The next big shake-up in the GLP-1 market? (Part 1 of 3)

0:05This is Beyond Biotech and today we're launching a special three part series on GOP1s and the future of metabolic health. a series we're calling the metabolic moment. In just a few years, GOP1s have become a phenomenon. They've transformed how we treat diabetes and obesity, created one of the biggest markets in pharma, and sparked a cultural conversation that reaches far beyond the clinic. Now that market is shifting. Cheaper alternatives are coming. New mechanisms are entering trials, and some companies are aiming for something closer to a cure. so what happens next for patients for the companies leading the field and for the startups hoping to overtake them across three conversations we'll follow the money the science and the people behind this metabolic moment

1:13GLP-1 drugs have gone from a diabetes niche to one of the biggest stories in modern medicine. Today, the market is at a turning point. Patents are expiring in India, China and Canada, and generics are on the horizon. Pills are challenging injections, Amgen is testing a monthly drug, and GLP-1s are moving into heart, kidney and liver disease. All the while, Novo and Eli Lilly hold a tight grip on the field. So what happens next? Will new players break through or will this market consolidate through M &As? To help us make sense of it, I'm joined by Valeria Simonovskia, founder and CEO of BioBrokers, an independent capital markets and strategic advisory firm for the life sciences.

1:58Trained at Harvard Medical School and based in Paris, Valeria tracks where the money in biotech is flowing. Valeria, welcome to Beyond Biotech. Hi, Dylan. Thank you so much for having me. I'm really happy to be here. Now, you're the founder, you're the CEO at BioBrokers, which is an independent capital markets and strategic advisory firm that works in biotech and life sciences. Tell me, what does BioBrokers actually do day to day? What sort of clients are you working with? BioBrokers sits at the intersection of science, capital and dealmaking. We work with biotech and life sciences companies that are raising capital, looking for strategic partners, exploring licensing opportunities or preparing for M &A.

2:46My role is really to connect the dots between the science and the transaction, understand what makes a company or technology compelling, sharpen the investment story, identify the right investors or strategic partners and stay involved through introductions, diligence and the real process. We also work from the other side of the table, helping investors to identify opportunities they might otherwise miss. You trained at Harvard Medical School, right, before moving into this capital markets and advisory work. Did that background end up shaping the way that you're looking at deals, the way you're looking at markets?

3:25Well, my academic background is in psychiatry, neuroscience, and I later completed additional training in oncology, autoimmunity, drug development and modern treatments through Harvard Medical School that absolutely affects how I look at deals. I don't look at biotech opportunity purely as a financing story. I want to understand the mechanism, translational rationale, patient population, endpoints, comparator, clinical design, and what the standard of care may look like by the time the product reaches market. Obesity is a perfect example here. A headline weight loss percentage is insufficient.

4:04You need to ask, compared with what, over what duration, under which estimates, with what tolerability and discontinuation, what happens to lean mass, and what will be the competitive environment look like at lunch? Now, you mentioned obesity there. This is the first episode in our three-part series looking at GLP-1. So I want to turn to GLP-1 and obesity there. Now, for listeners who've only followed GLP-1 through a Zempik, the Wegovi headlines, how would we frame the size of this market right now? I would separate the market that already exists from forecasts about where it might go, because forecasts vary enormously depending on what's included.

4:49This is already a pharmaceutical category worth tens of billions of dollars annually. Just in the second quarter of 2026, Lili reported approximately$9.9 billion in Monjero and$4.9 billion in Zedbong revenue. That's almost$15 billion in one quarter from the same molecule, terzepatide, marketed for different indications. So we're well beyond asking where there is a major obesity pharmacotherapy market. The questions now are how large treatment penetration becomes. how pricing evolves, and how that value gets divided across injectables, pills, and next-generation therapies. You're watching this space from a capital market vantage point rather than just following any single company.

5:39What does that view show you that maybe a company insider might miss? A company naturally looks vertically at its own program. From capital markets, you're forced to look horizontally across all of the assets competing for the same patient, physician, and capital. That means excellent absolute data can still be commercially disappointing if the comparator has moved faster. Cagrysima is a good recent example. In the rate of fine for head-to-head trial, patients adhering to treatment lost 23 % with keggrisema versus 25.5 with teresopetide at 84 weeks. And keggrisema did not meet the pre-specified non-inferiority endpoint.

