Turning off cancer’s growth switches. Interview with Steven Yatomi-Clarke, CEO of Prescient Therapeutics, on targeted medicine

This interview was conducted on the 12th of December, 2019. 

Cancer has been on the public radar for many years now and, although several drugs exist to treat the disease, none of them are effective to the point of being a cure. In many cases, patients become resistant to traditional drugs and there’s a large group of patients that are virtually untreatable.

Cancer research is an area with massive potential for developing new, more effective drugs. Prescient Therapeutics (PTX) is a biotech company that may have found an approach that could become a valuable aid to modern therapies. Steven Yatomi-Clarke, CEO of Prescient Therapeutics sat down with Reach Markets to answer some questions about the business and explain what set the company’s PTX-200 and PTX-100 drugs apart and why personalised medicine might be the future of cancer treatments.

 

[Reach Markets] What is targeted medicine and why is it so groundbreaking compared to traditional therapies such as chemo or radiation therapies?

[Steven] Chemotherapy and radiation therapy are both ways of killing any type of cell, especially cells that are growing quickly. Radiation is used to disrupt, amongst other things, the replication of the cell by messing with its DNA repair. Chemotherapy uses a similar approach, but a chemical one. For want of a better term, it’s basically poison. Many people on chemotherapy will lose their hair and suffer other side effects, because the drug is indiscriminately killing any cell that happens to be growing quickly, including the hair follicle cells involved in hair replication.

Targeted therapies have a different approach entirely. It specifically addresses the tumour switches that cancer growth rely upon, instead of indiscriminately killing off cells. The cancer switches that targeted drugs can disrupt are unique to cancer cells and so doesn’t kill off healthy cells in the process in the same way you would when using indiscriminate treatments like chemo or radiation. 

One analogy that explains the difference between traditional drugs and targeted medicine is to imagine you have a lawn infested with weeds. Chemotherapy and some older types of radiation therapies can be compared to spraying weed killer over the whole lawn. You will kill the weeds but you will kill a lot of the grass as well. The aim of targeted therapies is to only spot-kill those weeds, and you do this by targeting the switches that trigger cancer cell replication – not by exterminating cells indiscriminately.

 

[Reach Markets] Some patients become resistant to current cancer treatment. How can PTX’s drugs help solve this problem?

[Steven] The more we learn about cancer, the more we learn about the things that drive it. And when we learn more about the things that drive it, we’re gaining an understanding as to the things that will have an effect or no effect. Not all cancers are the same, even within the same type of tissue. Not all breast cancers are the same, and not all lung cancers are the same. They are all driven by these particular, various mutations and they are all different

 “Not all cancers are the same, even within the same type of tissue. Not all breast cancers are the same, and not all lung cancers are the same. They are all driven by these particular, various mutations and they are all different.”

Many patients become resistant to cancer drugs, in a bit the same way they would develop antibiotic resistance. Antibiotics kill bacteria: You give a drug to kill most of those bacteria, but if just a few survive, because they have a slightly different genetic makeup, all of a sudden those bacteria will grow, and then you’ve got a new population that are resistant. 

Cancer cells operate in a similar way. You might give a therapy initially and kill many of the cancer cells but it often won’t get all of them. The cancers that are left behind have genetic abnormalities that make them resistant. They might have mutated switches or any number of mechanisms to evade what is trying to kill it. That cell will then grow and replicate and before you know it, when the tumour returns, it is comprised of cells that are now resistant to the initial therapy that you tried to give it. So it’s all about trying to find the switches that drive the cancer growth and addressing those particular switches.

 

[Reach Markets] What makes your research different to other targeted cancer therapy research?

[Steven] Targeted therapies by definition address different targets that drive cancer or other disease for that matter. We’re looking at two different targets. One of them is an important tumour survival pathway called Akt, addressed by our drug PTX-200. There are also other pathways called Ras, Ral, Rac and Rho which are addressed by our drug PTX-100.

Other people are attempting Akt inhibition although there isn’t an approved drug on the market yet. There’s also not a Ras inhibitor on the market yet – and as for Rho, we believe we’ve got the only inhibitor in development. 

All of these pathways are different targets that drive cancer and there’s lots of room for everyone to play. As they are targeted therapies, they are approved for different types of targets and cancers. Indeed the more research that is conducted, often the more new targets people discover. 

Often it is the case that some of these can be used in combination as well. If a cancer happens to have several different targets, different therapies can be used in combination to address those respective targets.

 

[Reach Markets] Can targeted medicine also be used in combination with traditional chemotherapy?

[Steven] Yes, that would be one of the first ways of utilising these therapies. There are two reasons why that makes sense. 

Firstly, a lot of diseases are still treated with run of the mill chemotherapy as they have been for a long time. That is starting to change in some diseases, but chemotherapy is going to be entrenched for some time to come.

Secondly, the pathway Akt causes cancer, but it also drives resistance to chemotherapy. So if a tumour has high Akt, it is also more likely to become resistant to the effects of chemotherapy. Where chemotherapy would normally work, with high levels of Akt, it now no longer works.

That’s why it makes sense to use our drug PTX-200 which switches off Akt. By using our drug in combination with chemotherapy, you can get the double benefit of turning off that switch and re-sensitising the tumour to the chemotherapy once again and hopefully get a synergistic benefit.

