Trident Toxicology
Nonclinical Safety Assessment Consulting
Pathology
Interpretation of pathology findings
and relevance to humans
Report review
Integration of pathology findings into
full toxicity study reports
Drug Development Strategies
Optimized strategies to speed drug
development while minimizing resource
use in the spirit of 3Rs
Interactions with regulatory agencies
including document preparation and review
Toxicology and Pharmacology
Design and interpretation of nonclinical
toxicity and pharmacology studies
Understanding impacts from immunogenicity
Report preparation and review
Due diligence/in-licensing assessments
About
Michael W. Leach, DVM, PhD, DACVP is the President and CEO of Trident Toxicology, Inc. He is a veterinary pathologist, toxicologist, and drug developer with 3 decades of experience in the biopharmaceutical industry. Michael received his DVM from Purdue University, his PhD from the University of California-Davis, and is a diplomate of the American College of Veterinary Pathologists. He has worked for Schering-Plough, BASF Bioresearch Corporation, Abbott Bioresearch Center, Wyeth, and Pfizer with involvement in non-GLP early efficacy studies, in GLP-compliant toxicity studies and regulatory interactions supporting all phases of clinical development, in post-marketing activities, as well as in due diligence and licensing activities. In his various roles, he has had significant responsibility in the nonclinical and strategic aspects of successfully and safely bringing over 20 programs into clinical trials. He is an author/co-author on over 75 peer reviewed papers, invited reviews, and book chapters.
At Pfizer, his responsibilities within nonclinical Drug Safety Research and Development (DSRD) included serving as a Therapeutic Area Lead, as the Licensing and Acquisitions Lead, as the Biotherapeutics Safety Lead, and as the DSRD representative to the Large Molecule Candidate Quality Guideline Committee; he also founded and led the Biotherapeutics Safety Leadership Team. Externally, Michael was elected to the BioSafe Preclinical Safety Leadership Committee, the nonclinical safety committee within Biotechnology Innovation Organization (BIO), and served in that role for over 3 years. His expertise is in biotherapeutics, and in 2023 Michael received the Career Achievement in Biotechnology Award from the Society of Toxicology Biotechnology Specialty Section. Michael has given over 40 invited presentations, including to the Chinese regulators on ICH S6(R1) and biotherapeutic drug development. He is a member of the American Veterinary Medical Association, the Society of Toxicology, the Society of Toxicologic Pathology, and the American College of Veterinary Pathologists. In his spare time, Michael enjoys scuba diving and underwater photography.
Contact
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Publications and Invited Presentations
Peer-Reviewed Articles
1. Leach MW, Parker AJ, Ott-Joslin J. Sacrococcygeal dysgenesis in a crab-eating macaque. J Am Vet Med Assoc. 1986 Nov 1;189(9):1219. PMID: 3505993.
2. Leach MW, Higgins RJ, Lowenstine LJ, Shor B. Paramyxovirus infection in a Moluccan cockatoo. Assoc Av Vet Today. 1988 2:87-90.
3. Boermans HJ, Ruegg PL, Leach M. Ethylene glycol toxicosis in a pygmy goat. J Am Vet Med Assoc. 1988 Sep 15;193(6):694-6. PMID: 3192447.
4. Leach MW, Paul-Murphy J, Lowenstine LJ. Three cases of gastric neoplasia in psittacines. Avian Dis. 1989 Jan-Mar;33(1):204-10. PMID: 2930404.
5. Kahler JS, Leach MW, Jang S, Wong A. Disseminated aspergillosis attributable to Aspergillus deflectus in a springer spaniel. J Am Vet Med Assoc. 1990 Oct 1;197(7):871-4. PMID: 2228770.
6. Leach MW, Nichols DK, Hartsell W, Torgerson RW. Radiation therapy of a malignant chromatophoroma in a yellow rat snake (Elaphe obsoleta quadrivittata). J Zoo Wildlife Med. 1991 22:241-244.
7. Leach MW, Higgins RJ, Boggan JE, Lee SJ, Autry S, Smith KM. Effectiveness of a lysyl chlorin p6/chlorin p6 mixture in photodynamic therapy of the subcutaneous 9L glioma in the rat. Cancer Res. 1992 Mar 1;52(5):1235-9. PMID: 1737384.
8. Leach MW, Pool RR. Hypertrophic osteopathy in a Shetland pony attributable to pulmonary squamous cell carcinoma metastases. Equine Vet J. 1992 May;24(3):247-9. doi: 10.1111/j.2042-3306.1992.tb02825.x. PMID: 1606942.
9. Peaston AE, Leach MW, Higgins RJ. Photodynamic therapy for nasal and aural squamous cell carcinoma in cats. J Am Vet Med Assoc. 1993 Apr 15;202(8):1261-5. PMID: 8496082.
10. Leach MW, Khoshyomn S, Bringus J, Autry SA, Boggan JE. Normal brain tissue response to photodynamic therapy using aluminum phthalocyanine tetrasulfonate in the rat. Photochem Photobiol. 1993 May;57(5):842-5. doi: 10.1111/j.1751-1097.1993.tb09221.x. PMID: 8337258.
11. Leach MW, Higgins RJ, Autry SA, Boggan JE, Lee S-JH, Smith KM. In vitro photodynamic effects of lysyl chlorin p6: Cell survival, localization, and ultrastructural changes. Photochem Photobiol. 1993 Nov;58(5):653-60. doi: 10.1111/j.1751-1097.1993.tb04948.x. PMID: 8284320.
