Talking Biotech Podcast 375
New Cancer Drugs: Breaking the Cell Cycle -- Spiro Rombotis, Cyclacel Pharmaceuticals

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Kevin Folta: [00:00:00] Hi everybody, and welcome to this week's Talking Biotech podcast by Colabra. Now, one cell divides into two, two into four, four, and eight. You get the picture. The process of cell division is very carefully coordinated, and if you think about it, you need to double the amount of genetic material in that first cell dna, right?

You gotta make more. You need to make two copies, and they have to be perfect or almost identical. So in order to make new DNA N to split into two cells, you need to make the hardware to copy that DNA N and to double check it and make sure it's good and confirm its integrity. But to make that hardware, you need to have all of the other stuff in place to synthesize those enzymes, the ribosomes you need to make all of the other elements of the cell in order to double yourself.

and since this SE assembly line is so important and you have to have so much careful coordination [00:01:00] that there is a very orderly way in which this is done. And we call this the cell cycle. Each step in the cell cycle. Think of it, you know, as a, as a clock, each step has defined processes that occur. So before you can go from three to four o'clock on that cell cycle model, you need to have fulfilled.

Steps that allow the cell to progress forward. But some cells don't play by those rules. Cancer cells, for instance, ignore the internal stop signs that check and double check. D n A division flies through those stop signs and division is unbridled. It leads to more mutations, massive proliferation and creation of cells we recognize as cancer.

So what if drugs can be developed to target cancer? By breaking the cell cycle, by inhibiting the signals that tele [00:02:00] cells divide, divide, divide. Could this lead to the next generation of cancer drugs, or at least drugs that could work against certain subtypes of cancers? Scientists at Cyclo Cell pharmaceuticals say it looks very promis.

And today we're speaking with Spiro Rambo. He's the president and c e O of Cyclo Cell Pharmaceuticals. Welcome to the podcast s. , thank you. Yeah. This is a really good place to start because we haven't talked about cell cycle much in the podcast series. And so let's start at the beginning. What is the cell cycle and, and why is it important?

Spiro Rombotis: Well, this is the body's own clock. The body has its own defense mechanisms, and of course, it targets cells that are no longer useful or are dangerous, like cancer cells for des. The way he does that is through a process called apoptosis, which is a short, fancy word for programed suicide, where cells have no longer functioned to [00:03:00] fulfill, they're instructed to commit suicide.

So the cell cycle is fundamental to how the body destroys cells and well controls the function. And there is a Nobel Prize behind this field in 2001 for medicine describing cell cycle mechanics. 

Kevin Folta: Yeah, so there's a progression with cell cycle, like different phases of cell cycle that we usually think about with respect to division, which are so critical when we talk about cell cycle and cancer.

So what are those steps in cell cycle and how are they normally regulated? , 

Spiro Rombotis: that's an excellent question. The steps of cell cycle progression are denoted by a single letter, sometimes with a number G one or gat one where the cells are preparing to synthesize dna, which happens in the next stage, which is called SPH phase or synthesis.

Then we'll go to another gap stage, gap two g2, where cells prepare to divide, as you pointed out. And then the final stage of cell cycle called mitosis or MPH phase where the cell actually separates into [00:04:00] two daughter cells. And we have the cell division phenomenon, which every normal and sometimes cancer or cells undergoes before they are checked for.

So these four cycle stages, we can think of them as hours and a clock, is how the body actually control cells and they'll provide also convenient avenues for therapeutic intervention for pharmaceuticals. 

Kevin Folta: Very good. And are all cells going through this cycle all the time, or do they stop at certain points and sometimes are they even moving into quiescent?

Spiro Rombotis: Yes, the majority of cells at certain points in the life cycle will go through this check stages. The early stage, or we'll call this a cell cycle checkpoint control is G one slash s and the late stage, which is D two slash m, what these two cell cycle checkpoint control gates are, are points as you point out, where we check cells for damage.