6:3023 % weight loss is objectively substantial, but in this market, differentiation is relative to a rapidly moving standard of care. I would say good efficacy and competitive differentiation are not necessarily the same thing. Let's talk about this market, though, in a little bit more detail. How would you describe the state of the market right now? Is it still a land grab? Are we moving into some sort of consolidation between these players? I think both are happening, but at different levels. Commercially, there is still expansion because new formulations, new indications, and broader access can bring additional patients into treatment.

7:14But ownership of innovation is already consolidating through M &A and licensing. Pfizer completed the acquisition of Metzera at approximately$7 billion of upfront enterprise value, plus potential contingent payments, specifically adding next-generation obesity assets. Roche's collaboration around Zealand's Amlin Analog Patralantide carries potential consideration of up to 5.3 billion. So I would put it this way. Ownership of obesity innovation may consolidate even while the treatment market itself becomes more fragmented. What about the other side though? Because supply constraints have been really shaping this market for years, especially as these drugs are released onto the market.

8:04Has that eased? And how much has that really decided who's winning and who's not? Supply has eased substantially in the United States. FDA declared the national trisopatide injection shortage resolved in December 2024 and the semaglutide injection shortage resolved in February 25, while noting that intermediate local disruptions could still occur. Supply clearly constrained how quickly the category could expand during the early demand surge, but I wouldn't claim we can quantify now how much of today's competitive positioning was caused specifically by supply rather than efficacy, access, pricing, marketing, or physician preference.

8:53going forward manufacturing scale still matters enormously but competition is increasingly about the whole product proposition rather than simply where there is inventory you know one of the other things that is keeping coming up as a concern is that discontinuation rate the people who just drop away what are those numbers looking like and are they going to dent the long-term sales projections for these drugs? I separate real-world persistence from the biological consequences of stopping treatment. On persistence, a large U.S. claims analysis from Prime Therapeutics found that only 8 % of people initiating GLP-1 therapy for obesity without diabetes remained persistent at three years.

9:46Among patients initiating the newer high-potency obesity-approved products, persistence was better, but still only 14%. Those are observational data, so insurance coverage, access, and treatment era matter. But the randomized withdrawal evidence is very clear that regaining can occur after treatment stops. In the step one extension, participants regained approximately two-thirds of their prior semaglutide-induced weight loss within a year of withdrawal. In Sermon 4, people switched from trisopetide to placebo, regained 14 % of body weight between weeks 36 and 88, whereas those who remained on trisopetide lost another 5.5%.

10:36Commercially, that means models shouldn't assume every patient remains continuously treated forever. Scientifically, it creates a very important unmet need around long-term maintenance. You know, some of the people looking at those models are the investors. Is their appetite for these GLP-1 assets still as strong as it was a couple of years ago, or is it waning now? The evidence suggests obesity remains a highly attractive investment area, but the financing environment has become much more selective. Dealforma data complied by Stifo show venture investment into private obesity biotex rising roughly from$305 million in 2023 to$979 million in 2024, with the first half of 25 resulting at about 986 million.

11:38At the same time, the wider healthcare VC environment in 2026 is concentrating capital into fewer companies. SVB reports that healthcare financing counts reached a multi-year low in the first half of 26, even though biopharma still raised 12.6 billion. So I wouldn't say appetite disappeared. I would say the obesity premium remains, but investors are becoming much more selective about what deserves that premium. Let's talk a little bit more about that business side. Some of these GLP-1 patents have already expired in India, in China, in Canada. Even we wrote about that at Labiotech earlier this year.

12:28But in the US, those patent expiries are still more than a decade away. What does this timeline mismatch actually mean for global access? I would slightly qualify the word patents because active ingredient patent expiry, secondary patents and regulatory protection aren't necessarily the same thing. Novo's current patent table lists active ingredient protection for semaglutide products through 2032 in the US, 31 in Europe and Japan, and 2026 in China, while stating that formulation, manufacturing and use patents and regulatory protection can extend practical exclusivity. But earlier entry markets are already showing us what price competition can look like.

13:23In India, the semaglutide patent expired in March 2026, and more than 40 companies were preparing generic products. Initial generic pricing was expected at discounts of at least 50 to 60 percent. So countries such as India and Canada effectively become real-world experiments in what happens to access and volume when GLP-1 prices fall years before the major U .S. cliff. So we're already seeing generics and biosimilars move into those markets where the patents, at least part of the patent protection, has already lapsed. Yes, this is no longer theoretical. Health Canada approved the country's first generic semaglutide referencing Zempic in April 2026.