12. Powrie F, Leach MW, Mauze S, Caddle LB, Coffman RL. Phenotypically distinct subsets of CD4+ T cells induce and protect from chronic intestinal inflammation in C. B-17 scid mice. Int Immunol. 1993 Nov;5(11):1461-71. doi: 10.1093/intimm/5.11.1461. PMID: 7903159.
13. Leach MW, Peaston AE. Adverse drug reaction attributable to aluminum phthalocyanine tetrasulphonate administration in domestic cats. Vet Pathol. 1994 Mar;31(2):283-7. doi: 10.1177/030098589403100227. PMID: 8203103.
14. Powrie F, Leach MW, Mauze S, Menon S, Caddle LB, Coffman RL. Inhibition of Th1 responses prevents inflammatory bowel disease in scid mice reconstituted with CD45RBhi CD4+ T cells. Immunity. 1994 Oct;1(7):553-62. doi: 10.1016/1074-7613(94)90045-0. PMID: 7600284.
15. Berg DJ, Leach MW, Kühn R, Rajewsky K, Müller W, Davidson NJ, Rennick D. Interleukin-10 but not interleukin-4 is a natural suppressant of cutaneous inflammatory responses. J Exp Med. 1995 Jul 1;182(1):99-108. doi: 10.1084/jem.182.1.99. PMID: 7790826; PMCID: PMC2192105.
16. Vemulapalli S, Chui PJS, Kurowski S, Brown A, Hartman BD, Leach MW. In vivo inhibition of platelet adhesion by a cGMP-mediated mechanism in balloon catheter injured rat carotid artery. Pharmacology. 1996 Apr;52(4):235-42. doi: 10.1159/000139388. PMID: 8841086.
17. Leach MW, Mauze S, Menon S, Caddle LB, Bean AGD, Coffman RL, Powrie F. Inflammatory bowel disease in C. B-17 scid mice reconstituted with the CD45RBhigh subset of CD4+ T cells. Am J Pathol. 1996 May;148(5):1503-15. PMID: 8623920; PMCID: PMC1861555.
18. Powrie F, Carlino J, Leach MW, Mauze S, Coffman RL. A critical role for TGF-b but not IL-4 in suppression of Th1 mediated colitis by CD45RBlow CD4+ T cells. J Exp Med. 1996 Jun 1;183(6):2669-74. doi: 10.1084/jem.183.6.2669. PMID: 8676088; PMCID: PMC2192626.
19. Davidson NJ, Leach MW, Fort MM, Thompson-Snipes L, Kühn R, Müller W, Berg DJ, Rennick DM. TH1-type CD4+ T cells, but not B cells, mediate colitis in IL-10-deficient mice. J Exp Med. 1996 Jul 1;184(1):241-51. doi: 10.1084/jem.184.1.241. PMID: 8691138; PMCID: PMC2192682.
20. Berg DJ, Davidson N, Kühn R, Müller W, Menon S, Holland G, Thompson-Snipes L, Leach MW, Rennick D. Enterocolitis and colon cancer in interleukin-10-deficient mice are associated with aberrant cytokine production and CD4+ TH1-like responses. J Clin Invest. 1996 Aug 15;98(4):1010-20. doi: 10.1172/JCI118861. PMID: 8770874; PMCID: PMC507517.
21. Grünig G, Corry DB, Leach MW, Seymour BWP, Kurup VP, Rennick DM. Interleukin-10 is a natural suppressor of cytokine production and inflammation in a murine model of allergic bronchopulmonary aspergillosis. J Exp Med. 1997 Mar 17;185(6):1089-99. doi: 10.1084/jem.185.6.1089. PMID: 9091582; PMCID: PMC2196229.
22. Hudak S, Leach MW, Xu Y, Menon S, Rennick D. Radioprotective effects of FLK2/FLT3 ligand. Exp Hematol. 1998 Jun;26(6):515-22. PMID: 9620285.
23. Davidson NJ, Hudak SA, Lesley RE, Menon S, Leach MW, Rennick DM. IL-12, but not IFN‑g, plays a major role in sustaining the chronic phase of colitis in IL-10-deficient mice. J Immunol. 1998 Sep 15;161(6):3143-9. PMID: 9743382.
24. Fort MM, Leach MW, Rennick DM. A role for NK cells as regulators of CD4+ T cells in a transfer model of colitis. J Immunol. 1998 Oct 1;161(7):3256-61. PMID: 9759840.
25. Johnson RC, Dovey-Hartman BJ, Syed J, Leach MW, Frank DW, Sinha DE, Mirro EJ, Little JM, Halliwell WH. Vacuolation in renal tubular epithelium of Cd-1 mice: An incidental finding. Toxicol Pathol. 1998 Nov-Dec;26(6):789-92. doi: 10.1177/019262339802600611. PMID: 9864096.
26. Leach MW, Frank DW, Berardi MR, Evans EW, Johnson RC, Schuessler DG, Radwanski E, Cartwright ME. Renal changes associated with naproxen sodium administration in cynomolgus monkeys. Toxicol Pathol. 1999 May-Jun;27(3):295-306. doi: 10.1177/019262339902700305. PMID: 10356706.
27. Asseman C, Mauze S, Leach MW, Coffman RL, Powrie F. An essential role for interleukin 10 in the function of regulatory T cells that inhibit intestinal inflammation. J Exp Med. 1999 Oct 4;190(7):995-1004. doi: 10.1084/jem.190.7.995. PMID: 10510089; PMCID: PMC2195650.
