Radiopharmaceutical Companies to Watch

In the dynamic landscape of modern medicine, radiopharmaceuticals have emerged as a cornerstone of precision diagnostics and targeted therapies for the treatment of cancer. This article aims to highlight four prominent radiopharmaceutical companies that are moving the industry forward: Perspective Therapeutics, Aviko Radiopharmaceuticals, Evergreen Theragnostics, and RayzeBio. Each of these biotechs bring forth their own unique blend of scientific prowess, strategic vision, and commitment to revolutionizing patient outcomes. Join us as we explore the achievements, ambitions, and potential impact of these trailblazing companies at the forefront of the radiopharmaceutical industry.

Perspective Therapeutics

Perspective Therapeutics, Inc., is a medical technology and radiopharmaceutical company that is developing Targeted Alpha-Particle Therapies (TAT) to transform the treatment landscape of radiotherapies for cancer. The company is using alpha-particles as opposed to the currently approved beta-particle therapies (Lutathera, Pluvicto) because they generate more energy and travel shorter distances, making them more cytotoxic while reducing their effects on surrounding healthy tissues.?

Perspective is also the sole producer of Cesium-131 brachytherapy seeds. With higher energy and a shorter half-life than competitors, Cesium-131 is proven to be a highly customized and effective treatment for the rapid recovery of patients in the fight against prostate and other cancers throughout the body. As of August 9, Perspective announced a collaboration with GT Medical Technologies focused on increasing access to Cesium-131 brachytherapy for the treatment of certain brain cancers in the form of GT MedTech’s GammaTile? Therapy.?

Perspective has a proprietary technology that utilizes the isotope Pb-212 to deliver powerful alpha radiation specifically to cancer cells via specialized targeting peptides. They are also developing complementary imaging diagnostics using Pb-203 that incorporate the same targeting peptides which provide the opportunity to personalize treatment and optimize patient outcomes. This “theranostic” approach enables the ability to see the specific tumor via radiolabeled imaging and then treat it with the alpha-emitting isotope to improve efficacy and minimize toxicity associated with many other types of cancer treatments.?

Perspective CEO, Thijs Spoor, comments on this approach: “There’s a lot of work being done with the alpha-emitting radioisotope, Actinium-225, but in the lab it’s showing high toxicity left behind after treatment - leaving behind really toxic radioactive daughters even after the tumor is killed - which is obviously a concern. But by switching to a different isotope you don’t have this issue - we actually think Pb-212 is the perfect isotope. And we have a proprietary isotope generator (VMT-??-GEN) - that we set up at our partner CDMOs - that can produce Pb-212 everyday as needed on site.”?

When asked “what are you most excited about right now at Perspective?,” Thijs Spoor responded:

“What we're seeing is truly transformational. We had a patient that was treated under compassionate use, where the first dose of our drug had a major reduction of their neuroendocrine tumor. What we're finding is that if you just use a drug like Keytruda you’re only seeing a small benefit, but we have data from our preclinical studies showing that if we combine our drug with Keytruda, we get an almost 50% complete cure rate in patients with melanoma. We have injected new melanoma cancer cells into the animals we’re testing and the cancer cells never regrow. So we're looking at some extraordinary effects when combined with other therapies. And this is really enabled with an alpha particle, because it causes such a strong antigenic shock to the system, that the body knows what to do next and really amps up and then completely destroys every tumor of that type in the body. So there's some really amazing breakthroughs that are happening now that are just extraordinary. And that's what gets us excited.”

The company’s pipeline of melanoma (VMT-01) and neuroendocrine tumor (VMT-α-NET) programs are entering Phase 1/2a imaging and therapy trials for the treatment of metastatic melanoma and neuroendocrine tumors at several leading academic institutions. As of August 11, Perspective announced that the first patient was dosed in their Phase 1/2a dose escalation trial of VMT-01 for the treatment of metastatic melanoma - they look forward to presenting preliminary data from the study later this year.?

Aviko Radiopharmaceuticals

Deerfield Management-founded Aviko Radiopharmaceuticals is advancing an emerging modality known as boron neutron capture therapy (BNCT) to treat a variety of cancers. BNCT is a precision medicine approach for treating solid tumors that is being advanced to destroy cancerous cells while leaving healthy cells unharmed. BNCT is an approved treatment in Japan for locally recurrent unresectable head and neck cancer, and additional clinical research is currently underway in Europe, South America and Asia.?

