accessed November 10, 2025.
3. ClinicalTrials.gov. Assessing the Impact of Lipoprotein (a) Lowering With Pelacarsen (TQJ230) on Major Cardiovascular Events in Patients With CVD (Lp(a)HORIZON). Identifier: NCT04023552. Sponsor: Novartis Pharmaceuticals. Last Update Posted October 31, 2025. Accessed November 10, 2025.
4. Cho L, Nicholls SJ, Nordestgaard BG, et al. Design and rationale of Lp(a)HORIZON trial: assessing the effect of lipoprotein(a) lowering with pelacarsen on major cardiovascular events in patients with CVD and elevated Lp(a). Am Heart J. 2025;287:1-9. doi:10.1016/j.ahj.2025.03.019