PATENTS

Schmidt M, Kovalchin J, Furfine E. Therapeutic agents with increased ocular retention (WO/2016/073894A1).

Goldstein M, Furfine E, Celniker A, Kovalchin J. Treating ocular pain (WO/2015/0485226A1).

Schmidt M, Kovalchin J, Furfine E, Celniker A, Erbe D. Local delivery of IL-17 inhibitors for treating ocular disease (WO/2014/107737A2).

Baldwin S, Bonnin D, Johnson K, Krieger J, Rasmussen J, Yu B, Zanelli E, Zhang J, Collins K, Genova M, Kovalchin J. Effective quantification of complex peptide mixtures in tissue samples and improved therapeutic methods (WO/2009/075854).

PUBLICATIONS

Pinkstaff J, McCullagh E, Grover A, Melton A, Cherukuri A, Wait J, Nguyen A, Butt M, Trombley J, Reed R, Adams E, Boyd R, Chandra S, Henshaw J, O’Neill C, Zanelli E, Kovalchin J. Safety, pharmacokinetics and CNS distribution of tralesinidase alfa administered via intracerebroventricular infusion to juvenile cynomolgus monkeys. Toxicol Rep. 2023 Mar 1;10:357-366.

Muschol N, Koehn A, von Cossel K, Okur I, Ezgu F, Harmatz P, de Castro Lopez M, Couce M, Lin S, Batzios S, Cleary M, ,Solano M, Nestrasil I, Kaufman B, Shaywitz A, Maricich S, Kuca B, Kovalchin J, Zanelli E. A Phase I/II study on intracerebroventricular tralesinidase alfa in patients with Sanfilippo syndrome type B. J Clin Invest. 2023 Jan;133(2):1-13.

Ellinwood NM, Valentine BN, Hess AS, Jens JK, Snella EM, Jamil M, Hostetter SJ, Jeffery ND, Smith JD, Millman ST, Parsons RL, Butt MT, Chandra S, Egeland MT, Assis AB, Nelvagal HR, Cooper JD, Nestrasil I, Mueller BA, Labounek R, Paulson A, Prill H, Liu XY, Zhou H, Lawrence R, Crawford BE, Grover A, Cherala G, Melton AC, Cherukuri A, Vuillemenot BR, Wait JCM, O'Neill CA, Pinkstaff J, Kovalchin J, Zanelli E, McCullagh E. Tralesinidase Alfa Enzyme Replacement Therapy Prevents Disease Manifestations in a Canine Model of Mucopolysaccharidosis Type IIIB. J Pharmacol Exp Ther. 2022 Sep;382(3):277-286.

Okur I, Ezgu F, Giugliani R, Muschol N, Koehn A, Amartino H, Harmatz P, de Castro Lopez MJ, Couce ML, Lin SP, Batzios S, Cleary M, Solano M, Peters H, Lee J, Nestrasil I, Shaywitz AJ, Maricich SM, Kuca B, Kovalchin J, Zanelli E. Longitudinal Natural History of Pediatric Subjects Affected with Mucopolysaccharidosis IIIB. J Pediatr. 2022 Jun 13;249:50-58.

Rubio-Beltrán E, Labastida-Ramírez A, Haanes KA, van den Bogaerdt A, Bogers AJJC, Zanelli E, Meeus L, Danser AHJ, Gralinski MR, Senese PB, Johnson KW, Kovalchin J, Villalón CM, MaassenVanDenBrink A. Characterization of binding, functional activity, and contractile responses of the selective 5-HT 1F receptor agonist lasmiditan. Br J Pharmacol. 2019 Dec;176(24):4681-4695.

Kovalchin J, King B, Masci A, Hopkins E, Fry J, Hou J, Li C, Tenneson K, Weber S, Wolfe G, Collins K, Furfine E. Preclinical Development of EBI-005: An IL-1 Receptor-1 Inhibitor for the Topical Ocular Treatment of Ocular Surface Inflammatory Diseases. Eye Contact Lens. 2018, May;44(3):170-181.

Goldstein M, Tubridy K, Agahigian J, Furfine E, Magill M, Kovalchin J, Golden K, Zarbis- Papastoitsis G, Soong F, Salapatek A, Sternberg G, Celniker A. A phase 2 exploratory study of a novel interleukin-1 receptor inhibitor (EBI-005) in the treatment of moderate-to-severe allergic conjunctivitis. Eye Contact Lens. 2015, May;41(3):145-55.