If DNA is found to be. Then the cells stop progressing. DNA [00:05:00] repairs, circuits are activated by the body. If the DNA damage cannot be repaired, then the cell is instructed to commit suicide. So it's very important to understand how the body controls this process by accelerating and decelerating in accordance to its instructions, which are essential to the genetic code.

There is indeed a phase called G zero, as you pointed out, which is a stage that precedes entry into the cell cycle where cells are sitting in a state of dormancy, sometimes called scientifically senescence. Yeah, so this, 

Kevin Folta: this is a really important part of where we're going with respect to the pharmaceutical interventions, that there are these specific checkpoints where the cells kind of do an inventory and make sure that they have everything in place and that everything is correct before they move to the next phase of the cell cycle.

So what is unique about cancer cells that gives them a breakdown in cell cycle? 

Spiro Rombotis: Fabulous. I mean, essentially what [00:06:00] cancer cells do, there are normal cells that have become degenerative that they hijack the cell cycle control process. The way they hijack it is by fooling the immune system to think they're normal, so they can be allowed to progress despite having mistakes, errors in their DNA n a code.

And the way they do that is by increasing the levels of certain proteins that tell the body Do not. Do not send me to apoptosis. These proteins are therefore called anti-apoptotic proteins. They block death of cancer cells, which would happen in a healthy human being because the body is organized in a very systematic way, as you pointed out, to kill D cells via this program, suicide approach.

Unfortunately, in cancer patients, these mechanisms don't work. These molecular breaks are malfunctioning or are mu. And that is the opportunity, the advantage that cancer cells hijack to allow them to start to expand by proliferating out of control, eventually overwhelming immune system cells that are sent to kill them, and [00:07:00] finally taking over the immune system or the entire circulatory tree and ultimately succumbing the patient's succumbs to this disease because no more immune cells are there to fight.

Kevin Folta: So it really is this kind of hijacking of the cell cycle and a kind of evasion of immune detection. And so there's an arms erase here though because we've fought back with chemotherapy, and this goes back decades now where cell cycle inhibitors have been used to arrest the cancer cells that are dividing.

Apparently they have the sub baron proliferation. And so how, how, well, how long have those been used and maybe are there any good examples you can think of, of different ways in which cell cycle inhibitors have been used to slow that 

Spiro Rombotis: progression? Certainly, as you correctly point out, for the last half century or so, scientists have used chemotherapies in ways that are critical.

They're central to the cell cycle biology that we described a minute. [00:08:00] For example, cells can undergo S-phase, whether they synthesized dna, whether they're vulnerable to a drug called gem. Which is now generic, very widely used in pancreatic cancer, in lung cancer, and certain women's cancers. When cells transit through the S phase of the cell cycle, they're vulnerable to gemcitabine.

And if we combine this drug in a cocktail with another chemotherapy, which is platinum based, the combination of gemcitabine and platinum sometimes called GemCis is even more lethal. In other words, gemcitabine slows them through transit in SPH phase and platinum kill. Taxane drugs oftentimes known by their brand names Taxol and, and similar are also cell cycle inhibitors.

They work in MPH phase in the last stage of the cell cycle. Where they slow transit of cells through M phase and kill them. The problem with this chemotherapeutic approach is that they also destroy abundant numbers of normal cells. The more we give the drugs, the more damage we cause. [00:09:00] We hope and have been successful over the decades in doing less damage than we are causing benefit.

At the same time though, patients start to push. And of course these drugs are certainly crude sledgehammers. They're not chisels that allow us to take advantage of this beautiful selectivity that biology has given us as a present to use cell cycle checkpoint control to very selectively. Take cancer cells down the suicide path and spare largely a lot of the normal cells.

So this quest has given rise to a whole new field in cancer from oncology, which is how to harness cell psychobiology without destroying normal cells, as is the case with chemotherapy. . 

Kevin Folta: Yeah, that's what we'll talk about in just a few minutes. I think one of the things that people think about when they think about chemotherapy is the side effects that do happen.

So things like hair loss, digestive sys symptoms, other types of symptomology that have to do with breaking down rapidly dividing cells [00:10:00] that are not cancer cells. So normal cells of the body and. Are some of the new therapeutics potentially targeting, I think you even answered the question previously.

