AR degrader (RG6537, GDC-2992) is a small molecule, oral degrader of the androgen receptor, a disease driver in prostate cancer. GDC-2992 has the potential to treat patients with prostate cancer who have developed resistance to current therapies.

Mechanism of Action / Target

Androgen receptor (AR)

This molecule was licensed from Jemincare

Anti-PDL1 (MPDL3280A, RG7446) is an engineered monoclonal antibody that targets the ligand PD-L1 (programmed death ligand 1).

Mechanism of Action / Target

Tumor immunotherapy, programmed death ligand 1 (PD-L1)

Anti-PDL1 (MPDL3280A, RG7446) is an engineered monoclonal antibody that targets the ligand PD-L1 (programmed death ligand 1).

Mechanism of Action / Target

Tumor immunotherapy, programmed death ligand 1 (PD-L1)

Status

A Phase I clinical trial evaluating anti-PDL1 for solid tumors, a Phase Ib clinical trial evaluating anti-PDL1 in combination with Avastin® (bevacizumab) for solid tumor, and a Phase I trial evaluating anti-PDL1 in combination with Zelboraf® (vemurafenib) for metastatic melanoma are ongoing. A Phase II trial evaluating anti-PDL1 in patients with metastatic non-small cell lung cancer is planned. For Avastin full prescribing information, including Boxed WARNINGS and additional important safety information, please visit http://www.avastin.com. For Zelboraf full prescribing information, including Medication Guide and important safety information, please visit http://www.zelboraf.com.

Autogene cevumeran (RO7198457, RG6180) is a messenger RNA (mRNA) based personalized cancer vaccine. It is an individualized therapy designed and manufactured specifically to target each cancer patient's unique neoantigens (which result from tumor-specific mutations) to elicit an immune response against that patient's tumor.

Mechanism of Action / Target

Messenger RNA (mRNA) based personalized cancer vaccine that targets each patient's unique neoantigens (individualized neoantigen-specific immunotherapy, iNeST)

This program is being developed in collaboration with BioNTech.

Belvarafenib (RG6185, GDC-5573, HM95573) is a selective small molecule inhibitor of RAF family kinases designed to inhibit the MAPK pathway, which is frequently activated in human tumors and drives tumor growth.

Mechanism of Action / Target

Rapidly accelerated fibrosarcoma (RAF) kinase; mitogen activated protein kinases (MAPK)

This molecule is being developed in collaboration with Hanmi Pharmaceutical.

Cevostamab (BFCR4350A, RG6160) is a T-cell engaging bispecific antibody designed to target FcRH5 on myeloma cells and CD3 on T-cells. This dual targeting is designed to activate and redirect T-cells to attack FcRH5-expressing myeloma cells.

Mechanism of Action / Target

T-cell engaging bispecific antibody, FcRH5 and CD3

GDC-0973 (RG7421), a selective inhibitor of MEK, also known as mitogen activated protein kinase kinase (MAPKK), is a key component of the RAS/RAF/MEK/ERK pathway, which is frequently activated in human tumors. Inappropriate activation of the MEK/ERK pathway promotes cell growth in the absence of exogenous growth factors.

Mechanism of Action / Target

Receptor tyrosine kinase signaling, mitogen-activated protein kinase (MEK) selective inhibitor

Status

A Phase III and a Phase Ib clinical trial in combination with Zelboraf® (vemurafenib) for metastatic melanoma; a Phase Ib clinical trial in combination with GDC-0068, an Akt Inhibitor, for solid tumors; and a Phase Ib clinical trial in combination with GDC-0941, a PI3 Kinase Inhibitor, for solid tumors are ongoing. A Phase I clinical trial evaluating GDC-0973 as a single agent in solid tumor is ongoing.GDC-0973 is being developed in collaboration with Exelixis, Inc. and Zelboraf is being developed in collaboration with Plexxikon, Inc. co-developed under a 2006 license and collaboration agreement between Roche/Genentech and Plexxikon, a member of the Daiichi Sankyo Group.For Zelboraf full prescribing information, including Medication Guide and important safety information, please visit http://www.zelboraf.com.

