Hello Uterus

#51: AMY109 and The Journey to Ending Endo with Dr. Ayako Nishimoto-Kakiuchi

Episode Summary

In this episode, we are joined by Dr. Ayako Nishimoto-Kakiuchi from Chugai Pharmaceuticals to discuss AMY109 and its potential to manage endometriosis non-hormonally.

Episode Notes

This might be the most exciting episode yet! We’re watching medical history unfold all the way from Japan. 

Are we on the path to having a non-hormonal therapy for halting the progression of and potentially reversing endometriosis?

We are so honored to be joined by Dr. Ayako Nishimoto-Kakiuchi from Chugai Pharmaceuticals, which is the team behind this research. Dr. Ayako introduces us to the anti-IL-8 recycling antibody developed by the Chugai team called AMY109.

As with all clinical trials, there are hurdles and timelines, but we're grateful for research being done to find a possible solution for endometriosis patients.

Important disclaimer: Right now, the absolute gold standard for treating endometriosis is excision surgery by a well-trained, experienced endometriosis surgeon. Excision has brought many endo sufferers relief — but it is a highly complex surgery, invasive, and is hard to come by. There are few excision surgeons that specialize in treating endometriosis. It requires a multi-disciplinary team when the disease has spread outside the pelvis, and requires extensive experience and training that goes beyond the education received in med + surgical school.

Alternative, safe treatments that don't involve hormonal suppression or minimally invasive surgery would be a huge advancement.

During this episode, we dive into what role IL-8 plays in the progression of endometriosis, how AMY109 can inhibit it, what other conditions AMY109 could be effective for, and what current data from clinical trials look like. 

Thank you to everyone working hard at Chugai to create a better future for uterinekind! We’re all cheering you on!

Lastly, we end on a high note full of love! Congrats to Mr. and Mrs. Pickles! 🐢

Thanks for listening, learning, and being you. And join us back here every Tuesday for all things uterus, in service to you, uterinekind.

 

Links:

Gel nail polish article: https://health.clevelandclinic.org/you-guessed-right-gel-nail-polish-is-bad-for-your-nails/

Research publication on Chugai's AMY109: https://pubmed.ncbi.nlm.nih.gov/36812343/

Episode Transcription

Carol: As chronic conditions surge, so does production of chemicals. There's an elephant in the room with the coal mine canary sitting on. Its. I'm Carol Johnson and this is Hello Uterus.

 

Today we're thrilled to introduce you to the woman at the center of the most exciting clinical trial for endometriosis to date a non-hormonal drug candidate that isn't simply a symptom suppressor. Dr. Ayako Nishimoto-Kakiuchi of Chugai Pharmaceutical company in Japan has snuck out of the lab to give us insight into their exciting discovery that has a female name, Amy 109, but first uterus in the news –

 

In 1950, about 1.7 million. Of synthetic plastic were made each year 1.7 million tons. That's a lot, right? Well, not when you compare it to today, more than 400 million tons annually are produced. 400 million tons of synthetic plastic versus 1.7 million. In 1950, the vast majority of the chemicals used to make these plastics have not been thoroughly tested for safety.

 

Certainly not on the female endocrine and reproductive organs, but we do know what the long-term implications of chemical exposure are. Cancer, organ damage, weakening of the immune system, development of allergies, and or asthma. Reproductive problems and birth defects and effects on the mental, intellectual, and or physical development of children.

 

Those are some bad effects, yet it is 2023 and we still sit here looking at an E P A. That is is, you know, for the last 30 years, trying to figure out how to test endocrine disrupting chemicals yet passing. As generally regarded as safe and allowing them to be used in the production of products that we spend our money on and put on our bodies, and we eat them and drink them, and we're all getting really sick.

 

There are numerous articles published weekly on near daily, actually on chemical exposure and disease. There was one last week about, essentially about manicures, but it was specifically about the gel nail polish that if it's cured under an ultraviolet light, it ends up being very hard and it lasts for a really long time, which just seems a good thing, right?

 

Yeah. But it's not good. And the, I'm looking forward to the day when we look at something like that and we think in advance of ever using. Yeah, that's probably not a good thing for the body in this article. Which we will post on our social channels at Uterinekind on Instagram and TikTok. In this article, they show closeup pictures of multiple hands with blisters rashes, itchy looking skin cracking, skin inflamed, agitated skin.

