Leadership in next generation biologics


Shastri P, Zhu J, Skidmore L, Liang X, Ji Y, Gu Y, Tian F, Yao S, Xia G., “Nonclinical Development of Next-generation Site-specific HER2-targeting Antibody-drug Conjugate (ARX788) for Breast Cancer Treatment.” Molecular Cancer Therapeutics,Sep 19(9):1822-1832, 2020.

Skidmore L, Sakamuri S, Knudsen NA, Hewet A, Milutinovic S, Barkho W, Biroc S, Kirtley J, Marsden R, Storey K, Lopez I, Yu W, Fang SY, Yao S, Gu Y, Tian F., “ARX788, a Site-specific Anti-HER2 Antibody-Drug Conjugate, Demonstrates Potent and Selective Activity in HER2-low and T-DM1-resistant Breast and Gastric Cancers.” Molecular Cancer Therapeutics, Sep 19(9):1833-1843, 2020.

Barok M., Le Joncour V., Martins A., Isola J., Salmikangas M., Laakkonen P., Joensuu H. “ARX788, a novel anti-HER2 antibody drug conjugate, shows anti-tumor effects in preclinical models of trastuzumab emtansine-resistant HER2-positive breast cancer and gastric cancer.” Cancer Letters, 7(473):156-163, 2020.

Hu, X., Zhang J., Ji D., Xiong G., Xia G., Ji Y., Liang X., Yao S., Tian F. “A Phase 1 Study of ARX788, a HER2-Targeting Antibody Drug Conjugate, in Patients with Metastatic HER2-Positive Breast Cancer.” San Antonio Breast Cancer Symposium, December 2019.

Humphreys, R., Kirtley, J., Hewet, A., Biroc, S., Knudsen, N., Zhang, X., Skidmore, L., Kiener, P., and Wahl, A. “Site-specific conjugation of ARX788, an Antibody Drug Conjugate (ADC) targeting HER2, generates a potent and stable targeted therapeutic for multiple cancers.” AACR Philadelphia, 2015.

Antibody Drug Conjugates

Brandish, PE., Palmieri A., Antonenko S., Beaumont M., Benso L., Cancilla M., Cheng M., Firdos J., Garbaccio R., Garvin-Queen L., Gately D., Kern J., Knudsen N., 1, Ma H., Manibusan A., Shin JS., Stivers P., Sun Y., Tomazela D., Woo HC., Zaller D., Zhang S., Zhang Y., Zielstorff M., “Development of anti-CD74 antibody drug conjugates to target glucocorticoids to immune cells.” Bioconjug Chem, 29(7): 2357-2369, 2018.

Kern JC., Dooney D., Zhang R., Liang L., Brandish PE.., Cheng M, Feng G, Beck A., Bresson D, Firdos J., Gately D., Knudsen N., Manibusan A., Sun .Y, Garbaccio RM., “Novel phosphate modified cathepsin B linkers: improving aqueous solubility and enhancing payload scope of ADCs.” Bioconjug Chem, 27(9): 2081-2088, 2016.

Kern JC., Cancilla M., Dooney D., Kwasnjuk K., Zhang R., Beaumont M., Figueroa I., Hsieh S., Liang L., Tomazela D., Zhang J., Brandish PE., Palmieri A., Stivers P., Cheng M., Feng G., Geda P., Shah S., Beck A., Bresson D., Firdos J., Gately D., Knudsen N., Manibusan A., Schultz PG., Sun Y., Garbaccio RM., “Discovery of Pyrophosphate Diesters as Tunable, Soluble, and Bioorthogonal Linkers for Site-Specific Antibody-Drug Conjugates.” J. Am. Chem Soc, 1238(4): 1430-1445, 2016.

Tian F, Lu Y, Manibusan A, Sellers A, Tran H, Sun Y, Phuong T, Barnett R, Hehli B, Song F, Deguzman MJ, Ensari S, Pinkstaff JK, Sullivan LM, Biroc SL, Cho H, Schultz PG, Dijoseph J, Dougher M, Ma D, Dushin R, Leal M, Tchistiakova L, Feyfant E, Gerber HP, Sapra P. “A general approach to site-specific antibody drug conjugates.” Proc. Nat. Acad. Sci., 111(5):1766-71, 2014.

Jackson D1, Atkinson J1, Guevara CI1, Zhang C1, Kery V1, Moon SJ1, Virata C1, Yang P1, Lowe C1, Pinkstaff J2, Cho H2, Knudsen N2, Manibusan A2, Tian F2, Sun Y2, Lu Y2, Sellers A2, Jia XC1, Joseph I1, Anand B1, Morrison K1, Pereira DS1, Stover D1. “In vitro and in vivo evaluation of cysteine and site specific conjugated herceptin antibody-drug conjugates.” PLoS One, 9(1):e83865, 2014.

Axup, J.A., Bajjuri, K.M., Ritland, M., Hutchins, B.M., Kim, C., Kazane, S.A., Halder, R., Forsyth, J.S., Santidrian, A.F., Stafin, K., Liu, Y., Tran, H., Seller, A.J., Biroc, S.L., Szydlik, A., Pinkstaff, J.K., Tian, F., Sinha, S.C., Felding-Habermann, B., Smider, V.V., Schultz, P.G. “Synthesis of site-specific antibody-drug conjugates using unnatural amino acids.” Proc. Nat. Acad. Sci., 109(40):16101-16106, 2012.

