Table of Contents As filed with the Securities and Exchange Commission on March 27, 2026. Registration No. 333- UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 FORM S-1 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 Kailera Therapeutics, Inc. (Exact name of registrant as specified in its charter) (State or other jurisdiction of incorporation or organization) Delaware 2834 99-3088927 (Primary Standard Industrial Classification Code Number) 180 Third Avenue, 4th Floor Waltham, ...

Company Overview - Viking Therapeutics completed enrollment in the phase III VANQUISH-2 study for its obesity drug VK2735, targeting approximately 1,000 adults with type II diabetes who are either obese or overweight [1][7] - The study's primary endpoint is the percent change in body weight from baseline after 78 weeks of treatment, with patients randomized to receive either VK2735 at doses of 7.5 mg, 12.5 mg, or 17.5 mg, or a placebo [2][7] - The completion of enrollment is a significant milestone, as the study was initiated in June 2025, alongside the VANQUISH-1 study, which has enrolled nearly 4,650 adults with weight-related co-morbid conditions [3][4] Market Context - The obesity market is experiencing rapid growth, with strong demand for weight loss drugs, driven by the success of competitors like Eli Lilly's Zepbound and Novo Nordisk's Wegovy [4][9] - Goldman Sachs projects the U.S. obesity market will reach $100 billion by 2030, highlighting the competitive landscape as both Eli Lilly and Novo Nordisk optimize production and develop new GLP-1-based candidates [9] - Novo Nordisk recently received FDA approval for the oral version of Wegovy, which offers a more convenient administration option compared to injectables, potentially improving patient adherence [10] Competitive Landscape - Eli Lilly is also advancing in the oral obesity treatment space, with a regulatory filing for its oral candidate orforglipron currently under review, and a decision expected next month [11] - The introduction of effective oral GLP-1 therapies is likely to reshape preferences among patients and physicians in the obesity market [11] - Viking Therapeutics is advancing its oral version of VK2735 into late-stage development, expected to begin in the third quarter of 2026 [12]

Financial Data and Key Metrics Changes - Cash equivalents and marketable securities increased to $49.7 million as of December 31, 2025, up from $27.6 million at year-end 2024, reflecting a successful $60.3 million private placement and an upfront license payment from Chugai [12][13] - Contract revenue for Q4 2025 was $1.5 million, with total revenue for the year at $1.6 million, compared to $1 million for Q4 2024, all related to evaluation services [13][15] - Net losses for Q4 2025 were $9.1 million, down from $15.7 million in Q4 2024, while full-year net losses were $41 million compared to $56.6 million in 2024 [16][17] Business Line Data and Key Metrics Changes - Research and development expenses for Q4 2025 were $4.9 million, down from $6.8 million in Q4 2024, reflecting cost containment measures [15][16] - General and administrative expenses decreased to $5.1 million in Q4 2025 from $5.5 million in Q4 2024, primarily due to reductions in employee compensation [16] Market Data and Key Metrics Changes - The collaboration with Chugai Pharmaceutical is valued at up to approximately $1.1 billion, focusing on the development of an oral therapy using the Rani Pill platform [5][6] - The Rani Pill platform aims to replace injectable therapies with oral delivery, targeting high-value therapeutic areas such as rare diseases and immunology [6][8] Company Strategy and Development Direction - The company is focused on advancing the Rani Pill platform to enable oral delivery of biologics, with significant progress in clinical trials and strategic partnerships [4][11] - The partnership with Chugai highlights the scalability of the Rani Pill platform and the potential to apply it across various biologic molecules [6][11] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the potential of the Rani Pill platform to transform biologic medicine delivery, particularly in the obesity treatment market [18] - The company is well-capitalized to execute its development plans and advance its clinical pipeline, with a projected cash runway extending into Q4 2027 [13][18] Other Important Information - The company has initiated a phase I clinical trial for RT-114, which is designed to evaluate safety, tolerability, and pharmacokinetics [10][11] - The Rani Pill platform has shown high tolerability in preclinical studies, supporting the belief that oral biologics could improve patient experience [9][11] Q&A Session Summary Question: Will weight loss data be presented for RT-114? - Management confirmed that weight loss is one of the endpoints in the phase I-B study, and they will compare it to historical data for PG-102 [20][22] Question: What additional doses will be explored for RT-114? - Management indicated that they are focused on tolerability and may consider higher doses if the data supports it, emphasizing the importance of maintaining a good tolerability profile [22][23] Question: What additional value is expected from the phase I study for RT-114? - Management highlighted that this is the first pharmacodynamics study with the Rani Pill in humans, and positive results could unlock broader applicability for the platform across various therapeutic areas [28][30]

