Background:• BCMA (B Cell Maturation Antigen) is a low4density surface molecule highly specific forplasma cells well suited to T4cell engagementbased treatment of myeloma.

• The Teneobio antibody platform uses fullyhuman VH domains and an NGS4baseddiscovery pipeline.o NGS identifies multiple high affinity leads toany target within 344 months.

o Heavy4chain4only chemistry simplifiesconstruction of multivalent Abs.

o Simple protein chemistry improves yields(>4g/L), stability, and purification.

• We developed a novel BCMA x CD3 antibody(TNB4383B) that selectively activates T4cellsubsets with reduced cytokine secretion(Figure 1).

Pre.Clinical2Development2of2TNB.383B2a2Fully2Human2T.cell2Engaging2Bispecific2Antibody2Targeting2BCMA2for2the2treatment2of2multiple2myeloma.2

Figure 4: TNB.383B mediates clearance of BCMA(+) tumor cellsin mice and has a long half life in vivo. A. Luc4expressing RPMI48226 tumor cells were administered on day 0, human PBMCs on day7, and drug on day 10 (weekly x3) B. TNB4383B showed similarefficacy in a subcutaneous H929 model as in A. Both treated arms (inblue) received 10µg TNB4383B/Animal C. TNB4383B’s half4life is ~5.5day in mice (bottom) and ~13416 days in Cynomolgus (top)

Conclusions:• TNB4383B clears tumor cells in a BCMA4 andT4cell dependent manner in vitro and in vivo.

• TNB4383B lyses primary patient myelomacells ex vivo without exogenous T4cellsupplementation.

• TNB4383B induces less cytokine secretionthan a conventional T4cell engaging bispecificin vitro, without reduction of tumor cell kill invivo (Figures 345).

• TNB4383B has the half4life of a conventionalIgG4 in mice and Cynomolgus.

• TNB4383B is BCMA4specific in Tissue CrossReactivity studies (data not shown).

• Phase 1 FIH Trial to begin Q4 20184Q1 2019

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Treg TNB.383BCD82TNB.383BCD42TNB.383B

CD82(+)2ControlCD42(+)2Control

Treg (+)2Control

Figure 5: TNB.383B preferentially activateseffector T.cells (CD4/CD8) over Tregs. HumanT4cells from healthy donors were incubatedeither fresh or after high4density culture (48h)together with drug and plate4bound BCMA for24h. CD69 was measured by flow cytometry.

Copies'of'this'poster'obtained'through'Quick'Response'(QR)'Code'are'for'personal'use'onlyand'may'not'be'reproduced'without'permission'from'ASCO®'and'the'author'of'this'poster'

Abstract2#8034

Figure 1: TNB.383B DevelopmentTNB4383B is a fully human T4BsAb combiningfixed4light4chain (FLC) and heavy4chain4only(HCO) arms paired using knob4in4hole. The FLCarm weakly activates CD3. The HCO arm hastwo high4affinity anti4BCMA moieties. TNB4383Bhas a silenced human IgG4 Fc to limit non4specific activation and confer long half life.

Anti.CD3Flic2Ab

Anti.BCMAUniAb

TNB.383B

Figure 2: TNB.383B lyses BCMA(+) NCI.H929 & RPMI.8226 cellsin a dose.dependent manner but not BCMA(.) K562 cells. Whilethe EC50 for lysis by TNB4383B is ~2 logs greater than the PositiveControl (PC) antibody, it achieves the same max. lysis as the PC thathas a strong pan4T4cell activating αCD3 moiety.

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Figure 3: TNB.383B shows max. lysis similar to pos. control (PC)with minimal cytokine secretion. T4cells from 10 donors wereincubated with TNB4383B, PC, or isotype and NCI4H929 cells at lysissaturating doses for 18 hours, and tumor lysis measured by flow (leftpanel). IL42 and IFN4γ were measured by ELISA (middle and rightpanels). Other cytokines were tested, with levels similar to IL42 (heatmap, bottom panel; blue = low, red = high).

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Ben'Buelow1,'Duy'Pham1','Priya'Choudry2,'Shelley'Force'Aldred1,'Andrew'Boudreau1,'Starlynn'Clarke1,'Laura'Davison1,'Kevin'Dang1,'Katherine'Harris1,'Suhasini'Iyer1,'Brett'Jorgensen1,'Heather'Ogana1,'Payal'Pratap1,'Udaya'Rangaswamy1,'Ute'Schellenberger1,'Nathan'Trinklein1,'Harshad'Ugamraj1,'Arun'Wiita2,'Nina'Shah2,'and'Wim'van'Schooten11Teneobio)Inc.,)Menlo)Park,)CA 2University)of)California,)San)Francisco,)San)Francisco,)CA Contact:)bbuelow@teneobio.com

Donor2#

*Plasma2Cell2%

*E:T2Ratio

TNB.383B2Max2Lysis2(18h)

ABC

1 3.1% 142:21 45% 2792 0.0% ND ND ND3 0.2% 1022:21 35% 3354 0.2% 582:21 91% 1125 1.5% 242:21 13% 16006 0.9% 42:21 23% 8157 0.1% 3462:21 61% 20858 75.9% 12:232 2% 2765

Table 1: TNB.383B mediateslysis of primary patientmyeloma cells ex vivo. Aftercharacterizing plasma cell %and E:T ratio by flow, bonemarrow from MM patients wasincubated ~18h. With TNB4383B and max. lysisdetermined.*At time 0, prior to treatment.