Summary of Invivyd (IVVD) Conference Call - September 03, 2025 Company Overview - **Company**: Invivyd (IVVD) - **Product**: PEMGARDA, a monoclonal antibody authorized under Emergency Use Authorization for the prevention of COVID-19 in certain immunocompromised individuals [2][4] Core Points and Arguments 1. **Current Status**: Invivyd is a commercial-stage company with an authorized product, PEMGARDA, and is developing a next-generation monoclonal antibody, VYD2311, aimed at improving efficacy and safety compared to existing vaccines [2][3][4] 2. **Technological Advantage**: The company emphasizes its unique technology that allows for the evolution of antibodies to enhance their biophysical properties, which is expected to lead to better medical outcomes for patients [3][4] 3. **Regulatory Engagement**: Invivyd has had constructive dialogues with the FDA regarding the development of VYD2311, which is positioned as a potential alternative to vaccines for COVID-19 [4][5][22] 4. **Market Positioning**: The company aims to shift the reliance from vaccines to monoclonal antibodies for COVID-19 prevention, targeting both high-risk adults and pediatric populations [5][14] 5. **Clinical Efficacy**: PEMGARDA has shown an 85% to 94% reduction in the likelihood of getting sick, although it is described as a specialty medicine with logistical challenges for administration [8][10] 6. **Future Development**: The company plans to conduct clinical trials for VYD2311, which is expected to have a favorable product profile compared to vaccines, including higher efficacy, safety, and durability [24][25][39] 7. **Commercial Strategy**: Invivyd is focused on education and engagement with key opinion leaders and decision-makers to prepare for the commercialization of VYD2311 [40][41] 8. **Cost Structure**: The expected cost of goods sold (COGS) for VYD2311 is projected to be below $100, with a retail price potentially around several hundred dollars, aiming to provide a broad population medicine rather than a specialty product [44][45][46] Important but Overlooked Content 1. **Regulatory History**: The regulatory journey of PEMGARDA has been complex, with the FDA and EMA initially defining its role narrowly, which has impacted its market penetration [7][10] 2. **Public Perception**: The company acknowledges the challenges posed by public perception and misinformation regarding COVID-19 treatments and vaccines, emphasizing the need for clear communication of the benefits of monoclonal antibodies [28][30] 3. **Potential for Resistance**: Invivyd is aware of the potential for emerging resistance to antibodies but believes that their current product, VYD2311, will maintain efficacy due to its stable epitope [47][48] This summary encapsulates the key points discussed during the conference call, highlighting Invivyd's strategic direction, product development, and market positioning in the context of COVID-19 treatment.

Core Insights - Upstream Bio reported significant clinical advancements and financial results for Q2 2025, with a focus on its lead drug candidate, verekitug, aimed at treating respiratory diseases [1][5][12] Financial Performance - Revenue for Q2 2025 was $0.9 million, exceeding the estimate of $0.69 million and showing an 80% increase from $0.5 million in Q2 2024 [2][8] - Research and development expenses surged to $37.9 million, up 168.8% from $14.1 million in Q2 2024, primarily due to increased clinical and manufacturing costs related to verekitug [2][7] - General and administrative expenses rose to $7.4 million, an 85% increase from $4.0 million in Q2 2024 [2][7] - The net loss widened to $40.0 million compared to $14.7 million in Q2 2024, reflecting the transition to more expensive Phase 2 trials [2][8] - Cash reserves stood at $393.6 million as of June 30, 2025, expected to sustain operations through 2027 [8][12] Clinical Development - Upstream Bio is advancing verekitug through multiple Phase 2 clinical trials, with significant milestones achieved in severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) [1][4] - Patient enrollment for the VALIANT Phase 2 trial for severe asthma was completed in June 2025, with top-line results anticipated in early 2026 [5][12] - The VIBRANT Phase 2 trial for CRSwNP completed patient enrollment by January 2025, with efficacy data expected in Q3 2025 [5][12] - The company initiated dosing in the VENTURE Phase 2 trial for chronic obstructive pulmonary disease (COPD) in July 2025 [6][12] Product Pipeline and Competitive Position - Verekitug is the only monoclonal antibody in human trials targeting the TSLP receptor, which may offer longer intervals between doses compared to existing biologics [10][11] - The competitive landscape remains uncertain as there are no approved products or recent head-to-head data against other biologics [11] - The regulatory strategy focuses on trial endpoints that could support future marketing applications if successful [11] Future Outlook - Management highlighted two key upcoming catalysts: top-line data from the VIBRANT CRSwNP Phase 2 trial in Q3 2025 and the VALIANT severe asthma Phase 2 readout in Q1 2026 [12][13] - Investors are expected to closely monitor the outcomes of these trials, as positive results could lead to regulatory submissions and potential partnerships [13]

