Core Viewpoint - Oryzon Genomics has received a significant U.S. patent for iadademstat, a selective LSD1 inhibitor, which strengthens its position in the oncology market, particularly for treating acute myeloid leukemia (AML) in combination with existing therapies like venetoclax [1][5]. Patent Details - The U.S. patent US12,564,559 B2 covers therapeutic combinations of iadademstat for treating neoplastic diseases, including AML, and is set to expire in January 2039, with potential for further extensions [2][3]. - The patent includes claims for combinations with venetoclax, which is a standard treatment for first-line AML, enhancing the long-term value of Oryzon's clinical programs [5]. Clinical Development - Iadademstat is currently being evaluated in seven ongoing oncology clinical trials, including the Phase Ib ALICE-2 study, which has shown a 100% overall response rate (ORR) and a 90% strict complete remission (CR) rate in preliminary data [4][8]. - Updated data from approximately 15-16 patients in the ALICE-2 study are expected to be presented at the European Hematology Association Annual Congress in June 2026 [4]. Intellectual Property Portfolio - In addition to the U.S. patent, Oryzon has secured patent protection for iadademstat combinations in multiple countries, including Australia, Brazil, Canada, Europe, India, Israel, Japan, Korea, Malaysia, Mexico, New Zealand, and Russia, with additional applications pending [5]. - Oryzon also holds patents for iadademstat combinations with other AML therapies, such as azacitidine and decitabine, in the U.S. and other jurisdictions [5]. Company Overview - Founded in 2000 and headquartered in Barcelona, Spain, Oryzon is a clinical-stage biopharmaceutical company focused on epigenetics and personalized medicine for CNS disorders and oncology [6]. - The company has a robust clinical portfolio centered around two LSD1 inhibitors: iadademstat for oncology and vafidemstat for CNS disorders, with ongoing Phase I and II studies [6]. Mechanism of Action - Iadademstat is a small oral molecule that selectively inhibits the epigenetic enzyme LSD1, demonstrating significant potential in hematologic cancers [7]. - The drug has shown promising safety and clinical activity in combination therapies, including trials for relapsed/refractory AML and other hematological conditions [9].

Financial Data and Key Metrics Changes - Curis reported a net income of $19.4 million or $1.23 per share for Q4 2025, compared to a net loss of $9.6 million or $1.25 per share for the same period in 2024, primarily due to a $27.2 million one-time non-cash gain from the sale of Erivedge [10] - For the year ended December 31, 2025, the net loss was $7.6 million or $0.58 per share, a significant improvement from a net loss of $43.4 million or $6.88 per share in 2024 [10] - Research and development expenses decreased to $5.8 million in Q4 2025 from $9 million in Q4 2024, and for the year, they were $28.3 million compared to $38.6 million in 2024 [11] - General and administrative expenses also decreased to $2.9 million in Q4 2025 from $3.4 million in Q4 2024, totaling $14 million for the year compared to $16.8 million in 2024 [11] Business Line Data and Key Metrics Changes - The company is making progress in its Take Aim Lymphoma study for primary CNS lymphoma, with expectations for accelerated submissions to the FDA and EMA [4] - Curis is expanding studies of emavusertib into additional NHL subtypes, particularly focusing on its potential to change the treatment paradigm for CLL patients [5][6] Market Data and Key Metrics Changes - The company is actively enrolling patients in its registrational study for PCNSL, with expectations to complete enrollment within 12-18 months [23] - Initial data from the ongoing AML triplet study showed that five of eight evaluable patients achieved MRD conversion, indicating potential for deeper responses [8][9] Company Strategy and Development Direction - Curis is prioritizing its resources towards NHL studies, particularly PCNSL, while also initiating a proof of concept study in CLL [15] - The company aims to improve treatment outcomes by combining emavusertib with existing therapies to achieve deeper responses and potentially complete remission for patients [6][42] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the progress in clinical trials and the potential for significant advancements in 2026, particularly in the registrational study for PCNSL and the proof of concept study in CLL [9] - The company anticipates no meaningful revenue in 2026 due to the cessation of cash flows from Erivedge, but believes it has sufficient cash to fund operations into the second half of 2027 [12][29] Other Important Information - Curis has received initial gross proceeds of $20.2 million from financing in January 2026, with expectations for additional proceeds from warrant exercises [12] Q&A Session Summary Question: How is the company prioritizing trial progress between pivotal PCNSL versus CLL and AML? - Management indicated that resources are being prioritized towards NHL, particularly PCNSL, while CLL is in the early stages of study [14][15] Question: Can you provide updates on enrollment for PCNSL? - Management stated that enrollment is on track, with expectations for full enrollment within 12-18 months [23] Question: Should revenue modeling for 2026 reflect no meaningful revenue? - Management confirmed that there will be no meaningful revenue in 2026, as cash flows from Erivedge have ended [29] Question: What kind of data should be expected at ASH 2026 regarding CLL? - Management indicated that they hope to present meaningful data at ASH, focusing on the potential for deeper responses in patients [39][40]

