Calypso Enters into Agreement to Be Acquired by Novartis

• Calypso is a European biotech translating Interleukin-15 biology into medical breakthroughs by developing CALY-002, an anti-IL-15 monoclonal antibody, for an array of autoimmune indications

• The acquisition of Calypso gives Novartis full rights to CALY-002, a pipeline-in-a-drug with potential in dermatology, gastro-intestinal and rheumatology indications

Calypso Biotech BV (‘Calypso’), a leader in the development of Interleukin15 (IL-15) targeted therapies, announced today that it has entered into an agreement to be acquired by Novartis AG (‘Novartis’). Calypso’s shareholders will receive an upfront payment of $250 million upon closing and are eligible to receive development milestones of up to $175 million based on the achievement of certain predetermined milestones.

Calypso, a spin-out from Merck, is focused on the research and development of monoclonal antibodies for an array of autoimmune indications, with an expertise in IL-15 biology. IL-15 is a broad, untapped immune axis that controls barrier function and downstream immune cascades in many chronic autoimmune diseases. Calypso’s lead product candidate, CALY-002, is a potential best-in-class therapeutic antibody that binds to and neutralizes Interleukin-15.

The acquisition gives Novartis full rights to CALY-002. Novartis intends to further explore CALY-002 across a wide variety of autoimmune indications with high unmet medical need. CALY-002 is currently evaluated in a Phase 1b trial in patients with Celiac Disease and Eosinophilic Esophagitis.

Alain Vicari, Chief Executive Officer & Co-Founder, Calypso, commented: “We are excited for this transaction with Novartis, a company with relentless commitment to the development of innovative therapies for autoimmune conditions. As part of the Novartis portfolio, CALY-002 is in the best position to be developed effectively, so that it can promptly address unmet medical needs in multiple indications”

Bernard Coulie, Chairman, Calypso, commented: “The transaction with Novartis constitutes the high point in the development path of CALY-002 for the Calypso team. Calypso has established a significantly de-risked profile for CALY-002 as a potential best-in-class therapeutic anti-IL-15 antibody”

Richard Siegel, Head of Immunology Research at Novartis, commented: “Novartis is committed to bringing innovative treatment options forward for patients living with immunological diseases. We’re thrilled to add Calypso’s potential best-in-class antibody to our Immunology pipeline and explore it in a spectrum of autoimmune indications.”

Lazard acted as financial advisor and Goodwin Procter LLP acted as legal counsel to Calypso.

About Calypso Biotech BV

Calypso is a private biotechnology company focused on the research and development of novel biologics to address unmet medical need in autoimmune and inflammatory diseases.

Calypso is developing a novel anti-IL-15 monoclonal antibody to treat a broad range of chronic autoimmune diseases by blocking Interleukin-15 (IL-15) and its wide-ranging functions at many levels of the immune response cascade. CALY-002, a highly potent monoclonal antibody, neutralizes all forms of IL-15 through a uniquely effective molecular mode of action to reduce inflammation and prevent tissue destruction.

Calypso was founded by M Ventures, the corporate strategic venture arm of Merck, and is headquartered in Amsterdam, The Netherlands, with offices and laboratories in Geneva, Switzerland. Investors include M Ventures, Inkef Capital, Gilde Healthcare, Fountain Healthcare Partners and Johnson & Johnson Innovation – JJDC, Inc.

Contact

Calypso Biotech BV
info@calypsobiotech.com

Calypso Biotech Announces First Patient with Eosinophilic Esophagitis Dosed in Anti-Interleukin-15 (IL-15) Monoclonal Antibody CALY-002 Phase 1a/b Trial, and Animal POC Data in Atopic Dermatitis

• Healthy volunteers phase completed showing differentiating target engagement biomarker data and favorable safety data

• On track for top-line histology data in 2023 in Celiac Disease and Eosinophilic Esophagitis

• Proof-of-concept data of CALY-002 in humanized Atopic Dermatitis model supports “pipeline-in-a drug” value proposition

Calypso Biotech, a leader in the development of Interleukin-15 (IL-15) targeted therapies, announces today dosing of the first Eosinophilic Esophagitis patient in the multiple dosing part of the Phase 1 clinical trial of CALY-002, a novel humanized - and highly differentiated - monoclonal antibody neutralizing IL-15. The ongoing Phase 1 clinical study of CALY-002 includes a single ascending dose (SAD) in Healthy Volunteers as well as multiple ascending dosing (MAD) in cohorts of patients with Celiac Disease or Eosinophilic Esophagitis, two indications with significant unmet medical need where IL-15 plays a critical role in their pathogenesis [NCT04593251].

The SAD part of the study has been completed. Across the wide range of tested dose levels in Healthy Volunteers, CALY-002 was well tolerated, with a PK profile typical for IgG monoclonal antibodies. Importantly, target engagement (i.e., IL-15 blockade) was demonstrated through the reduction of NK cell numbers in blood, owing to the well-known role of IL-15 as a homeostatic factor for NK cells. CALY-002 is the first IL-15-specific antibody to demonstrate blood NK cell reduction in humans, underpinning its unique and differentiated profile.

The MAD part of the study in patients with Celiac Disease or Eosinophilic Esophagitis is currently progressing into the highest dose cohorts. This phase investigates safety, PK, pharmacology, disease biomarkers and clinical efficacy endpoints including histology of multiple doses of CALY-002 or placebo over either an 8-week treatment period in a gluten-challenge setting (Celiac Disease) or a 12-week period of open label CALY-002 treatment (Eosinophilic Esophagitis). Top-line histology data will be generated in 2023 for both indications.

