Zymeworks Releases Positive Clinical Trial Data

Zymeworks (NYSE:ZYME;TSX:ZYME) announced on Wednesday (November 14) positive clinical trial data for the early stages of development for its drug candidate at a medical conference.

Presented at the 30th EORTC-NCI-AACR Symposium in Dublin, this was the first time the durability of Zymeworks’ HER2-expressing cancer treatment drug, ZW25, has been exhibited in anti-tumor activity.

The overall disease control rate, including patients which had partial response and stable disease, was 82 percent. The medical progression-free survival rate in all patients was over 6  months.

The Investing News Network (INN) spoke with Ryan Dercho, Zymeworks head of corporate development and Diana Hausman the chief medical officer, about the data presented.

This data is from the second part of Zymeworks’ Phase 1 trial and featured 24 patients with multiple cancers expressing the HER2 protein. Patients involved in this trial were heavily pretreated.

Hausman said difficulties of treating heavily pretreated patients is that they may be tolerant to different types of treatments. Patients may also have multiple diseases resistance to multiple treatments all of which can narrow down the disease response rate, she added.

“It makes it really hard to see a signal from patients and it makes it harder for patients to tolerate drugs,” Hausman said.  . On the plus side, Hausman explained when a response from treatment is seen in these patients it means it’s more significant.

This can be seen when a patients can stay on without a big dose reduction or discontinuation because of treatment side effects. Additionally, seeing activity in patients whose tumor had mutated to be resistant to standardized treatment makes both these responses “really meaningful,” Hausman said.

Hausman said each response was important and positive, regardless if it led to stable disease or partial responses. The patients have no other option, some have even gone through other clinical trials before this, she added.

Especially meaningful for this set of data was during this portion of the trial, patients were only on ZW25.

“You really need to add this with chemotherapy or cytotoxin to see activity,” Hausman said. This is also a big move for the patients involved which feel “beaten up” from extensive previous treatments to receive responses with limited side effects.

Currently there is no further approved HER2-targeted agent for these patients once their cancer has returned.

Three quarters of the patients in this trial were previously treated with another HER2-expressing treatment, Trastuzumab. The patients had disease progression even on this treatment, leading them to less options to treat their cancers.

HER2 is expressed in multiple cancers, including: gastroesophageal cancers, colorectal cancer, gall bladder, cervical and more. Patients with these cancers and others were enrolled in the trial.

Other results from the data include eight gastroesophageal cancer patients had a response rate of 50 percent, and the four colorectal and five other cancer patients had 33 percent. Hausman pointed out the statistical difference doesn’t have a big significance due to the small patient population.

For colorectal cancer patients, only one out of the four had seen a response. Later in the presentation, it was announced that one of these patients did have a response in their liver—which would have increased the original amount to two, she said.

Dercho said the company will be initiating a number of trials next year, such as chemo-combo trials which will include  some with certain lines of therapy. These Phase 2 studies will also be conducted with different indications. Part three of this Phase 1 study is ongoing and moving into the chemo-combo trials.

Zymeworks is also developing ZW49, another HER2 bispecific antibody. The company is preparing the drug’s investigational new drug application (IND) and plans to have it submitted by the end of the year.

“ZW49 is the antibody drug conjugate version of ZW25,” Hausman said. “It’s been well-tolerated in toxicology studies and we plan to start dosing patients in the very near future.”

She added it may have the potential to work as a single-agent approach even for low HER2 expressing cancers. “We’re seen really nice results in the preclinical setting in animals models,” she said.

Investor Takeaway

Zymeworks’ share price decreased by 4.30 percent on the TSX to C$16.46 as of 12 p.m. November 15. For the NYSE, the share price decreased 4.14 percent for the same time period to US$12.76.

According to TipRanks the latest analyst reports were two months ago for the company. These consisted of two “Buy” ratings with US$21 and US$27 price targets.

As mentioned, there are many milestones investors can look forward to throughout the end of the year and 2019. Dercho added investors should expect to hear data readouts from future and ongoing trials at major medical meetings. The company has previously presented at ASCO and ESMO, but future trial presentations will depend on data cut offs.

What has been confirmed is the company will present its IND-enabling data for ZW49 at the San Antonio Breast Cancer Conference in early December, Dercho said.

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

The Investing News Network does not guarantee the accuracy or thoroughness of the information reported in the interviews it conducts. The opinions expressed in these interviews do not reflect the opinions of the Investing News Network and do not constitute investment advice. All readers are encouraged to perform their own due diligence.