Parabilis’ Zolucatetide: The Societal Value of a Drug That Wasn’t Supposed to Exist 

For thirty years, the most important switch in cancer biology was considered unflippable. A Cambridge company just flipped it, firing the first shots in a new oncology revolution.

Hundreds of thousands of Americans and millions of people around the world currently suffer from cancers caused by mutated or dysregulated beta catenin. This protein is at the root of 10% of all cancers and figuring out how to make a drug that binds to its comparatively smooth surface has been one of the hardest problems in oncology for over 30 years. Most people have never heard of beta catenin; without drugs on the market against it, oncologists don’t discuss it with patients.

But just as millions of women with breast cancer have learned about estrogen receptors, millions of men with prostate cancer have learned about androgen receptors, and now pancreatic cancer patients are learning about the importance of KRAS – all because we now have drugs that block those proteins – someday there will be millions of people who know about beta catenin.

But not yet. The emerging beta catenin revolution is known only to a few. And while the consequences of the first shots fired in the American Revolution 250 years ago at Lexington and Concord were under-estimated by many, there were those with the imagination to think ahead to the new world to come. 

The opening battles of the beta catenin revolution

If we someday look back at the beta catenin revolution to ask how it began, then its Lexington and Concord will no doubt be the desmoid tumor battleground. Desmoid tumors are rare (11,000 patients are actively managed under physician care in the US) but among the clearest demonstrations of what can go wrong when beta catenin is mutated. This is where we’ll see how profoundly effective a drug against beta catenin can be.

Desmoid tumors occur when one myofibroblast cell with a chance mutation in the CTNNB1 gene encoding the beta catenin protein grows into a mass that can take over a person’s abdomen. These tumors can wrap around internal organs and cause severe pain; sometimes they’re deadly. Desmoid tumors arise at any age and because they aren’t metastatic and don’t spread throughout the body like many aggressive cancers do, people can live with them their whole lives. In this regard it’s a comparatively benign cancer. 

But it’s no walk in the park. Lots of medical appointments to monitor for growth; every time it grows, that’s a personal crisis. Over several years, tumors may regress at least partially in about 20% of patients. Very infrequently, the tumors can completely regress on their own. Sometimes it can be removed entirely with surgery. But in many cases it’s just tolerated and managed with radiation, chemotherapy, and/​or surgery – the standard blunt oncology toolkit – with all the side-effects of those treatments that you can imagine. There’s only one drug approved specifically for desmoid; it works indirectly to slow the tumor’s growth, doesn’t work for everyone, and comes with its own side effects.

The myofibroblasts cells that give rise to desmoid tumors are normally involved in wound repair. They show up, replicate, do their job, and then are supposed to die. Beta catenin binds to another protein called TCF to orchestrate the temporary replication process. And when the wound is repaired, beta catenin is literally tagged for destruction by a protein called APC. Without beta catenin binding to TCF, the cells stop replicating and, with the wound healed and their job completed, they die off. That’s how it’s supposed to happen. 

But if, in the process of replicating on the scene of some injury, one of the cells is unlucky enough to develop a mutation in a special region of beta catenin where the destruction tags are supposed to be attached, then that cell starts to make beta catenin that can’t be tagged for destruction. So it stays on. And the cell divides and divides. 

After Lexington and Concord, the American Revolution’s next milestone was Ethan Allen’s capture of Fort Ticonderoga in New York. Beta catenin’s Fort Ticonderoga is a condition called Familial Adenomatous Polyposis (FAP), which affects around 34,000 people in the US born with one mutated, non-functional copy of the APC gene. The good news is that all you need is one good copy of that gene to do the job of destroying beta catenin. The bad news is that when a cell, by chance, picks up a mutation in the one remaining good copy of APC, then it now has no way to shut off beta catenin. And the result is the same as with desmoid; that cell starts to divide and divide.

The epithelial cells that make up our gut lining are constantly turning over. All that food we eat and its digestion are hard on the gut, so it’s constantly repairing. That means that gut cells are constantly flipping beta catenin on and off. But when one of those cells loses its second copy of APC and keeps dividing, it turns into a precancerous growth called an adenoma. Let them grow long enough and adenomas can accumulate additional mutations and evolve further into aggressive, metastatic cancer that we would call colorectal or gastric cancer. 

Patients with FAP don’t just get an adenoma or two. Their gut lining is constantly spawning adenomas and so they live with a high risk of cancer. Many even elect to have their colon and rectum removed and some live with an ostomy (fecal matter is collected in a bag worn outside the body). But they still have a risk of adenomas and cancer arising in their small intestine and stomach, so they must be frequently monitored to catch and clip them. Removing the colon means that FAP isn’t the guaranteed death sentence it once was, but like desmoid, it’s a lifelong commitment to intense monitoring and interventions.

