Financial Data and Key Metrics Changes - In Q1 2025, the company reported total revenues of approximately €183 million, a slight decrease from €188 million in Q1 2024, reflecting expected seasonality in the COVID-19 vaccine market [26] - Research and development expenses increased to €526 million in Q1 2025 from €508 million in the prior year, driven by late-stage clinical studies [26] - The net loss for Q1 2025 was €416 million, compared to a net loss of €350 million in Q1 2024, with a basic and diluted loss per share of €1.73 versus €1.31 in the prior year [27][28] Business Line Data and Key Metrics Changes - The oncology segment is advancing with multiple clinical trials, including BNT327 and mRNA cancer immunotherapies, which are expected to establish new standards of care [10][13] - The COVID-19 vaccine franchise remains a significant revenue driver, although the company is preparing for a variant-adapted vaccine rollout [10][26] Market Data and Key Metrics Changes - The company estimates the second-line market for endometrial cancer to be around 10,000 patients in the US and Europe, indicating a sizable market opportunity [40] - The company is diversifying its manufacturing supply base, currently reliant on a China-based CDMO, to mitigate risks associated with tariffs [40] Company Strategy and Development Direction - The company aims to become a fully integrated biopharmaceutical company with a focus on oncology, particularly through combination therapies that exploit synergistic effects [12][13] - Significant investments are being made in clinical development and commercial capabilities to support the launch of BNT323 in oncology, expected as early as 2026 [35] Management's Comments on Operating Environment and Future Outlook - Management acknowledges 2025 as a transition year, focusing on long-term growth strategies while maintaining financial discipline [28] - The company is actively monitoring potential impacts from tariffs and evolving public sentiment regarding vaccines and mRNA technology [30][31] Other Important Information - The company announced the appointment of a new CFO, Ramon Sapater, effective July 1, 2025, as Jens Holstein prepares for retirement [11][32] - The company plans to present multiple updates from its oncology pipeline at the ASCO Annual Meeting, highlighting its commitment to advancing clinical programs [25][36] Q&A Session Summary Question: Addressable population for endometrial cancer launch - The estimated second-line market in endometrial cancer is about 10,000 patients in the US and Europe, indicating a sizable opportunity [40] Question: Impact of tariffs on manufacturing - Manufacturing for BNT323 is currently supplied by China, with plans to diversify supply bases in the coming years [40] Question: Long-term outlook for NSCLC - The company believes both bispecifics and ADCs will play a role in the evolving NSCLC market, with ongoing development in both areas [47][49] Question: COVID-19 vaccine recommendations - The company is tracking upcoming decisions regarding COVID-19 vaccine recommendations and anticipates that vaccination rates will remain stable [52][54] Question: Differences between bispecifics - The company is focusing on a bispecific with PD-L1, which is expected to be superior in the tumor microenvironment, and is exploring various combinations with ADCs [88][90]

Coherus BioSciences (CHRS) Update Summary Company Overview - **Company**: Coherus BioSciences - **Focus**: Development of CHS-114, a cytolytic CCR8 targeting antibody for cancer immunotherapy Key Points from the Call Industry and Product Development - **Phase I Study**: The call discussed the Phase I study results of CHS-114 as a CCRA antibody, evaluated both as monotherapy and in combination with Torpalumab in patients with advanced solid tumors, particularly head and neck cancer [2][4] - **Target**: CHS-114 targets CCR8, a G protein-coupled receptor, which is selectively expressed on tumor-resident T regulatory cells (Tregs) [7][6] - **Mechanism**: The goal is to deplete Tregs to enhance the immune response against tumors, turning "cold" tumors "hot" by allowing CD8 T cells to infiltrate [5][6] Clinical Results - **Preclinical Data**: Preclinical models showed that treatment with CHS-114 led to significant depletion of Tregs and enhanced antitumor activity when combined with PD-1 inhibitors [8][9] - **Patient Population**: The study included patients with advanced solid tumors, primarily head and neck cancer, with a median age of around 60 years and a majority being male [23] - **Safety Profile**: The Phase I study demonstrated an acceptable safety profile with no dose-limiting toxicities (DLTs) and a stable disease rate of approximately 50% in heavily pretreated patients [17][25] Efficacy and Biomarker Data - **Response Rates**: The combination therapy showed promising results, with a notable partial response in a patient who had previously failed multiple lines of therapy [26][29] - **Biomarker Analysis**: Significant reductions in CCR8 positive Tregs were observed, with a decrease of 52% to 97% after treatment, indicating a shift towards a more inflamed tumor microenvironment [43][44] - **Durability of Response**: The combination therapy demonstrated durable responses, with ongoing evaluations to assess long-term efficacy [28][26] Future Directions - **Expansion Studies**: Coherus is expanding its studies to include gastric cancer, with ongoing recruitment for trials assessing CHS-114 in combination with Torpalumab [20][19] - **Market Potential**: The second-line treatment space for metastatic head and neck cancer is identified as an unmet medical need, with current standard treatments showing low response rates [77][78] Additional Insights - **Combination Therapy**: The potential for combining CHS-114 with T cell engagers and bispecific antibodies was discussed, emphasizing the importance of a robust CD8 T cell infiltrate for effective treatment [64][65] - **Patient Characteristics**: The responder in the study had a low PD-L1 score, suggesting that targeting Tregs may provide benefits even in patients with traditionally low immunogenicity [81][82] Conclusion - Coherus BioSciences is advancing its clinical development of CHS-114, showing promising early results in targeting CCR8 positive Tregs to enhance immune responses in cancer therapy. The ongoing studies aim to address significant unmet needs in the treatment of advanced solid tumors, particularly in head and neck cancer.

As filed with the Securities and Exchange Commission on June 26, 2024. Registration No. 333-280226 UNITED STATES SECURITIES AND EXCHANGE COMMISSION WASHINGTON, D.C. 20549 AMENDMENT NO.1 TO FORM S-1 Delaware 2834 81-1567056 (I.R.S. Employer Identification Number) 2401 4th Avenue, Suite 1050 Seattle, Washington, 98121 (206) 838-0500 REGISTRATION STATEMENT UNDER THE SECURITIES ACT OF 1933 APTEVO THERAPEUTICS INC. (Exact Name of Registrant as Specified in Its Charter) (State or Other Jurisdiction of Incorporati ...