Financial Data and Key Metrics Changes - Curis reported a net income of $19.4 million or $1.23 per share for Q4 2025, compared to a net loss of $9.6 million or $1.25 per share for Q4 2024, primarily due to a $27.2 million one-time non-cash gain from the sale of Erivedge [10] - For the year ended December 31, 2025, Curis reported a net loss of $7.6 million or $0.58 per share, an improvement from a net loss of $43.4 million or $6.88 per share for the same period in 2024 [10] - Research and development expenses decreased to $5.8 million in Q4 2025 from $9 million in Q4 2024, and for the year, they were $28.3 million compared to $38.6 million in 2024 [11] - General and administrative expenses also decreased to $2.9 million in Q4 2025 from $3.4 million in Q4 2024, totaling $14 million for the year compared to $16.8 million in 2024 [11] Business Line Data and Key Metrics Changes - The Take Aim Lymphoma study is progressing well, focusing on primary CNS lymphoma, with expectations for accelerated submissions in the U.S. and Europe [4][9] - Curis is exploring the potential of emavusertib to change treatment paradigms in CLL, aiming to improve upon the current standard of care with BTK inhibitors [5][6] Market Data and Key Metrics Changes - Enrollment in the Take Aim Lymphoma study is on track, with expectations for full enrollment within 12-18 months, potentially leading to data availability in 2027 [23] - The company is prioritizing NHL studies over AML, with a focus on registrational approval for PCNSL [15][16] Company Strategy and Development Direction - Curis aims to change the treatment paradigm for CLL by combining emavusertib with BTK inhibitors, targeting deeper responses and potential complete remission [6][7] - The company is actively engaging with key opinion leaders to expand studies into additional NHL subtypes, indicating a strategic focus on broadening its clinical research [5] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the progress in clinical trials and the potential for significant advancements in 2026, particularly in the registrational study for PCNSL and the proof of concept study for CLL [9] - The management acknowledged the challenges in patient enrollment for PCNSL but remains confident in the study's trajectory [23] Other Important Information - Curis' cash and cash equivalents as of December 31, 2025, along with expected proceeds from financing, should support operations into the second half of 2027 [12] Q&A Session Summary Question: How is Curis prioritizing trial progress between pivotal PCNSL versus CLL and AML? - Management indicated that resources are being prioritized towards NHL, particularly PCNSL, while CLL is also a focus but at a smaller scale currently [14][15] Question: Can you provide updates on enrollment for PCNSL? - Management confirmed that enrollment is on track, with expectations for full enrollment within 12-18 months [23] Question: Should revenue modeling for 2026 reflect no meaningful revenue? - Management confirmed that there will be no meaningful revenue for 2026, as revenue effectively ended in November 2025 [29] Question: What kind of data should be expected at ASH 2026 for CLL? - Management stated that they hope to present meaningful data at ASH, focusing on the execution of the study and patient enrollment [38][40]