Are they really targeting selectively cancer cells and leaving the normal body 

Spiro Rombotis: cells intact? . That's right. Although we don't do this in the magic bullet context that some other earlier generation cancer drugs have been doing. In other words, instead of trying to find a mechanism that only addresses cancer cells, it's better to give a drug that applies to all cells, but takes advantage of the fact that cancer cells are more.

In other words, if we stop a cell that is cancerous at the checkpoint, tollgate are the G one s or G two M. By using a novel pharmaceutical, if the duration of the stopper is sufficiently long, that cell will be targeted with immune system and instructed to commit suicide. It will turn over and die.

Normal cells like our hair or our nails stop growing. But [00:11:00] when the drug effect wears out, they go on and happily divide and therefore restore their function, which temporarily stopped. In other words, cancer cells are much more vulnerable to this approach than normal cells. So when we talk about selectivity, we need to think about not so much a magic bullet that targets only cancer cells, rather the easier task of giving a drug that affects all cells, but works particularly well for cancer cells who are not.

To defend themselves against this type of. 

Kevin Folta: Very good. So we'll talk about that on the other side of the break. We're speaking with Spiro Rambos, he's the president and c e O of Cyclo Cell Pharmaceuticals. This is the Talking Biotech podcast by Col Collabora, and we'll be back in just a moment. And now we're back on collabs talking biotech podcast.

We're speaking with Spiro Rambos, he's the president and c e o of Cyclo Cell Pharmaceuticals. And we're talking about cancer therapies that target the cell cycle. So when you're discovering these specific cell [00:12:00] cycle inhibitors, is it possible to target certain cancers because they maybe exhibit defects in a specific aspect of cell cycle regulation?

And maybe what's a good example? 

Spiro Rombotis: Well, that's an excellent question because perhaps the best analogy is, can we write poetry? Poetry is necessary when you understand how to stitch words together in elegant ways. Targeting cancer indications by using these approaches is very difficult. So instead of writing poetry, going through the process of learning how to put words together and hope that they make elegant sentences, what this means is that there is an empirical element we test in the.

Our novel drugs in patients with different types of cancer histologies, which. Anatomical areas of origin, breast, liver gut and so forth, and hope to find subtypes of cancer that are more sensitive to this approach than others. And there are specific biomarkers biological parameters we can use to target these patients.

When we see, for example, a patient with colon [00:13:00] cancer that has elevated parameters. Mc one or K R A S, which denote other anti apoptosis proteins or cancer genes, and we find that patients with these parameters respond better and faster than the population at large. That is a very good example of how we might find specific cancer types that are sensitive to our approach.

Of course, we're supported in this. Quest is not totally empirical by extensive preclinical studies in animal. As well as the fact that we can do experiments in both Petri dishes and simulate systems, which are usually using modern approaches like artificial intelligence to simulate what we might see in humans.

We can also model using sophisticated modeling techniques, how long to dose these drugs. This is important just to know which tissue, which type of cancer to target, but also of how long we need to expose these cells to our novel pharmaceutical in the hope of restoring the body's own defense mechanism, which is apoptosis.[00:14:00] 

So all of this information is multifactorial, converge, and give us evidence of where the drug works. For instance, in the case of cyclo cells drugs, this appears to be particularly true for women's cancers as well as certain types of liquid blood cancers like lymph. . 

Kevin Folta: And what are some of the cancers that are specifically targeted by cyclo cells products are and are there some, what are the recent candidates?

Spiro Rombotis: Right. So for example, our most advanced drug, which is a CDK two and nine inhibitor CDKs, are enzymes that have been found to control the cell cycle. In fact, they were part of the 2001 Nobel Prize in medicine citation. So CDK 2 0 9 are particularly important as it appears from our own clinical results in endometrial ovarian.

Uterine and cervical cancers. There are specific biologic parameters that are overexpressed or have elevated levels in these types of cancers, [00:15:00] which may explain if sufficient data is collected in due course. Why these tumors are so sensitive for regions that are less well understood. It appears that certain types of lymphoma.