“By using our drug in combination with chemotherapy, you can get the double benefit of turning off that switch and re-sensitising the tumour to the chemotherapy once again and hopefully get a synergistic benefit.“

That’s what we see with ovarian cancer for example. These women are resistant to platinum based chemotherapies, such as a drug called carboplatin. These women are either unresponsive to carboplatin or they’ve never been responsive to it. And what we’ve been trying to demonstrate under this current study is that, by adding our drug to it, we are able to switch off Akt and re-sensitise those tumours to carbo-platin again. Indeed, this is what our earlier work has shown. So it gives clinicians another tool where all other tools had stopped working.

 

[Reach Markets] Did you anticipate PTX-200’s ability to inhibit drug resistance?

[Steven] All our trials have a good foundation in translational science so there were a lot of pre-clinical studies done in mice using various cancer cells showing that PTX-200 was able to overcome that resistance and kill those cancer tumours. And that’s what gave the investigators the encouragement to try this in the clinic.

 

[Reach Markets] What is the time and pathways for selling PTX’s therapies once they have passed the clinical research phase?

[Steven] Biotech companies like ours are in the business of research and development. If the pre-clinical research is successful, the company may go on to conduct human studies, which is where we’re at. After that, it’s a matter of providing your information to regulators who will permit you or otherwise to sell the drug. 

If we get to that stage, we’ll likely do so as a partner. In terms of being able to monetise our portfolio, we could do so sooner as a partner than if we were carrying the program ourselves. 

That said, the nature of the development path we’re taking with respect to PTX-100 especially is a truncated development path that we can do because of the innovative basket study trial design that we wish to continue with. If we’re able to do that, we might be able to carry this much further into development and perhaps towards commercialisation, where biotechs typically wouldn’t otherwise be able to. 

We hope to complete the current trial for PTX-100, and maybe get to a registration study in a basket trial of solid cancers or a basket trial of blood cancers. That would take three to four years in a single-arm study to get that recruited and registered. If we’re successful after that, we could potentially launch with a partner. This class of targeted therapies, at least in the US, typically cost many hundreds of thousands of dollars per course per year so these are high value types of drugs as opposed to the more generic type drugs.

 

[Reach Markets] What are your most recent research studies and what kind of results have you been seeing?

[Steven] We’ve announced the results of a couple of research studies in the past couple of weeks. One of them were in AML, which stands for Acute Myeloid Leukemia. We’re in the relapsed refractory setting for that disease which means that these are leukemia patients who have failed other therapies. This is a very very sick patient population. Their life expectancy is six months or less. Nothing tends to work for these sorts of patients. What we’re able to do is use our drug in combination with the standard of care for that disease, in this case cytarabine which is a type of chemotherapy. 

Of our fifteen patients we were able to get three complete responses – meaning complete eradication of the tumour – which we were very pleased to see. And that is now progressing with a protocol amendment to try to optimise the dose of the two drugs. We’re trying to capture as much of the efficacy as possible whilst minimising the side effects.

“Of our fifteen patients we were able to get three complete responses – meaning complete eradication of the tumour – which we were very pleased to see.”

We’ve also recently announced the result of ovarian cancer study. The patients in this study were relapsed refractory to platinum therapies which means that carboplatin and other similar drugs do not work for them anymore. 

The results were encouraging – it looks like that, not only is this safe and tolerable which was the aim of the study, but most patients also achieved disease control. Disease control means either partial response or stable disease. This is encouraging for a couple of reasons. One, they normally don’t normally respond to platinum therapy once they’re resistant and secondly, we don’t even believe we’ve hit the optimal dose of PTX-200 yet. We’re still looking to explore what the highest dose we can administer is. So that’s exciting too. We’ve got breast cancer results due out very soon. We’re still auditing the data from that study and that will be out very shortly.   

We’re going to report out the breast cancer study which we’re looking forward to finally getting done. And in the meantime we’ve also got our PTX-100 trial ongoing which is great, as well as our other collaborations, so we’re definitely going to have our plate full in 2020. There’s going to be a lot of evaluating events hopefully in the new year and then there will be other parts of the business that we can start to talk about too.

[Reach Markets] What are you hoping to achieve with your collaboration with Carina Biotech?

[Steven] Carina Biotech specialises in developing CAR-T therapy, which is a new type of therapy that gained a lot of attention a few years ago when it had spectacular success in a certain type of blood cancer called B-cell cancers. Carina is attempting to translate this into solid tumours. 

CAR-T therapy works by taking immune cells from the patient’s body that fight infection – called T-cells – and training them up outside of the body to recognise the cancer. They’re then grown in large numbers and reinjected into the patient whereby they can track down and kill the patient’s cancer cells. But it didn’t get the success in other types of cancers that it got in B-cell cancers.

Carina is a company that has particular expertise in CAR-T while we have expertise in targeted therapies and signalling pathways. Without giving too much away, we believe there is an enormous area of benefit by combining our respective knowledge to help overcome some of the problems that a lot of people are finding with CAR-T therapy in terms of bringing down the cost of the therapy and the speed of which it can be delivered to patients.

As mentioned before, we’re in the business of personalised medicine. Targeted medicine is a type of personalised medicine but, with Carina, we’re extending our footprint into other areas of personalised medicine. And in some ways, CAR-T is the ultimate personalised medicine because you’re using the patient’s own cells.

 “In some ways, CAR-T is the ultimate personalised medicine because you’re using the patient’s own cells.”

Our collaboration with Carina will be our first foray into a very exciting area, and we believe that is an area that is ripe for transformation and would love to be part of that. 

Reach Markets have been engaged by PTX to assist with private investor management.