Schmidt M, Townson S, Andreucci A, King B, Schirmer E, Murillo A, Dombrowski C, Tisdale A, Lowden P, Masci A, Kovalchin J, Erbe D, Wittrup K, Furfine E, Barnes T. Crystal structure of an HSA/FcRn complex reveals recycling by competitive mimicry of HSA ligands at a pH- dependent hydrophobic interface. Structure. 2013, Nov 5;21(11):1966-78.

Schirmer E, Golden K, Xu J, Milling J, Murillo A, Lowden P, Mulagapati S, Hou J, Kovalchin J, Masci A, Collins K, Zarbis-Papastoitsis G. Reduction of product-related species during the fermentation and purification of a recombinant IL-1 receptor antagonist at the laboratory and pilot scale. Biotechnol J. 2013, Aug;8(8):946-56.

Hou J, Townson S, Kovalchin J, Masci A, Kiner O, Shu Y, King BM, Schirmer E, Golden K, Thomas C, Garcia K, Zarbis-Papastoitsis G, Furfine E, Barnes T. Design of a superior cytokine antagonist for topical ophthalmic use. Proc Natl Acad Sci, 2013, Mar;110(10):3913-8.

Kovalchin J, Krieger J, Genova M, Kawamoto N, Augustyniak M, Collins K, Bloom T, Masci A, Hittinger T, Dufour I, Strominger J, Zanelli E. Macrophage-specific chemokines induced via innate immunity by amino acid copolymers and their role in EAE. PLoS One 2011, 6(12):e26274.

Kovalchin J, Krieger J, Collins K, Genova M, Augustyniak M, Masci A, Avril T, Gandon G, Patat A, Fauchoux N, Toutin C, Lacoste E, Patel U, Mascioli E, Zanelli E. Safety, pharmacokinetic, and pharmacodynamic evaluations of PI-2301, a potent immunomodulator, in a first-in-man, single-ascending-dose study in healthy volunteers. J Clin Pharmacol. 2011, 51(5):649-60.

Kovalchin J, Krieger J, Genova M, Collins K, Augustyniak M, Masci A, Hittinger T, Kuca B, Edan G, Braudeau C, Rimbert M, Patel U, Mascioli E, Zanelli E. Results of a phase I study in patients suffering from secondary-progressive multiple sclerosis demonstrating the safety of the amino acid copolymer PI-2301 and the induction of an anti-inflammatory immune response. J Neuroimmunol. 2010, 225(1-2):153-63.

Kovalchin J, Wang R, Wagh M, Azoulay J, Sanders M, Chandawarkar R. In vivo delivery of heat shock protein 70 accelerates wound healing by upregulating macrophage-mediated phagocytosis. Wound Repair Regen 2006, 14(2):129-37

Wang R, Kovalchin J, Muhlenkamp P, Chandawarkar R. Exogenous heat shock protein-70 binds macrophage lipid raft microdomain and stimulates phagocytosis, processing and MHCII presentation of antigens. Blood 2006, 107(4):1636-42.

Kovalchin J, Mendonca C, Wagh M, Wang R, Chandawarkar R. In vivo treatment of mice with heat shock protein, gp96, improves survival of skin grafts with minor and major antigenic disparity. Transpl Immunol 2006, 15(3):179-85.

Doody A, Kovalchin J, Mihalyo M, Hagymasi A, Drake C, Adler A. Glycoprotein 96 can chaperone both MHC Class I- and class II-restricted epitopes for in vivo presentation, but selectively primes CD8+ T cell effector function. J Immunol 2004, 172(10):6087-92.

Chandawarkar R, Wagh M, Kovalchin J, Srivastava P. Immune modulation with high-dose heat shock protein gp96: therapy of murine autoimmune diabetes and encephalomyelitis. Int Immunol 2004, 16(4):615-24.

Kovalchin J, Murthy A, Horattas M, Guyton D, Chandawarkar R. Determinants of efficacy of immunotherapy with tumor derived heat shock protein gp96. Cancer Immun 2001, 1:7.

POSTERS/PRESENTATIONS

Zanelli E, Kovalchin J, Kuca, B, Muschol N, Koehn A, von Cossel K, Okur I, Ezgu F, Hartmatz P, de Castro Lopez M, Luz Couce M, Lin SP, Batzios S, Cleary M, Solano M, Nestrasil I. Tralesinidase alfa modies the course of Sanfilippo Syndrome Type B. 19th Annual WORLDSymposium™, Orlando, Florida, 2023.