Wave Life Sciences Conference Call Summary Company Overview - **Company**: Wave Life Sciences (NasdaqGM: WVE) - **Focus**: Development of transformational medicines leveraging human genetics, specifically targeting obesity with WVE-007, a GalNAc siRNA. Key Industry Insights - **Obesity Treatment Landscape**: Current therapies primarily focus on caloric restriction and appetite suppression, often leading to muscle loss and high discontinuation rates. There is a significant unmet need for therapies that promote fat loss while preserving muscle mass. Core Points from the Call 1. **Positive Interim Data**: The interim data from the Phase I ENLIGHT trial of WVE-007 shows a clinically meaningful 14% reduction in visceral fat and a 3.3% reduction in waist circumference after 6 months following a single dose, alongside a 1% weight loss [4][5][29]. 2. **Mechanism of Action**: WVE-007 silences inhibin E to lower serum activin E, which promotes fat storage. By reducing activin E, WVE-007 enhances lipolysis, leading to fat loss and muscle preservation [10][11][12]. 3. **Safety Profile**: The treatment has shown a clean safety profile with no serious adverse events reported across all cohorts, supporting its potential for widespread use [27][28]. 4. **Next Steps**: The company plans to advance WVE-007 into Phase II A trials targeting a higher BMI population (35-50) with comorbidities, expected to start in Q2 2026 [34][36]. 5. **Dosing Strategy**: WVE-007 may allow for infrequent dosing (once or twice a year) due to its durable suppression of activin E, with ongoing studies to confirm optimal dosing regimens [28][46]. Additional Important Insights - **Comparative Advantage**: WVE-007 is positioned to outperform current obesity treatments by reducing visceral fat without the associated muscle loss seen in other therapies, such as GLP-1s [9][19]. - **Clinical Biomarkers**: The trial will also assess clinical biomarkers related to metabolic health, including HbA1c, lipid levels, and muscle function, which are critical for understanding the broader implications of fat loss on health [35][39]. - **Market Potential**: There is a significant opportunity for WVE-007 in the obesity market, particularly among individuals who cannot tolerate existing therapies due to muscle loss concerns [56][57]. Conclusion Wave Life Sciences is making significant strides in the development of WVE-007 as a novel treatment for obesity, with promising interim clinical data and a clear path forward for further trials. The focus on preserving muscle while reducing visceral fat positions WVE-007 as a potentially transformative therapy in the obesity treatment landscape.

Core Insights - Biomea Fusion, Inc. has made significant progress in clinical trials for its lead asset, icovamenib, targeting type 2 diabetes, with promising 52-week clinical data reported [2][5] - The company has initiated two Phase II trials for icovamenib and advanced its next-generation oral GLP-1 receptor agonist, BMF-650, into a Phase I study [2][4] - Financial results for the year ended December 31, 2025, show a net loss of $61.8 million, a reduction from $138.4 million in 2024, indicating improved financial management [7][14] Clinical Development - Icovamenib demonstrated a persistent 1.2% mean reduction in HbA1c in patients with type 2 diabetes, maintained through Week 52 after a 12-week treatment [5] - Two Phase II trials, COVALENT-211 and COVALENT-212, have been initiated, with primary endpoint data expected in the fourth quarter of 2026 [4][11] - BMF-650 is undergoing a Phase I trial, with initial 28-day weight reduction data anticipated in the second quarter of 2026 [4][11] Financial Performance - As of December 31, 2025, the company reported cash, cash equivalents, and restricted cash of $56.2 million, a slight decrease from $58.6 million in 2024 [11][17] - Research and Development (R&D) expenses decreased to $62.0 million in 2025 from $118.1 million in 2024, primarily due to a strategic realignment [11][14] - General and Administrative (G&A) expenses also decreased to $19.3 million in 2025 from $26.0 million in 2024, reflecting cost-saving measures [11][14] Company Overview - Biomea Fusion is focused on developing oral small molecule therapies for diabetes and obesity, addressing a significant global health challenge [8] - The company's mission is to deliver transformative treatments for patients with diabetes, obesity, and related conditions [8]