In patients with FAP, every cell in the body has a non-functioning copy of APC, so when a myofibroblast cell loses its second, functional copy of APC and also starts dividing, it gives rise to a desmoid tumor. In fact, because surgery triggers myofibroblast-driven wound repair and repair-related cell division increases the odds of mutation, FAP patients face increased odds of a desmoid tumor from one or more myofibroblast cells picking up a beta catenin or APC mutation. 

And the beta catenin revolution has already opened a third front – Bunker Hill, if you will – this one in the brain. About 15,000 Americans live with adamantinomatous craniopharyngioma, or ACP (not to be confused with the APC protein/​gene we were just talking about). It starts near the pituitary gland, deep in the center of the skull, from a cluster of embryonic cells that never finished their job during development and eventually turn malignant. Like desmoid, ACP doesn’t spread through the body. And like desmoid, that’s about where the reassurance ends. 

The pituitary and the hypothalamus just above it run some of the most basic functions in the human body. A tumor in that neighborhood causes trouble just by being there: it can press on the optic nerves and cause blindness; it can scramble the hormonal signals that tell a child’s body how to develop; and it can trigger a form of obesity so severe that patients gain weight no matter what they do. ACP disproportionately strikes children between the ages of five and fourteen, who then spend the rest of their lives managing the consequences.

Surgery is the main tool, and the problem with surgery here is the location. The tumor grows sticky. It wraps itself around the optic chiasm, the carotid arteries, the hypothalamus. A surgeon who tries to remove it completely risks permanently damaging what she’s trying to protect. So in practice, surgeons often stop short, leave some tumor behind, and hope for the best. About half of all patients see their tumor come back within ten years. Each recurrence means more surgery, more radiation, more brain damage. There is no approved drug to treat ACP. 

The cells that give rise to ACP tumors carry mutations in the exact same region of the CTNNB1 gene as in desmoid tumors. The result is identical: a beta catenin protein that can’t be destroyed and unrelentingly drives cells to divide. It’s not just the same accelerator stuck in the same position. It’s the same mechanical defect, in the same part of the accelerator, producing the same outcome – just in a different cell type, in a part of the body that’s much harder to reach.

Unsticking the accelerator

Think of a mutated, overactive beta catenin as an accelerator stuck in the on position on a hybrid car. Ideally, you would get that accelerator unstuck. Do that and all the problems are solved. But there are other ways to slow down the car: you could shut down the battery, for example. That would at least kill the acceleration. But it also kills the radio, nav system, and air conditioning. Those are side effects. And the car could switch to its fuel tank, so it could keep going. Better to get the accelerator unstuck. That’s how cancer works, too. Mutations that cause beta catenin to stay on are called ​“drivers.” And while many cancers are driven by beta catenin, all we’ve been able to do until now is mess with other subsystems of the car but not actually get the accelerator unstuck. 

The roughly 60,000 Americans living with desmoid, FAP, or ACP need a drug that would shut off this aberrant beta catenin activity that is driving their tumors. Scientists have known for decades that if you could block the beta-catenin:TCF interaction – the specific molecular handshake that activates the downstream tumor-promoting genes – you might be able to stop these tumors at their root.

But nobody could do it. For thirty years, essentially every major pharmaceutical company tried and failed.

Parabilis Medicines, a newly public company based in Cambridge, MA, has, to our knowledge, become the first to do it. They have fired the first shots of the beta catenin revolution.

And the societal value of winning the beta catenin war shouldn’t be underestimated.

Parabilis and Zolucatetide: The molecule that shouldn’t exist

To understand why Parabilis succeeded where others failed, it helps to understand the fundamental drug-discovery problem that plagued everyone else.

Conventional small-molecule drugs work by finding a pocket on a protein’s surface – a nook or groove into which the drug fits, like a key in a lock. Beta catenin doesn’t have useful pockets. Its interaction surface with TCF is comparatively featureless, smoothly spread across a broad face of the protein rather than concentrated in an easily druggable groove. Small molecules can’t bind these surfaces tightly enough to disrupt that interaction and make a difference clinically.

Cells are densely filled with all kinds of proteins and other molecules that interact with one another, like a crowded arcade filled with people, machines of all kinds, everything touching everything, balls rolling, balls flying, lights blinking, a cacophony. It’s chaos. And yet, if you look closely, there is a lot of logic.

There are rules to each game. An order to everything. First one player goes. Then the next. Round and round. But sometimes there’s bad behavior.