28. Yang BT, Chen S-C, Leach MW, Manfra D, Homey B, Wiekowski M, Sullivan L, Jenh C-H, Narula SK, Chensue SW, Lira SA. Transgenic expression of the chemokine receptor encoded by human herpesvirus 8 induces an angioproliferative disease resembling Kaposi’s sarcoma. J Exp Med. 2000 Feb 7;191(3):445-54. doi: 10.1084/jem.191.3.445. PMID: 10662790; PMCID: PMC2195818.
29. Bober LA, Rojas-Triana A, Jackson JV, Leach MW, Manfra D, Narula SK, Grace MJ. Regulatory effects of interelukin-4 and interelukin-10 on human neutrophil function ex vivo and on neutrophil influx in a rat model of arthritis. Arthritis Rheum. 2000 Dec;43(12):2660-7. doi: 10.1002/1529-0131(200012)43:12<2660::AID-ANR5>3.0.CO;2-4. PMID: 11145023.
30. Fort MM, Lesley R, Davidson NJ, Menon S, Brombacher F, Leach MW, Rennick DM. IL-4 exacerbates disease in a Th1 cell transfer model of colitis. J Immunol. 2001 Feb 15;166(4):2793-800. doi: 10.4049/jimmunol.166.4.2793. PMID: 11160346.
31. Scheerens H, Hessel E, de Waal-Malefyt R, Leach MW, Rennick D. Characterization of chemokines and chemokine receptors in two murine models on inflammatory bowel disease: IL-10-/- mice and Rag-2-/- mice reconstituted with CD4+CD45RBhigh T cells. Eur J Immunol. 2001 May;31(5):1465-74. doi: 10.1002/1521-4141(200105)31:5<1465::AID-IMMU1465>3.0.CO;2-E. PMID: 11465103.
32. Wiekowski MT, Leach MW, Evans EW, Sullivan L, Chen S-C, Vassileva G, Bazan JF, Gorman DM, Kastelein RA, Narula S, Lira SA. Ubiquitous transgenic expression of the IL-23 subunit p19 induces multiorgan inflammation, runting, infertility and premature death. J Immunol. 2001 Jun 15;166(12):7563-70. doi: 10.4049/jimmunol.166.12.7563. PMID: 11390512.
33. Fort MM, Cheug J, Yen D, Li J, Zurawski S, Lo S, Menon S, Clifford T, Hunte B, Lesley R, Muchamuel T, Hurst SD, Zurawski G, Leach MW, Gorman DM, Rennick DM. IL-25 induces IL-4, IL-5, and IL-13 and Th2-associated pathologies in vivo. Immunity. 2001 Dec;15(6):985-95. doi: 10.1016/s1074-7613(01)00243-6. PMID: 11754819.
34. Chen S-C, Leach MW, Lira S. CNS inflammation and neurological disease in transgenic mice expressing the CC chemokine CCL21 in oligodendrocytes. J Immunol. 2002 Feb 1;168(3):1009-17. doi: 10.4049/jimmunol.168.3.1009. PMID: 11801633.
35. Waegell W, Babineau M, Hart M, Dixon K, McRae B, Wallace C, Leach M, Ratnofsky S, Belanger A, Hirst G, Rossini A, Appel M, Mordes J, Greiner D, Banerjee S. A420983, a novel, small molecule inhibitor of LCK prevents allograft rejection. Transplant Proc. 2002 Aug;34(5):1411-7. doi: 10.1016/s0041-1345(02)02909-3. PMID: 12176420.
36. Marusic S, Leach MW, Pelker JW, Azoitei ML, Uozumi N, Cui J, Shen MWH, DeClerq CM, Miyashiro JS, Carito BA, Thakker P, Simmons DL, Leonard JP, Shimizu T, Clark JD. Cytosolic phospholipase A2a-deficient mice are resistant to experimental autoimmune encephalomyelitis. J Exp Med. 2005 Sep 19;202(6):841-51. doi: 10.1084/jem.20050665. PMID: 16172261; PMCID: PMC2212947.
37. Carter LL, Leach MW, Azoitei ML, Cui J, Pelker JW, Jussif J, Benoit S, Ireland G, Luxenberg D, Askew GR, Milarski K, Groves C, Brown T, Carito BA, Percival K, Carreno BM, Collins M, Marusic S. PD-1/PD-L1, but not PD‑1/PD-L2, interactions regulate the severity of experimental autoimmune encephalomyelitis. J Neuroimmunol. 2007 Jan;182(1-2):124-34. doi: 10.1016/j.jneuroim.2006.10.006. Epub 2006 Dec 19. PMID: 17182110.
38. Thakker P, Leach MW, Kuang W, Benoit SE, Leonard JP, Marusic S. IL-23 is critical in the induction but not in the effector phase of experimental autoimmune encephalomyelitis. J Immunol. 2007 Feb 15;178(4):2589-98. doi: 10.4049/jimmunol.178.4.2589. PMID: 17277169.
39. Losco PE, Leach MW, Sinha D, Davis P, Schmahai TJ, Nomier A, Kakkar T, Reyderman L, Lynch ME. Administration of an antagonist of neurokinin receptors 1, 2, and 3 results in reproductive tract changes in beagle dogs, but not rats. Toxicol Pathol. 2007 Feb;35(2):310-22. doi: 10.1080/01926230701198766. PMID: 17366326.
40. Marusic S, Thakker P, Pelker JW, Stedman NL, Lee KL, McKew JC, Han L, Xu X, Wolf SF, Borey AJ, Cui J, Shen MWH, Donahue F, Hassan-Zahraee M, Leach MW, Shimizu T, Clark JD. Blockade of cytosolic phospholipase A2a prevents experimental autoimmune encephalomyelitis and diminishes development of Th1 and Th17 responses. J Neuroimmunol. 2008 Nov 15;204(1-2):29-37. doi: 10.1016/j.jneuroim.2008.08.012. PMID: 18829119.
