Core Insights - Immutep Limited has reported a median Overall Survival (OS) of 17.6 months in Cohort B of the TACTI-003 Phase IIb trial for patients with recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) with PD-L1 expression below 1 [1][2] Group 1: Clinical Trial Results - The 17.6-month median OS in evaluable patients (N=31) is significantly better than historical results from standard-of-care treatments, which include 10.7 months from cetuximab + chemotherapy, 11.3 months from anti-PD-1 therapy + chemotherapy, and 7.9 months from anti-PD-1 monotherapy [2] - Efti in combination with pembrolizumab has shown a high overall response rate with multiple complete responses, indicating a promising efficacy profile [4][5] Group 2: Unmet Medical Need - Patients with CPS <1 in 1L HNSCC represent a high unmet medical need, as up to 20% of these patients lack approved immunotherapy-only treatment options [3][6] - The combination of efti and pembrolizumab addresses this gap, as current treatments for this population typically involve chemotherapy [3][6] Group 3: Safety and Regulatory Path - The combination therapy continues to be well-tolerated with no new safety signals reported, reinforcing its potential as a viable treatment option [4] - Immutep has requested a meeting with the U.S. FDA to discuss potential paths to approval for efti in 1L HNSCC with PD-L1 CPS <1, following its Fast Track designation [7][10] Group 4: About Efti - Efti is a proprietary soluble LAG-3 protein that stimulates both innate and adaptive immunity, enhancing the immune response against cancer [8] - The drug is under evaluation for various solid tumors, including non-small cell lung cancer and metastatic breast cancer, highlighting its broad therapeutic potential [9] Group 5: Company Overview - Immutep is a late-stage biotechnology company focused on developing novel immunotherapies for cancer and autoimmune diseases, leveraging its expertise in LAG-3 [11]

Financial Data and Key Metrics Changes - The company ended Q1 2025 with a strong cash position of approximately $361 million and is now debt-free after paying off all debt in Q4 2024 [40]. - GAAP R&D expenses for Q1 2025 were $51.2 million, slightly down from $51.4 million in Q4 2024, while non-GAAP R&D expenses remained flat at $47.1 million [41]. - GAAP G&A expenses increased to $15.6 million in Q1 2025 from $14.2 million in Q4 2024, primarily due to increased professional services [42]. Business Line Data and Key Metrics Changes - The company is advancing its lead investigational asset, ivanismab, with significant progress in clinical trials, including four Phase 3 trials completed and five ongoing [13][14]. - The HARMONY trials are pivotal, with HARMONY three and HARMONY seven evaluating ivanismab against pembrolizumab in frontline non-small cell lung cancer [15][32]. Market Data and Key Metrics Changes - The addressable market for non-small cell lung cancer is expected to approach $20 billion for checkpoint inhibitors, with a broader market opportunity of approximately $90 billion globally across all checkpoint inhibitor indications [33][34]. - The company is exploring additional indications beyond non-small cell lung cancer, including colorectal cancer and pancreatic cancer, where ivanismab has shown promise [34]. Company Strategy and Development Direction - The company aims to build a viable organization that addresses serious unmet medical needs, focusing on ivanismab's potential as a platform blockbuster drug [11][33]. - Strategic collaborations, such as with MD Anderson and Pfizer, are in place to expand clinical development and explore innovative combinations [20][21]. Management's Comments on Operating Environment and Future Outlook - Management expressed enthusiasm about the ongoing clinical progress and the potential of ivanismab, particularly in the context of upcoming data releases from the HARMONY trials [5][13]. - The management team highlighted the importance of demonstrating the differentiated mechanism of action for ivanismab compared to existing therapies [22][28]. Other Important Information - The company has strengthened its leadership team with the appointment of a new Chief Commercial Officer to refine its commercial strategy [39]. - The full dataset for the HARMONY six trial is planned to be presented at a major medical conference later this year, which is expected to provide further insights into ivanismab's efficacy [24]. Q&A Session Summary Question: What is the bar for success regarding the upcoming HARMONY eGFR dataset? - The company is not prescribing a specific bar but emphasizes the importance of overall data package consistency with prior data from China [48]. Question: Will there be separate hazard ratios for geographic data in HARMONY? - The top-line data will provide qualitative context, and a forest plot may be used to illustrate geographic breakdowns [58]. Question: What is the expected overall survival benefit to replace PD-1 standard of care? - A statistically significant improvement of two to three months in overall survival is generally considered transformative by clinicians [90]. Question: How does the safety profile in global populations compare to that in China? - The safety profile reported in trials has been reassuring, and while there may be minor cultural differences in reporting adverse events, significant differences are not expected [79]. Question: What are the plans for accelerated approval discussions with the FDA? - The company has had multiple discussions with the FDA regarding HARMONY three but does not disclose specific details of these conversations [96].

