Syros Releases Early Clinical Trial Data

Syros (NASDAQ:SYRS) presented data from a portion of its Phase 1 trial of SY-1365 for solid tumors at the 30th EORTC-NCI-AACR Symposium on Thursday (November 15).

This part of the trial was for dose escalation and demonstrated proof-of-mechanism at tolerable doses of the drug. This is also the first clinical data set reported on a selective CDK7 inhibitor for Syros.

This data was just from SY-1365 as a stand-alone agent. In preclinical cancer models, the drug showed activity in relapsed and treatment-refractory tumors.

“Now that we have demonstrated proof-of-mechanism at tolerable doses, we are committed to thoroughly exploring the potential of CDK7 inhibition for currently underserved patients,” David Roth, Syros’ chief medical officer, said in the press release. “We are working to rapidly enroll the expansion cohorts in our ongoing Phase 1 study”

The portion of the trial also demonstrated the safety, pharmacokinetics (PK) and pharmacodynamics (PD) of the drug for patients. The proof-of-mechanism was established using a range of assays, including PD and CDK7 occupancy.

Dose-dependent effects on CDK7 occupancy and downstream gene expression changes in blood cells, also validating the proof-of-mechanism. The gene occupancy was more than 50 percent when measured three days after the dose administration. This exceeded the target for occupancy based on preclinical model activity that matches with anti-tumor activity.

Seven out of the 19 patients that were evaluable for clinical responses had partial and stable disease from the treatment. For most, this lasted between 50 and 127 days, with these patients receiving 32 mg/m2, or higher doses.

The press release said a total of 32 patients were treated with the drug while enrollment finished in September. The dose ranged from 2 mg/m2 to 112 mg/m2 using either a weekly or twice weekly dosing regimen. The patients were treated on their respective doses for three weeks out of a four-week cycle.

Based on the presented data, Syros has chosen a twice-weekly dose of 80 mg/m2 of SY-1365 when administered as a single agent. When used in combination with other agents, a once-weekly target dose of 80 mg/m2 of SY-1365 will be given.

Ovarian, breast and endometrial cancers represented the highest enrollment for this trial. Patients’ age ranged from 25-78, all of which had undergone one to 13 other treatments before this trial.

From the data cutoff on October 15, the median treatment duration was just over 45 days while the longest was 147 days. Four patients are still on the treatment.

For safety, side effects were low-grade and generally manageable and ranged from nausea, headache to fatigue. Dose-limiting toxicities were in line with the common side effects. A maximum dose wasn’t chosen from these side effects.

No drug accumulation in patients was noticed with repeat dosing, and plasma PK exposure was linear between doses.

As Roth mentioned, expanding cohorts for further assessment is already underway. This will assess the safety and anti-tumor activity of SY-1365, focusing on ovarian and breast cancer patients.

These cohorts are testing SY-1365 as a single-agent for ovarian patients which have undergone previous treatment regimens. Other cohorts will test the drug in combination with chemotherapies, and the final cohort will open the trial to any patients with any solid tumor accessible for biopsy.

Syros is pioneering the understanding of the non-coding regulatory region of the genome which controls gene expression. The company’s pipeline represents and range of gene controlling candidates to analyze this unexploited region of DNA. This method is linked with genomically defined patients, such as the CDK7.

Investor Takeaway

Syros’ share price increased over five percent to US$7.90 during the trading period on Thursday.

According to TipRanks two analysts have issued “Buy” positions for the company the same day with price targets ranging from US$12 to US$26. The first price target was from Roth Capital analyst Jotin Marango, who said his report his firm views Syros’ data favorably, representing a “good and clean oncology drug.”

Roth added the company is also working on building the company’s leadership to advance its highly selective and potent oral CDK7 inhibitor SY-5609. This is the company’s next development candidate currently in preclinical development.

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Securities Disclosure: I, Gabrielle Lakusta, hold no direct investment interest in any company mentioned in this article.