41. Martone RL, Zhou H, Atchison K, Comery T, Xu JZ, Huang X, Gong X, Jin M, Kreft A, Harrison B, Mayer SC, Aschmies S, Gonzales C, Zaleska MM, Riddell DR, Wagner E, Lu P, Sun SC, Sonnenberg-Reines J, Oganesian A, Adkins K, Leach MW, Clarke DW, Huryn D, Abou-Gharbia M, Magolda R, Bard J, Frick G, Raje S, Forlow SB, Balliet C, Burczynski ME, Reinhart PH, Wan HI, Pangalos MN, Jacobsen JS. GSI-953 (begacestat): A novel, selective thiophene sulfonamide inhibitor of amyloid precursor protein g-secretase for the treatment of Alzheimer's disease. J Pharmacol Exp Ther. 2009 Nov;331(2):598-608. doi: 10.1124/jpet.109.152975. Epub 2009 Aug 11. PMID: 19671883.
42. Vugmeyster Y, Allen S, Szklut P, Bree A, Ryan M, Ma M, Spaulding V, Young D, Guay H, Bloom L, Leach MW, O’Toole M, Adkins K. Correlation of pharmacodynamic activity, pharmacokinetics, and anti-product antibody responses to anti-IL-21R antibody therapeutics following IV administration to cynomolgus monkeys. J Transl Med. 2010 Apr 26;8:41. doi: 10.1186/1479-5876-8-41. PMID: 20420683; PMCID: PMC2880981.
43. Enright BP, Leach MW, Pelletier G, LaBrie F, McIntyre BS, Losco PE. Effects of an antagonist of neurokinin receptors 1, 2 and 3 on reproductive hormones in male beagle dogs. Birth Defects Res B Dev Reprod Toxicol. 2010 Dec;89(6):517-25. doi: 10.1002/bdrb.20274. PMID: 21086439.
44. Leach MW, Halpern WG, Johnson CW, Rojko JL, MacLachlan TK, Chan CM, Galbreath EJ, Ndifor AM, Blanset DL, Polack E, Cavagnaro JA. Use of tissue cross-reactivity studies in the development of antibody-based biopharmaceuticals: History, experience, methodology, and future directions. Toxicol Pathol. 2010 Dec;38(7):1138-66. doi: 10.1177/0192623310382559. Epub 2010 Oct 6. PMID: 20926828.
45. Bussiere JL, Leach MW, Price KD, Mounho BJ, Lightfoot-Dunn R. Survey results on the use of the tissue cross-reactivity immunohistochemistry assay. Regul Toxicol Pharmacol. 2011 Apr;59(3):493-502. doi: 10.1016/j.yrtph.2010.09.017. Epub 2010 Oct 14. PMID: 20951178.
46. Thakker P, Marusic S, Stedman N, Lee K, McKew J, Wood A, Goldman S, Leach M, Collins M, Kuchroo V, Wolf S, Clark J, Hassan-Zahraee M. Cytosolic phospholipase A2α blockade abrogates disease during the tissue-damage effector phase of experimental autoimmune encephalomyelitis by its action on APCs. J Immunol. 2011 Aug 15;187(4):1986-97. doi: 10.4049/jimmunol.1002789. Epub 2011 Jul 11. PMID: 21746963.
47. Wright DJ, Adkins KK, Minck DR, Bailey S, Warner G, Leach MW. Reproductive performance and early postnatal development in interleukin (IL)-13-deficient mice. Birth Defects Res B Dev Reprod Toxicol. 2012 Oct;95(5):346-53. doi: 10.1002/bdrb.21023. Epub 2012 Aug 28. PMID: 22930549.
48. Iatropoulos MJ, Duan J-D, Jeffrey AM, Leach MW, Hayes AN, Stedman NL, Williams GM. Hepatocellular proliferation and hepatocarcinogen activation in mice with diet-induced fatty liver and obesity. Exp Toxicol Pathol. 2013 May;65(4):451-6. doi: 10.1016/j.etp.2012.01.003. Epub 2012 Mar 28. PMID: 22459205.
49. Maggi RG, Mascarelli PE, Balakrishnan N, Rohde CM, Kelly CM, Ramaiah L, Leach MW, Breitschwerdt EB. ‘Candidatus Mycoplasma haemomacaque’ and Bartonella quintana bacteremia in cynomolgus monkeys. J Clin Microbiol. 2013 May;51(5):1408-11. doi: 10.1128/JCM.03019-12. Epub 2013 Feb 13. PMID: 23408694; PMCID: PMC3647913.
50. Ryan AM, Sokolowski SA, Ng C-K, Shirai N, Collinge M, Shen AC, Arrington J, Radi Z, Cummings TR, Ploch SA, Stephenson SA, Tripathi NK, Hurst SI, Finch GL, Leach MW. Comparative nonclinical assessments of the proposed biosimilar PF-05280586 and rituximab (MabThera®). Toxicol Pathol. 2014 Oct;42(7):1069-81. doi: 10.1177/0192623313520351. Epub 2014 Mar 6. PMID: 24604381.
51. Hurst S, Ryan AM, Ng C-K, McNally JM, Lorello LG, Finch GL, Leach MW, Ploch SA, Fohey JA, Smolarek TA. Comparative nonclinical assessments of the proposed biosimilar PF‑05280014 and trastuzumab (Herceptin®). BioDrugs. 2014 Oct;28(5):451-9. doi: 10.1007/s40259-014-0103-4. PMID: 25001079; PMCID: PMC4176567.