In particular, the so-called T-cell lymphoma subtype, which is much more difficult to treat than the more common B-cell type, are also very sensitive. And we think that, for example, loss of some of the anti apoptosis proteins by using a pharmaceutical can result in death of cancer cells selectively. So these are all working hypotheses that have been generated by phase one.

We recently completed enrollment in our Phase one trial, and we're very pleased to see in the population of all camera patients without selection that some of these patients achieved responses that were confirmed by subsequent estimation by the physicians. To a single drug used by cyclo cell to test this hypothesis.

This type of monotherapy benefit is extremely unusual in early studies [00:16:00] and portends very promising results in phase two trials, which are about to get under the way, but will test multiple tumor types. To answer the question you put to me in a more sophisticated way. Well, you 

Kevin Folta: mentioned that this is c, d, K, maybe 2 0 9 or one of the Cyclin-dependent kinases.

When we say Cyclin-dependent kinase, what is this kind of enzyme doing to regulate the cell cycle? 

Spiro Rombotis: So CDKs are found to be active in a critical component of the cell cycle checkpoint control process. What we mean by that is that we are in a situation where the cell is checked at the cell cycle control checkpoint.

If it's found to have, if you recall, damage in its dna, it's instructed to commit suicide. The way this is done at the molecular level is that the CTIC enzyme actually interacts with the protein. It's cyst aprotinin called a cycline. So CDKs phosphorate, e cycline, they interact [00:17:00] molecularly with the cycline.

And this phenomenon is what actually causes this cellpoint control process to occur. But we, I do with the pharmaceutical is restore. What happens in the healthy human being will like to block the CDK enzymes by denying the cycling. Its a chaperone. Its molecular partner who can then disrupt this phenomenon and stop the cancer cell from hijacking this whole me.

Yeah. 

Kevin Folta: You mentioned cyclins there. I don't know that we've mentioned them yet today, but Cyclin and C D K together work as a pair to regulate these processes. Right? So these are like a molecules that may be on their own, don't have much function, but when they come together, together can help to regulate these different spots that allow progression through cell cycle.

So these are really, really important targets. And you mentioned before that there was a. The, the compound was really targeting, T-cell lymphomas was a specific one there versus B-cell. Is there a lot of specificity in the way in which these different inhibitors [00:18:00] work? 

Spiro Rombotis: No, I don't think we can say that the finding about T-cell lymphoma was empirical.

Although there was evidence that both B-cell lymphomas and T-cell lymphomas are sensitive pre clinically up to now the only clinical evidence was in B-cell lymphoma or the effect was typically short-lived. So it was kind of surprising that we're So activity also in T-cell and a plausible explanation for that is the per different number of blood cells called lymphocytes from which the term lymphocytic leukemia comes from, which are prominent in the progression of lymphoma.

It is therefore reasonable to hypothesize that our drug, our CDK two nine inhibitor fib or fadra for short, is particularly active against lymphocytes. And this could explain the phenomenon where we see activity in a lymphoma type that was not previously seen with earlier drugs in the same family. 

Kevin Folta: and what are your leading candidates these days?

You mentioned a couple of names there. What are [00:19:00] the leading drug candidates and, and you mentioned one in clinical trials, but what are the others in the pipeline? 

Spiro Rombotis: Well, we have two drugs in clinical trials at the moment. One is the one I mentioned, the CDK inhibitor, which is called Fadra cib, but we usually talk about it in the first half of the word fadra makes it easier on the.

The second one still has a number code, but is about to get an international name by the World Health Organization and is noted as CYC one 40. Unlike Fadra, that works on early stages of the cell cycle, C YC one 40 works on the last stage in mitosis. It's a mitotic inhibitor. It works by a novel mechanism, which is still being discovered as we speak in the clinic together with the clinical observations, and it's in about six months to a year behind our similar program with.

So both of these drugs are entering mid-stage development. We've seen activity for both drugs on their own as monotherapies, and they both look exceedingly well tolerated so far. 