Guigliani R, Okur I, Ezgu F, Muschol N, Harmatz P, de Castro Lopez M, Luz Couce M, Lin S, Batzios S, Cleary M, Amartino H, Peters H, Lee J, Kovalchin J, Zanelli E, Maricich S. Natural history of Sanfilippo Syndrome Type B in young patients: ongoing results from two large, prospective studies. 17th Annual WORLDSymposium™, Virtual Event, 2021.

Muschol N, Okur I, Ezgu F, de Castro Lopez M, Luz Couce M, Harmatz P, Batzios S, Cleary M, Lin S, Guigliani R, Amartino H, Peters H, Lee J, Kovalchin J, Zanelli E, Maricich S. Tralesinidase alfa (AX 250) enzyme replacement therapy for Sanfilippo Syndrome Type B. 17th Annual WORLDSymposium™, Virtual Event, 2021.

Labastida-Ramírez A, Rubio-Beltrán E, Haanes K, Danser A, Kovalchin J, Johnson K, Villalón C, MaassenvandenBrink A. Lasmiditan inhibits dural CGRP release from the rat trigeminovascular system. 17th Biennial Migraine Trust International Symposium, London, England, 2018.

Rubio-Beltrán E, Labastida-Ramírez A, van den Bogaerdt A, Bogers A, Zanelli E, Meeus L, Danser A, Johnson K, Kovalchin J, Villalón C, MaassenvandenBrink A. In vitro characterization of agonist binding and functional activity at a panel of serotonin receptor subtypes for lasmiditan, triptans and other 5-HT receptor ligands and activity relationships for contraction of human isolated coronary artery. 18th Congress of the International Headache Society, Vancouver, Canada, 2017.

Labastida-Ramírez A, Rubio-Beltrán E, Garrelds I, Haanes K, Chan K, Kovalchin J, Johnson K, Danser A, Villalón C, MaassenVanDenBrink A. Lasmiditan inhibits CGRP release in the mouse trigeminovascular system. 18th Congress of the International Headache Society, Vancouver, Canada, 2017.

Kovalchin J, Ghiglieri A, Zanelli E, Ings R, Mathers T. Lasmiditan acts specifically on the 5- HT1F receptor in the central nervous system. 5th European Headache and Migraine Trust International Congress, Glasgow, Scotland, 2016.

Rubio-Beltran E, Haanes K, Labastida A, de Vries R, Danser A, Gralinski M, Senese P, Kovalchin J, Villalón C, MaassenVanDenBrink A. Lasmiditan and sumatritpan: comparison of the in vivo vascular constriction in the dog and in vitro contraction of human arteries. 5th European Headache and Migraine Trust International Congress, Glasgow, Scotland, 2016.

Vila-Pueyo M, Strother L, Page K, Loraine H, Kovalchin J, Goadsby P, and Holland P. Lasmiditan inhibits trigeminovascular nociceptive transmission. 5th European Headache and Migraine Trust International Congress, Glasgow, Scotland, 2016.

Schmidt M, Matsumoto Y, Tisdale A, Lowden P, Kovalchin J, Wu P, Golden K, Lain B, Dombrowski C, Furfine E. Optimized intravitreal IL-6 antagonist for the treatment of diabetic macular edema. The Association for Research in Vision and Ophthalmology Annual Meeting, Denver, Colorado, 2015.

Tubridy K, Goldstein M, Agahigian J, Magill M, Zarbis-Papastoitsis G, Golden K, Kovalchin J, Furfine E, Celniker A. Clinical development of EBI-005, a novel interleukin-1 receptor inhibitor, for patients with ocular surface inflammation. The Association for Research in Vision and Ophthalmology Annual Meeting, Denver, Colorado, 2015.

Goldstein M, Tubridy K, Agahigian J, Furfine E, Magill M, Kovalchin J, SoongF, Salapatek A. Comparison of two clinical repeat allergen challenge models to evaluate EBI-005 in the late phase inflammatory response in allergic conjunctivitis. The Association for Research in Vision and Ophthalmology Annual Meeting, Denver, Colorado, 2015.

Goldstein M, Tubridy K, Agahigian J, Furfine E, Magill M, Kovalchin J, Celniker A. Novel therapy for allergic conjunctivitis patients using EBI-005, a topical intereukin-1 receptor inhibitor. The American Society of Cataract and Refractive Surgery Annual Symposium, San Diego, California, 2015.