52. Frazier KS, Engelhardt JA, Fant P, Guionaud S, Henry SP, Leach MW, Louden C, Scicchitano MS, Weaver JL, Zabka TS; Society of Toxicologic Pathology Vascular Injury Working Group. Scientific and Regulatory Policy Committee Points-to-consider Paper*: Drug-induced Vascular Injury Associated with Nonsmall Molecule Therapeutics in Preclinical Development: Part I. Biotherapeutics. Toxicol Pathol. 2015 Oct;43(7):915-34. doi: 10.1177/0192623315570340. Epub 2015 Feb 26. PMID: 25722122.
53. Engelhardt JA, Fant P, Guionaud S, Henry SP, Leach MW, Louden C, Scicchitano MS, Weaver JL, Zabka TS, Frazier KS; Society of Toxicologic Pathology Vascular Injury Working Group. Scientific and Regulatory Policy Committee Points-to-consider Paper*: Drug-induced Vascular Injury Associated with Nonsmall Molecule Therapeutics in Preclinical Development: Part 2. Antisense Oligonucleotides. Toxicol Pathol. 2015 Oct;43(7):935-44. doi: 10.1177/0192623315570341. Epub 2015 Feb 24. PMID: 25717082.
54. Nolte T, Brander-Weber P, Dangler C, Deschl U, Elwell MR, Greaves P, Hailey R, Leach MW, Pandiri AR, Rogers A, Shackelford CC, Spencer A, Tanaka T, Ward JM. Nonproliferative and Proliferative Lesions of the Gastrointestinal Tract, Pancreas and Salivary Glands of the Rat and Mouse. J Toxicol Pathol. 2016;29(1 Suppl):1S-125S. doi: 10.1293/tox.29.1S. Epub 2016 Feb 13. PMID: 26973378; PMCID: PMC4765498.
55. Derzi M, Johnson T, Shoieb A, Conlon H, Sharpe P, Saati A, Koob K, Bolt M, Lorello L, McNally J, Kirchhoff C, Smolarek TA, Leach MW. Nonclinical evaluation of PF-06438179, a proposed biosimilar to Remicade® (infliximab). Adv Ther. 2016 Nov;33(11):1964-1982. doi: 10.1007/s12325-016-0403-9. Epub 2016 Sep 1. PMID: 27585978; PMCID: PMC5083783.
56. Peraza MA, Rule KE, Shiue MHI, Finch GL, Thibault S, Brown PR, Clarke DW, Leach MW. Nonclinical assessments of the potential biosimilar PF-06439535 and bevacizumab. Regul Toxicol Pharmacol. 2018 Jun;95:236-243. doi: 10.1016/j.yrtph.2018.03.020. Epub 2018 Mar 21. PMID: 29574193.
57. Derzi M, Shoieb AM, Ripp SL, Finch GL, Lorello LG, O'Neil SP, Radi Z, Syed J, Thompson MS, Leach MW. Comparative nonclinical assessments of the biosimilar PF-06410293 and originator adalimumab. Regul Toxicol Pharmacol. 2020 Apr;112:104587. doi: 10.1016/j.yrtph.2020.104587. Epub 2020 Jan 30. PMID: 32006671.
59. MacLachlan TK, Price S, Cavagnaro J, Andrews L, Blanset D, Cosenza ME, Dempster M, Galbreath E, Giusti AM, Heinz-Taheny KM, Fleurance R, Sutter E, Leach MW. Classic and evolving approaches to evaluating cross reactivity of mAb and mAb-like molecules - A survey of industry 2008-2019. Regul Toxicol Pharmacol. 2021 Apr;121:104872. doi: 10.1016/j.yrtph.2021.104872. Epub 2021 Jan 22. PMID: 33485926.
59. Leach MW, Clarke DO, Dudal S, Han C, Li C, Yang Z, Brennan FR, Bailey WJ, Chen Y, Deslandes A, Loberg LI, Mayawala K, Rogge MC, Todd M, Chemuturi NV. Strategies and Recommendations for Using a Data-Driven and Risk-Based Approach in the Selection of First-in-Human Starting Dose: An International Consortium for Innovation and Quality in Pharmaceutical Development (IQ) Assessment. Clin Pharmacol Ther. 2021 Jun;109(6):1395-1415. doi: 10.1002/cpt.2009. Epub 2020 Nov 3. PMID: 32757299.
60. Chien HT, Prior H, Andrews L, van Aerts L, Cauvin A, Clarke DO, Datta K, Dempster M, Dybdal N, Freebern W, de Haan L, Herzyk D, Hey A, Kissner T, Kronenberg S, Leach MW, Lee D, Schutte K, Sewell F, Trouba K, Ulrich P, Weir L, van Meer P. Re-evaluating the need for chronic toxicity studies with therapeutic monoclonal antibodies, using a weight of evidence approach. Regul Toxicol Pharmacol. 2023 Feb;138:105329. doi: 10.1016/j.yrtph.2022.105329. Epub 2022 Dec 30. PMID: 36592682.
61. Prior H, Andrews L, Cauvin A, Chien H, Clarke DO, Datta K, Dempster M, Dybdal N, Freebern W, de Haan L, Herzyk D, Hey A, Kissner T, Kronenberg S, Leach MW, Lee D, Reid K, Schutte K, Sewell F, Trouba K, Ulrich P, van Aerts L, van Meer P, Weir L. The use of recovery animals in nonclinical safety assessment studies with monoclonal antibodies: further 3Rs opportunities remain. Regul Toxicol Pharmacol. 2023 Feb;138:105339. doi: 10.1016/j.yrtph.2023.105339. Epub 2023 Jan 14. PMID: 36649820.