Core Insights - Invivyd, Inc. announced full Phase 1/2 clinical data for VYD2311, a next-generation monoclonal antibody (mAb) candidate aimed at preventing and treating COVID-19 [1] - VYD2311 is structurally 99%+ identical to previous antibodies and is designed to enhance potency and resistance against SARS-CoV-2 variants [2][10] - The Phase 1/2 study demonstrated that VYD2311 was well tolerated with mild to moderate adverse events and a long half-life, suggesting potential for long-term protection [4][5] Company Overview - Invivyd, Inc. is focused on developing innovative monoclonal antibodies to combat serious viral infectious diseases, starting with SARS-CoV-2 [18] - The company utilizes a proprietary technology platform to create antibodies that can adapt to viral evolution [18] Clinical Trial Details - The Phase 1/2 study involved 40 subjects and tested various routes of administration (IV, IM, SC) and doses to maximize flexibility for future registrational pathways [3] - VYD2311 showed a half-life ranging from 61 days (IV) to 76 days (IM), significantly longer than pemivibart's 49 days [5] Safety and Efficacy - All adverse events reported were mild to moderate, with no serious adverse events linked to the study drug [4] - The modeling analysis indicated that VYD2311 could provide robust protection against symptomatic COVID-19, potentially surpassing vaccine efficacy [8][10] Regulatory Plans - Invivyd plans to engage with the FDA in early Q3 2025 to discuss registration pathways for VYD2311 and subsequent COVID-19 mAbs [6][8] - The company aims to provide non-vaccine mediated protection for vulnerable populations, including the elderly and immunocompromised individuals [8][10]

Financial Data and Key Metrics Changes - The company reported a significant increase in the overall response rate for its lead drug, tevesimig, in the second line biliary tract cancer study, with a response rate of 17.1% compared to 5.3% for the control arm, indicating a more than tripling of the response rate [12][13] - The study also showed a statistically significant difference with a p-value of 0.031, highlighting the drug's efficacy [13] Business Line Data and Key Metrics Changes - The lead program, tevesimig, is a bispecific antibody targeting DLL4 and VEGF A, which has shown promising results in clinical trials [4][7] - The company is also advancing CTX-471, a monoclonal antibody agonist targeting CD137, which has shown a 28% response rate in a post-PD-1 patient population [22][23] Market Data and Key Metrics Changes - The company identified a significant unmet medical need in the second line biliary tract cancer market, where there are currently no labeled therapies for the majority of patients [11] - The basket study for tevesimig in DLL4 positive cancers is expected to explore a range of solid tumor indications, indicating a broad market opportunity [19] Company Strategy and Development Direction - The company aims to leverage its unique StitchMaps platform to develop next-generation antibody therapeutics, focusing on dual blockade strategies to enhance efficacy in oncology [3][7] - Future plans include a Phase II basket study for tevesimig and potential label expansion studies following its approval [19] Management's Comments on Operating Environment and Future Outlook - Management expressed enthusiasm about the upcoming readouts for progression-free survival and overall survival, indicating a positive outlook for tevesimig's clinical development [17] - The company is optimistic about the performance of the control arm in clinical trials, suggesting a potential treatment effect that could lead to fewer deaths than initially expected [17] Other Important Information - The company has fast track status for tevesimig, which could expedite its approval process, with potential approval in the second half of 2026 [19][32] - The company is also developing CTX-8371, a PD-1 PD-L1 bispecific antibody, which is currently in Phase I studies and is expected to present clinical data in the second half of the year [29] Q&A Session Summary Question: Can you provide an overview of tevesimig's clinical data? - The overall response rate for tevesimig plus paclitaxel was 17.1%, significantly higher than the 5.3% for paclitaxel alone, with a statistically significant p-value of 0.031 [12][13] Question: What is the rationale behind the DLL4 positive cancers basket study? - DLL4 notch signaling is involved in various malignancies, and the company aims to explore the efficacy of tevesimig in these cancers due to its demonstrated monotherapy activity [19] Question: What are the upcoming catalysts for the company? - Key upcoming catalysts include readouts from the tevesimig study, the initiation of several important clinical trials, and data from the CTX-471 basket study [34]