Further, CALY-002 was demonstrated to be active in a recently developed humanized model of Atopic Dermatitis, results presented at the 51st European Society for Dermatological Research conference (Amsterdam, 28 September – 01 October 2022). These important data further highlight the potential of CALY-002 in multiple auto-immune indications.

Calypso Biotech Chief Medical Officer, Dr. Jos Houbiers, MD, PhD, comments “the demonstrated pharmacological efficacy highlights the potency of CALY-002 and is promising for the clinical histology results in the MAD parts of the study. New and improved treatments are much needed for Celiac Disease and Eosinophilic Esophagitis patients who have limited treatment options. For patients with celiac disease, clinical practice learns that adherence to a gluten-free diet is very difficult and many patients continue to experience symptoms; in asymptomatic patients, histological damage to the small intestine can be present unnoticed, studies show.’’

About Calypso Biotech BV

Calypso Biotech BV is a private biotechnology company focused on the research and development of novel biologics to address unmet medical need in autoimmune and inflammatory diseases, with a unique expertise in IL-15 biology. IL- 15 controls immune pathways critically involved in disease onset and maintenance (‘’disease memory’’), as well as tissue destruction, in addition to its broad effect on inflammation. Calypso’s approach offers significant advantages over traditional cytokine interventional therapies and could provide for unprecedented long lasting disease-modifying effects in multiple autoimmune diseases. Calypso Biotech is a spin-off by the healthcare business of Merck KGaA and is headquartered in Amsterdam, The Netherlands, with offices and laboratories in Geneva, Switzerland.

Calypso Biotech announces first patient with Celiac Disease dosed in anti-Interleukin-15 (IL-15) monoclonal antibody CALY-002 Phase 1b Trial, and extension of Series A to €28M

• Single ascending dose administration of CALY-002 to Healthy Volunteers successfully completed

• Dr Jos G.A. Houbiers MD, PhD joins Calypso Biotech as Chief Medical Officer

• Fountain Healthcare Partners join existing investors to extend Series A financing

• Proceeds to accelerate development of CALY-002 for auto-immune diseases including Celiac Disease, Eosinophilic Esophagitis and Dermatology

Calypso Biotech, a leader in the development of Interleukin-15 (IL-15) targeted therapies, announces today completion of dosing of first Celiac Disease patient in the Phase 1 clinical trial of CALY-002, a novel humanized monoclonal antibody neutralizing IL-15. The ongoing clinical study of CALY-002 includes a single ascending dose in Healthy Volunteers, now successfully completed, as well as ascending dosing of cohorts of patients with Celiac Disease and Eosinophilic Esophagitis, two indications with significant unmet medical need where IL-15 plays a critical role.

The company is now expanding the senior clinical management to reflect this important transition to clinical evaluation. Dr Jos G.A. Houbiers MD, PhD joined Calypso Biotech as Chief Medical Officer on June 1st. Dr Houbiers brings to Calypso Biotech over 25 years of experience in pharmaceutical clinical development from large pharma companies and from biotech, where he has implemented medical and clinical development strategies, creative trial design and comprehensive medical safety monitoring across therapeutic areas, including immunology, urology and pain. He most recently served as Chief Medical Officer at Summit Therapeutics. Dr. Houbiers received his MD from Leiden University Medical Center and PhD (immunology) and MSc in medicine from Leiden University

Reflecting this exciting clinical progression, Calypso Biotech raised an additional €8M to the 2019 Series A round, bringing its total Series A financing to €28M from new and returning investors. Fountain HealthCare Partners joins renowned syndicate of Gilde Healthcare, Inkef Capital, Johnson & Johnson Innovation - JJDC, Inc. (JJDC), and the company’s founding investor M Ventures. Dr. Ena Prosser from Fountain’s Dublin (Ireland) office has also joined the Board of Calypso Biotech. The additional proceeds of the Series A will be used to accelerate the development of CALY-002 in the core gastroenterology indications, further de-risk the asset, and develop a solid translational package to support the development of CALY-002 in additional auto-immune disease indications.

Alain Vicari, CEO of Calypso Biotech, commented: “We are delighted to welcome Dr Jos Houbiers to the team and to announce the extension of the Series A syndicate with Fountain Healthcare Partners. This further validates our ability to attract high-quality investors, and bodes well for our future fundraising campaign. These funds will accelerate the development of CALY-002 and bring us one step closer to propose a new treatment paradigm for auto-immune diseases to patients in need.”

About Calypso Biotech BV

Calypso Biotech BV is a private biotechnology company focused on the research and development of novel biologics to address unmet medical need in immunological diseases, with a unique expertise in IL-15 biology. IL- 15 controls immune pathways critically involved in disease onset and maintenance, as well as tissue destruction, in addition to its broad effect on inflammation. Calypso’s approach offers significant advantages over traditional cytokine interventional therapies, and could provide for unprecedented long lasting disease-modifying effects in multiple auto-immune diseases. Calypso Biotech is a spin-off by the healthcare business of Merck KGaA and is headquartered in Amsterdam, The Netherlands, with offices and laboratories in Geneva, Switzerland. The Company raised their initial Series A funding in 2018 with Gilde Healthcare, Inkef Capital, Johnson & Johnson Innovation - JJDC, Inc. (JJDC), and the company’s founding investor M Venture; Fountain Healthcare Partners joined this syndicate in 2021. For more information see www.calypsobiotech.com