Core Insights - Bolt Biotherapeutics announced promising preclinical results for its next-generation Boltbody™ Immune-Stimulating Antibody Conjugates (ISACs) targeting CEACAM5 and PD-L1 at the AACR Annual Meeting [1][2] - The CEA-targeted ISAC demonstrated complete and durable anti-tumor responses in mice and was well-tolerated in non-human primates (NHPs) [2][5] - PD-L1 ISACs showed the ability to activate and reprogram PD-L1-expressing myeloid cells, promoting both innate and adaptive anti-tumor immunity [5][6] Group 1: CEA-targeted ISAC - The CEA ISAC is designed with a fully human antibody that specifically targets CEACAM5, commonly found in gastrointestinal cancers [2][4] - It enhances phagocytosis of CEA-positive tumor cells and stimulates the production of immune-activating cytokines such as IL-12p70, IFNg, and TNFa [2][5] - In a non-GLP NHP toxicity study, the CEA ISAC was well-tolerated at doses up to 15 mg/kg, with no significant drug-related adverse events observed [5] Group 2: PD-L1 ISAC - The PD-L1 ISAC utilizes a novel human anti-PD-L1 antibody conjugated to a next-generation TLR7/8 agonist, targeting both tumor and immune cells expressing PD-L1 [3][5] - It has shown complete regressions and the induction of immunological memory in models resistant to PD-1/PD-L1 checkpoint inhibitors [5] - The efficacy of PD-L1 ISACs does not rely on the blockade of the PD-1/PD-L1 axis, suggesting a complementary mechanism to existing therapies [5] Group 3: Company Overview - Bolt Biotherapeutics is a clinical-stage biopharmaceutical company focused on developing novel immunotherapies for cancer treatment [7] - The company's pipeline includes BDC-3042, an agonist antibody targeting dectin-2, and BDC-4182, a next-generation Boltbody™ ISAC targeting claudin 18.2, with clinical trials expected to begin in Q2 2025 [7]

Core Insights - Medicenna Therapeutics is advancing MDNA113, a novel IL-13Rα2 tumor-targeted and "masked" anti-PD-1-IL-2 Superkine, aimed at treating immunologically cold tumors with high unmet needs, such as pancreatic, liver, brain, breast, colon, and prostate cancers, affecting over 2 million patients annually worldwide [1][7] - The company presented new pre-clinical data at the 2025 AACR Annual Meeting, highlighting MDNA113's differentiated approach compared to existing anti-PD-1-IL-2 therapies, showcasing its optimized safety and efficacy profile [1][2] Company Overview - Medicenna is a clinical-stage immunotherapy company focused on developing Superkines targeting cancer and autoimmune diseases, with MDNA113 being the first candidate from its BiSKIT platform [1][8] - The company also has other candidates in development, including MDNA11, a long-acting IL-2 super agonist, which has shown durable anti-tumor activity in ongoing clinical studies [2][8] Product Highlights - MDNA113 is designed to selectively bind to IL-13Rα2, which is overexpressed in various solid tumors, while avoiding binding to the functional IL-13R⍺1, enhancing its therapeutic potential [5][6] - The product demonstrates promising pre-clinical results, including significant anti-tumor activity, enhanced memory responses, and preferential localization in the tumor microenvironment for at least 72 hours [6][2] Market Context - There is growing commercial interest in bi-specific anti-PD-1 therapies, with recent transactions validating this emerging class of immunotherapies, indicating potential for MDNA113 to offer new hope to cancer patients [2][6]

Core Insights - CERo Therapeutics Holdings, Inc. is advancing its Phase 1 clinical trial of CER-1236 for treating acute myeloid leukemia (AML) at TriStar Centennial Medical Center in Nashville, Tennessee, with patient enrollment currently underway and expected dosing of the first patient in the first half of 2025 [1][2][3] Company Overview - CERo is an innovative immunotherapy company focused on developing next-generation engineered T cell therapeutics for cancer treatment, utilizing a proprietary approach that integrates characteristics of both innate and adaptive immunity [4] - The company's Chimeric Engulfment Receptor T cells (CER-T) are designed to engage the body's full immune response to eliminate tumors, potentially offering greater therapeutic applications than current CAR-T therapies [4] Clinical Trial Details - The Phase 1/1b study of CER-1236 aims to evaluate safety and preliminary efficacy in patients with relapsed/refractory AML, measurable residual disease, or TP53 gene mutations, with a two-part design for dose escalation and expansion [2] - Primary outcome measures include the incidence of adverse events, dose-limited toxicities, overall response rate, complete response, composite complete response, and measurable residual disease [2]

