Summary of Vaxcyte FY Conference Call (December 02, 2025) Company Overview - **Company**: Vaxcyte (NasdaqGS:PCVX) - **Industry**: Vaccine Development, specifically focusing on pneumococcal vaccines Key Points FDA Engagement and Development Plans - Vaxcyte is actively engaging with the FDA and other government entities to advocate for their vaccines, particularly focusing on a 31-valent vaccine for adults, with a phase three program expected to start in December 2025 [2][3] - The company has received consistent feedback from the FDA regarding their development plans, which remain aligned with their original strategy despite recent political discussions surrounding vaccine efficacy [4][5] - The adult phase three program will include a non-inferiority study, with results anticipated in 2026 [25] Infant Vaccine Development - Vaxcyte is also developing a 31-valent vaccine for infants, which is projected to capture a significant portion of the $6 billion infant vaccine market [24] - The company is modifying its phase two study based on data from a previous 24-valent program, with expectations to report results by mid-2027 [26] - Discussions with the FDA regarding infant vaccines are ongoing, with a focus on demonstrating efficacy through outcomes related to otitis media, which is prevalent in infants [9][16] Clinical Study Insights - The company is exploring the possibility of conducting head-to-head studies for infant vaccines to demonstrate efficacy without a placebo control [9][14] - The phase two study for the 31-valent vaccine has shown promising results, with a focus on optimizing dose levels based on previous data [28][29] - The company aims to ensure that the immunogenicity of their vaccines meets public health standards, particularly for serotypes that are critical in preventing disease [35][39] Financial Position and Future Outlook - Vaxcyte reported a strong balance sheet with $2.7 billion in cash as of September 2025, which is expected to fund operations through mid-2028, covering both adult and infant vaccine programs [48] - The company is also investing in manufacturing capabilities to meet anticipated market demand upon product launch [49] Market Context and Competitive Landscape - The infant vaccine market is highly competitive, with Vaxcyte's products expected to address significant public health needs, particularly in reducing antibiotic use related to otitis media [16][19] - The company is aware of the evolving political landscape surrounding vaccines and is prepared to adapt its strategies accordingly [5][6] Additional Important Insights - The company is focused on maintaining a robust pipeline and is optimistic about the potential for their vaccines to meet both clinical and market needs [46][47] - Vaxcyte's approach to vaccine development includes a strong emphasis on safety, tolerability, and immunogenicity, which are critical for regulatory approval and market acceptance [27][43]

Core Insights - China's expanding pipeline of novel drug candidates is attracting global pharmaceutical companies and investors seeking licensing opportunities due to the country's clinical trial capacity now matching that of the US [1][3] Group 1: Clinical Trials in China - There is a growing interest from multinational corporations in conducting investigator-initiated trials for cell and gene therapies in China, as they can access patient data more quickly than in other markets [2] - As of 2024, China's clinical trial volumes have reached 80% of those in the US and are 10% higher than in Europe, indicating significant growth in the sector [3] - In 2024, China recorded 2,694 new clinical trials, a 13% increase from the previous year, with multinational companies accounting for 14.3% of these trials, reflecting a 7% compound annual growth rate since 2019 [4] Group 2: Market Dynamics and Future Outlook - Despite geopolitical tensions, multinational firms are not expected to slow down their clinical trials in China, as it remains the second-largest pharmaceutical market globally [5] - Chinese policymakers are anticipated to provide more targeted support for research and development and commercialization in the biomedical manufacturing sector, which could further enhance the growth of innovative clinical trials [5]