Entrectinib (RXDX-101, RG6268) is a CNS-active tyrosine-kinase inhibitor being evaluated for the potential treatment of locally advanced or metastatic tumors that harbor NTRK or ROS1 gene rearrangements.

Mechanism of Action / Target

Neurotropic tropomyosin receptor kinase (NTRK) gene fusions; ROS proto-oncogene 1 (ROS1) gene fusions

This molecule was obtained through the acquisition of Ignyta.

GPRC5D x CD3 (RG6324) is a novel T-cell engaging bispecific antibody, targeting both GPRC5D, on the surface of plasma cells, and CD3, a component of the T-cell receptor (TCR) complex, on the surface of T cells.

Mechanism of Action / Target

GPRC5D X CD3

GPRC5D x CD3 (RG6324) is a novel T-cell engaging bispecific antibody, targeting both GPRC5D, on the surface of plasma cells, and CD3, a component of the T-cell receptor (TCR) complex, on the surface of T cells.

Mechanism of Action / Target

GPRC5D X CD3

Giredestrant (GDC-9545) is a selective estrogen receptor degrader (SERD) that is designed to bind to the estrogen receptor to limit its function. In addition, when SERDs bind to the estrogen receptor, they may be able to change the shape of the receptor in such a way that the cell eliminates it by degradation.

Mechanism of Action / Target

Selective estrogen receptor degrader

Glofitamab (Anti-CD20 x CD3 TCB, RG6026) is a 2:1 format T cell-engaging bispecific antibody, designed to engage both CD20 on B cells and CD3 on T cells. By engaging both targets simultaneously, the antibody activates the T cells to attack and eliminate the B cells, demonstrating preclinical activity in B cell malignancies.

Mechanism of Action / Target

CD20xCD3 T-cell engaging bispecific antibody with bivalent binding to CD20 and monovalent binding to CD3 (2:1 format)

IL-15/IL-15Ra-Fc (RG6323, XmAb24306) is designed to stimulate the expansion and activation of natural killer (NK) cells and cytotoxic T cells and may present a potential new way to leverage the immune system to target cancer.

Mechanism of Action / Target

IL-15 complexed with IL-15 receptor alpha (IL-15Rα)

This molecule is being developed in collaboration with Xencor.

Inavolisib (GDC-0077, RG6114) is a small molecule PI3 kinase (PI3K) inhibitor. Dysregulation of PI3K signaling is implicated in a broad range of human cancers and activating mutations in the PI3K alpha-isoform gene (PIK3CA) are common oncogenic drivers. The PI3K/Akt/mTOR pathway regulates cell growth and survival.

Mechanism of Action / Target

Receptor tyrosine kinase signaling, phosphoinositide 3-kinase (PI3K) inhibitor

Ipatasertib (GDC-0068, RG7440) is a small molecule pan-Akt inhibitor. The PI3K/Akt/mTOR pathway regulates cell growth and survival.

Mechanism of Action / Target

Receptor tyrosine kinase signaling, Akt pan-inhibitor

This molecule was discovered in collaboration with Array BioPharma Inc.

Lunsumio (mosunetuzumab, anti-CD20/CD3 TDB, RG7828) is a humanized full-length T cell-dependent bispecific antibody designed to target both CD20 on B cells and CD3 on T cells. This dual-targeting antibody is designed to redirect T cells to attack cancer cells.

Mechanism of Action / Target

CD20xCD3 T-cell engaging bispecific antibody with monovalent binding to CD20 and monovalent binding to CD3 (1:1 format)

Pertuzumab (Perjeta) is a humanized monoclonal antibody designed to prevent HER2 dimerisation, a process that is believed to play an important role in the growth and formation of several different cancer types. For Perjeta full prescribing information, including Boxed WARNINGS, Medication Guide and additional important safety information, please visit http://www.perjeta.com or call: 1-888-249-4918.

