- Turning Point Therapeutics, a San Diego-based biotech six weeks from its public market debut, unveiled fresh clinical results Friday that keep it on track to challenge Pfizer, Roche, and Eli Lilly in the fast-moving field of targeted cancer therapies.
- Expanded data from an early Phase 1/2 trial showed treatment with repotrectinib, Turning Point's experimental tyrosine kinase inhibitor, caused tumors to shrink in nine of 11 lung cancer patients never treated with similar drugs, and seven of 22 previously treated.
- That latter group of patients is particularly important for the biotech. Drugs like Pfizer's Xalkori are commonly used as initial treatment for people diagnosed with a type of non-small lung cancer driven by a mutation known as ROS1. Treatment resistance can develop for some, however, after which options are limited.
Turning Point raised nearly $200 million from an initial public offering last month, capitalizing on widespread enthusiasm for targeted cancer therapies.
Both Loxo and Ignyta drew attention with drugs designed to home in on tumors spurred to grow by rare genetic mutations, posting encouraging data that lured their eventual pharma buyers. In the case of Loxo, positive results for patients with solid tumors harboring abnormal fusions of a gene called NTRK to other strips of DNA led to the approval of Vitrakvi (larotrectinib). Bayer acquired rights to Vitrakvi before Lilly's acquisition.
Turning Point believes it can outdo its targeted cancer peers with repotrectinib, which it's developing for NTRK positive as well as ROS1 positive cancers.
Friday's data, which will be presented at the annual meeting of the American Society of Clinical Oncology, is the first look at repotrectinib that new investors in Turning Point have had since October.
Results among patients never treated with tyrosine kinase inhibitors, or TKIs, are from just 11 patients. But the response rates to repotrectinib appear on par at this early stage with those for Xalkori (crizotinib) and entrectinib in ROS1 positive lung cancer.
Notably, repotrectinib also looks active in individuals already treated with TKIs. A 2017 study of lung cancer patients given Xalkori found more than half of tumor specimens studied had developed resistance, mutating in response to treatment.
One type of genetic alteration, known as solvent front mutations, are particularly problematic for most of the TKIs approved or in development due to the way the drugs bind to the targeted kinase. According to Turning Point, repotrectinib's design allows the drug to sidestep this type of resistance mutation, potentially making the drug a better candidate for patients who no longer respond to Xalkori or similar therapies.
The company's claim is bolstered by having J. Jean Cui as founder and chief scientific officer. Cui worked for Pfizer from 2003 to 2013 and is described in Turning Point's prospectus as an inventor for Xalkori and the pharma's more recently approved lung cancer drug Lorbrena (lorlatinib).
Results presented Friday showed 32% of TKI-pretreated patients responded to repotrectinib, a rate that rose to 55% when only counting those patients who received what Turning Point sees as its therapeutic dose. In five study participants who tested positive for one of the more common resistance mutations, two experienced confirmed partial responses.
It's worth noting, however, that none of the four patients previously treated with two or more TKIs responded.
Athena Countouriotis, Turning Point's CEO, said the data give her confidence repotrectinib can stand out from its rivals.
"Patients will get tested and if they have solvent front mutations, I don't believe physicians will give anything else other than repotrectinib," Countouriotis said in an interview with BioPharma Dive.
Investors, however, didn't appear as convinced. Shares in Turning Point fell by more than 15% Friday morning, bringing the company's market value close to dropping below $1 billion.
Turning Point plans to start the Phase 2 portion of its study later this year, with plans to enroll up to 190 patients with ROS1 positive non-small cell lung cancer. Patients will be divided into three cohorts: those TKI-naive, those pretreated with 1 prior ROS1 TKI and those with 2 previous lines of ROS1 TKI therapy.
While repotrectinib's activity in pretreated patients may give it a competitive edge, Countouriotis says the company's plan is to go after both patient populations.
"The Phase 2 design accommodates multiple paths to approval," she said.
The Food and Drug Administration has proved willing to consider accelerated approval for targeted drugs that show clear activity against genetically defined cancer types — although some are now wondering whether the bar has been set too low.
Vitrakvi, for example, was conditionally approved on strong response rate data from 55 patients. Turning Point could feasibly pursue a similar route to market.
Even if repotrectinib is approved, though, Turning Point will compete with much larger rivals. Pfizer earned more than $500 million from sales of Xalkori last year and is studying Lorbrena in ROS1 positive tumors. Roche expects a decision from the FDA on entrectinib by August and Lilly is advancing a successor to Vitrakvi in TRK positive cancer, another target of Turning Point's.
Such powerful competitors are notable given the small number of patients involved. Turning Point estimates between 2% and 3% of patients with advanced non-small cell cancer have tumors positive for ROS1. Estimates by the investment bank Leerink put the second-line population at 1,900.
Investors may see an opportunity for Turning Point to be acquired as Loxo and Ignyta were before it. For now, though, Turning Point thinks it can take on the challenge solo. "Our intention is to take repotrectinib all the way," said Countouriotis.