Neuralink Accomplishments & Current Status - Neuralink's N1 device, a wireless high-bandwidth brain-computer interface (BCI), is being used by at least 13 human patients [2] - Trial participants have accumulated over 15,000 hours of independent use of the BCI at home [2] - Patients are averaging around 50 hours per week of BCI usage, with peak usage exceeding 100 hours per week in some cases [7] - Neuralink received FDA approval for human trials in 2023, focusing on patients with paralysis and ALS [5] - The company has solved the thread retraction problem by updating brain signal decoding algorithms and shallower thread insertion [12] Expansion & Regulatory Approvals - Neuralink is now conducting studies in four countries: the United States, Canada, the UK, and the UAE [13][14] - International trials are a crucial step toward market readiness for treating paralysis, blindness, and other conditions [15] Future Products & Research - Neuralink plans to launch a thought-to-speech clinical trial in the US for patients who have lost the ability to speak [22] - Blind sight technology is expected to reach human trials next year, aiming to restore basic navigation and eventually full vision [25] - Neuralink is exploring hearing restoration and accessing deeper brain regions for helping with pain, mood, and memory regulation [26] - The company expects to work on helping with epilepsy and tinnitus in 2028 [27] Scaling & Technology - Engineers are working to increase electrode count from 1,000 channels to 10,000 and then 25,000 and beyond [28] - Neuralink aims to perform thousands of surgeries every month using the R1 surgical robot and dedicated clinics [29]

Core Insights - Veru Inc. is a late clinical stage biopharmaceutical company focused on developing innovative medicines for cardiometabolic and inflammatory diseases [3] - The company announced the presentation of two abstracts at ObesityWeek 2025, highlighting its drug enobosarm's potential in weight management [1][2] Company Overview - Veru Inc. is developing two late-stage novel small molecules: enobosarm and sabizabulin [3] - Enobosarm is a selective androgen receptor modulator (SARM) aimed at enhancing weight reduction by making fat loss more tissue-selective while preserving lean mass [3] - Sabizabulin is being developed for treating inflammation in atherosclerotic cardiovascular disease [3] Clinical Studies - The Phase 2b QUALITY clinical study demonstrated that enobosarm, when combined with semaglutide, led to greater fat loss while preserving lean mass in older patients [4] - The study involved 168 older patients (≥60 years) and showed that while weight loss was similar across treatment groups, the preservation of lean mass is expected to enhance energy expenditure [4] - A planned Phase 2b PLATEAU clinical study will evaluate enobosarm's effect on total body weight and physical function in approximately 200 patients initiating GLP-1 RA treatment [5][6] - The primary efficacy endpoint for the PLATEAU study is the percent change in total body weight at 72 weeks, with an interim analysis at 36 weeks [5][7]

Core Insights - Arcutis Biotherapeutics shares surged nearly 30% following strong third-quarter earnings and an investor day presentation that provided positive guidance exceeding analyst expectations [1] Company Growth Plans - Management aims to establish Arcutis as a leader in medical dermatology through its Zoryve (roflimilast) portfolio, which includes FDA-approved treatments for plaque psoriasis, atopic dermatitis, and seborrheic dermatitis [2] - Zoryve is a selective phosphodiesterase-4 (PDE4) inhibitor, known for its anti-inflammatory effects [2] Regulatory Developments - Zoryve has been submitted for FDA approval for plaque psoriasis in children aged 2 to 5 and is undergoing phase 2 trials for vitiligo and hidradenitis suppurativa [3] Sales Projections - Management forecasts Zoryve sales could reach between $2.6 billion and $3.5 billion over time, with near-term sales estimates for 2026 projected at $455 million to $470 million, significantly above the $438 million anticipated by analysts [4] - The high end of the sales target for Zoryve exceeds the company's market cap of less than $3 billion, indicating strong growth potential [6] Market Outlook - The company is expected to experience over 30% sales growth in the coming years, supported by less risky clinical trials currently in progress [6] - The positive medium-term sales target for the Zoryve franchise has generated excitement among investors [8]