 

People complain of pain in their fingertips of not being able to sleep through the night cuz their fingers are, are hurting so badly that it wakes them up and everyone is, is rightfully up in arms. Like, wow, look at what happened to my nails. Like I used to have the most beautiful nails, and now after getting these manicures, look at how gross my hands look.

 

But we need to connect the dots here. If it's gonna do that to your nails, there is the possibility, if not certain. That the chemicals are drawn into the body, through the skin, and even just small amounts of these chemicals can negatively impact our endocrine systems. The system that runs everything in our body.

 

It is so essential that we talk about this, that we talk about with our, our friends, our loved ones in our communities, that we don't blow over. The amount of chemicals that we're exposed to every day that we actually talk about it because just like we see with insulin prices, for example, when everyone started talking about how expensive insulin was and, and people started to become educated on when insulin was invented, and the fact that the inventors of insulin sold the patent for a dollar because they didn't think that the medication should be withheld from people just because they can't financially.

 

Swing buying the medication. When we all started learning that stuff and then we started calling on these companies to stop the ridiculous, profiting, the the excessive extreme, extraordinary profiting off of the health of someone else or health condition that someone has, they rolled back their price.

 

It works. And it's kind of interesting that that example just came to mind, but diabetes is a condition that appears to be connected in some way to chemical exposure, disrupting our natural balance in our bodies. I found a study called Environmental Determinants of Chronic Disease and Medical Approaches, recognition, avoidance, supportive Therapy, and Detoxification.

 

This conclusion in this study, which we'll post in our show notes, is both science backed and common sense back. And I will read it to you. Healthcare professionals in government, public health research and the clinic will only be successful against the onslaught of chronic debilitating diseases once environmental contributors are recognized, researched, and addressed.

 

It's right there in a study and it's exactly. It's spot on. Everyone has to be talking about this, not just people like me or you know, the, the people who are health conscious and take the time to educate themselves. And by health conscious, I don't mean like diet conscious, I mean health conscious in terms of like wanting to understand how their bodies operate and how they can best support this very complex, delicate system that we inhabit.

 

So education is. We see the effects of the loudest narratives as a society. We are so focused on what happens to the exterior of our bodies, but we are. Virtually not at all concerned about how the interior operates. If the chemical exposure that the people who received those gel manicures only affected the interior of the body, and they were not able to visibly see the damage on their hands, n they probably wouldn't connect the dots between the chemicals that they're exposed to and some other condition that they're experiencing, like abnormal uterine bleeding or endometriosis or fibroid.

 

Or until it's too late. Cancer. So education is key. We need to be talking about this and I hope that you all don't get bored of me talking about chemicals because I'm gonna keep talking about them. It's really important at Uterine Kind we believe. That bringing research into the spotlight and introducing the scientists, breaking new trails to our audiences will shift the arc of this narrative to one that honors the human system over how that system appears to the world.

 

That's one of our main priorities is to make. That our members can access research and that it's summarized for them to be able to understand these studies. And take that learning into their daily lives and take it back to their communities to educate them. And then we'll shift to that narrative. It, it will not be exclusively focused on the shape of your body or how many wrinkles you have, or you know how long your fingernails are, or how straight your hair is.

 

But it will be about the balance of your hormones, the health of your endocrine. Symptoms that you may not be connecting and how you benefit from being very in tune with your body and the experiences that it's having on the inside, not on the outside. It's super important. So we're gonna take a break and when we come back, I'm going to introduce you to this most amazing scientist.

 

Before we go, however, I wanna let you know that the app is now available in both the Google Play and Apple Stores, and it is free to download and use. It's packed with useful and accurate content that will support you no matter where you're at in your health journey. Best of all, it enables you to easily.

 

This is so important, your own symptoms, medical record over time. 90% of a diagnosis comes from your symptoms data and uterine kind makes it easy and safe to record and share this data with your care teams. So visit uterinekind.com to learn more and head to the app store to download. Thank you for your support.

 

Follow the Uterinekind team and. Over on Instagram and TikTok at Uterinekind.

