Pipeline

A powerful approach

We are leveraging the principle of synthetic lethality and the power and productivity of our discovery engine to discover and validate multiple novel targets each year. Our growing pipeline consists of programs for genetically defined subsets of multiple cancers which have limited treatment options. Our pipeline is summarized below:

Development Pipeline

Program
Patient Selection
Discovery
IND-Enabling
Clinical Trials
Anticipated Milestones
PRMT5 TNG908
MTAP-del cancers
Phase 1
Phase 2
Phase 3
IND filing 4Q 2021
IND-Enabling
Patients: MTAP-del cancers
Anticipated Milestones: IND filing 4Q 2021
Opportunity

Our lead program, TNG908, a protein arginine methyl transferase 5 (PRMT5) inhibitor that is synthetic lethal with MTAP deletion, is being developed as a treatment for cancers with MTAP deletions. Loss of MTAP is not tumor-promoting by itself, but is linked to the deletion of CDKN2A, a frequently deleted tumor suppressor gene. MTAP deletions occur in 10% to 15% of all human cancers, including many common cancers with high unmet need such as squamous cell lung, esophageal and bladder cancer, creating a significant therapeutic opportunity for patients.

Challenge

The function of PRMT5 is required for normal cell survival and therefore will result in toxicity if inhibited in normal cells (bone marrow cells in particular). Non-synthetic lethal PRMT5 inhibitors can kill normal cells as effectively as cancer cells and cause hematologic toxicity for this reason. Thus, the dose of non-synthetic lethal PRMT5 inhibitors needed to kill cancer cells often cannot be delivered.

Approach

Synthetic lethality is the selective killing of cancer cells with specific genetic alterations by identifying drug targets that selectively kill cells with that specific genetic change while sparing normal cells. We are developing TNG908, a potent, selective, synthetic lethal, small molecule inhibitor of PRMT5 that selectively kills cancer cells with MTAP-deletion, while sparing cells that have normal MTAP function.

Rationale

Treatment with a selective PRMT5 inhibitor like TNG908 is a new approach to causing cancer cell death without killing normal cells, which is an important difference from non-selective PRMT5 inhibitors. In preclinical studies, TNG908 demonstrated 15-fold greater potency in cells with MTAP deletions than those without. Further, the selectivity for MTAP-deleted cancer cells may allow for the near-complete and sustained inhibition of PRMT5 needed to induce tumor cell death while sparing normal cells. We plan to evaluate this approach in clinical studies planned for the 2022.

Development Pathway

After determining the optimal dose and schedule for TNG908, efficacy will be studied in multiple cohorts, including the rare tumor MPNST (malignant peripheral nerve sheath tumor), as well as squamous and non-squamous non-small cell lung cancer, bladder cancer, and cholangiocarcinoma. Finally, a histology-agnostic “bucket” arm will evaluate other histologies where MTAP deletions occur. All patients enrolled in both the dose-finding and efficacy phases of the study will be required to have cancers with documented MTAP deletion. We plan to file an Investigational New Drug (IND) application for TNG908 in Q4 2021 and initiate a Phase 1/2 clinical trial in the first half of 2022.

USP1
BRCA 1-mut cancers
IND filing 2022
Lead Optimization
Patients: BRCA 1-mut cancers
Anticipated Milestones: IND filing 2022
Opportunity

We leverage our discovery platform to identify novel targets and develop new drugs directed at tumor suppressor gene loss. Ubiquitin-specific protease 1 (USP1) inhibitor is a synthetic lethal target with potential applications to the treatment of cancers with BRCA1 mutations. BRCA1 mutations are present in approximately 15% of ovarian cancer, 5% of breast cancers, and 1% of prostate cancers.  We believe the market opportunity is comparable in size to approximately half of the patient population for PARP inhibitors.

Approach

Synthetic lethality is the selective killing of cancer cells with specific genetic alterations by identifying drug targets that selectively kill cells with that specific genetic change while sparing normal cells. We are developing a USP1 small molecule inhibitor that will selectively kill cancer cells with BRCA1 mutations while sparing normal cells without loss of BRCA1 function.

Rationale

Following the discovery of USP1 as a synthetic lethality target for BRCA1 loss-of-function using our target discovery platform, we began discovery efforts to identify a potent and selective USP1 inhibitor for the treatment of BRCA1-mutant breast, ovarian, and prostate cancers. In vitro and in vivo preclinical data demonstrate potent anti-tumor activity in BRCA1-mutant breast cancer as a single agent and synergy with PARP inhibitors, USP1 inhibitors have potential for single agent activity in PARPi-naïve, and PARPi-resistant BRCA1 mutant cancers and could synergize with PARP inhibitors in these cancers as well.

Development Pathway

We plan to advance a clinical candidate and file an IND for this program in 2022.

Multiple wholly owned targets in discovery phase
Discovery phase projects with Gilead options and Gilead licensed targets not listed

Partnerships

Our global strategic collaboration with Gilead Sciences is focused on the discovery, development and commercialization of a pipeline of innovative targeted immune evasion therapies for patients with cancer. We are responsible for discovering and validating targets and for advancing select programs through clinical proof-of-concept. Gilead has options to worldwide rights on up to 15 of those targets. We retain the option to co-develop and co-promote the lead products for up to five of those programs in the U.S. with Gilead.

The collaboration, which was originally signed in 2018 and expanded in 2020, does not include our three lead programs. We retain all rights to those programs, along with the right to targets we have identified outside of the immune evasion space. We are committed to advancing the programs in our wholly owned pipeline into the clinic and beyond, as part of our mission to deliver the next generation of transformational targeted therapies to patients in need.

Tango Therapeutics Gilead

The Gilead logo is a trademark of Gilead Sciences, Inc.

We aim to become a fully-integrated biotechnology company bringing transformative medicines to people with cancer. We believe strategic collaborations with pharma and other biotech companies can help us achieve this goal and deliver more novel cancer drug targets and medicines to patients. Please reach out if you are interested in exploring ways to work together: bd@tangotx.com.

Learn more about the culture of innovation at Tango.Learn more about the culture of innovation at Tango.