14:18Then in June, it approved Apotexis, the first generic semaglutide, specifically referencing Vigobi for weight management. India has also seen multiple generic semaglutide launches following the March patent expiry. I would call them generic semaglutide products where the regulator does rather than casually using biosimilar for all of them. So if you're Novo, if you're Lilly and thinking about defending your share in a market where they can't rely on patent protection anymore, what's their strategy going to be? I think it's important not to treat Novo and Lily as though they're facing identical pattern cleaves.

15:07Novo has the immediate semaglutide problem in some markets. In India, for example, Novo had already reduced Bigoli pricing substantially as generic competition approaches. Its broader defense is lifecycle management, pricing, brand distribution, additional indications, oral, we go be and next generation products. Lily's Terzepatite portfolio has a different and newer IP timeline. So its current strategy is less about defending an expired Terzepatite patent and more about maintaining differentiation and portfolio succession. Mongearo, Zivon today, Fondeo as an oral small molecule and potentially retetridite next.

15:59Once core molecular exclusivity weakens, evidence, outcomes, manufacturing, brand, distribution, and the next molecule in the portfolio becomes increasingly important in months. You mentioned the oral pill there. These oral GOP ones are clearly the next big shift in delivery. How much does moving from injection to pill actually change the competitive landscape? I'd actually update the premise slightly. The oral shift has already begun. FDA approved one's daily oral Wigovi 25 milligram in December 2025, making it the first oral GLP-1 approved for weight management. And FDA approved Lilly's oral small molecule GLP-1 found Ayo in April 2026.

16:54It adds another competitive dimension, not just efficacy, but root of administration, daily versus weekly treatment, manufacturing architecture, and patient preference. I don't think pills simply replace injections. I think they're appearing as a separate market segment. Yeah, that was really my next question, I guess, because there are manufacturing, there are pricing factors, which are going to decide whether pills take over from injectables or just make them a second option? You think it's probably more likely a second option? Well, the important point is that not all oral GLP-1s are technologically equivalent.

17:39Oral Regovi is still the peptide semaglutide. Its maintenance tablet is 25 milligram daily and has specific administration requirements. It has to be taken in the morning on an empty stomach with no more than four ounces of water, followed by at least a 30-minute wait before food, other drinks, or oral medicines. Or for glyprone is a non-peptide small molecule. Its FDA label allows one daily administration with or without food, and it's stored at room temperature. So competition will depend on API requirements, manufacturing capacity, stability, administration burden, efficacy, tolerability, reimbursement, and price.

18:30I would not say that small molecules are automatically cheaper to manufacture unless we have actual cost of goods data. The potential manufacturing advantages need to translate into real commercial economics. So do these oral formulations actually open the market to a bigger, different set of patients, or is it convenient for people who are already willing to inject and just looking for an alternative? I think it probably does both, but we don't yet have enough evidence to quantify the split. An oral option clearly removes needle aversion as a barrier and could fit more naturally into primary care.

19:17But an existing injectable patient switching to a pill is substitution within the market, whereas a patient who would never have started an injection is genuinely incremental demand. And early commercial uptake suggests meaningful interest in oral treatment, but we shouldn't pretend that prescription numbers alone tell us exactly how many people are truly new to obesity pharmacotherapy. So the real question is not just oral versus injectable share. It's whether oral formulation expands the denominator. So of the big players, the ones already in the market now, who do you think is the best position in this oral technology?

20:09That's an interesting one. Commercially today, Nava has the first mover advantage because we go be peel launched first. Lily, however, has a very different oral architecture with Fondeo, a non-peptide small molecule that can be taken with or without food. The race is already becoming competitive. As of mid-September, Lily said Fondeo was capturing more than 30 % of new U.S. patients starting an oral obesity drug, while WeGoVPO remained the established leader. so I wouldn't declare a long-term winner yet. Novo currently has first mover scale and semaglutides enormous evidence base. Lily has a highly convenient small molecule platform and rapidly growing uptake.