 

The first time we attempted to record this most important conversation, San Francisco was hit by a bomb cyclone, which impacted our audio. Dr. Nishimoto made time to speak with us, so she and her team can connect with you, which is so important because sometimes it seems nothing is being done on behalf of those living with endo and adenomyosis and other conditions.

 

But the work is happening. Her passion and enthusiasm are contagious. Imagine going to work each day thinking that the research you are running could one day release millions from the painful clutches of endometriosis and possibly. Adenomyosis two. To listen to our full conversation, please download the Uterinekind app and you will find the video recording of the interview with a transcript for following along in the explorer section of the app.

 

Before we begin: a primer on the key characters in our conversation today, IL-8 and the AMY109 antibody. 

 

So when there is an infection or injury, immune cells release interleukin eight, which attracts other immune cells to the site of the inflammation. The accumulation of immune cells at the site of inflammation helps to fight off the infection or repair the injury.

 

Neutrophils are a type of white blood cell that are important for fighting infections. IL-8 attracts them to the site of inflammation and once at the site of inflammation, neutrophils help to clear the infection by engulfing and killing bacteria. IL-8 is also involved in angiogenesis, which is the formation of new blood vessel.

 

IL-8 can stimulate the growth of blood vessels, which is important for wound healing and tissue repair. So those are the good things, right? It's got its good side and it's got its not so good side. IL-8 has been implicated in the development and progression of cancer. It can promote tumor growth by stimulating angiogenesis and promoting the recruitment of immune cells that can support tumor.

 

IL-8 has been implicated in the development of autoimmune diseases such as rheumatoid arthritis and psoriasis. In these diseases, the immune system attacks healthy tissue in the body leading to inflammation and tissue damage. IL-8 is a versatile protein that plays an important role in the immune response.

 

Inflammation wound healing and the development of new blood vessels. However, disregulation of IL-8 can lead to the development of diseases such as cancer and autoimmune diseases. And finally, IL-8 may act as a growth factor in the endometrium, and may also play a role in the development of endometriosis by promoting the vicious cycle of endometrial like cell attachment, cell growth, and the further secretion of IL-8.

 

Now little bit of a spoiler alert because we're gonna talk about the super exciting discovery, AMY109 in our interview, but a little bit of an introduction. First, AMY109 is an antibody that binds to IL-8 and was created by Chugai. It is developed to apply to guys unique recycling antibody technology.

 

Which means that the, the IL-8 antibody, it remains active in the body for a fairly long period of time. So instead of having to take daily medications or weekly medications, even. AMY109 is thought to be effective with only a one month dose, so a dose each month with its anti-inflammatory action. AMY109 is expected to offer patients a non-hormonal related therapy, and that is the most exciting part of all.

 

I mean, kind of, it's just, it's really exciting that so far, in their research, it's effective, but it's also exciting that it's non-hormonal. Right? I can hear people cheering. I'm like, thank you, thank you, thank you to Chugai and their team.

 

So typically the only effective treatment for endometriosis is excision surgery, which is a really intense procedure that requires a highly skilled surgeon, highly skilled, and absolute specialist.

 

This is not an everyday kind of gynecologic surgeon that can do this by any means. This is someone who specialize. In excision surgery, right? So you have excision surgery as the gold standard treatment for endometriosis, and then you have symptom suppressors. AMY109 fits that sweet spot that is non-surgical and is not designed to, to merely suppress symptoms, but it is, is designed to actually halt and reverse endometriosis.

 

So now that we have that little primer out of the way, Let's continue. We are grateful and honored to have one of the lead researchers spend time with us today on Hello Uterus, Dr. Ayako Nishimoto-Kakiuchi has a PhD in biological science and is the global project leader of the translational research division of Chugai Pharmaceutical Company in Japan.

 

She and others published the paper titled A Long-Acting Anti IL-8 Antibody improves inflammation and fibrosis in endometriosis and we're grateful for her time today. Welcome to Hello Uterus, doctor.

 

[Full transcript edited by Dr. Ayako in the free Uterinekind app. Download on both app stores or visit www.uterinekind.com]

 

Dr. Ayako: Thank you. I’m honored to have this great opportunity and I'm very happy to be talking with you.

 

Carol: Great. I'm so excited as well.