Kevin Folta: And one, [00:20:00] the c YC one 40. Is that targeted to a specific type of cancer? 

Spiro Rombotis: Yes. The molecular target, unlike the federal compound, is not cdk.

It's a new target called p l k Polo like kinase. P L K is a group of enzymes that were discovered by cyclists chief scientist for a decade. Professor David. Was a world famous geneticist who used to be the chairman of genetics department in the University of Cambridge in England, and now is a professor emeritus at Caltech in California.

So during the decade, he was sickle cell chief scientist who set out the business of improving on an earlier stage, PK one inhibitor, but had very promising earlier results. , but then had the unsuccessful phase three program because of excessive toxicity. We found that the main reasons for that is that this drug had a very long circulation time in the blood several days, and actually developed not only a short half-life drug, which actually lasts for a few hours in the body about 11 hours, but also made it oral, [00:21:00] which means that we can take it by mouth as opposed to the alt drug that was given by I.

So this is a very exciting program for us. We are just in the early innings of escalating through phase one dose levels, but it looks very promising even though we are at a lower dose level. But 

Kevin Folta: when you talk about disrupting cell cycle at mitosis, you know, you think about that going back, even old drugs that were used for chemotherapy, like colchicine was used for a while, maybe still is in some applications.

But does this have a, an effect on all cells, like those rapidly dividing ones? That are in skin and nails. Well, as you mentioned before, where does this just kind of put them on hold or does it really stop them and cause more symptoms for the people who are taking them? So 

Spiro Rombotis: it's more what you pointed out about them stopping the cells from progressing cells momentarily stop.

If they're normal, they're allowed to continue. If they're degenerate or cancer cells that are instructed to commit suicide, the specific mechanics of that are still being worked out, but it appears that PL K one. Is lethal for [00:22:00] cancer cells, they cannot sustain the insult, whereas normal cells that loose LK one do not die.

They stop progressing and they eventually, when the drug effect wears out, go back into dividing and perform their function. That's why the time the drug lasts in the bloodstream is so critical. A drug that will stick around for five days is gonna cause a lot of damage after it stops being. Was a drug that only works for half a day and we can give once or twice a day or for the whole week or continuously, which is the ideal is going to be be putting more pressure on the target without necessarily excessive toxicity.

And that's part of the secret that C C one 40 addresses in a very promising class that went ORI in the early stages of discovery in this field. . No. Very 

Kevin Folta: cool. So this, the lk target is an interesting one to me because I, I didn't know about this before. Is, is this a hallmark of many different kinds of cancers or really specific ones?

Spiro Rombotis: Early clinical evidence suggests that there is a particular kind of cancer which is [00:23:00] very sensitive to loss of LK one, and that is colon cancer in particular. This is true not only for what we call wild type colon cancer, meaning colon cancer without a specific mutation, but also colon cancers that have a very dangerous look mutation called K R A S K R A S.

there is one F D A approved drug for K R A S and the second one was approved this week, in fact, but they only address a specific sub mutation called G 12 C. That only accounts for about 10% of all K R A S mutated colon cancer. So imagine if the pl K family of compounds can address the remaining 50 or 60% of these TAL cancers that are not addressed by the FDA approved drugs.

It could address fabulously unmet medical. That's why there's a lot of excitement in the cancer pharmacology community about PL K one drugs and what they might do. But we're still in the early innings of this class and learn more about theologies. We go through more patient clinical data. 

Kevin Folta: Oh, very good.

P LK class [00:24:00] and, and the other types of inhibitors that you, that you have at cyclo cell have these shown promise against solid tumors. I know that colon cancer certainly, you know, is neoplasia that it, you have the K R A S and P C are early mutations, but are they, are these useful maybe in more advanced tumors as.

Yes, 

Spiro Rombotis: we actually have a very ambitious program in pH two in mid-stage development that should start in 2023 with our PK drug C one 40. To answer exactly the question you put to me. For example, there are specific tumor types that preclinical data suggest might be very sensitive to PK one loss with c C one 40.