Look at the bowling lane and you’ll see a big kid who won’t stop rolling his favorite ball down the lane even though it’s time for other kids to bowl. That’s a problem. To block the bully from bowling, you could stuff a thumbtack into one of the finger holes of his favorite ball. When the bully’s finger hits the thumbtack, the ball drops. Most small-molecule drugs work exactly this way; they find a pocket on a protein’s surface and lodge in it, blocking the protein from doing what we don’t want it to do.

But beta-catenin is more like the basketball in the pop-a-shot game. It interacts with its partner protein TCF the way a basketball is gripped by a player’s hand – across a broad, smooth surface, all at once, with no single point of attachment. And some kid is throwing basketballs at other kids. How do you block him from grabbing those balls? There’s no finger hole to put a thumb tack into.

Turns out we have the tools. They are called antibodies. They are large proteins that can bind to all kinds of protein surfaces. They are like NBA players whose hands are easily large enough to palm a ball and keep it away from everyone else. The problem is that beta catenin is inside of cells, but antibodies can’t get inside cells. We normally use antibodies to block proteins that are on the outside of cells. In our somewhat strained analogy that’d be like a height restriction at the children’s arcade. The NBA player gets turned away at the door. We have to get that big hand into the arcade.

Is there such a thing as just a hand that can walk its way into the arcade? Have you seen The Addams Family? It’s called Thing. 

That’s zolucatetide. It’s just the basketball player’s hand and it keeps TCF from getting a grip on the beta catenin basketball, disrupting the growth signaling that’s driving the tumor. And while Thing is fictional, zolucatetide is not. 

This entire extended analogy is absurd; but for so long, so was the existence of a molecule like zolucatetide. 

Zolucatetide is small enough to penetrate the cell membrane and precisely designed to grip the surface of beta catenin that TCF normally latches onto. It’s one of the most remarkable achievements of modern drug development. And we may someday look back on this drug as the beginning of a wave of breakthroughs.

A big challenge in drug development is that an estimated 80% of biologically validated disease targets like beta catenin (proteins so relevant to a disease that we are confident that a drug against it would help treat the disease) are considered ​“undruggable,” largely because they reside inside cells (so antibodies can’t help) and present smooth interaction surfaces (so small-molecule drugs can’t stick to them). It’s why cancer has proven so daunting.

Building on technology originally developed in Greg Verdine’s lab at Harvard University, Parabilis’s founders, including Verdine himself, set out to solve this class of problem systematically. They’ve created stabilized helical peptides (mini proteins) engineered to penetrate cell membranes and bind flat intracellular surfaces with high precision. These ​“Helicons” mimic the natural helical structures proteins use to bind to each other. By ​“stapling” the helix chemically, creating a linkage between the two ends of the helix, they aimed to combine a small molecule’s ability to penetrate a cell with an antibody’s ability to bind lightly-featured protein surfaces.

The scientific community had long been skeptical that this could be done well enough to make a drug. Maybe, some argue, it would work in a lab but only very inefficiently so that a person couldn’t take enough drug to get a benefit. Or maybe it wouldn’t bind specifically to just the intended target and would cause all kinds of side effects. As is expected of scientists, many will doubt until a safe and effective drug is proven possible. 

Parabilis has spent over a decade developing its Helicons, building the computational and experimental platform to make them work. It has generated millions of data points across hundreds of thousands of Helicons, optimizing them for dozens of drug-like properties. Zolucatetide is their lead molecule and the result of that process. And it works. Not just in a laboratory but in patients.

We and Parabilis believe zolucatetide is the first drug to directly block the beta catenin:TCF interaction. It hits the central node of the pathway, the actual protein-protein handshake that activates tumor-promoting transcription. And after decades of theorizing what the effects of such a drug might be in patients with a beta catenin-driven tumor, we finally have an answer.

The company included clinical data in its pitch to public investors that are remarkable for a drug this early in development. These are the first shots of the beta catenin revolution. 

Early signals of zolucatetide’s effectiveness and tolerability

As of February 2026, Parabilis has treated 38 patients with desmoid tumors. Of the 25 with sufficient follow-up to be response-evaluable, all 25 showed tumor reductions. Of the 19 patients with at least two post-baseline scans, 74% (14÷19) had an objective response per standard criteria. This trial isn’t placebo controlled, but these response rates are well beyond anything that one would expect to occur on placebo. Responses were observed in patients naïve to prior drug therapy, patients who had failed nirogacestat (the only approved desmoid drug), and patients who had discontinued nirogacestat due to toxicity. 