 

So let's dive right in. We have a lot to cover and there are so many people that are excited to hear information directly from you who was in charge of the research. So what is IL-8 and what role does it play in endometriosis?

 

Dr. Ayako: IL-8 induces the progression of endometriosis, especially fibrosis. IL-8 is known to be high expression in endometriosis patients and Chugai had the anti-IL-8 antibody.

 

We challenged to overcome these hurdles. The first hurdle was a lack of appropriate animal model. Mice and rats are common experimental animals, but they don't have IL-8, and only limited primates have cyclic menstrual bleeding. To solve these problems, we collaborated with Dr. Sankai in Primary Research Center, National Institute of Biomedical Innovation, Health and Nutrition in Japan, and using endometriosis monkey models.

 

Is a very unique point of our research. And the second hurdle was a precise, laparoscopic observation. We needed a gynecologist who is an excellent expert or laparoscopic observation for evaluation. So Professor Konno in Jichi Medical University joined our research and overcome this. And also contributed as a gynecologist for evaluation aligned clinical practice.

 

So our collaborative research was succeeded to evaluate the role of IL-8.

 

Carol: Excellent. So a lot of hurdles to overcome before you could get to the point where you could begin the research. You identified and named AMY109, and you named it AMY109 to have a female name associated. Um, and can you tell us about AMY109?

 

Dr. Ayako: AMY109 is a long acting anti-IL-8 antibody with our recycling technology.

 

The female name, uh, is a drug is for the female, so we named the female name Amy one as a very high-tech antibody. The pH dependent binding function. AMY109 binds to IL-8 in neutral pH like blood, but releases in an acidic condition. Basically, antibodies work in blood and travels through the bloodstream and endosome is an intracellular organelles like a garbage disposal box cause endosome is a place to digest protein.

The key point is recycling antibody uses are different pH between blood and endosome in the cell. So blood is neutral pH condition and endosome is a acidic condition, so conventional antibodies continue to bind to IL-8 in the endosome. So both antibodies and IL-8 are digested in the endosome. On the other hand, AMY109 can release IL-8 in endosome under acidic condition.

So AMY109 comes back to the blood. So they can bind to IL-8 again. This is a recycling antibody.

 

Carol: Yeah. It's very high tech. Yes, that's why we're so glad we have you to explain it.

 

Dr. Ayako: Yes. Recycling antibodies has an advantage of being a convenient drug like self-injection. Actually in cynomolgus monkey studies conventional anti was administrated biweekly intravenous injection.

On the other hand, Amy one nine was administrated every four week with subcutaneous injection, so very convenient.

 

Carol: Yes, that's fantastic. And Amy, when, so that it recycles, it's able, it, it is able to remain in the body because it is a recycling antibody. Mm-hmm. Yes. And when it encounters i L eight, what does it do to it?

 

Dr. Ayako: So endometriosis progresses with adhesion to surrounding organs, uh, such as fallopian tube and overly that's the cause of infertility. In nonclinical study using the monkeys with endometriosis, AMY 109 showed not only the deduction of the lesion size, but also the reduction of adhesions and fibrosis in endometriosis.

 

Carol: Were you surprised by the results?

 

Dr. Ayako: Yes, we're surprised at the result that higher inhibition showed the reduction of fibrosis because, uh, we had considered process of fibrosis was not reversible, so we are very surprised.

 

Carol: Yeah. So did you celebrate, because I imagine when you explain all the hurdles that you had to get across mm-hmm.

 

Then, then you finally arrive at this point in time and was there, was there a celebration in the lab? Did everyone, was everyone thrilled?

 

Dr. Ayako: Yeah, when we found the sign of irate inhibition, we are very happy. However, these signs were absorbed in small scale using the conventional antibody, so we wanted to obtain more robust data with a new antibody.

These data were great motivation to generate recycling antibodies.

 

Carol: So a lot of, a lot of research to get to Amy 1 0 9. We had some questions from people on TikTok that were very excited to hear about this paper. And one of the questions was, well, given that IL-8 is needed for many functions in in the body, and Amy 1 0 9 is used to target it.

 

Will that have other effects on the body? Hmm.