Examples are bladder cancer, not very well served by current therapies. A subtype of breast cancer, which is called triple. pancreatic cancer, which is oftentimes overexpressing, k r a s, very frequently, most types of lung cancer, both non-small cell and small cell subtypes of lung cancer, as well as [00:25:00] lymphomas.

So this ambitious program looks at seven different tumor types. Trying to identify in mid-stage trials, which tumor types are most sensitive to our approach. And then if we see that there is sufficient evidence of single agent activity that could potentially open the avenue for early approval by the fda.

Yeah, that's a 

Kevin Folta: really impressive set that are there. Like, those are seven subtypes that are really aggressive and, and lack good current therapeutics. Is this something that could potentially. Knock out a large set of very lethal cancers if it was successful. 

Spiro Rombotis: I think it's the second point that you raised that we will want to have new medicines that address a large swath of cancer, different tumor types.

The problem here is that the historical classification doesn't help us. You know, Hippocrates discovered a tumor in the stomach. They have the shape of a crab, and that's why we have the word cancer, which means crab in Greek. However, this is. Anatomical definition of cancer, which is completely [00:26:00] obsolete today.

We talk about genetic subtypes. For example, we're gonna have a drug approved for k s mutant colon cancer that can help a patient with lung cancer, that has the k s mutation, even though it's not approved for that type of lung cancer. And it's amazing that reimbursement authorities and payers will reimburse for that cause they understand there's clinical benefits.

So we're moving rapidly to a world. Genetically defined cancer types will, the anatomy is an important feature of the disease, but not the sole determinant. And then we'll have drugs that will be multi targeted. They will provide relief for patients with multiple tumor types, so long as they have the mechanism that drug addresses.

Finally, on the longer term horizon, I would say between 15 years or so from now, and maybe a little bit more of a certain tumor test, but the vast majority of cancers, the goal is not cure. The goal is, We want patients to live like they live with diabetes. They can pinch their skin, administer insulin, and they can live a normal lifespan.

We think that cancer can be [00:27:00] converted to a chronic disease, which requires usually durable treatment benefit, and drugs given by a mouth of patients can take at home with convenience without having to suffer side effects. 

Kevin Folta: These seem to be very promising targets for drug development. So are there other companies that are working on drugs that target different CDKs or P L K?

Spiro Rombotis: Yes, there are. As a matter of fact, we're in a busy area and because we were one of the pioneering companies, we in a way have created a busy area of activity. In some ways perhaps a bit too much as we all competing for the same patients. For example, we have competitors who are. Multinational pharmaceutical companies with a lot more resources than we have in a small company, as well as some smaller companies.

In the CDK area, though there is one particular aspect of competition, which is peculiar to me. Although we have a drug that for very specific reasons, targets both CDK two and CDK nine, none of the competitors have decided to go after both of these enzymes. They either chose to go after [00:28:00] cd, K two, or cd.

And we think that's important because we found in early clinical trials that patients overexpressed proteins that can be addressed by having both enzymes in the target profile of the drug. A similar situation occurs in the PL K family, although they will only have one competitor. It's another small company and they have produced excellent early data, but the drug appears to work by somewhat different mechanism.

They both hit the same enzyme, LK one, but the secondary and tertiary targets tend to be differentiated, so lots of competition. , we're all learning together. We fighting the same war, but at least in the case of the CDK drugs, we have a highly differentiated agent, and we're the only ones so far to have shown partial responses and complete response in patients that have been given just our drug without any combinations.

We think that certainly distinguishes Fadra also because it's available by mouth and because it's very well tolerat. 

Kevin Folta: A lot of listeners to the podcast, when we talk [00:29:00] about cancers, we talk about what's happening right now in terms of the next wave of therapeutics. In a lot of people know somebody who is suffering or who is getting through who these kinds of discussions are extremely hopeful.

What, what kind of timeline are we looking for for some of the new developments from your company? 

Spiro Rombotis: Well, certainly if you look at the broad picture, the, from the 65,000 foot level, we've made incredible progress in certain tumor types. When I started my career after graduate training in Chicago in the eighties, lung cancer was death sentence.