Nirogacestat was developed by SpringWorks (acquired by Merck KGaA) and approved as Ogsiveo for the treatment of desmoid in 2023, and is also in development for treating other tumors. By inhibiting gamma secretase, it works on a different part of the cellular machinery from beta catenin that is also involved in cell division. In its registrational study, 41% of patients on the drug experienced an objective response compared to 8% in the placebo arm. Only 7% of patients on the drug and none in the placebo arm had their tumors completely shrink.

If beta catenin is the accelerator in our car analogy, then the gamma secretase pathway is the battery. And since the tumor is like a hybrid, it can switch from the battery to gas to keep going. And much like something that shuts off the battery, nirogacestat slows the tumor but causes other side effects, since it shuts off the battery in every cell in the body and not just in the tumor. For example, nirogacestat can cause ovarian toxicity, potentially causing infertility, which makes it a potentially tough choice for the young women who make up a substantial portion of the desmoid patient population.

That’s how it is with many cancers. Our toolkit is rarely perfectly suited to just stopping the cancer. Unfortunately, patients usually have few choices. 

By getting to the root cause of desmoid tumors, Parabilis created a drug that is likely to be not only more effective but also better tolerated. We won’t summarize the safety data here as the S‑1 does a good job of it (safety starts on Page 129). Because of how important beta catenin is in normal cell function, it’s worth considering how an inhibitor can be safe. Yes, healthy cells such as those involved in wound repair, hair growth, and bone turnover use beta catenin, but only intermittently. Most drivers don’t drive around with the accelerator stuck to the floor. So a drug that unsticks beta catenin has a big effect on a cancer cell that’s dependent on keeping that pedal floored but has much less of an effect on other cells. It’s telling that, during the initial higher dose induction phase of treatment, zolucatetide causes some hair loss in some patients, but once patients drop to lower maintenance doses, hair continues to grow normally. To pre-emptively protect bone, patients on zolucatetide get prophylactic treatment with anti-resorptive drugs that strengthen bones. Considering the drug’s modest impact on hair growth, the long-term impact on bone may also be modest. Indeed, zolucatetide’s tolerability profile appears more favorable than nirogacestat’s, which is meaningful given that desmoid primarily affects young patients with near-normal life expectancy who may need treatment for years or decades. This is not a trivial point. 

To be clear-eyed about this data: these are early-stage results from a single-arm study. The Phase 3 trial in desmoid tumors is planned for the first half of 2027. Durability, the size and composition of the pivotal trial, and the regulatory pathway will all matter. But a 74% ORR (and 100% disease control) stemming from hitting the disease biology right at its source is an extraordinary starting point. For patients with desmoid tumors, the future has never looked brighter.

And because some of the patients with a desmoid tumor actually have FAP, Parabilis was able to see how well zolucatetide worked on their adenoma.

In that same investor pitch, Parabilis reported that two FAP patients treated in the desmoid cohort showed significant improvement in duodenal polyposis burden at 10 and 60 weeks following treatment. As of February 16, 2026, six FAP-desmoid patients have been enrolled. A dedicated FAP-only study cohort should start in the second half of 2026.

FAP standard of care today is surgery: prophylactic colectomy, typically in a patient’s 20s or 30s, followed by ongoing surveillance and often additional surgeries as polyps develop in the duodenum and ileal pouch over the ensuing decades. But surgery is a last resort, not a first choice. In clinical practice, gastroenterologists and colorectal surgeons managing FAP patients spend years trying to delay colectomy. They perform endoscopic polypectomies, monitor closely, and accept incomplete control of polyp burden precisely because the surgery is so consequential. It’s not just a major operation; removing the colon permanently alters bowel function, affects quality of life in ways patients describe as life-defining, and often requires subsequent revisions. Physicians and patients alike understand that delaying or avoiding it has enormous value. This shapes the regulatory and commercial logic for zolucatetide in FAP in an important way: polyp reduction is not a surrogate endpoint that requires separate justification – it is the clinically meaningful outcome that physicians and patients are already optimizing for in daily practice. 

So Parabilis shouldn’t need to demonstrate a reduction in cancer incidence to drive adoption. Demonstrating that zolucatetide reduces polyp burden, as the early data suggest it can, should be sufficient to establish it as the standard of care for patients who still have tissue to protect. The clinical community will not need to be convinced that polyp clearance matters – they already know it does but they have no drug to achieve it. Zolucatetide is shaping up to be the first.

Parabilis also enrolled three ACP patients in its ongoing trial. Two achieved partial responses. The third has stable disease with approximately 20% tumor reduction so far.

Like FAP, there is no approved drug for ACP. The neurosurgical community has spent years debating how aggressively to operate, increasingly concluding that protecting quality of life means accepting incomplete resection – and living with the recurrence that follows. Radiation helps slow things down but carries its own long-term risks, particularly in children whose developing brains are more vulnerable to its effects. The field has arrived, more or less, at a philosophy of damage limitation. It is not a satisfying place to be.