 

Dr. Ayako: We connected the nonclinical safety study with high dosage of nine up to 200 milligram package G, that is 24 higher than efficacy dosage. And we found that in all the test animals, there were no abnormalities in the measure cycle and reproductive organ.

 

Except for injection site reactions, but this injection site reactions are common and not specifically attributable to AMY109 and reversible. So we don't have enough information in human, but uh, from the non-clinical safety, We consider the, AMY109 has no concern to inhibit the other effect, but we have not enough data as of now.

So we will carefully monitor to and evaluate whether AMY109 have other effects on body in clinical studies.

 

Carol: Well, that's certainly positive at this stage to know that with the data that you do have, it appears that it does not negatively impact other than the injection site. Um, so that's very exciting and certainly human trials.

 

Will need to be conducted in order to validate whether or not there's any impact in the human body. Yes. Yeah. So would this treatment have any impact on adenomyosis?

 

Dr. Ayako: Oh, we hope Amy nine becomes new treatment for adenomyosis. We might seek the possibility to evaluate the efficacy on adenomyosis,

 

Carol: that would be amazing to be able to impact both conditions, especially because they coexist in a large percentage of the patient population.

 

I'm assuming that it's a similar answer to whether or not this treatment might work for fibroids. Uh,

 

Dr. Ayako: unfortunately fibroid is completely other disease. It's pathophysiologically different.

 

Carol: a different, different disease. Yeah, well, certainly being able to have a positive impact on endometriosis and potentially adenomyosis with a non-hormonal treatment.

 

That's something that we actually haven't mentioned yet that's really important. Um, is that this is a non-hormonal treatment for endometriosis or will be after, after human trials are completed. Yeah. Um, is there a way that the I l. Protein can be used to detect endometriosis without surgery. Hmm,

 

Dr. Ayako: good idea.

 

It could be, uh, helpful to, for early diagnosis.

 

Carol: That would be fantastic. And yes, we know that it can take up to 10 years to be diagnosed with endometriosis and, and that the entire time that someone is seeking a diagnosis, the disease is progressing. So having, having diagnostics is, is really, um, important.

 

I wanna. That I believe I'm asking you for a theory rather than, or a hypothesis rather than, um, a definitive data backed answer. But does this treatment, or would this treatment potentially have any implications on the general immune function and infection response in the body? Yeah, in

 

Dr. Ayako: non-clinical study, there was no implication on immune function, but there is a possibility to inhibit the immune function in human.

 

So we will carefully monitor the safety in clinical studies.

 

Carol: Excellent. And a question for you, um, about the classification of endometriosis as a disease. Do you consider this now with the information about i L eight coming to light? Do you consider it an autoimmune disease?

 

Dr. Ayako: Uh, I'm not sure. Some researcheres think endometriosis is an autoimmune disease, but I'm not sure.

 

Carol: Okay, so we await data from human trials. Have those human trials began? Uh,

 

Dr. Ayako: studying for safety evaluation was completed. So analysis is ongoing and we are preparing for phase two Study for efficacy, evaluat.

 

Carol: Excellent. And do you foresee having any clinical trials conducted in the United States? Uh,

 

Dr. Ayako: this point is not fixed, so I can comment on the details.

 

Absolutely.

 

Carol: And you. Have, as I said before, a lot of fans on TikTok, there were so many comments that where people were, were saying that they were crying at the, the thought of being able to have a treatment that's non-hormonal, that actually for the first time wouldn't just suppress symptoms but would actually halt and potentially.

 

The disease. What would you like to say to them about the work that you are doing and, you know, knowing that they're rooting for you, um, that they're cheering you on? What would you like to say to them about the work you're doing and about you guys' dedication to to female health? Yeah. Our team

 

Dr. Ayako: is very encouraged to hear the patient's.

 

So development of uh, innovative drug with new mechanism is challenging for us, but we will do our best and challenge to accelerate the development of nine for patients. Or over

 

Carol: you. Excellent. I actually just got butterflies when you said that, like butterflies in my stomach feeling, you know, because it is very challenging.

 

You're breaking new ground and all of the research while, while we all want to get so excited, we understand that you need to wait for the day to c to come in before you can get excited and um, so it's one of those. Periods in time where there's a lot of hope and we hope that the data comes in quickly and we just, we wanna thank you and thank you guy for dedicating resources to study this condition that is so destructive and damaging to the people who live with it.

