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December 1, 2022 On the Record | Q&A

Cancer In The Crosshairs: Cybrexa’s development drug aims to act as ‘heat-seeking missile’ against tumors

PHOTO | CONTRIBUTED Cybrexa Therapeutics’ leadership team includes (from left) Chief Scientific Officer Vishwas Paralkar, CEO Per Hellsund, and Chief Financial Officer Stephen Basso.
By Michelle Tuccitto Sullo

New Haven-based biotech company Cybrexa Therapeutics has had a spate of good news in recent months — from positive anti-tumor results in a drug trial to reaching a $702-million deal to help bring its cancer treatments to market.

In 2022, roughly 1.9 million Americans were expected to be diagnosed with cancer, with 609,360 cancer-related deaths in the country, according to American Cancer Society projections.

In late October, Cybrexa announced that the first in-human study of its oncology drug candidate, CBX-12, showed evidence of effectiveness against tumors in patients with advanced or metastatic solid tumors.

One patient with ovarian cancer achieved complete response, a breast cancer patient achieved partial response, and 13 patients maintained stable disease, according to Cybrexa.

The phase one data also showed the drug was safe and well tolerated, according to the five-year-old, clinical-stage oncology company. The ongoing study continues to evaluate safety and tolerability, and the data will be used to determine dosage in a phase two study.

Cybrexa’s pipeline aims to combat breast, ovarian and non-small cell lung cancers and a range of other tumors. The company is developing novel tumor-targeting peptide drug conjugate (PDC) therapeutics.

Shortly after its encouraging phase one trial results, Cybrexa announced in November it had reached a $702-million deal for an exclusive collaboration agreement with California company Exelixis Inc., which grants the latter the right to acquire CBX-12.

Exelixis Inc., founded in 1994, already has anti-cancer medications on the market, such as Cabometyx.

Exelixis will pay an upfront fee of $60 million for the right to acquire CBX-12. Cybrexa may also be eligible to receive up to an additional $642.5 million, such as for development, regulatory and commercial milestones, and CBX-12 acquisition.

As part of the recent investment and in preparation for phase two clinical trials, the 24-employee company has plans to hire 10 more people in clinical development and other roles.

New Haven Biz recently chatted with Per Hellsund, president and CEO of Cybrexa, about what the study results mean, and what his hopes are for the new collaboration with Exelixis.

How does Cybrexa’s drug candidate, CBX-12, work?

It is based on a peptide technology that was originally discovered at Yale, and further developed at the University of Rhode Island. This particular peptide reacts to a low pH or highly acidic environment.

Cancer cells are very acidic. This peptide forms an alpha helix, or you can think of it as a corkscrew that translocates or crosses the cell membrane of cancer cells when it comes in contact with this acidic environment.

What we are doing is utilizing this peptide to deliver highly potent cytotoxics, or chemotherapeutics, directly to the cancer cells. The objective is to target the cancer cells and spare normal tissue. We can take very potent cytotoxics that are very effective at killing cancer cells. You can look at it as a heat-seeking missile. Folks have referred to it as a ‘smart bomb.’

How is it delivered to patients?

It is an IV infusion.

What is the significance of the results of the phase one study in humans?

With the phase one study there were two primary objectives. One was to establish safety and tolerability of the drug to make sure that it is safe. The other is to establish the recommended phase two dose.

You go through a dose escalation process, where you increase the dose until you hit a level that is not tolerable, that is too toxic, and then you back off. That is the dose you want to use as you go into your phase two trial.

You are always hoping to see some amount of efficacy, or responses in patients. We did see a number of responses, and we have had a number of patients who have stable disease, so we are pretty excited about the early response data that we have seen in the phase one trial.

I think our enthusiasm has been validated or echoed by Exelixis in their willingness to move forward with this collaboration.

When you say one of the patients in the study, an individual with ovarian cancer, “achieved complete response,” what does that mean exactly? Is the person now in remission?

Thankfully, yes. This particular patient had a lesion in the lymph node. After treatment, the lymph node returned to normal size. A lymph node is a normally occurring organ so it doesn’t disappear completely, but if it gets reduced to 10 millimeters, then it is considered to be free from cancer.

This patient had a complete response, has stayed on treatment, and is on her 19th cycle, so she has been on treatment without recurrence for greater than a year at this point.

We also had a significant reduction in CA-125 (cancer antigen 125), which is a marker that is indicative of ovarian cancer activity, and that CA-125 as of the last measurement was still in the normal range.

What is the anticipated timeline for the phase two study?

Right now we are still working out the details, and we are not providing any guidance on timing. Part of that is at the request of Exelixis. We are collaborating and coordinating with them in terms of what type of information we are going to reveal about the timing of the trials.

What are the expectations in terms of going to the Food and Drug Administration for approval? Is that still years away?

Yeah, it is. In terms of the sequence of events, we need to finish out the phase one trial. We will then in collaboration with Exelixis do a number of phase two trials.

Based on those results, those could potentially go directly into a registration trial. Exelixis would be the one that would take the product forward in those later-stage trials, through registration and on to commercialization.

What do you hope this will mean for patients who have cancer?

Our hope is that it will prove to be a viable therapeutic for one of the cancer types we are looking at. We are looking at ovarian, colorectal and a number of others. The objective is to provide these patients with a viable treatment that has a better safety profile, or less side effects. We are looking for a combination of efficacy and patient quality of life.

How will the recently announced collaboration agreement with Exelixis Inc. work?

Initially, they will provide both funding as well as support, not necessarily in terms of resources, but in terms of collaboration, advice and oversight.

They will help provide expertise in terms of running these trials. At some point, when we have generated more data, if they like the data, they have the right to acquire CBX-12, and at that point they would do the later-stage trial as well as commercialization.

We are really excited about this collaboration with Exelixis. It definitely is going to be very helpful and even transformational for the company. Having a great partner like Exelixis will help both with financial resources as well as the ability to move these drugs into later-stage trials, successfully commercialize them and get them to patients.

What are the company’s plans for its future in New Haven?

We plan to stay in New Haven. We like New Haven. We like what is happening relative to the biotech sector and the ecosystem. We are hoping that it is going to continue to grow and become a significant biotech hub.

We also are happy with the space we have at 5 Science Park. We have additional space that we have essentially reserved (also at 5 Science Park) just anticipating the need for it in the future.

Have you had any trouble finding talent in the Greater New Haven region?

The labor market is tight, particularly in the biotech sector. To date, we haven’t had any real trouble recruiting and hiring folks. We don’t have a huge number of employees.

As we go forward with the lab and clinical team, we are anticipating it is going to be somewhat challenging, but hopefully the collaboration and the announcement helps.

Certainly, (the Exelixis collaboration) validates the technology, it validates the company, and it provides a significant amount of financial stability.

Where would you like the company to be in five years and in 10 years?

In five years, we would hope we have at least one drug on the market helping patients. Our objective is to continue to build out our pipeline with follow-on drugs.

I would think 10 years from now we would probably be working with different classes of drugs.

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