Financial Performance - Q3 2025 net product revenues reached $99.2 million, a 122% increase compared to Q3 2024[28,33] - Net product revenues increased by 22% quarter over quarter[28,33] - The company reported a net profit of $7.4 million in Q3 2025, a significant improvement from a net loss of $41.5 million in Q3 2024[33] - Cash, cash equivalents, and marketable securities totaled $191.4 million as of September 30, 2025[35] - The company projects product sales of $455-$470 million in 2026[138] ZORYVE Product and Market - Weekly TRx (Total Prescriptions) for the ZORYVE portfolio reached approximately 17,500 on a rolling 4-week basis[29] - TRx growth for ZORYVE showed a 13% increase compared to Q2 2025 and a 92% increase compared to Q3 2024[30] - The company estimates a total addressable market of 30 million patients across Psoriasis (PsO), Atopic Dermatitis (AD), and Seborrheic Dermatitis (SD)[50,84] - The serviceable obtainable market (SOM) is estimated at 8 million patients receiving topical prescriptions in dermatology[50] Growth Strategy - The company aims to expand ZORYVE into new markets and indications, including vitiligo and hidradenitis suppurativa (HS)[39,119] - Peak sales potential for current indications is estimated at $2.3 - $3.0 billion, with an additional $0.3 - $0.5 billion from label expansion and data generation[122]

Table of Contents As filed with the Securities and Exchange Commission on October 7, 2025 Registration No. 333-287675 UNITED STATES SECURITIES AND EXCHANGE COMMISSION Washington, D.C. 20549 Amendment No. 1 to FORM S-1 REGISTRATION STATEMENT Under The Securities Act of 1933 TVARDI THERAPEUTICS, INC. (Exact name of Registrant as specified in its charter) (State or other jurisdiction of incorporation or organization) (Primary Standard Industrial Classification Code Number) Delaware 2834 75-3175693 (I.R.S. Empl ...

AXPAXLI's Clinical Development and Regulatory Strategy - Ocular Therapeutix is targeting the FIRST SUPERIORITY LABEL vs anti-VEGFs for AXPAXLI [26, 29, 32, 35, 38] - AXPAXLI has SPA Agreements for SOL-1 & HELIOS-2 Trials, supporting a regulatory path for a superiority label [36] - SOL-1 is designed for success with FDA alignment through SPA, randomization of strong anti-VEGF responders, and the potential for a superiority claim on the label [133, 134, 136, 137, 140, 141, 152, 153] - SOL-R is designed for seamless, immediate adoption with methodical patient selection to exclude subjects with early persistent fluid [93, 94, 95, 96, 97, 181, 182, 183, 184, 185, 186, 187, 188, 189, 190, 191, 192, 193, 194, 195, 196, 197, 198, 199, 233, 234, 235, 236, 237] - The company plans for AXPAXLI NDA submission following SOL-R 56-Week Topline Data, with a package expected to exceed the requirements for FDA's safety database [230, 231, 232] AXPAXLI's Commercial Potential and Market Opportunity - The 2024 Global Branded Anti-VEGF Revenue is $15 Billion, indicating a significant market size [49, 52, 55] - AXPAXLI has the opportunity to significantly expand the $15B Global Retina Market by redefining the treatment attrition curve in wet AMD and establishing a standard of care in NPDR [57, 58, 59, 60, 82, 83, 84, 85, 86, 87, 88, 89, 90] - There are 18 million people with wet AMD in the U S, with 40% discontinuing treatment in the first year, presenting an opportunity for AXPAXLI to improve adherence [57, 59, 83, 86] - There are 64 million people with NPDR in the U S, with less than 1% of patients currently treated, indicating a large undertreated population [86, 89] Expansion into Diabetic Retinopathy - The company is targeting a broad indication in Diabetic Retinopathy, aiming to treat the full spectrum of diabetic retinal disease, including patients with or without DME [418, 419, 420, 421, 422, 423, 424, 425, 426, 427, 428, 429, 431, 432, 433, 434, 435, 436, 437, 438, 439, 440] - The HELIOS-1 study showed a 231% 2-step DRSS improvement in the AXPAXLI arm at Week 48 compared to 0% in the sham arm [397, 398, 399]