Core Insights - Lexicon Pharmaceuticals and Novo Nordisk are collaborating on LX9851, an oral non-incretin candidate for obesity and metabolic disorders, with Novo Nordisk initiating a Phase 1 study [1][4] - Lexicon has received a second $10 million milestone payment from Novo Nordisk and is eligible for up to $1 billion in total payments, including royalties on net sales [3] Group 1: LX9851 Development - LX9851 is a first-in-class oral small molecule inhibitor of Acyl CoA Synthetase 5 (ACSL5), which regulates fat accumulation and energy balance [5] - The Phase 1 study will assess safety, tolerability, pharmacokinetics, and pharmacodynamics in 96 participants with overweight or obesity, expected to complete in Q1 2027 [4] Group 2: Financial Aspects - Lexicon is eligible for a total of three $10 million milestone payments, with the second payment received in 2026 following initial dosing in the Phase 1 study [3] - The collaboration agreement allows Lexicon to receive up to $1 billion in upfront and milestone payments, along with tiered royalties on net sales of LX9851 [2][3] Group 3: Company Perspectives - Lexicon's CEO expressed enthusiasm about the progress made by Novo Nordisk in advancing LX9851, highlighting its potential as a differentiated treatment for obesity [4] - Novo Nordisk's Senior Vice President emphasized the novel approach of LX9851 in treating obesity and related metabolic conditions, marking it as a significant addition to their pipeline [4]

Core Insights - Eli Lilly's next-generation obesity drug retatrutide has successfully completed its first late-stage trial for Type 2 diabetes patients, demonstrating significant improvements in blood sugar management and weight loss [1][2][3] Group 1: Drug Efficacy - Retatrutide reduced hemoglobin A1c levels by an average of 1.7% to 2% at 40 weeks compared to placebo, achieving the primary study goal [1] - At the highest dose, retatrutide helped patients lose an average of 16.8% of their weight, equating to 36.6 pounds, over 40 weeks [2] - The drug's A1C reduction, while not the highest in Lilly's portfolio, is still considered strong compared to other diabetes medications that do not target gut hormones [6] Group 2: Patient Experience and Safety - The discontinuation rate due to side effects was relatively low, at up to 5%, indicating a favorable safety profile [3] - Common side effects included gastrointestinal issues, with 26.5% of patients experiencing nausea, and lower rates for diarrhea and vomiting [10] Group 3: Competitive Landscape - Retatrutide is positioned as a key component of Lilly's obesity portfolio, alongside its existing drug Zepbound and the upcoming orforglipron [4] - Novo Nordisk is developing a competing drug that also targets multiple hunger-regulating hormones, but it is still in earlier stages of development [12][13] Group 4: Market Strategy - Lilly plans to report findings from seven additional phase three trials by the end of the year, although it has not yet filed for approval for retatrutide [5] - The company emphasizes the importance of having multiple treatment options for obesity and diabetes, as individual patient needs may vary [7][8]

Core Insights - The company reported significant weight loss results from its investigational oral drug, aleniglipron, designed for treating obesity, contributing to a rise in stock price while broader markets showed mixed movements [1] Group 1: Clinical Trial Results - Aleniglipron achieved a placebo-adjusted mean weight loss of 16.3% (39 lbs) at the 180 mg dose and 16.0% (37 lbs) at the 240 mg dose after 44 weeks, with no evidence of a weight loss plateau [2] - Interim data from the ongoing ACCESS Open Label Extension study showed continued weight loss of up to 16.2% (40.5 lbs) with the 120 mg dose at 56 weeks, demonstrating the drug's efficacy and favorable safety profile [2][3] Group 2: Regulatory and Development Plans - The company plans to hold an FDA end-of-Phase 2 meeting in Q2 2026, with Phase 3 initiation on track for the second half of 2026 [4] - The trial is designed with a starting titration dose of 2.5 mg, intending to evaluate multiple doses up to 240 mg [4] Group 3: Competitive Advantages - CEO Raymond Stevens highlighted four factors that could make aleniglipron competitive, including its efficacy, with a higher dose leading to weight loss of up to 15.3% at 36 weeks [5] - The drug's manufacturing cost is favorable as a small-molecule pill, allowing for efficient production at scale for the U.S. market [6] - Aleniglipron can be combined with other therapies, showing synergistic effects when paired with an amylin-targeting drug [6] Group 4: Stock Performance and Technical Indicators - The stock is currently trading 6.5% below its 20-day simple moving average (SMA) but 1.3% above its 100-day SMA, indicating short-term weakness while maintaining longer-term strength [7] - Over the past 12 months, shares have increased by 146.67%, positioned closer to their 52-week highs than lows [7] Group 5: Analyst Consensus and Market Position - The stock carries a Buy Rating with an average price target of $101.20, indicating positive analyst sentiment [9] - Recent analyst actions include a Buy rating from HC Wainwright & Co. with a target raised to $114.00 [10]