Then if there are people going over a couple of years of survival, there was a notable event. In any hospital nowadays, we routinely have patients who survive five to 10 years With the lung cancer, we are already there and maybe 20 to 30 years of survival with breast. However, some tumor taps remain essentially intractable pancreatic cancer.

Acute myeloid leukemia have survival in months, and the goal is to find the more difficult tumor types understand by subdividing them into smaller [00:30:00] groups, sensitivities of cancer cells to new therapeutic approaches, and then sizzling away. It's a big white space, of course, for many, two more times, but we're becoming smarter every day as biochemists are relentlessly discovering new targets for pharmaceutical approaches.

So we're in a golden age. Of drug discovery and I remain very optimistic that this chi in away by thousands of scientists and thousands of companies, as well as academic laboratories is going to produce results that will be meaningful for the average person that is watching this tremendous battle to control cancer as a disease that can be dealt chronically as opposed to a curable disease, which I think is not very realistic for most tumor.

Kevin Folta: I know that anecdotes usually are not terribly exciting evidence, but in your clinical trials or in different trials of these drugs, it would seem that you would see some evidence that they may be working to help people. So have you actually seen any evidence that these are working positively to at least appear to reverse different cancers for actual 

Spiro Rombotis: patients?

We have [00:31:00] and the effect, of course in early development, what we call phase one studies is very difficult to predict because by definition, phase one patients are very near hospice care, terminal care or death, and they altruistically volunteer their livelihood and comfort in the last weeks of life so that somebody else with the same disease can learn.

So it's pretty exciting for us in the drug development community when we see a patient. To monotherapy with an investigational drug early in development. For these reasons, we've helped a few patients with farra at this point. Mostly as I mentioned earlier with women's cancers, patients with ovarian breast, cervical and uterine cancer have seen tumor shrinkage.

And very impressively, a patient with endometrial cancer went through four cycles, which is a month and a half of f. And achieved the 46% shrinkage of her target tumor lesions. She stayed on therapy for another year, at which point 100% all of the [00:32:00] lesions detected when she was first diagnosed, had disappeared.

She's on her third year of single agent therapy with Fadra, and still her tumor hasn't come back, so she's functionally cured after recent PET scan showed she had no residual foresight of cancer. So this phenomena are exceedingly rare in our. Anecdotes don't make a trend, but they're extremely encouraging to have other patients volunteer their time to motivate physicians to explain to these patients the benefits and handicaps of participating in trials and to allows to then study these new approaches in a larger population, hopefully bring 'em to the bedside.

Well, that's 

Kevin Folta: a really good note to end on. If there people wanted to learn more about your company, where would they look? Well, 

Spiro Rombotis: our website ww. Cyc LA c e l.com is a good resource. We also are active in social media if you wish to follow our story, but I'll also urge you to look at literature [00:33:00] searches and also publicly available databases describing cell cycle phenomena.

There is an large amount of literature accessible to the public, which we can learn more about this phenomenon, how scientists use these important biological tools to design new therapeutic. 

Kevin Folta: Very good. Well, thank you very much for joining me today, and I hope that as time goes on and as new breakthroughs happening, you, you'll consider coming back on the podcast to keep us up to date because this is really exciting stuff that I think is just the, the future is, you mentioned now is the golden age, but I think even more golden ages in front of us.

So Spi Rambos, thank you so much for joining me on today's podcast. . Thank you 

Spiro Rombotis: for having me, Kevin. 

Kevin Folta: And as always, thank you for listening to this Week's Talking Biotech podcast by Collabora. It's estimated something like one in three people will contract some sort of cancer in their lifetime, and knowing that there are therapies that are coming [00:34:00] that can add to the arsenal of ways to confront these insidious disease.

He can be really optimistic, especially for those who are affected right now and living with it and battling through it. There's lots of good scientists who are working hard to exploit these vulnerabilities of cell biology to be able to attack cancer cells and win that war. This is Collabs talking Biotech podcast, and we'll talk to you again next week.