Core Insights - After-hours trading in the biotech and therapeutics sector saw significant price movements, particularly among small- and mid-cap companies, driven by clinical updates and strategic announcements [1] Company Summaries - **Cyclerion Therapeutics, Inc. (CYCN)**: Shares surged 48.01% to $4.47 after announcing a strategic relaunch focused on neuropsychiatric therapies, including a licensing agreement with MIT for its treatment-resistant depression program. The stock had closed at $3.02, down 0.66% during regular trading. A Phase 2 trial for the TRD program is expected to start in 2026, with initial data anticipated in 2027 [2][3] - **Clearside Biomedical Inc. (CLSD)**: The stock rose 6.82% to $4.23 after a regular session close of $3.96, despite a 9.79% decline during the day. The increase followed presentations at the EURETINA Congress regarding its Phase 2b ODYSSEY trial for wet age-related macular degeneration. The next key catalyst is the initiation of the Phase 3 trial, incorporating FDA feedback [3][4] - **Reviva Pharmaceuticals Holdings Inc. (RVPH)**: Shares increased by 11.50% to $0.32 after closing at $0.287, following a 6.61% decline during regular trading. The price action comes ahead of the company's participation in the Lytham Partners Fall 2025 Investor Conference [4][5] - **Acumen Pharmaceuticals, Inc. (ABOS)**: The stock advanced 5.69% to $1.30 after a regular session close of $1.23, despite a 3.91% decline during the day. The company reported that topline data from its Phase 2 ALTITUDE-AD trial is on track for late 2026 and plans to decide on advancing a preclinical candidate in early 2026 [5][6] - **PepGen Inc. (PEPG)**: Shares rose 5.13% to $2.05 after closing at $1.95, following an 8.02% decline during the day. The company completed patient dosing in its Phase 1 FREEDOM-DM1 trial and is on track to report topline data in early Q4 2025 [6][7] - **Corcept Therapeutics Inc. (CORT)**: The stock gained 4.54% to $87.10 after a regular session close of $83.32. The company announced it will present late-breaking data from its Phase 3 ROSELLA trial at the 2025 ESMO Annual Meeting. Two upcoming PDUFA dates were confirmed for relacorilant in hypercortisolism and platinum-resistant ovarian cancer [7][8][9]

Acquisition of Metsera - Pfizer plans to acquire Metsera, Inc, with the transaction expected to close in 4Q 2025 and drive growth from the late 2020s and beyond[16] - The acquisition will be funded primarily with available cash and proceeds from new debt and is not expected to impact Pfizer's credit rating[19] - The enterprise value is based on Metsera's June 30 reported cash balance of approximately $500 million[19] Pipeline and Clinical Trials - Pfizer and Roche have a global collaboration for the p40 x TL1A bispecific antibody (PF-07261271)[23] - Pivotal trials are ongoing or initiation is planned before or during 1H 2026 for several drug candidates[22] - MET-097i is a fully biased ultra-long-acting next-generation GLP-1 receptor agonist[33] MET-097i Clinical Data - In a Phase 2a trial, a monthly dose of MET-097i after 12 weekly doses was well tolerated with continued weight loss observed[38] - Phase 1 data demonstrate robust efficacy and placebo-like tolerability at potential starting doses for MET-233i[41] - Placebo-adjusted weight change in adherence to treatment subgroup was -14.2% with 1.2 mg → 4.8 mg of MET-097i[40] Market Opportunity - Obesity and associated conditions are on track to become among the largest pharmaceutical opportunities[27] - The acquisition aligns with Internal Medicine R&D strategy and expertise, leveraging significant primary care commercial infrastructure and field force[27] - The deal structure is risk-managed using a Contingent Value Right (CVR), sharing risk and upside with Metsera shareholders[28] - The acquisition has the potential for attractive returns for Pfizer shareholders[28] - The acquisition targets a market impacting over 1 billion lives globally[48]