21:06Maybe we should talk for a second about some of these players beyond those big two. I mean, Novo and Lily are so dominant right now. Is there still room for other companies to break into the GLP-1 space? Sure, but the bar is much higher than simply demonstrating that another GLP-1 can reduce weight. A new entrant can potentially differentiate on efficacy, tolerability, oral delivery, less frequent dosing, body composition, maintenance, a specific comorbidity, or a complementary mechanism. The fact that Pfizer paid roughly$7 billion for Metzera and Rush structured a transaction worth up to$5.3 billion around Zealand's Amelon program is concrete evidence that major pharmaceutical companies still see substantial value outside the incumbent portfolios.

22:08but undifferentiated me too biology has a much harder investment case you know one that we're keeping an eye on right now is amgen's maritide this is really interesting it's monthly dosing and it blocks the receptors instead of activating it like a manjaro does do you think something like this could pan out and if it does how does the market change once we go to monthly dosing Meritide deserves to be taken seriously but I wouldn't call its ultimate success proven before the phase three mechanistically it is genuinely different it combines GLP-1 receptor agonism with GIP receptor antagonism whereas terzepatide activates GLP-1 and GIP receptors In the peer-reviewed Phase 2 study of 592 participants, people with obesity without diabetes had mean weight reductions ranging from 12.3 % to 16.2 % at 52 weeks, depending on regimen, versus 2.5 % with placebo.

23:24Gastrointestinal adverse effects were common. The potentially important differentiator is dosing frequency. Amgen's phase 3 program is testing monthly, every eight weeks, and even quarterly maintenance schedules, including a switch trial in people coming from weekly semiglutide or terizipatide. if phase three confirms acceptable efficacy tolerability and durability at those intervals the competitive advantage may be persistence and treatment burden rather than simply another percentage point of weight loss beyond amgen though are there smaller biotechs or other things you've read about in in the pipeline of certain companies that we should be watching I would watch different approaches rather than try to predict one winner.

24:24For example, Structure Therapeutics, L-N-Glyprone, is a once daily oral non-peptide GLP-1. The company reported placebo-adjusted mean weight loss of 16.3 % at 180 mg and 16 % at 240 mg after 44 weeks in Phase 2. Those are company-reported top-line data, not yet the same evidentiary level as a peer-reviewed Phase 3 study. There is another example, it is Viking's VK2735, which is a dual GLP-1 GIP agonist being developed both orally and subcutaneously. Viking reported up to 12.2 % mean weight loss after 13 weeks with the oral formulation in phase 2. Again, this is company reported phase two data and 13 weeks is far too short for direct comparison with 52 or 72 week trials.

25:37And Zealand's Petrolentide is interesting because it's a long acting Amelian analog rather than simply another conventional GLP-1 program. and Roche's decision to partner it validates the strategic interest in that mechanism. So given the duopoly really that we see today, do you think the market's going to consolidate further as we're reinvesting mergers and acquisition? Or is there a real path forward to a more fragmented, multiplayer market that might emerge over time? I'd expect both. The enormous cost of late-stage obesity trials, outcome studies, global manufacturing, and commercialization gives big pharma a structural advantage.

26:26So I expect continued acquisition and licensing of successful biotech programs. But clinically, the market can fragment into oral versus injectable, weekly versus monthly or quarterly, maximum weight loss treatment versus maintenance, different combinations, and potentially different therapies for different comorbidity profiles. So my view is consolidated ownership does not necessarily mean consolidated treatment. Let's talk about some of the other things that we're tracking around GLP-1s. And one of them is really using them for non-metabolic indications. So cardiovascular, kidney disease, MASH, sleep apnea, even addiction.

27:15Which of these sorts of expansions or applications of these GLP ones surprised you the most? Scientifically, addiction surprised me most because that's my topic, because it raises the possibility that increasing biology effects reward related behavior, as well as appetite and metabolism. But I would be extremely careful about the evidence level. A randomized phase two trial published in JAMA Psychiatry included only 48 adults with alcohol use disorder. Semaglutide reduced alcohol consumed in a lab self-administration experiment and reduced some measures of craving and drinking. but it did not improve every alcohol use endpoint.

28:09The authors explicitly concluded that larger trials are needed. So I would describe addition as a fascinating early signal, absolutely not an established GLP-1 indication. Do you think any of those or maybe even something else has the potential to rival obesity and diabetes in terms of the opportunity size at scale? I wouldn't confidently say that any single adjacent indication rivals obesity and diabetes as an independent market because the populations overlap heavily. Cardiovascular disease may be the most strategically important extension because we already have hard outcome evidence. In the select program, major cardiovascular events occurred in 6.5 % of semaglutide-treated participants versus 8.0 % with placebo, which led FDA to approve VGOVI for cardiovascular risk reduction in adults who already have cardiovascular disease and overweight or obesity.