 

And it, it's very difficult to get funding for research to study. Endometriosis. And so we would like to just express our gratitude to you and to your team, and to Chugai for investing in this treatment and in this research to bring forward a non-hormonal treatment for endometriosis. Thank you so much.

 

Yeah. Yeah. Thank

 

Dr. Ayako: you for the great opportunity to talking about our, and I'm very happy to hear the direct patient's voice that is very encourage us I to material random disease. So we would like to change this situation and uh, I would like to, uh, provide the very. For you in the future. New future,

 

Carol: and we, we want you to do that too.

 

Well, thank you so much, doctor, for spending this time with us today. We really appreciate it. Thank you. As they say

 

As we said at the top of the interview, we are going to post the full interview to the app in our explorer section with transcripts so you can follow along. The app is free to download and use and all of the features, all of the content, the ability to easily track and record your symptoms. It's all available to you for free.

 

So head to the Apple Store or the Google Store, or head to uterine kind.com and download the app and visit the Explorer section, which is kind of like a magazine full of content, and you will find our conversation, including the transcript for you to. Listen to and share with your friends. And now ending on a high note.

 

I just, I'm so excited to be the first person to tell you, cuz I'm, I'm probably the first person to tell you this, but Mr. Pickles is a dad. Why is this exciting? Well, because he's a first time dad. And why is that exciting? Well, because he's 90, but there's another reason why it's. Mr. Pickles and those like him are critically endangered.

 

You're like, okay, so Mr. Pickles isn't a person, right? Mr. Pickles is a radiated tortoise and the oldest animal at the Houston Zoo. By chance, this is an important part of this story. By chance, stop at the zoo. Noticed that his 53 year old. Mrs. Pickles was digging a hole. And you know what that means? They rescued the eggs and moved them to a location where they could hatch under the right humidity and temperature conditions.

 

And now Mr. And Mrs. Pickles have triplets. You wanna know what their names are? Of course you do. Who wouldn't? Well, their names are Dill, Gerkin, and jalapeno. Jalapeno, like is that a vegetable challenged person who named that third turtle? Because last I checked, jalapeno is not a pickle. Maybe pickled jalapeno, but then if they used pickled jalapenos, the name, it would be like pickled jalapeno pickle, which would be, I don't know, cute maybe.

 

Um, but a little Hollywood perhaps. So Dill, gerkin, and jalapeno, and the babies are all doing really well. I just feel really bad for jalapeno because, you know, as, as a freckled redhead, when I was growing up, I was definitely like, you know, on the outside of pretty. Every cool group and clique that you could ever imagine, and I just feel like, you know, you've got dill and gerkin and then you have jalapeno, and it's like, wow.

 

It's kinda like a redhead, just kinda sitting out there all alone. Names aside though the event is key as we work to save endangered species, and so we are so excited that Mr. And Mrs. Pickles are parents. Thank you to our producer, angel, and the team at Uterine Kind for your dedication To those we serve, Maryelle is over at the helm of our social channels, so please go check us out on TikTok and Uterine Kind where we are having robust conversations on all things female health.

 

Our handles at Uterine Kind, and by the time you hear this, she will have completed the Boston Marathon with the team from Mass General Hospital. Go Team Go. They've raised a lot of money and ran a lot of miles to get to the finish line, and we're super, super proud of them all. We will be back next week with another episode of Hello Uterus, so please subscribe and if you.

 

Leave a review about the podcast. If you find this information helpful, and if you know of people who you think would benefit from knowing about Hello Uterus or Uterine Kind, please direct them to uterine kind.com or share the podcast with them so that people can have access to this information, and we are just so delighted to support you.

 

It's a bananas world. And it's going to take all of us to make sure that we work together to keep each other healthy, and that we help each other out when we're dealing with really difficult health issues, and we're dealing with a very stressed, fractured healthcare system. So we're really delighted to be part of this amazing community to help everybody.

 

Get well without delay and we'll be back next week. So until then, be well, be cool, be kind.

 

The podcast is for informational use only. Here is not used to or treat medical condition. Please ask your physician about your health and call 9 1 1 if it's an emergency. And thank you uterine kind for listening.