62. Leach MW, Rana P, Hu W, Mittapalli RK, Pinkstaff J, Potter D, Qiu XM, Ramaiah L, Rohde C, Xia F, Khan KN. Translation of nonclinical to clinical safety findings for 27 biotherapeutics. Toxicol Appl Pharmacol. 2024 Mar;484:116854. doi: 10.1016/j.taap.2024.116854. Epub 2024 Feb 10. PMID: 38346540.
63. Hu W, Buetow B, Sachdeva K, Leach MW. immune-mediated liver effects associated with administration of a human anti-IL-21 receptor antibody (ATR-107) in rats. Accepted Toxicol Pathol.
Invited Reviews/Articles/Opinion Pieces/Symposium Reviews
1. Leach MW. Photodynamic therapy of cancer in animals. Adv Small Anim Med Surg. 1991 3:3-4.
2. Leach MW. A survey of neoplasia in pet birds. Semin Avian Exotic Pet Med. 1992 1:52-64
3. Powrie F, Leach MW. Genetic and spontaneous models of inflammatory bowel disease in rodents: Evidence for abnormalities in mucosal immune regulation. Ther Immunol. 1995 Apr;2(2):115-23. PMID: 8729882.
4. Leach MW, Snyder EA, Sinha DP, Rosenblum IY. Safety evaluation of recombinant human interleukin-4. I. Preclinical studies. Clin Immunol Immunopathol. 1997 Apr;83(1):8-11. doi: 10.1006/clin.1997.4303. PMID: 9073526.
5. Leach MW, Rybak ME, Rosenblum IY. Safety evaluation of recombinant human interleukin-4. II. Clinical studies. Clin Immunol Immunopathol. 1997 Apr;83(1):12-4. doi: 10.1006/clin.1997.4304. PMID: 9073527.
6. Leach MW, Davidson NJ, Fort MM, Powrie F, Rennick DM. The role of IL-10 in inflammatory bowel disease: “Of mice and men”. Toxicol Pathol. 1999 Jan-Feb;27(1):123-33. doi: 10.1177/019262339902700124. PMID: 10367687.
7. Davidson NJ, Fort MM, Muller W, Leach MW, Rennick DM. Chronic colitis in IL-10-/- mice: Insufficient counter regulation of a Th1 response. Int Rev Immunol. 2000;19(1):91-121. doi: 10.3109/08830180009048392. PMID: 10723680.
8. Pandher K, Leach MW, Burns-Naas LA. Appropriate use of recovery groups in nonclinical toxicity studies: Value in a science-driven case-by-case approach. Vet Pathol. 2012 Mar;49(2):357-61. doi: 10.1177/0300985811415701. Epub 2011 Aug 1. PMID: 21810619.
9. Vugmeyster Y, Xu X, Theil FP, Khawli LA, Leach MW. Pharmacokinetics and toxicology of therapeutic proteins: Advances and challenges. World J Biol Chem. 2012 Apr 26;3(4):73-92. doi: 10.4331/wjbc.v3.i4.73. PMID: 22558487; PMCID: PMC3342576.
10. Leach MW. Differences Between Protein-based Biologic Products (Biotherapeutics) and Chemical Entities (Small Molecules) of Relevance to the Toxicologic Pathologist. Toxicol Pathol. 2013 Jan;41(1):128-36. doi: 10.1177/0192623312451371. Epub 2012 Jun 28. PMID: 22744226.
11. Leach MW, Rottman JB, Hock MB, Finco D, Rojko JL, Beyer JC. Immunogenicity/ Hypersensitivity of Biologics. Toxicol Pathol. 2014 Jan;42(1):293-300. doi: 10.1177/0192623313510987. Epub 2013 Nov 14. PMID: 24240973.
12. Chapman K, Adjei A, Baldrick P, da Silva A, De Smet K, DiCicco R, Hong SS, Jones D, Leach MW, McBlane J, Ragan I, Reddy P, Stewart DIH, Suitters A, Sims J. Waiving in vivo studies for monoclonal antibody biosimilar development: National and global challenges. MAbs. 2016;8(3):427-35. doi: 10.1080/19420862.2016.1145331. PMID: 26854177; PMCID: PMC4966840.
13. Harrill AH, Moggs JG, Adkins KK, Augustin HG, Johnson RC, Leach MW. A Synopsis of the "Influence of Epigenetics, Genetics, and Immunology" Session Part A at the 35th Annual Society of Toxicologic Pathology Symposium. Toxicol Pathol. 2017 Jan;45(1):114-118. doi: 10.1177/0192623316670781. Epub 2016 Oct 5. PMID: 27708198.
Book Chapters
1. Todd M, Leach MW. Nonclinical Toxicology Testing Strategies and Applicable International Regulatory Guidelines for Using Nonhuman Primates in the Development of Biotherapeutics. Chapter 16, pp 316-336. In: Bluemel J, Korte S, Schenck E, Weinbauer GF, eds. The Nonhuman Primate in Nonclinical Drug Development and Safety Assessment. 1st ed (2015). Amsterdam: Elsevier.
2. Leach MW. Antibodies (Abs) and Related Products Containing Complementarity-Determining Regions (CDRs). Chapter 20, pp 235-266. In: Cavagnaro J, Cosenza ME eds. Translational Medicine. Optimizing Preclinical Safety Evaluation of Biopharmaceuticals. 1st ed (2021). Boca Raton: CRC Press. DOI: 10.1201/9781003124542-23.