29:22MASH would be one of the largest instinct disease opportunities. FDA estimates around 14.9 million U.S. adults have MASH. In the interim phase three analysis supporting Regovi's accelerated approval, 63 % versus 34 % achieved MASH resolution without worsening fibrosis and 37 % versus 22 % showed fibrosis improvement without worsening MASH. So I wouldn't simply add cardiovascular, mesh, CKD, and obesity populations together and call that the total addressable market. Many of these are the same patients. You know, one thing that's maybe a little bit under the radar is if we talk about GLP-1s as almost like a miracle drug with these particular indications where there might be opportunities, there might be markets, Are there also risks in having sort of these indication stacking strategies, whether that's regulatory, whether when it comes to reimbursement that companies need to be thinking about and markets need to be thinking about?

30:40Yes. And one of the biggest is simple double counting. The same person can have obesity, diabetes, cardiovascular disease, kidney disease, sleep apnea and MASH. Those aren't six independent commercial populations. Second, each indication can require a very different evidentiary package. The cardiovascular indication for Wigobe came from a trial of more than 17 ,600 patients. The MASH approval is accelerated and the ongoing trial must determine whether histologic improvements translate into clinically meaningful liver outcomes. Third, reimbursement can differ by indication and patient risk. So indication stacking can increase medical value substantially, but you cannot automatically translate six labels into six additive markets.

31:46We're coming up a bit on time here, but I want to put a couple of final questions to you. If you had to bet on one underappreciated trend in this GLP-1 space, what would you bet on? What should we be watching? I think that the underappreciated shift is what happens after the initial weight loss. For several years, the market has focused on pushing peak efficacy higher and higher. But randomized withdrawal studies show that the maintenance is a genuine biological problem. So the next competitive frontier may increasingly be the whole treatment architecture. How do you maintain weight loss, reduce chronic treatment burden, preserve lean mass and combine mechanisms intelligently?

32:32We already have human proven concept on body composition in a randomized phase two trial published in Nature Medicine in 2026, adding the myostatin inhibitor to terzapatite preserved an additional 1.9 kilo of lean mass or roughly 55 % more lean mass versus terzapatite plus placebo, while total body weight loss was similar. And there is an interesting complementary biology outside direct in cretin agonism. One triclinical example is MOGA-2 inhibition. MOGA-2 participates in intestinal resynthesis of dietary triglycerides. published mouse work found that VB87531 enhanced weight loss when combined with semaglutide or terzepidide, that is preclinical mouse evidence, not yet clinical proof in humans.

33:39So to sum up, I don't think the future question is simply GLP-1 versus non-GLP-1. Increasingly, it may be GLP-1 plus what? And what happens after the weight has been lost? What advice can you give to a founder who's trying to find themselves a defensible niche, put a little bit of a moat up in a market that's already dominated by two giants like Novo and Lilly? I would tell them not to begin with, I have another obesity drug. Start with a specific limitation of the future standard of care that you are solving. Is it tolerability, maintenance after withdrawal, lead mass preservation, oral delivery, much less frequent administration, manufacturing scalability, a specific patient subgroup, or is it a mechanism that complements increasing therapy.

34:40And importantly, design your development strategy for the competitive landscape you will face at launch, not the market today. An early stage program entering development now may eventually compete against oral GLP-1s, triple agonists, amylin combinations, maintenance regimens, and much cheaper semaglutide in many countries. The fancible niche has to survive that future market. You know, this is all fascinating. Where can listeners follow up on your work? Where can they read more about what Biobrokers is doing in the sector? I publish market and transaction analysis through LinkedIn. Most of my work is around the intersection of life sciences, innovation, capital markets and strategic transactions and people can also find us at biobrokers.net perfect i want to thank you so much for joining us today on beyond biotech thank you thank you so much for having me and i really enjoyed the conversation that's it for this episode don't forget to check out all the latest news and analysis at labiotech.eu.

35:58I hope wherever you are in the world, you have a great week ahead. Thanks for listening, and I hope you'll join us again next time for another Beyond Biotech.