Goldstein M, Zarbis-Papastoitsis G, Golden K, Wheeler C, Kovalchin J, Agahigian J, Tubridy K, Furfine E. Reduced rescue artificial tear use in subjects using a topical interleukin-1 (IL-1) receptor-1 (R1) blocker for ocular treatment of dry eye disease (DED). The Association for Research in Vision and Ophthalmology Annual Meeting, Orlando, Florida, 2014.

Schmidt M, Tisdale A, Lowden P, Kovalchin J, Furfine E. Optimized IL-6 blockade for the treatment of diabetic macular edema. The Association for Research in Vision and Ophthalmology Annual Meeting, Orlando, Florida, 2014.

Goldstein M, Agahigian J, Zarbis-Papastoitsis G, Golden K, Kovalchin J, Wheeler C, Tubridy K, Furfine E, Celniker A. Novel therapy for patients with moderate to severe dry eye disease: topical IL-1 receptor blocker. The American Society of Cataract and Refractive Surgery Annual Symposium, Boston, Massachusetts, 2014.

Goldstein M, Tubridy K, Agahigian J, Furfine E, Magill M, Kovalchin J, Golden K, Zarbis- Papastoitsis G, Soong F, Salapatek A, Sternberg G, Celniker A. Treating moderate to severe allergic conjunctivitis with EBI-005, a topical interleukin-1 receptor inhibitor. 21st Annual Meeting of the Medical Contact Lens and Ocular Surface Association, London, England, 2014 (won best poster award).

Kovalchin J. Designing and engineering a protein therapeutic for topical treatment of ocular surface inflammatory disorders to have low immunogenic potential. Cambridge Healthtech Institutes 11th Annual Protein and Antibody Engineering Conference, Boston, Massachusetts, 2014.

Tisdale A, Schmidt M, Kovalchin J, Golden K, Lowden P, Dombrowski C, Furfine E. Antibodies binding to novel PCSK9 epitopes for the treatment of hypercholesterolemia. Cambridge Healthtech Institutes 11th Annual Protein and Antibody Engineering Conference, Boston, Massachusetts, 2014.

Furfine E, Barnes T, Saban D, Masci A, Collins K, Goldstein M, Li C, Tenneson K, Escobar D, McNeil G, Milling J, Lowden P, Wolfe G, Kovalchin J. Preclinical development of EBI-005: a potent interleukin-1 (IL-1) receptor-1 (R1) blocker for topical ocular administration was safe in GLP toxicology studies and active in a mouse model of dry eye disease (DED). The Association for Research in Vision and Ophthalmology Annual Meeting, Seattle, Washington, 2013.

Goldstein M, Zarbis-Papastoitsis G, Golden K, Chowdhury S, Wheeler C, Foulks G, Kovalchin J, Agahigian J, Escobar D, Furfine E. Early clinical development of EBI-005, a potent interleukin-1 (IL-1) receptor-1 (R1) blocker for topical ocular treatment of dry eye disease (DED). The Association for Research in Vision and Ophthalmology Annual Meeting, Seattle, Washington, 2013.

Kovalchin J, Masci A, Schmidt M, Pegman P, Lowden P, Milling J, Hou J, Shu Y, Murillo A, Barnes T, Dombrowski C. Use of galectin-3 fusions to extend the surface residence time of proteins topically applied to the eye. The Association for Research in Vision and Ophthalmology Annual Meeting, Seattle, Washington, 2013.

Goldstein M, Agahigian J, Zarbis-Papastoitsis G, Golden K, Kovalchin J, Wheeler C, Celniker A, Furfine E. Safety and efficacy of a novel topical IL-1 receptor inhibitor (EBI-005) in the treatment of patients with moderate to severe dry eye disease. 52nd Annual Cornea Society and Eye Bank Association of America Meeting, New Orleans, Louisiana, 2013.

Kovalchin J. Assessing the immunogenicity of EBI-005: a novel protein therapeutic for topical treatment of dry eye disease. 2nd Novel Immunothepaeutics Summit, San Diego, California, 2013.

Kovalchin J. EBI-005: A novel protein therapeutic interleukin-1 receptor inhibitor for the topical ocular treatment of dry eye disease. 14th Annual Immunogenicity for Biotherapeutics Conference, Baltimore, Maryland, 2013.

Goldstein M, Agahigian J, Zarbis-Papastoitsis G, Golden K, Kovalchin J, Wheeler C, Chowdury S, Celniker A, Furfine E. Use of novel IL-1 receptor inhibitor (EBI-005) in the treatment of patients with moderate to severe dry eye disease The 7th International Conference on the Tear Film and Ocular Surface: Basic and Clinical Relevance, Taormina, Sicily, 2013.