Status

This study was completed and published in Lancet Oncology Jan 2021

Forimtamig (GPRC5D x CD3, RG6324) is a novel T-cell engaging bispecific antibody, targeting both GPRC5D, on the surface of plasma cells, and CD3, a component of the T-cell receptor (TCR) complex, on the surface of T cells.

Mechanism of Action / Target

CD19 4 1BBL

CD19 x CD28 (RG6333) is a co-stimulatory bispecific antibody that simultaneously binds CD19 expressed on B cells/B lymphoma cells and CD28 expressed on the majority of T cell subsets. Strictly in the presence of a so-called signal 1 (T cell activation), as provided by a T-cell engaging antibody (e.g. glofitamab, mosunetuzumab), CD19 x CD28 provides a co-stimulatory signal (signal 2) which further enhances the effector function.

Mechanism of Action / Target

CD19xCD28

P-BCMA-ALLO1 (RG6538) is an off-the-shelf, donor derived, allogeneic anti-BCMA CAR T therapy with potent antitumor function for the treatment of multiple myeloma. P-BCMA-ALLO1 is produced using two key platform technologies: the nonviral piggyBac® DNA Modification System and the high-fidelity Cas-CLOVER™ Site-Specific Gene Editing System delivering a high percentage of TSCM cells. P-BCMA-ALLO1 is designed to be fully allogeneic, with genetic edits to eliminate or reduce both host-vs-graft and graft-vs-host alloreactivity.

Mechanism of Action / Target

P-BCMA-ALLO1

This molecule is being developed in collaboration with Poseida Therapeutics

Runimotamab (HER2xCD3, RG6194) is a T-cell engaging bispecific antibody designed to target both HER2 on cancer cells and CD3 on T-cells. This dual targeting is designed to redirect T-cells to attack HER2-expressing cancer cells.

Mechanism of Action / Target

T-cell engaging bispecific antibody, HER2 and CD3

SHP2i (RG6433, GDC-1971) is being evaluated in combination with the KRAS G12C inhibitor (RG6330, GDC-6036).

Mechanism of Action / Target

SHP2 is a non-receptor protein tyrosine phosphatase that is an important regulator of growth factor receptor signaling. SHP2 promotes cell survival and proliferation primarily through activation of RAS signaling.

This molecule is being developed in collaboration with Relay Therapeutics.

Tiragolumab (anti-TIGIT, MTIG7192A, RG6058) is a fully human monoclonal antibody designed to bind to TIGIT and prevent its interaction with poliovirus receptor (PVR).

Mechanism of Action / Target

T cell immunoglobulin and ITIM domain protein (TIGIT), a member of the immunoglobulin super family, is a novel immune inhibitory receptor

Trastuzumab emtansine (T-DM1) is a novel antibody-drug conjugate that is designed to specifically target cells over expressing HER2. It is being tested in a variety of HER2 positive cancers.

Vemurafenib (Zelboraf) is an oral, small molecule, BRAF kinase inhibitor. The BRAF protein is a key component of the RAS-RAF pathway involved in normal cell growth and survival. Mutations that keep the BRAF protein in an active state may cause excessive pathway signalling, leading to uncontrolled cell growth and survival.

Please see accompanying full Prescribing Information and Medication Guide for additional important safety information.

Venetoclax (RG7601) is a novel small molecule Bcl-2 selective inhibitor designed to restore apoptosis, also known as programmed cell death, by blocking the function of a pro-survival Bcl-2 family protein. The Bcl-2 family proteins, which are expressed at high levels in many tumors, play a central role in regulating apoptosis.

Mechanism of Action / Target

Bcl-2 selective inhibitor

This molecule is being developed in collaboration with AbbVie.

Vismodegib(Erivedge) is an oral, small molecule designed to selectively inhibit abnormal signaling in the Hedgehog pathway.  It is being tested in a variety of cancers.

For Erivedge full prescribing information, including Boxed WARNINGS, Medication Guide and additional important safety information, please visit http://www.erivedge.com or call 1-855-737-4833.