3. Leach MW, Hammerman K. Protein Therapeutics. Chapter 6. In: Heinz K, Rudmann D eds. Haschek and Rousseaux's Handbook of Toxicologic Pathology, 4th Ed., Volume 2 - Safety Assessment and Environmental Toxicologic Pathology. 4th ed (2023). Amsterdam: Elsevier. Hardcover ISBN: 9780128210475. eBook ISBN: 9780323910521.
Invited Presentations
1. Leach MW, Freeman DM, Higgins RJ, Boggan JE, Elkhaled S, Lee S, Smith KM. Spatially localized phosphorous spectroscopy for evaluating response of the 9L rat glioma to photodynamic therapy. Presented at the GE NMR Instruments 1990 Users' Meeting, New York City, New York; August 19, 1990.
2. Leach MW. Fellowships and Grants: An experienced graduate student perspective. Presented at the First Annual Fellowships and Grants Workshop, Davis, California; November 29 1990.
3. Leach MW. Integration of drug safety with drug discovery and preclinical biology: A case study of interleukin-10. Presented at The 4th International Course on the Safety Assessment of Pharmaceuticals. Part I - Regulatory Aspects, White Plains, New York, October 20-25, 1996.
4. Leach MW, Schmahai TJ. Preclinical development of recombinant human IL-4 and IL-10. Presented at the Seventeenth Annual Meeting of the American College of Toxicology, King of Prussia, Pennsylvania, November 10-13, 1996. Program and Abstracts p 41.
5. Leach MW. Preclinical safety assessment of antibody-based therapeutics. Presented at IBC’s Second Biennial Conference on Antibody-Based Therapeutics, Boston, Massachusetts, June 5-6, 1997.
6. Leach MW. IL-4: Toxicology studies in the monkey. Presented at “Biotechnology-Derived Therapeutics: Current Perspectives in Pharmacology and Toxicology”, Tahoe City, California, June 1-2, 1998.
7. Leach MW, Davidson NJ, Fort MM, Powrie F, Rennick DM. The role of IL-10 in inflammatory bowel disease: “Of mice and men”. Presented at the 17th International Symposium of the Society of Toxicologic Pathologists, Vancouver, British Columbia, Canada, June 28-July 2, 1998.
8. Leach MW. Issues and strategies in the development of recombinant human interleukin-4 (rhuIL-4). Presented at the 1999 Society of Toxicology Annual Meeting, New Orleans, Louisiana, March 14-18. Toxicol Sci (Suppl) 48:40, 1999.
9. Leach MW. Preclinical safety evaluation of antibody-based therapeutics. Presented at the Twentieth Annual Meeting of the American College of Toxicology, Continuing Education Course #3, McLean, Virginia, November 7-10, 1999.
10. Leach MW. Toxicologic pathology of the thymus, spleen, and lymph nodes. Presented at the 2002 Society of Toxicology Annual Meeting, Continuing Education Course AM #2, Nashville, Tennessee, March 17-21, 2002.
11. Leach MW. Drug safety and metabolism. Presented at the Tufts University Medical School in Boston, MA as part of the course "Special Topics In Pharmacology (PHARM 294)". April 15, 2004.
12. Leach MW. Safety validation of new drug targets. Presented at Discovery on Target - Target Validation: Making Informed Choices, Boston, MA, November 11-12, 2004.
13. Leach MW. Safety evaluation strategies in discovery and early development. Presented at R&D Leaders’ Forum, Coral Gables, Florida, March 20-22, 2006.
14. Leach MW, Warner GL. ICH S6: hERG, reproductive toxicology, and carcinogenicity. Presented at BioSafe General Membership Meeting, Indianapolis, Indiana, October 5-6, 2006.
15. Leach MW. Safety evaluation strategies: Can they be standardized in early stages? Presented at Discovery on Target: Executives on Target, Boston, Massachusetts, October 24-25, 2006.
16. Leach MW. Tissue cross-reactivity. Presented at the 28th Annual Meeting of the American College of Toxicology, Charlotte, North Carolina, November 11-14. Int J Toxicol 26:597, 2007.
17. Leach MW. Preclinical safety evaluation of biopharmaceuticals: Opportunities and challenges. Presented at bioLOGIC Europe 2008, Geneva, Switzerland, September 16-19, 2008.
18. Leach MW, Sagartz JE. Pathology of inflammatory bowel disease models in mice. Presented at Inflammatory Bowel Disease Summit (meeting held by Inflammation Research Association), St. Louis, Missouri, September 14-16, 2009.
19. Leach MW. Tissue cross-reactivity. Presented at BioSafe General Membership Meeting, San Francisco, California, October 6-7, 2009.
20. Leach MW. Use of tissue cross-reactivity studies in the development of antibody-based biopharmaceuticals: History, experience, methodology and future directions. Presented at The Boston Area Pharmaceutical Toxicology Group, Cambridge, Massachusetts, February 18, and broadcast as a Webinar globally by the Society of Toxicologic Pathology, 2011.
21. Leach MW. What is adverse?: Biopharmaceutical perspective. Presented at 2011 Applied Pharmaceutical Toxicology (APT) Meeting, South San Francisco, California, May 18-20, 2011.
22. Leach MW. Appropriate use of recovery groups in toxicity studies. Presented at 2012 Applied Pharmaceutical Toxicology (APT) Meeting, Baltimore, Maryland, May 16-18, 2012.