Furfine E, Hou J, Collins K, Townson S, Golden K, Schirmer E, Kovalchin J, Zarbis- Papastoitsis G, Barnes T. EBI-005: an IL-1 receptor inhibitor designed for the treatment of dry eye syndrome. The Association for Research in Vision and Ophthalmology Annual Meeting, Fort Lauderdale, Florida, 2012.

Zanelli E, Kovalchin J, Edan G, Patat A, Juhasz M, Braudeau C, Rimbert M, Patel U, Mascioli E. Clinical and biological results of a twelve-week double blind, multiple ascending dose study evaluating the safety and tolerability of peptide copolymer PI-2301 in patients with the secondary progressive form of multiple sclerosis. 25nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis, Dusseldorf, Germany, 2009.

Kovalchin J, Krieger J, Collins K, Rafuse K, Avril T, Gandon G, Patat A, Fauchoux N, Patel U, Zanelli E. Evidence of specific T-cell priming from the first-in-man single ascending dose study of peptide comploymer PI-2301 for the treatment of multiple sclerosis. 24nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis, Montreal, Canada, 2008.

Kovalchin J, Krieger J, Carrillo-Rivas B, Augustyniak M, Dufour I, Genova M, Rafuse K, Sutton B, Ward A, Paine S, Baldwin S, Kolbeck R, Zanelli E. Copolymer PI-2301, a novel immunomodulator of experimental autoimmune encephalomyelitis. Keystone Symposia: Immunological Intervention in Human Disease, Big Sky, Montana, 2007.

Carrillo-Rivas B, Krieger J, Kovalchin J, Augustyniak M, Dufour I, Johnson K, Genova M, Rafuse K, Ward A, Baldwin S, Kolbeck R, Gutierrez-Ramos J, Zanelli E. Immunomodulation of experimental autoimmune encephalomyelitis by the novel copolymer PI-2301. 22nd Congress of the European Committee for Treatment and Research in Multiple Sclerosis, Madrid, Spain, 2006.

Musselli C, O’Donnell D, Gwalani L, Burke J, Kovalchin J, Srivastava P, Chicz R, Levey D. Therapeutic preclinical activity of tumor derived gp96 combined with other immunomodulatory and chemotherapeutic agents. J Immunother 2006, 29(6): 652-53.

Kovalchin J, Wang R, Wagh M, Azoulay J, Sanders M, Chandawarkar R. In vivo delivery of heat shock protein 70 accelerates wound healing by upregulating macrophage-mediated phagocytosis. The American Association of Immunologists (AAI) Meeting at the Experimental Biology Conference, San Diego, California, 2005.

Chandawarkar R, Muhlenkamp P, Kovalchin J. The role of heat shock proteins in tissue repair: a new class of exogenous wound modifiers. 72nd Annual ASPA/PSEF/ASMA Scientific Meeting of ASPS, San Diego, California, 2003.

Kovalchin J, Muralimohan G, Chandawarkar R, Udono H, Srivastava P. Local, antigen non- specific rejection of tumors by tumor specific immunizations. 90th Anniversary American Association of Immunologists (AAI) Meeting, Denver, Colorado, 2003.

Kovalchin J, Chandawarkar R, Wagh M, Srivastava P. Immunosuppressive effects of high dose gp96 in Type I Diabetes. Keystone Symposia: Mechanisms of Immunologic Tolerance and Its Breakdown, Snowbird, Utah, 2003.

Kovalchin J, Chandawarkar R, Srivastava P. Immunosuppressive activity of high dose gp96 in type 1 diabetes. 3rd International Conference of Heat Shock Proteins in Immune Response, Farmington, Connecticut, 2002.

Kovalchin J, Mendoca C, Chandawarkar R, Srivastava P. Immunosuppressive activity of high dose gp96 in graft rejection. 3rd International Conference of Heat Shock Proteins in Immune Response, Farmington, Connecticut, 2002.

Kovalchin J, Murthy A, Horattas M, Guyton D, Chandawarkar R. Primary and postoperative adjuvant immunotherapy of cancer using tumor derived heat shock proteins: determinants of efficacy. 2nd International Conference of Heat Shock Proteins in Immune Response, Farmington, Connecticut, 2000.

Kovalchin J, Murthy A, Horattas M, Guyton D, Chandawarkar R. Optimizing immunotherapy of solid tumors using tumor derived heat shock proteins. 1St International Conference of Heat Shock Proteins in Immune Response, Farmington, Connecticut, 1998.