Alexandra Flemming, Nature Reviews Drug Discovery 13, 178-178 doi:10.1038/nrd4266

Kularatne SA1, Deshmukh V, Ma J, Tardif V, Lim RK, Pugh HM, Sun Y, Manibusan A, Sellers AJ, Barnett RS, Srinagesh S, Forsyth JS, Hassenpflug W, Tian F, Javahishvili T, Felding-Habermann B, Lawson BR, Kazane SA, Schultz PG.  “A CXCR4-Targeted Site-Specific Antibody-Drug Conjugate.” Angew Chem Int Ed Engl.  2014 Sep 11. doi: 10.1002/anie.201408103.   


Cao Y, Axup JY., Ma JS., Wang RE., Choi S., Tardif V., Lim RK., Pugh HM., Lawson BR., Welzel G., Kazane SA., Sun Y., Tian F., Srinagesh S., Javahishvili T., Schultz PG., Kim CH., “Multiformat T-cell-engaging bispecific antibodies targeting human breast cancers.” Angew Chem Int Ed Engl, 54(24): 7022-7077, 2015.

Kim, C., Axup, J.Y., Lawson, B., Yun, H., Tardif, V., Choi, S., Zhou, Q., Dubrovska, A., Biroc, S.L., Marsden, R., Pinkstaff, J., Smider, V.V., Schultz, P.G., “A bispecific small molecule antibody conjugate targeting prostate cancer.” Proc Natl Acad Sci USA, 110(44):17796-801, 2013.

Paper on ARX201

Cho, H.S., Daniel, T., Buechler, Y.J., Litzinger, D.C., Maio, Z., Putnam, A-M. H., Kraynov, V., Sim, B-C., Bussell, S., Javahishvilli, T., Kaphle, S., Viramontes, G., Ong, M., Chu, S., GC, B., Lieu, R., Knudsen, N., Castiglioni, P., Norman, T., Axelrod, D.W., Hoffman, A.R., Schultz, P.G., DiMarchi, R., Kimmel, B.E. “Optimized clinical performance of growth hormone with an expanded genetic code.” Proc. Nat. Acad. Sci., 108(22):9060-5, 2011.

Paper on Leptin

Clemmensen C, Chabenne J, Finan B, Sullivan L, Fischer K, Küchler D, Sehrer L, Ograjsek T, Hofmann S, Schriever SS, Pfluger PT, Pinkstaff J, Tschöp MH, Dimarchi R, Müller TD. “GLP-1/glucagon co-agonism restores leptin responsiveness in obese mice chronically maintained on an obesogenic diet.” Diabetes Epub, 2013.

Papers on FGF-21

Müller TD, Sullivan LM, Habegger K, Yi CX, Kabra D, Grant E, Ottaway N, Krishna R, Holland J, Hembree J, Perez-Tilve D, Pfluger PT, DeGuzman MJ, Siladi ME, Kraynov VS, Axelrod DW, DiMarchi R, Pinkstaff JK, Tschöp MH. “Restoration of leptin responsiveness in diet-induced obese mice using an optimized leptin analog in combination with exendin-4 or FGF21.” J. Pept. Sci., 18(6):383-93, 2012.

Mu J, Pinkstaff J, Li Z, Skidmore L, Li N, Myler H, Dallas-Yang Q, Putnam AM, Yao J, Bussell S, Wu M, Norman TC, Rodriguez CG, Kimmel B, Metzger JM, Manibusan A, Lee D, Zaller DM, Zhang BB, DiMarchi RD, Berger JP, Axelrod DW. “FGF21 analogs of sustained action enabled by orthogonal biosynthesis demonstrate enhanced antidiabetic pharmacology in rodents.” Diabetes, 61(2):505-12, 2012.

Ambrx Core Technology

Kang, M., Lu, Y., Chen, S., Tian, F. “Harnessing the power of an expanded genetic code toward next-generation biopharmaceuticals.” Curr Opin Chem Biol, 46: 123-129, 2018.

Javahishvili T, Manibusan A, Srinagesh S, Lee D, Ensari S, Shimazu M, Schultz PG. “Role of tRNA Orthogonality in an Expanded Genetic Code.” ACS Chem Biol., Epub, 2014.

Xie, J., Schultz, P.G. “A chemical toolkit for proteins – an expanded genetic code.” Nat. Rev. Mol. Cell Biol., 7(10):775-82,2006.

Kim, C., Axup, J., Schultz, P.G., “Protein conjugation with genetically encoded unnatural amino acids,” Curr Opin Chem Biol, 17(3):412-9, 2013.

siRNA Delivery

Lu, H., Wang. D., Kazane, S.A., Javahishvili, T., Tian, F., Song, F., Sellers, A., Barnett, B., Schultz, P.G., “Site-specific antibody-polymer conjugates for siRNA delivery.” J Am Chem Soc, 135(37):13885-91, 2013..

Papers on other applications of potential interest

Kazane, S.A., Sok, D., Uson, M.L., Cho, E.H., Kuhn, P., Schultz, P.G., Smider, V.V. “Site-specific DNA-antibody conjugates for specific and sensitive immuno-PCR.” Proc. Nat. Acad. Sci., 109(10):3731-6, 2012

Making Sense From Nonsence, EBR, October 2015