Financial Data and Key Metrics Changes - The company reported sales of approximately $2.3 million in Q2 of the previous year, which increased to $9.3 million in Q3, and further to $13.8 million in Q4. In Q1 of the current year, sales reached $11.3 million, reflecting a transition to an internalized sales force [5][6][7]. Business Line Data and Key Metrics Changes - The company has launched a product for COVID-19 pre-exposure prophylaxis under emergency use authorization, with a focus on internalizing the sales force to drive growth [2][6]. - The sales force was fully trained and operational by the end of Q1, leading to positive trends in new account orders and interactions with healthcare providers [8][9]. Market Data and Key Metrics Changes - The COVID-19 therapy market was valued at over $9 billion last year, with the company currently capturing only a small share of the potential patient population eligible for its product [11][12]. - The company has been added to the NCCN guidelines for certain B-cell lymphomas, indicating a growing recognition of its product as a standard of care [12]. Company Strategy and Development Direction - The company is focusing on the development of next-generation antibodies, particularly VYD2311, which is expected to be more potent and have a longer half-life than existing products [17][24]. - There is an emphasis on expanding into other at-risk populations beyond the immunocompromised, including healthcare workers [25]. Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing relevance of their targeted epitopes against evolving SARS-CoV-2 variants, supported by extensive variant monitoring and surveillance [28][30]. - The company anticipates updates on RSV and measles programs by the end of 2025, indicating a strategic focus on addressing unmet medical needs in these areas [41]. Other Important Information - The FDA denied the treatment request for PEMGARDA, but the company sees this as an opportunity to engage with the new administration for future treatment indications [17][19]. - The company is open to business development discussions, including potential partnerships or government collaborations [46]. Q&A Session Summary Question: Can you provide updates on the sales force and its impact? - The internalized sales force has shown promising trends in new account orders and healthcare provider interactions, contributing to a return to growth [8][9]. Question: What is the company's strategy regarding payer reimbursement? - The company is covered by Medicare and Medicaid under EUA, with positive outcomes from major commercial payers [10]. Question: How does the company view the future of monoclonal antibodies in COVID treatment? - There is potential for monoclonal antibodies in treating COVID-19, especially for immunocompromised patients [14][15]. Question: What are the next steps for the measles and RSV programs? - The company anticipates updates on both programs by the end of 2025, with a focus on identifying candidates [41][42]. Question: How does the company plan to engage with regulatory agencies? - The company plans to engage with the FDA regarding treatment indications for next-generation antibodies and seeks alignment on expectations for monoclonal antibodies [18][20].

Commercial Performance & Strategy - Invivyd's Q1 2025 net product revenue for PEMGARDA was $11.3 million[82] - HCP interactions increased by 37% from 8,608 on January 1 to 11,669 on April 30[12] - The number of accounts called on increased by 37% from 4,566 on January 1 to 6,242 on April 30[12] - Accounts ordering PEMGARDA increased by 20% from 534 on January 1 to 642 on April 30[12] - PEMGARDA is priced lower than nearly all FDA-approved monoclonal antibodies launched in the past 5 years, ranking 59 out of 63 mAb drugs based on annual pricing[24] Research & Development - VYD2311 is designed to target a highly conserved epitope on SARS-CoV-2, with >15x improved neutralization potency relative to VYD222 (PEMGARDA)[47, 51] - The in-life phase of the Phase 1 clinical trial for VYD2311 has been completed, with data read-out anticipated later in Q2 2025[50] - Invivyd is conducting discovery programs for RSV and measles, with progress updates expected by the end of 2025[5, 41, 45] Financial Status - Operating expenses decreased to $27.4 million in Q1 2025 from $32.3 million in Q4 2024[82] - The company ended Q1 2025 with approximately $48.1 million in cash and cash equivalents[82] - A $30 million loan facility was secured in April 2025[5, 82]

Core Insights - Invivyd, Inc. reported financial results for Q1 2025, highlighting a strategic shift to internalize its sales force, which initially created challenges but is now showing signs of growth and momentum [2][6][7]. Financial Results - For Q1 2025, Invivyd reported net product revenue of $11.3 million from PEMGARDA™, a decrease from $13.8 million in Q4 2024, with no revenue reported in Q1 2024 [7][15]. - The company recorded a net loss of $16.3 million for Q1 2025, an improvement from a net loss of $43.5 million in the same period of 2024, resulting in a net loss per share of $0.14 compared to $0.38 in Q1 2024 [15][28]. Cash Position and Funding - As of March 31, 2025, Invivyd had cash and cash equivalents of $48.1 million and secured a $30 million non-dilutive term loan facility to support its operations and potential growth [4][15]. Business Highlights - The company is targeting near-term profitability by the end of the first half of 2025, supported by anticipated growth in net product revenue and a reduction in operating expenses [2][7]. - PEMGARDA's uptake is increasing among healthcare providers for immunocompromised patients, aided by the internalized sales force [8]. Pipeline Developments - VYD2311 Phase 1 clinical trial data read-out is expected later in Q2 2025, with ongoing evaluations for pipeline expansion beyond SARS-CoV-2, including potential targets like respiratory syncytial virus (RSV) and measles [5][8][19]. - The FDA declined Invivyd's request to expand the EUA for PEMGARDA to treat mild-to-moderate COVID-19, but the reasoning may provide a near-term pathway for VYD2311 [8]. Regulatory and Safety Updates - Since the EUA of PEMGARDA in March 2024, no documented cases of anaphylaxis have been reported across thousands of doses administered [7][8]. - In vitro data indicate sustained neutralizing activity of PEMGARDA against dominant SARS-CoV-2 variants, which represent over 75% of circulating variants in the U.S. [8].