Three patients is not a clinical trial. We are not claiming victory. But in a disease this rare, this genomically uniform, and this devoid of pharmacotherapy options, all three tumors moving in the right direction after treatment with a beta catenin inhibitor is the same kind of early signal the field saw in desmoid and FAP – biology behaving the way decades of science said it should. Zolucatetide would not need to replace surgery in ACP. It would just need to change what surgeons have to leave behind, and give patients something to take when the tumor comes back. For the children and families living with this disease, that would be everything.

The battles to come

After seeing desmoid tumors respond to the drug, its activity in FAP adenomas and ACP shouldn’t be a surprise. The drug is, in a very literal sense, a pharmacological replacement for the function that APC normally provides: inhibiting beta catenin. There is scarcely a disease in oncology with a more straightforward mechanistic rationale for a particular drug. 

In oncology, we have long-held theories that if only we could drug certain proteins, like KRAS, beta catenin, and MYC, then cancers should respond to treatment. This has worked for drugging the estrogen receptor in breast cancer, androgen receptor for prostate cancer, BCR-ABL for leukemia, EGFR for lung cancer, and several other such drivers. We’ve finally seen this play out for KRAS thanks to the efforts of several companies, including most recently Revolution Medicine in pancreatic cancer. We have not yet seen that for MYC, which remains an undrugged target. But Parabilis has generated the early evidence that beta catenin inhibition is working as predicted. First it worked in desmoid tumors. And next it shrank FAP adenomas and ACP tumors. 

It’s fairer to think of zolucatetide as an advance in the treatment of beta catenin-driven disease and not just a desmoid drug or a FAP drug. It may alone prove sufficient to treat some tumors while being useful as part of a more complex regimen for other tumors. 

While the beta catenin pathway is implicated in over 70 cancers, not all of them are purely driven by beta catenin. Some, like colon cancer, have multiple mutations. When Parabilis tested zolucatetide in patients with colon cancer, they only observed disease stabilization and reductions in circulating tumor DNA. That’s a start; preclinical data suggests combinations with other tumor driver inhibitors, especially KRAS, could be much more effective. We expect that many cancers will fall somewhere along the spectrum of beta catenin dependency represented by desmoid, FAP, and ACP on one end and colon cancer on the other.

Also provocative is the idea that KRAS-driven tumors lean on dysregulating the beta catenin pathway for potentiating KRAS inhibition resistance pathways, which means that zolucatetide might potentiate the activity of a KRAS inhibitor in KRAS-driven tumors such as NSCLC and PDAC that are initially wild-type for APC and beta catenin. 

That so many tumors share a common root cause has implications for how broadly zolucatetide could be developed using exactly the kind of basket trial design that has been used for other drugs targeting driver mutations or tumors with specific genetics (e.g., pembrolizumab-MSI‑H). While desmoid, FAP, and ACP are common enough orphan tumors to represent attractive markets for drug development, many other beta catenin-driven tumors are very rare, with fewer than 100 patients per year. That’s too rare for standard drug development. But when you have a drug that works on the root cause of many types of tumors, it’s reasonable to just show that a few patients respond to a drug to confirm that the underlying logic does indeed hold up. A basket trial of a beta catenin inhibitor therefore would give hope to thousands more patients suffering from a range of ultra-rare tumors that would otherwise never have earned the attention of drug developers. 

The FDA has recently indicated a desire to take a creatively pragmatic approach to approving drugs that demonstrate that they work as expected via the so-called ​“Plausible Mechanism Framework.” If there were ever a case for common sense drug approvals, a beta catenin inhibitor that shrinks tumors like desmoid, FAP, ACP, and others that are cleanly driven by beta catenin dysregulation would be a finalist for consideration. The key outstanding question is probably the durability of responses, with only a few desmoid patients treated for more than a year at this point, but there are no signs of tumors becoming resistant. Odds seem good that the responses will prove durable, but there’s no way to know except to wait. But that’s what accelerated approvals are for; it hardly makes sense to deny patients access to a drug that controls and shrinks tumors for one year just because you don’t know if it will work for two or more. Get patients on it and then see how long it works.

Right now the evidence is already very compelling that zolucatetide will be a very useful drug. As the data continue to pile up, we expect its durable efficacy will eventually be recognized as proven. And then the revolution will have been won.

The value of a successful revolution 

What’s the societal value of all that? To be clear, that is not the same as asking what the valuation of Parabilis should be. Nor is it the same as asking how zolucatetide should be priced or what its revenue will be. Rather, let’s consider how much patients, their loved ones, and others in our society might gain if this biomedical advance is real.