Aviko is committed to advancing the BNCT field in the US. As a Deerfield Management-founded biotech, Aviko is uniquely positioned to make that a reality by using their network to form partnerships with medical device manufacturers, healthcare providers, and academic medical centers. Aviko has already formed a strategic partnership with Neutron Therapeutics, the leading provider of accelerator-based neutron delivery systems for targeted radiation therapy of solid tumors. The partnership aligns the two companies’ efforts to build the first BNCT treatment center in the United States and to establish additional BNCT facilities through collaborations with premier academic medical centers.

I had the chance to chat with David Greenwald, CEO of Aviko and VP of BD at Deerfield. Here is what he had to say about the benefits of BNCT:?

“In spite of improvements in patient outcomes over the past several decades, there is still a significant need for cancer therapies that effectively target cancer cells while leaving healthy tissue unharmed. At Aviko we are developing medicines that utilize BNCT, which delivers non-toxic boron selectively to the cancer cells.? When low-energy, safe neutrons hit the boron an alpha particle is emitted and only travels approximately 10 microns, which is the distance of a cell. So the result is a very localized dose of radiation to kill the cancer cells while sparing healthy tissues.?

In addition to a precision medicine approach to radiation therapy, it only takes one or two treatments (fractions), so patients don’t have to come back to the hospital for treatment 30-50 times as you would with traditional radiation therapies. That's not only important for patients but for hospitals as well. Medical centers can treat more patients per year if patients need fewer treatments. So everyone wins – the patient, the hospital, and the health care system.

At Aviko we not only want to bring BNCT to the US but we also want to develop better ways to deliver boron. We have preliminary pre-clinical data which is very encouraging and we have multiple programs underway. In addition, we now have a partnership with Neutron Therapeutics, which has the only BNCT beam that meets the standards of the IAEA for BNCT clinical treatment. So with the best neutron beam and several promising drug programs, we are excited for BNCT’s future role for cancer treatment.?

There is room for us to improve outcomes for patients. For example, in the US, the standard of care for head and neck cancer after surgery and chemo is Cetuximab and PD1. With that treatment regimen, there is approximately a 15% to 25% response rate. In Japan, BNCT showed a 70% response rate, which is an impressive improvement on the current standard of care. It’s still early, and durability is important- but the clinical data is really compelling. It's a super exciting space to be in!”

Evergreen Theragnostics?

Evergreen Theragnostics, headquartered in Springfield, NJ, is focused on improving the available options for cancer patients using radiopharmaceuticals. Founded in 2019, the company is engaged in three core areas: CDMO, Products, and Drug Discovery. The CDMO business unit offers research and commercial scale, centralized production capacity for therapeutic and long-lived diagnostic products. The Products business unit develops and commercializes Evergreen-owned assets. Evergreen Discovery is focused on developing novel radiopharmaceuticals for cancer therapy, focusing on unprecedented and first-in-class radiopharmaceuticals.

I had the pleasure of speaking with Evergreen’s Chief Scientific Officer, Dr. Thomas Reiner, about what makes Evergreen’s approach unique and the goals they are currently working towards:?

What do you believe sets Evergreen's approach apart in the radiopharma sector??

In my mind, Evergreen Theragnostics is the most dynamic and fastest growing small company there is, because we have these three separate pillars: CDMO, products, and discovery. For the CDMO pillar, we have a manufacturing site in Springfield, New Jersey where we produce radiopharmaceuticals on behalf of our clients, who run clinical trials. That involves incorporating their processes within our facility (tech transfer), routine clinical manufacturing, under current GMP standard, quality control testing, and therapeutic level quality assurance - essentially a full scale factory for radiopharmaceuticals.?

Our second pillar involves the commercialization of products that have existing clinical data, but have supply or distribution challenges. We are currently looking forward to the FDA approval of our first medicine - it's an imaging agent, labeled with Gallium 68, that is called Octevy?. Octevy is on track to be the first of hopefully many drugs that Evergreen brings to the market. That will be a big milestone for us.