23. Leach MW. Cytokine therapy for cancer: The history of therapeutic cytokine storm begins. Presented at The Charles River Workshop on Toxicology. Early Warning Signs of Phase I Trial Risks: Novel Immunologic and Cancer Drugs, Cambridge, Massachusetts, February 26, 2013.
24. Leach MW. Nonclinical development of biosimilars: Adjusting the strategy to fit the program. Presented at the 52nd Annual Meeting of the Society of Toxicology, San Antonio, Texas. In Continuing Education course entitled: Approval of Biosimilar Monoclonal Antibodies: Scientific, Regulatory, and Legal Challenges, March 10, 2013.
25. Leach MW. Two case studies in immunogenicity: Anaphylaxis in cynomolgus monkeys and immunogenicity-related hepatic necrosis in rats. Presented at the 32nd Annual Symposium of the Society of Toxicologic Pathology, Portland, Oregon. In Continuing Education course entitled: Immunogenicity/Hypersensitivity of Biologics, June 16., 2013.
26. Leach MW. Patient deaths following IL-12 and other cytokine immunostimulants: It’s not just recent history. Presented at 19th Annual Biotech Symposium, Carlsbad, California, September 9-11, 2013.
27. Leach MW. Nonclinical development of proposed biosimilars to rituximab, trastuzumab and other monoclonal antibodies. Presented at 19th Annual Biotech Symposium, Carlsbad, California, September 9-11, 2013.
28. Leach MW. Nonclinical development of proposed biosimilars to five monoclonal antibodies. Presented at the 2nd Annual Biosimilars & Biobetters Congress, London, April 3-4, 2014.
29. Leach MW. Reducing animal use in nonclinical development of biosimilars. Presented at the IQPC Biosimilars Clinical Studies and Analytical Similarity Summit, Boston, March 22-23, 2016.
30. Leach MW. Regulatory and Scientific Challenges in Biosimilar Development: Nonclinical Considerations. Presented at the American College of Toxicology webinar, April 27, 2016.
31. Leach MW. The role of nonclinical studies and considerations for the nonclinical study design in biosimilar development programs. Presented at the American Association of Pharmaceutical Sciences (AAPS) National Biotechnology Conference Workshop entitled “The Totality of Evidence in Biosimilar Development Programs”, Boston, Massachusetts, May 15-18, 2016.
32. Leach MW. The role of nonclinical in vivo studies in monoclonal antibody biosimilar development. Presented at the XIVth International Congress of Toxicology Workshop, in conjunction with the X Mexican Congress of Toxicology, entitled “Advancing the 3Rs through global harmonisation: Case studies and future perspectives”, Merida, Mexico, October 2-6, 2016. Tox Lett 259S:S23-S24.
33. Leach MW. The Challenge of Minimizing or Eliminating Nonclinical In Vivo Studies in Monoclonal Antibody Biosimilar Development. Presented at the Boston Area Pharmaceutical Toxicology Group (BAPTG) meeting, Cambridge, Massachusetts, April 7, 2017.
34. Leach MW. High dose selection for nonclinical studies of biotherapeutics: How high is high enough?, 23rd Annual Biotech Symposium, Carlsbad, California, September 11, 2017.
35. Leach MW. The Immune System as it Relates to Immunogenicity. Presented at the American College of Toxicology 39th Annual Meeting, West Palm Beach, Florida, November 4-7, 2018.
36. Leach MW. Immunogenicity- and immune-related toxicity. Presented at the American College of Toxicology 39th Annual Meeting, West Palm Beach, Florida, November 4-7, 2018.
37. Leach MW. Industry-Wide Survey of MABEL-Based FIH Starting Dose. Webinar hosted by Biotechnology Specialty Section of Society of Toxicology, March 4, 2019.
38. Leach MW. Are Animal Studies Necessary for Development of Biosimilars? Presented at NC3Rs Pharma Showcase - Applying the 3Rs in Pharma: Improving Delivery of Innovative Treatments to Patients, London, England, June 26, 2019.
39. Leach MW. Animal-Free INDs and CTAs: A Reality or Dream? Are Animal Studies Necessary for Development of Biosimilars? 15th International Congress of Toxicology, Honolulu, Hawaii, July 17, 2019.
40. Leach MW. Differences in nonclinical safety assessment of biotherapeutics versus small molecules. Presented at the 10th Industrial Toxicology and Pathology Short Course: Integration of Toxicology and Pathology in Drug Discovery and Development, Indianapolis, Indiana, August 14-16, 2019.
41. Leach M. Determination of the dose, dose frequency, and duration for repeat-dose toxicity studies of biologics. Presented at the Symposium on ICH S6 Safety Assessment for Biologics, Beijing, China, October 25, 2019.
42. Leach MW. A data-driven and risk-based approach to FIH dose selection. Mid-Atlantic Society of Toxicology (MASOT) 2019 Fall Meeting, Edison, New Jersey, October 31, 2019.
43. Leach MW. Immunogenicity and immune-related toxicity: A biopharmaceutical perspective. Presented at the American College of Veterinary Pathologists Annual Meeting, San Antonio, Texas, November 9-13, 2019.
44. Leach MW. Immuno-Therapies and MABEL for FIH Dose Selection. Presentation 1151d. Presented at the Society of Toxicology Annual Meeting, San Diego, California, March 26-31, 2022.
45. Leach MW. Introduction to IQ MABEL Working Group and Survey Results. Presented at the IQ FIH/MABEL Workshop with CDE (Center for Drug Evaluation, China), Virtual, October 25, 2022.
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