Core Insights - The Phase II COVALENT-111 study results indicate that icovamenib has a favorable safety profile and shows potential in transforming diabetes treatment through significant reductions in HbA1c levels [1][2] Company Overview - Biomea Fusion is a clinical-stage company focused on developing oral covalent small-molecule drugs for metabolic diseases, utilizing its proprietary FUSION System discovery platform [7] - The principal drug candidate, icovamenib, is being investigated for its effects on type 1 and type 2 diabetes, as well as obesity [8] Clinical Study Results - The COVALENT-111 study demonstrated that severe insulin-deficient patients experienced an HbA1c reduction of 1.2% at Week 52, with the most effective dosing regimen achieving a mean reduction of 1.5% [2] - The study maintained a favorable safety profile with no serious treatment-related adverse events reported throughout the 52-week observation period [1] Market Performance - Biomea Fusion shares were up 3.68% at $1.41, indicating positive market sentiment following the study results [11] - The stock is currently trading 2.9% above its 20-day simple moving average and 4.0% above its 100-day simple moving average, suggesting short-term strength [4] Analyst Outlook - The stock carries a Buy Rating, with recent analyst actions including maintaining a target price of $12.00 by D. Boral Capital and a lowered target of $6.00 by Citigroup [11] - The next financial update is expected on March 30, 2026, with an EPS estimate of a loss of 23 cents, improved from a previous estimate of a loss of 81 cents [11]

Protagonist Therapeutics FY Conference Summary Company Overview - Protagonist Therapeutics focuses on innovation through novel peptides, with expertise in both injectable and oral peptides since 2008, a time when peptides were largely overlooked [8][9] - The company went public in 2016 with the assistance of Barclays [4] Key Assets and Developments - **Icotrokinra**: An oral IL-23 blocker, the first of its kind, with phase 3 data showing promise. Approval is sought for psoriasis, with additional studies in psoriatic arthritis, ulcerative colitis, and Crohn's disease [9][10][12] - **Rusfertide**: A weekly injectable mimetic of hepcidin, targeting polycythemia vera, with a partnership with Takeda established in January 2024. Priority review has been granted, potentially accelerating approval [14][15][16] - Both drugs are expected to be approved in Q3 2026, marking significant milestones for the company [15] Future Pipeline - Protagonist is developing an oral IL-17 program and has preclinical studies in IL-4, aiming to create a portfolio of oral peptides to differentiate from existing injectable options [19][22][27] - The company is also working on an oral triple GLP-GIP-GCG for obesity, with clinical studies expected to begin in the second half of the year [25][131] Clinical Strategy and Evaluation - The company emphasizes rigorous preclinical evaluation to ensure oral bioavailability and efficacy, taking longer than typical assessments to select the right candidates [36][38] - For icotrokinra, J&J is leading the launch strategy, leveraging extensive data from head-to-head studies against competitors [41][45] Competitive Landscape - Protagonist acknowledges competition in the hepcidin space but believes their approach of creating a mimetic offers a distinct advantage over others enhancing endogenous hepcidin production [62][66][70] - The company is confident in its market position due to its early development stage and unique drug mechanisms [78] Business Development and Partnerships - Protagonist plans to take assets to clinical proof of concept before seeking partnerships for larger indications, while considering retaining more backend economics through creative cost-sharing arrangements [102][123] - The company aims to avoid external fundraising, focusing on internal funding for studies [125] Obesity Market Insights - The obesity treatment landscape is seen as a significant opportunity, with Protagonist aiming to differentiate through oral peptides in a crowded market [128][131] - The company is developing both weekly subcutaneous and daily oral formulations, with a focus on creating a diverse portfolio to address various patient needs [133][137] Conclusion - Protagonist Therapeutics is positioned to leverage its innovative peptide technology and strategic partnerships to address unmet medical needs in various therapeutic areas, particularly in immunology and obesity, while maintaining a strong focus on clinical efficacy and market differentiation [131][140]