To do this, we conducted a back-of-the-envelope calculation to derive some conservative estimates of its societal value. This calculation leaned on the principles of Generalized Cost-Effectiveness Analysis, or GCEA – a framework a group of leading health economists laid out in 2024 that measures what a medicine might be worth to society, as opposed to what it costs or what it sells. Conventional cost-effectiveness analysis tends to systematically undervalue medicines. It considers only the sticker price, captures a limited part of the patient experience, and fails to consider how a drug impacts patients’ family members, colleagues, and friends. GCEA insists on painting a full picture: the reduced anxiety from knowing that a cancer is less likely to recur in the long run, the years of productivity and life it preserves, the burden it lifts off the family members who organize their lives around a loved one’s disease, the way a drug’s price collapses toward pennies once it goes generic, and the fact that, once invented, a medicine keeps delivering that value essentially forever, long after the roughly fourteen years an innovator is allowed to profit from it.

We are not modeling Parabilis’s sales. We’re asking a bigger question: if the beta catenin theory is right – as desmoid, FAP, and ACP data suggest – what is a drug that addresses beta catenin worth to the US? 

We lay out our key assumptions below. A reader who disagrees with any of them can change the inputs (detailed technical documentation here) and watch the answer change; we’ve made the model available to do exactly that. We also welcome your feedback on input sources that might be better suited for this analysis. 

The people. About 11,000 Americans live with desmoid, about 34,000 with FAP, and about 15,000 with ACP – all treated, in our assumption, for life. Over 150,000 colorectal cancers (CRC) are diagnosed each year, around 80% of them driven by the same APC/​beta catenin breakage. Add about 33,000 liver cancers (HCC), a quarter to a third of them beta catenin-driven, call it 11,000. And then the long tail: beta catenin is implicated in roughly 10% of all cancers – on the order of 200,000 new diagnoses every year in the US, and well over a million Americans living with one at any given time. Our analysis was based on five disease states: desmoid, FAP, ACP, CRC, and HCC. 

How well it works. We examined two scenarios, conservative and optimistic, in our analyses. In the conservative scenario: for desmoid, FAP, and ACP, we used the available trial data – a 74% response rate for desmoid and ACP, and lifelong polyp suppression in 74% of the patients. For the common cancers, where zolucatetide would be a combination agent rather than a solo act, we assumed one year of overall survival benefit. This is based on results from trials where you finally unstick a true driver with successfully validated mechanisms of action (e.g., PD-L1 inhibitor) across different cancer types (overall survival benefits range: 12.9 months to 17.6 months). In the optimistic scenario: we assumed that 100% of the patients achieved response or lifelong polyp suppression in desmoid, FAP, and ACP; and the life extension for CRC and HCC patients were 1.5 years. 

What a year of life and health is worth. $150,000 at perfect health (i.e., the best possible health state and quality of life you can imagine) – a standard, middle-of-the-road figure.

What it saves besides life extension and quality-of-life improvement. Reduced health resource utilization from more effective treatments (e.g., averted colectomies, surgeries, radiation, and the endless surveillance of scans and scopes); the productivity and earnings patients and employers keep from reduced absenteeism and presenteeism; the toll lifted from caregivers. 

How we treated the future. We discounted everything at 2% – the rate the GCEA guide now recommends. We first modeled the lifetime benefits for a patient today, and then calculated the aggregate societal benefits by considering 70 future incident cohorts of patients, exactly as the guide prescribes. We assume the same lifetime benefits for each future cohort of patients, and let the population grow and age, which means more cancer over time. While the cost of the care this drug averts will rise in real terms, we did not explicitly model this time-varying trend to be conservative. 

Add it up, and the societal value of getting beta catenin right lands north of a trillion dollars (1.11 trillion in the conservative scenario and 1.28 trillion in the optimistic scenario) – to the US alone. Not Parabilis’s value, society’s value. 

Table 1. Lifetime Societal Value Per Patient

Table 2. Population-level Societal Value (Current and Future Patients)

And that figure rests almost entirely on the conservative pieces we can reasonably defend. It leaves out the ​“insurance value” every healthy person gets from knowing a treatment will be there if they’re ever diagnosed; the scientific spillover of proving that an entire ​“undruggable” class can in fact be drugged; and the ​“bridging” value of simply keeping patients alive long enough to reach the next innovation. GCEA counts all three as real. For now, we’ve omitted these elements. And keep in mind that US GDP over that time period adds up to over $4 quadrillion, so $1 trillion is both a lot and plausibly modest. If these numbers seem absurd, it’s because we don’t typically talk about societal value. But we should.