Core Viewpoint - BriaCell Therapeutics Corp. is presenting clinical data from its pivotal Phase 3 study of Bria-IMT™ for metastatic breast cancer, emphasizing the role of specific biomarkers in predicting patient responses to treatment [1][5]. Group 1: Clinical Data and Biomarkers - The Phase 3 study (BRIA-ABC) supports the use of biomarkers to predict clinical responses, potentially improving patient outcomes such as response rates and survival benefits [2][7]. - Early Phase 3 biomarker data indicates that positive delayed-type hypersensitivity (DTH) and a favorable Neutrophil-to-Lymphocyte Ratio (NLR) are linked to longer progression-free survival (PFS) [7][8]. - Kaplan Meier analysis of early clinical data (n=62) shows a median PFS of 3.67 months across all study arms [6]. Group 2: Treatment Efficacy and Safety - Positive DTH is associated with better PFS (4.5 months vs 2.5 months, p = 0.001), while specific NLR values correlate with lower median PFS [8]. - The Bria-IMT regimen has demonstrated a favorable safety profile, with no treatment discontinuations related to Bria-IMT, indicating excellent tolerability [9]. Group 3: Study Design and Future Prospects - The multicenter randomized open-label study compares the Bria-IMT regimen combined with a checkpoint inhibitor against physician's choice in advanced metastatic breast cancer patients [10]. - Interim data will be analyzed upon reaching 144 patient events, with positive results potentially leading to full approval and marketing authorization for Bria-IMT [11].

Financial Data and Key Metrics Changes - Total revenues for Q3 2020 were $1.1 billion, with year-to-date revenues of $1.6 billion [21] - Product sales reached $267 million in Q3, with year-to-date product sales of $706 million [21] - Collaboration revenues significantly increased to $758 million in Q3, compared to $18 million in the same period of 2019 [22] - The company ended Q3 with $1.7 billion in cash and investments, bolstered by $725 million in upfront payments from Merck [25][26] Business Line Data and Key Metrics Changes - ADCETRIS sales were $163 million in Q3, a 3% decrease from Q3 2019, attributed to the pandemic's impact on new diagnoses [16][18] - PADCEV sales were $62 million in Q3, an 8% increase over Q2 2020, indicating strong adoption in both academic and community settings [19] - TUKYSA generated $42 million in net product revenues in its first full quarter since launch, with strong adoption and reimbursement coverage exceeding expectations [20] Market Data and Key Metrics Changes - The pandemic has led to a 15% decrease in new Hodgkin lymphoma diagnoses, impacting ADCETRIS sales [16][18] - The company is seeing a shift in site of care that negatively affected gross to net pricing for ADCETRIS [17] - The collaboration with Merck is expected to enhance global reach and patient access for TUKYSA and LV [10] Company Strategy and Development Direction - The company aims to invest in clinical development for ADCETRIS, PADCEV, and TUKYSA, while advancing late-stage pipeline products [12] - Strategic collaborations with Merck are focused on co-developing LV and TUKYSA, enhancing the company's market position [10][12] - The company plans to continue expanding its international infrastructure to support TUKYSA's launch in Europe [9] Management's Comments on Operating Environment and Future Outlook - Management expressed concern over the long-term impact of COVID-19 on cancer patient diagnoses and treatment [48][49] - The company remains optimistic about maintaining market share despite the pandemic's challenges [49] - Future guidance for ADCETRIS has been adjusted to $650 million to $660 million due to fewer new patient diagnoses [26] Other Important Information - The company is pursuing legal action against Daichi Sankyo for patent infringement related to a breast cancer drug [13] - Upcoming R&D Day is scheduled for November 16, where the company will discuss its pipeline and development activities [12] Q&A Session Summary Question: Can you comment on ADCETRIS market dynamics and diagnosis rates? - Management noted that product sales have increased year-over-year, but the pandemic has led to fewer patients starting treatment, which is concerning for future diagnoses [48][49] Question: What is the outlook for PADCEV's growth? - Management indicated that the launch has been strong, and while there may be a slight slowdown in growth, they are maintaining guidance and expect significant developments ahead [54][56] Question: Can you provide details on TUKYSA's launch and adoption hurdles? - The company reported strong uptake in both community and academic settings, with ongoing efforts to enhance awareness and access despite COVID-19 challenges [72][73] Question: How does the cash influx from Merck affect capital allocation? - Management emphasized that the priority is to drive existing products into blockbuster status while exploring new drug opportunities and maintaining innovation [89][92]

