Press Releases

Turning Point Therapeutics Presents Preclinical Data For Novel RET Inhibitor Candidate, TPX-0046

May 29, 2020
Poster Presentation at American Society of Clinical Oncology (ASCO) Annual Meeting Highlights TPX-0046 Potent Inhibition of Wildtype RET and RET Mutations

SAN DIEGO, May 29, 2020 (GLOBE NEWSWIRE) -- Turning Point Therapeutics, Inc. (NASDAQ: TPTX), a precision oncology company developing next-generation therapies that target genetic drivers of cancer, today at the ASCO Annual Meeting presented a preclinical update for its novel, clinical-stage, selective RET-inhibitor drug candidate, TPX-0046.

In the updated preclinical studies comparing proxy molecules for approved and investigational RET inhibitors, TPX-0046 demonstrated potent in vitro and in vivo activity against a range of RET alterations, including greater potency against solvent-front mutations, G810S, G810R, G810C and G810N.

A phase 1/2 trial of TPX-0046 in RET TKI-naïve and -pretreated patients is ongoing.

“TPX-0046 was designed as a potent RET inhibitor with the potential to address TKI-naïve and RET inhibitor-resistant RET-dependent cancers,” said Alexander Drilon, M.D., medical oncologist and acting chief of the Early Drug Development Service, Memorial Sloan Kettering Cancer Center, and a principal investigator for the TPX-0046 clinical study. “Specifically, in preclinical studies, TPX-0046 inhibited RET solvent front mutations that have been observed in biopsies from patients with progression on a prior RET inhibitor. Developing a next-generation RET inhibitor is an unmet need.”

In enzymatic and cellular assays presented at ASCO, TPX-0046 was potent against wildtype RET and multiple RET mutations and fusions.TPX-0046 also demonstrated antitumor activity in RET-driven cell-derived and patient-derived xenograft tumor models, including those that harbor a RET G810R solvent-front mutation.

The ongoing Phase 1/2 open-label, single-arm, multi-center clinical study of TPX-0046 is enrolling TKI-naïve and -pretreated patients with RET-altered non-small-cell lung, thyroid, and other advanced cancers in a Phase 1 dose escalation study of approximately 50 patients, and Phase 2 expansion study of approximately 300 patients with multiple cohorts, to assess safety, tolerability, pharmacokinetics (PK) and clinical activity. The study design allows intra-patient dose escalation based on tolerability. For more information, visit and search NCT04161391.

“The preclinical studies we are presenting today support a potential role for TPX-0046 in both TKI-naïve and TKI-pretreated patients,” said Athena Countouriotis, M.D., president and chief executive officer of Turning Point Therapeutics. “With a compact design, and lower molecular weight than other investigational or approved RET inhibitors, TPX-0046 has shown encouraging preclinical activity against multiple RET G810 mutations, where there are currently no approved therapeutic options for patients.”

TPX-0046 is a multi-targeted RET and SRC kinase inhibitor with a novel three-dimensional macrocyclic structure that is smaller and structurally distinguished from other approved or investigational RET inhibitors. Activation of RET-- a receptor tyrosine kinase --through gain-of-function mutations or fusions has been found in multiple tumor types, including non-small-cell lung and thyroid cancers. In preclinical studies TPX-0046 spared vascular endothelial growth factor (VEGF) receptors 1, 2 and 3. According to research published in the European Journal of Cancer1, hypertension was the most common adverse effect (up to 46 percent) among multiple anti-cancer therapeutics that inhibit VEGF. Dual inhibition of RET and SRC represents a novel therapeutic strategy to target abnormal RET signaling in cancers. Inhibition of SRC family kinases has the potential to reduce bypass resistance from signaling through multiple receptor tyrosine kinases and therefore has the potential to increase the therapeutic effect of TPX-0046.
About Turning Point Therapeutics Inc.
Turning Point Therapeutics is a clinical-stage precision oncology company with a pipeline of internally discovered investigational drugs designed to address key limitations of existing cancer therapies. The company’s lead drug candidate, repotrectinib, is a next-generation kinase inhibitor targeting the ROS1 and TRK oncogenic drivers of non-small cell lung cancer and advanced solid tumors. Repotrectinib, which is being studied in a registrational Phase 2 study in adults and a Phase 1/2 study in pediatric patients, has shown antitumor activity and durable responses among kinase inhibitor treatment-naïve and pre-treated patients. The company’s pipeline of drug candidates also includes TPX-0022, targeting MET, CSF1R and SRC, which is being studied in a Phase 1 trial of patients with advanced or metastatic solid tumors harboring genetic alterations in MET; TPX-0046, targeting RET and SRC, which is being studied in a Phase 1/2 trial of patients with advanced or metastatic solid tumors harboring genetic alterations in RET; and TPX-0131, a next-generation ALK inhibitor in IND-enabling studies. Turning Point’s next-generation kinase inhibitors are designed to bind to their targets with greater precision and affinity than existing therapies, with a novel, compact structure that has demonstrated an ability to potentially overcome treatment resistance common with other kinase inhibitors. The company is driven to develop therapies that mark a turning point for patients in their cancer treatment. For more information, visit

1 Schmidinger, EJC 2013 Sep; 11(2): 172–191, (

Forward Looking Statements
Statements contained in this press release regarding matters that are not historical facts are “forward-looking statements” within the meaning of the Private Securities Litigation Reform Act of 1995. Such forward-looking statements include statements regarding, among other things, the efficacy, safety and therapeutic potential of Turning Point Therapeutics’ drug candidate TPX-0046, the results, conduct, progress and timing of and the Phase 1/2 clinical study of TPX-0046Because such statements are subject to risks and uncertainties, actual results may differ materially from those expressed or implied by such forward-looking statements. Words such as “plans”, “will”, “believes,” “anticipates,” “expects,” “intends,” “goal,” “potential” and similar expressions are intended to identify forward-looking statements. These forward-looking statements are based upon Turning Point Therapeutics’ current expectations and involve assumptions that may never materialize or may prove to be incorrect. Actual results could differ materially from those anticipated in such forward-looking statements as a result of various risks and uncertainties, which include, without limitation, risks and uncertainties associated with Turning Point Therapeutics’ business in general, risks and uncertainties related to the impact of the COVID-19 pandemic to Turning Point’s business and the other risks described in Turning Point Therapeutics’ filings with the SEC. All forward-looking statements contained in this press release speak only as of the date on which they were made. Turning Point Therapeutics undertakes no obligation to update such statements to reflect events that occur or circumstances that exist after the date on which they were made.

Jim Mazzola



Source: Turning Point Therapeutics, Inc.

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