To help you argue with us, we show you our work in detail in the technical appendix. And we encourage you to pressure test these assumptions using the NPLB GCEA Calculator. 

Plausible sales will be a bargain

When we consider the fundamental inputs for any serious analysis of zolucatetide’s commercial potential, we think the risk is not that analysts will be wrong about the biology – it’s that they’ll be timid about the sales math.

Start where we have data. Between desmoid, FAP, and ACP, roughly 60,000 Americans live with a tumor driven, in essentially every case, by the very protein zolucatetide shuts off. These are young patients with near-normal life expectancy and a disease that never really goes away – which means they’d take a well-tolerated drug that controls it for years, and in many cases for life. For a population that size, treated chronically, addressing the root genetic driver, with no real competition in FAP or ACP and a superior profile to the only approved desmoid drug, we’d put plausible pricing around $300,000 – $350,000 a year (around the price of Trikafta, Vertex’s cystic fibrosis drug, which serves a similar-sized population, and in line with SpringWorks’ nirogacestat, already priced there for desmoid). Nirogacestat poses some competition in desmoid, but if zolucatetide keeps looking more effective and more tolerable, we’d expect it to win the patient. In FAP and ACP there is nothing else.

Treat all of those patients chronically and zolucatetide is an $18-to-$21 billion-a-year drug in the US alone. And because these patients are diagnosed young, it’s largely a commercially insured drug. That’s a major franchise built on three diseases most physicians have never knowingly treated. Since even Vertex has to offer some rebates to gain coverage, we would assume that as zolucatetide climbs towards peak sales, its net price comes down to $250,000; some desmoid tumors might actually end up fully resolved and allow patients to discontinue therapy and maybe not all patients stay on therapy all the time, so we can sandbag $18 billion down to a still very respectable $12 billion. But that could just be the beginning of the story.

Now consider colorectal cancer. About 150,000 Americans are diagnosed every year, and roughly 80% (120,000/year) of those tumors carry the same broken APC/​beta catenin wiring that defines FAP and ACP. This is no longer an orphan indication; it’s one of the most common cancers. While many are cured with surgery, 55,000 people die of colorectal cancer each year and we clearly still need better drugs. 

But metastatic colorectal tumor is not a desmoid tumor. It’s a genetic mess, with beta catenin dysregulation due to APC loss piled together with mutations in KRAS, TP53, SMAD4, and other drivers. And we’ve learned the hard way that hitting a single driver in a crowded tumor can disappoint: KRAS inhibitors, a case in point, worked far better in lung and pancreatic cancer than they did as solo agents in colorectal. So why would a beta catenin inhibitor be any different? Because beta catenin dysregulation is often the mutation that starts the whole thing. Unlike the driver mutations a tumor picks up along the way, including KRAS, APC loss is typically truncal – the founding event, present in essentially every cell of the tumor. A drug that shuts off the consequence of that founding break is attacking something the entire tumor still depends on, not a side mutation that only some cells carry. That doesn’t guarantee a desmoid-like response in a disease this complex, but it’s why beta catenin is a better-than-average bet to matter even in a messy tumor, and why we’d expect zolucatetide to earn its keep as a backbone of combination therapy, added to the existing regimen to attack the one driver the rest of the drugs miss.

Zolucatetide would enter where new oncology drugs always enter: in advanced, metastatic disease. That’s some 50,000 patients a year, the overwhelming majority of them with ​“microsatellite-stable” tumors that do not respond to today’s immunotherapies. And then, as zolucatetide proves itself, it would move earlier into the adjuvant setting, where the populations are larger and the goal is a cure.

How long would a patient stay on it? Our model assumed zolucatetide buys responders something like a year to a year and a half in the metastatic setting; in practice a patient stays on a working combination until the disease outruns it, so call it one-to-two years per patient, and longer as the drug moves into earlier-stage, longer-horizon use. Volume of this kind also pulls price down – a drug treating a hundred thousand people a year is not priced like one treating eleven thousand – so assume the per-patient net price settles closer to $200,000. Start with metastatic disease, about 25,000 patients a year with concomitant tumor drivers, of whom perhaps 20,000 carry the targetable beta catenin lesion. At full penetration, that math – 20,000 eligible patients, on drug for eighteen months or so, at $200,000 – suggests a $6 billion-a-year drug, and real net revenue would build toward it over years rather than arrive at launch. Let it then earn its way into earlier lines, toward the full 60,000-patient beta catenin pool across all stages, and colorectal cancer alone eventually becomes a $10-to-$13 billion franchise. By itself.

