Actinic keratosis is a rough, scaly patch caused by sun exposure that appears on sun-exposed areas of the skin, such as the face, scalp, and hands. Left untreated, it may become cancerous. It is a common condition, affecting approximately 20% of people in the United States, and 14% of people globally.1,2 Actinic keratosis is one of several senescence-driven and GPX4-moderated inflammatory skin conditions identified by Rubedo's proprietary, AI-driven drug discovery platform, ALEMBIC?, and shown in the company's ex vivo studies of human tissue. ALEMBIC identifies cellular and molecular targets for pathologic senescent cells and develops selective medicines that restore tissue homeostasis for these targets. RLS-1496 is also being studied in psoriasis and atopic dermatitis. Approximately 3% of adults in the United States, and 4.4% of adults globally, have psoriasis.3,4 About 7.3% of U.S. adults have atopic dermatitis, while globally the prevalence among adults is approximately 2.0%.5,6

"We are thrilled to reach another important milestone with our lead candidate RLS-1496," said Rubedo CEO Frederick Beddingfield, III, MD, PhD, FAAD, FACMS. "This second IND clearance supports our focus on the potential of RLS-1496 as the first-ever GPX4 modulator to treat an array of age-related diseases and conditions, which will allow us to have the greatest impact for patients."

Rubedo Chief Scientific Officer Marco Quarta, PhD, said, "This IND clearance comes just four months after the initiation of a Phase 1 study with RLS-1496 in patients with psoriasis in Europe. We are excited to begin this new trial and showcase the breadth of therapeutic impact that can be made by targeting inflammatory and aging mechanisms like GPX4."

Rubedo has also welcomed a new member to its Clinical Advisory Board (CAB), Emma Guttman-Yassky, MD, PhD, Waldman Professor and Chair of the Kimberly and Eric J. Waldman Department of Dermatology at the Icahn School of Medicine at Mount Sinai. She is the Director of the Occupational Dermatitis Clinic and Director of the Laboratory for Inflammatory Skin Diseases.

With the addition of Dr. Guttman, the CAB - led by Rubedo Chief Medical Officer and dermatologist Mary Spellman, MD - now includes five leading dermatologists who are practicing clinicians and researchers, and are supporting Rubedo as strategic and scientific consultants and advisors.

Dr. Guttman said, "Millions of people are affected by dermatologic inflammatory skin conditions, including psoriasis and actinic keratosis. As a researcher and clinician, I am inspired by cutting-edge longevity science and recognize the need for new innovations that can improve patient health. This IND clearance is an important step forward in making these types of innovations a reality, and I am delighted to be working with the Rubedo team at this exciting time."

About RLS-1496 and GPX4 Modulation

Rubedo's lead candidate RLS-1496, being developed for topical and oral administration, is a potential first-in-class, disease-modifying selective GPX4 modulator targeting pathologic senescent or "aged" cells that drive chronic degenerative diseases and conditions associated with biological aging processes. These include immunology and inflammation (I&I), dermatology and skin aging, metabolic syndrome (obesity, diabetes, liver fibrosis), sarcopenia, and neurodegenerative disease.

In certain pathologic cells, aging is associated with an imbalance in GPX4. Modulation of GPX4 sensitizes cells to ferroptosis, which is a type of programmed cell death and is believed to be an achilles heel of senescent zombie cells. By modulating GPX4 in ferroptosis-sensitive senescent "aged" cells, RLS-1496 may be able to clear these cells to not only fight disease, but also support healthy cells to function properly and restore tissue homeostasis.

About Rubedo Life Sciences

Rubedo Life Sciences is a clinical-stage biotech developing a broad portfolio of innovative selective cellular rejuvenation medicines targeting aging cells that drive chronic age-related diseases. Our proprietary AI-driven ALEMBIC? drug discovery platform is developing novel first-in-class small molecules to selectively target pathologic and senescent cells, which play a key role in the progression of pulmonary, dermatological, oncological, neurodegenerative, fibrotic, and other chronic disorders. Our lead drug candidate - RLS-1496, a potential first-in-class disease-modifying selective GPX4 modulator - is currently in Phase I clinical trials. The Rubedo leadership team is composed of industry leaders and early pioneers in chemistry, AI technology, longevity science, and life sciences, with expertise in drug development and commercialization from both large pharmaceutical and leading biotechnology companies. The company is headquartered in Mountain View, CA, USA, and has offices in Milan, Italy. For additional information, visit www.rubedolife.com.

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1 Theodore Rosen, Mark G Lebwohl. Prevalence and awareness of actinic keratosis: barriers and opportunities. J Am Acad Dermatol. 2013 Jan;68(1 Suppl 1):S2-9. 10.1016/j.jaad.2012.09.052 2 Christopher D George, Truelian Lee, Loes M Hollestein, Maryam M Asgari, Tamar Nijsten. Global epidemiology of actinic keratosis in the general population: a systematic review and meta-analysis. British Journal of Dermatology. 2024 Apr;190(4):465-476. https://doi.org/10.1093/bjd/ljad371 3 April W Armstrong, Manan D Mehta, Clayton W Schupp, George C Gondo, Stacie J Bell, Christopher EM Griffiths. Psoriasis Prevalence in Adults in the United States. JAMA Dermatol. 2021 Jun;157(8):940-946. doi: 10.1001/jamadermatol.2021.2007 4 Skayem, Charbel, Charles Taieb, Bruno Halioua, Catherine Baissac, and Marketa Saint Aroman. Epidemiology of Psoriasis: A Worldwide Global Study. Acta Dermato-Venereologica. 2025 Mar;105:adv42945. https://doi.org/10.2340/actadv.v105.42945.5 Asthma and Allergy Foundation of America and National Enczema Association. (n.d.). Atopic Dermatitis in America | AAFA.org. Asthma and Allergy Foundation of America | AAFA. 2018 Oct https://aafa.org/asthma-allergy-research/our-research/atopic-dermatitis-in-america/ 6 Tian, J., Zhang, D., Yang, Y., Huang, Y., Wang, L., Yao, X., & Lu, Q. (2023, September 14). Global epidemiology of atopic dermatitis: a comprehensive systematic analysis and modelling study. British Journal of Dermatology, 190(1), 55-61. https://doi.org/10.1093/bjd/ljad339

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Contact

Investor Contact:Rubedo Chief Business Officer Ali [email protected] 781-974-9559

Media Contact:Peter [email protected] 908-499-1200

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