The third pillar is the discovery and development of novel radiopharmaceuticals. Which is where I fit in as Chief Scientific Officer; my team and I are working to build a pipeline for really unprecedented, difficult to treat targets. They're intended to be the next generation of radiopharmaceuticals and to develop products for cancers that are untreatable today. This is what we are working on, and we really are seeking to provide additional options for patients with cancer. All three of our pillars within Evergreen are working towards that goal.

Also as mentioned, I’ve worked at Novartis and before that I was part of the faculty and a member of the Chemical Biology Program at Memorial Sloan Kettering Cancer Center. I was at Novartis during the time that Pluvicto came out and James Cook, our CEO, was the head of the US operations for AAA when AAA was developing Lutathera. James also worked on their first imaging agent, Netspot. So there's a lot of aggregated expertise here at Evergreen and we really hope that we can capitalize on that.

Looking towards the future, what prospects or goals is Evergreen working towards? Can you share some upcoming projects or areas of focus?

For our CDMO business, we certainly hope to be growing with our CDMO clients, delivering doses for larger and more complex clinical trials. From a Discovery perspective, we are going after the most severe and untreatable diseases. So one of our projects is focused on glioblastoma, which has a median survival rate of just about 14 months. The reason I think this is so important is because there's currently only limited hope for those patients. And the current standard of care is radiating a quadrant of the brain with external beam radiotherapy, which can have substantial side-effects. By using a molecularly targeted radiopharmaceutical, our hope is to not only to increase the survival rate, but also to reduce side effects and give the patients a better quality of life.

Pancreatic cancer, glioblastoma, these are cancers that affect adolescents; and where patients have limited overall survival under the current standards of care. This is where we believe that radioligand therapies can provide new options. We have seen that with castration-resistant metastatic prostate cancer, where patients who had substantial metastasis ended up responding very well to radioligand therapy. These drugs make a real difference in everyday life. At the end of the day it's science, but it’s really impressive.

I really hope that the radioligand therapy field will identify a follow-on drug to Pluvicto. Even if it’s not us, I hope that there is one company, out of all those radiopharma companies being founded, that finds the next big therapeutic breakthrough. Radioligand therapy is very multifaceted and my hope is that 10 years from now, it'll be something that is as well-known or as natural to drug development as antibody drug conjugates are today.

RayzeBio

RayzeBio is a San Diego-based radiopharmaceutical company developing an innovative pipeline using targeted radioisotope, alpha-emitter Actinium-225, against validated solid tumor targets to improve outcomes for cancer patients. They prosecute diverse sets of binders against clinically validated cancer targets through an iterative process. RayzeBio has completed over 500 in vivo studies, which has provided them with broad proprietary and critical insights on identifying key attributes essential in discovering novel RPT drug candidates.

Through this approach RayzeBio has built a portfolio of potential RPT drug and development candidates from discovery to late-stage clinical programs. They only file an IND and advance programs beyond IND enabling studies and into formal clinical development once they’ve conducted rigorous preclinical evaluation and early human imaging studies. Their current pipeline is targeting gastroenteropancreatic neuroendocrine tumors (GEP-NETS), small cell lung cancer, and liver cancer.?

The company plans to IPO soon to push their lead radiotherapy candidate RYZ101 through phase 3 trials. A phase 3 trial of the radiopharmaceutical in patients with somatostatin receptor (SSTR)-positive gastroenteropancreatic neuroendocrine tumors kicked off in May. As of September 11th, the company has detailed hopes to raise $206 million in their Nasdaq debut, offering 13.2 million shares of common stock.

I spoke with RayzeBio Senior Medical Director, Denis Ferreira, on July 14th about his take on some of the key trends, challenges, and opportunities in the radiopharmaceutical market today. He noted that while radiotherapeutics are a lot less toxic than other treatments, more can be done to make them even more effective. The challenge is to intensify treatment and have even better results. Patients and doctors would not choose a treatment that’s harder to produce and distribute if it provides the same result.?

Denis explained, “It’s important to optimize the molecules (binders) to reduce radiation to normal organs while simultaneously increasing the dose to make it more effective - it’s about figuring out the best dosing for safety and efficacy.” That is why alpha-emitters are surpassing beta-emitters; beta is more readily available, but alpha proves to be more effective (higher potency) and more precise (hits the tumor target while reducing harm to surrounding tissues).