Core Insights - Medicenna Therapeutics Corp. presented updated clinical data for MDNA11, a long-acting IL-2 super-agonist, at the 2025 AACR Annual Meeting, highlighting its potential in treating advanced solid tumors, particularly in patients resistant to immune checkpoint inhibitors [1][2][10] Clinical Activity - Ten patients achieved an objective response (5 confirmed) with MDNA11 alone or in combination with KEYTRUDA, showing an objective response rate (ORR) of 36% (5 of 14) in all tumor types and 31% (4 of 13) in cancers planned for the Phase 2 combination expansion cohort [1][5] - In the monotherapy dose expansion, patients treated at ≥ 60 µg/kg had an ORR of 29.4% (5 of 17) across all tumor types and 40% (4 of 10) in the Phase 2 monotherapy expansion cohort [1][7] - The highest ORR of 50% was observed among MSI-H patients receiving MDNA11 monotherapy and endometrial cancer patients receiving the combination treatment [1][6] Safety Profile - MDNA11 demonstrated an acceptable safety profile, with over 90% of treatment-related adverse events being Grade 1-2 and transient, and no dose-limiting toxicities observed at doses up to 120 µg/kg [3][5] Immunodynamics - The study showed robust expansion of immune effector cells in both monotherapy and combination settings, with notable increases in critical T cell populations necessary for sustained anti-tumor responses [6][9] Future Directions - Enrollment in the Phase 2 combination dose expansion arm is ongoing, with the recommended dose for expansion established at 90 µg/kg every 2 weeks alongside KEYTRUDA [1][10] - Additional clinical data from the ABILITY-1 study is expected to be shared at future medical conferences throughout the year [2][8]

Core Insights - Compass Therapeutics, Inc. presented promising preclinical data on CTX-471, a CD137 agonist antibody, at the AACR Annual Meeting, indicating enhanced efficacy in models of immune checkpoint failure through simultaneous blockade of neo-angiogenesis [1][2][3] Company Overview - Compass Therapeutics is a clinical-stage biopharmaceutical company focused on developing proprietary antibody-based therapeutics for oncology, with a scientific emphasis on the interplay between angiogenesis, the immune system, and tumor growth [10] Product Development - CTX-471 is currently in a Phase 1b clinical trial for patients with solid tumors that have progressed after at least three months on approved PD-1 or PD-L1 inhibitors, showing partial responses in melanoma, small cell lung cancer, and mesothelioma [5] - The combination of CTX-471 with tovecimig has demonstrated significant anti-tumor efficacy in murine models resistant to conventional immune checkpoint inhibitors, suggesting a potential therapeutic regimen for patients who have failed checkpoint inhibitors [7][9] Mechanism of Action - The combination therapy appears to enhance innate and adaptive anti-tumor immunity, including increased tumor cell killing and interferon signaling, which may provide clinical benefits for patients previously unresponsive to standard treatments [3][7] Ongoing Trials - The ongoing COMPANION-002 trial is evaluating the efficacy of tovecimig in combination with paclitaxel for patients with previously treated, unresectable advanced metastatic or recurrent biliary tract cancers [9]

Core Insights - BriaCell Therapeutics Corp. is presenting positive data from its Phase 2 study of Bria-IMT™ in metastatic breast cancer and its preclinical Bria-OTS+ platform at the 2025 AACR Annual Meeting [1][2] - The company reports that Bria-IMT shows impressive survival and clinical efficacy in heavily treated patients who have failed multiple prior treatments [2][3] - The Phase 3 formulation of Bria-IMT has demonstrated a clinical benefit rate of 83% in evaluable patients [5][6] Phase 2 Study Findings - The Phase 2 study involved 54 metastatic breast cancer patients, with 37 receiving the Bria-IMT formulation currently used in the ongoing pivotal Phase 3 study [3] - Patients had a median of 6 prior treatments, including Antibody-Drug Conjugates (ADCs) and checkpoint inhibitors (CPIs) [3] - Overall survival (OS) for HR+ patients was reported at 17.3 months, while for triple-negative breast cancer (TNBC) patients, it was 11.44 months [6] Bria-OTS+ Platform - Bria-OTS+ is an enhanced immunotherapy platform that expresses multiple immune-activating cytokines and co-stimulatory molecules [8] - The platform aims to induce powerful and long-lasting immune activity against cancer [4][8] - The company anticipates that additional immune-activating factors will enhance the efficacy of the Bria-OTS+ platform [7] Future Developments - Phase 3 early biomarker data will be presented as a late-breaking abstract on April 30, 2025 [1][5] - The company plans to investigate Bria-BRES+ for breast cancer and Bria-PROS+ for prostate cancer in upcoming Phase 1/2a clinical studies [8]