Since a lot of colorectal cancer would be covered by Medicare and it’s not an orphan indication, any Helicon regulated under the NDA path like small molecules would be price controlled nine years after launch (i.e., it would face the pill penalty). Since desmoid and FAP are orphan indications, they are exempt from this Inflation Reduction Act policy. Therefore, it might make sense for Parabilis to develop a second zolucatetide-like molecule for colorectal cancer so as not to clip zolucatetide’s branded period. Or else pursue a novel combination with another agent so as to restart the IRA clock. (That’s not the most efficient development path and it doesn’t benefit patients, but it’s the one Congress is steering companies down.)

Other beta catenin tumors stack on top of colorectal cancer. In liver cancer, roughly a quarter to a third of the 33,000 annual cases are beta catenin-driven – call it 10,000 patients a year – that’s another $1.5 billion at combination pricing. Hepatocellular carcinoma is orphan so zolucatetide itself could be developed here without blowing its IRA exemption. Parabilis has treated three patients with HCC and observed a response in one.

Compared to the patient numbers of the tumors we have already touched on, we won’t bother to quantify the remaining cluster of rarer tumors where beta catenin is as central as in desmoid; these include solid pseudopapillary neoplasm, salivary gland tumors, and ameloblastoma. They are each ultra-rare but so dependent on this one pathway that they’re exactly the kind of pure-biology indications that establish a tumor-agnostic beachhead – and several are diseases of children and young adults who, once controlled, could be on the drug for a very long time. Parabilis has reported tumor shrinkage in all five patients with these rare beta catenin tumors and objective responses in four of them.

The biggest prize is that beta catenin is implicated in more than 10% of all cancers – on the order of 200,000 newly diagnosed Americans every year. A tumor-agnostic approval based on a tumor’s genomic signature rather than its organ of origin – the path blazed by NTRK inhibitors and other molecularly-defined drugs – is a precedented, increasingly well-worn regulatory strategy. Capture even a slice of those 200,000 patients and the tumor-agnostic opportunity rivals the desmoid/​FAP/​ACP orphan and colorectal franchises combined.

Add it all together and a fully realized zolucatetide amounts to a $25-to-40-billion-a-year drug in the US alone, with additional sales in other countries. That feels unprecedented. A lot more has to go right clinically. One can come up with all kinds of ways to discount it. Maybe CRC won’t respond to a beta catenin inhibitor even in combination with a KRAS inhibitor. Maybe resistance will emerge in desmoid tumors. 

Maybe there will be competitors; while drugging beta catenin is clearly extremely hard, the prize for doing so is so large that others will try and we assume others will figure out how to do it. Zolucatetide is an injectable drug that’s likely to be administered with a thin-needle autoinjector every one-to-two weeks. In this age of Ozempic, we don’t think patients will mind this route of administration for a drug that controls their tumors. But if anyone were to crack the code for developing an oral beta catenin inhibitor that had similar safety and efficacy to zolucatetide, that would take market share. (That’s why Parabilis would be wise to work on its own.)

So rather than talk about zolucatetide itself as being a $30 billion drug, let’s instead consider it the first of a $30 billion/​year drug class that might be branded for a period of even as long as twenty years. That assumes the first generation drugs go generic 13 – 14 years after launch and the next generation launches six years later and goes generic 13 – 14 years after that. Allowing the drugs to ramp towards $30 billion over the first decade in the US and then plateau for the next decade, we’re talking about a total of $450 billion spent by the US to get what we estimate is at least $1 trillion of societal value.

It’s worth noting that with Vertex earning about 60% of its global CF sales in the US, a $25 – 40 billion US drug class might scale to $40 – 60 billion/​year worldwide. CF skews towards more European ethnicities whereas beta catenin-driven cancers are more evenly distributed, so worldwide sales might actually be much larger. This is a class worthy of the biggest pharmas. 

It’s too early in the validation of zolucatetide itself to try to get precise about what its sales trajectory would be, but it doesn’t take much imagination to get to large numbers. There’s enough in the beta catenin thesis alone to grow Parabilis into the next Vertex. And then there’s the pipeline, which includes other hard-to-drug targets that Helicons are built to take down.

The beta catenin revolution is underway. The first shots have been fired. The first battles are being fought now and will expand to many indications. Parabilis and any others who may crack the beta catenin code are likely to make a giant contribution to humanity’s war on cancer. 

RA Capital Management is a long-term investor in Parabilis Medicines and participated in the company’s Series E, Series F, and IPO. This article is for informational purposes only and does not constitute investment advice. Please see Disclosure for additional important information.

All clinical data cited above is drawn from Parabilis Medicines’ S‑1 registration statement filed with the SEC on May 19, 2026. AI-generated content in this article has been independently reviewed; please verify all specific data points against primary sources before reliance.