Financial Data and Key Metrics Changes - Curis reported a net income of $19.4 million or $1.23 per share for Q4 2025, compared to a net loss of $9.6 million or $1.25 per share for Q4 2024, primarily due to a $27.2 million one-time non-cash gain from the sale of Erivedge [10] - For the year ended December 31, 2025, the net loss was $7.6 million or $0.58 per share, a significant improvement from a net loss of $43.4 million or $6.88 per share in 2024 [10] - Research and development expenses decreased to $5.8 million in Q4 2025 from $9 million in Q4 2024, and for the year, they were $28.3 million compared to $38.6 million in 2024 [11] - General and administrative expenses also decreased to $2.9 million in Q4 2025 from $3.4 million in Q4 2024, totaling $14 million for the year compared to $16.8 million in 2024 [11] Business Line Data and Key Metrics Changes - The Take Aim Lymphoma study in primary CNS lymphoma is progressing well, with expectations for accelerated submissions in the U.S. and Europe [4] - Initial data from the ongoing AML triplet study showed that 5 of 8 evaluable patients achieved MRD conversion, indicating potential effectiveness of the treatment combination [8][9] Market Data and Key Metrics Changes - The company is focusing on expanding emavusertib studies into additional NHL subtypes, particularly CLL, where current treatments have limitations [5][6] - The company is prioritizing NHL studies over AML due to resource allocation and the potential for registrational approval in PCNSL [14][15] Company Strategy and Development Direction - Curis aims to improve the treatment paradigm for CLL by combining emavusertib with BTKI regimens, targeting deeper responses and potential complete remission [6][39] - The company is actively engaging with clinical sites in the U.S. and Europe to advance its studies and expects to present initial data at the ASH annual meeting in December [7][9] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the progress in clinical trials and the potential for significant advancements in treatment options for patients with CLL and NHL [4][9] - The company anticipates no meaningful revenue in 2026 due to the cessation of cash flows from Erivedge, but is confident in its financial position to support operations into the second half of 2027 [12][27] Other Important Information - Curis has secured initial gross proceeds of $20.2 million from financing, which will support its operations and clinical trials [12] Q&A Session Summary Question: How is the company prioritizing trial progress between pivotal PCNSL versus CLL and AML? - Management indicated that resources are being prioritized towards NHL, particularly PCNSL, while CLL is in the early stages of study [14][15] Question: Can you provide updates on PCNSL enrollment? - Management confirmed that enrollment is on track, with expectations for full enrollment within 12-18 months [22] Question: Should revenue modeling reflect no meaningful revenue for 2026? - Management confirmed that there will be no meaningful revenue, as cash flows from Erivedge have ended [27][28] Question: What data should be expected at ASH 2026 for CLL? - Management stated that they hope to present meaningful data regarding the treatment's effectiveness, focusing on deepening patient responses [35][36]

Group 1 - US Bank plans to invest $25 billion in private credit transactions, extending its existing direct lending business through its capital markets division [2] - Accenture mandates senior employees to regularly use internal AI tools to qualify for promotions, tracking usage frequency as a performance metric [3] - Nvidia is nearing a $30 billion investment in OpenAI, replacing a previous $100 billion long-term commitment [2] Group 2 - Meta has reduced equity-based awards for most employees by approximately 5%, marking the second consecutive year of cuts [2] - Newmont Corporation expects a 10% decrease in gold production by 2026 due to underperformance at two jointly operated mines with Barrick [2] - AppLovin is developing its own social network platform, which could enhance user data access and increase competition with established social media giants [3] Group 3 - AstraZeneca's Calquence combination therapy has been approved by the FDA for treating chronic lymphocytic leukemia and small lymphocytic lymphoma [3] - Google has released the Gemini 3.1 Pro model, which boasts double the inference performance compared to its predecessor [3]

Core Insights - The U.S. FDA has granted Breakthrough Therapy Designation for investigational therapy IPN60340 in combination with venetoclax and azacitidine for first-line treatment of unfit acute myeloid leukemia (AML) [1][2] - IPN60340 is a first-in-class monoclonal antibody targeting BTN3A, which is crucial for immune regulation in cancer [1][4] - The designation aims to expedite the development of therapies for serious conditions, highlighting the urgent need for new treatment options in AML [2] Group 1: Breakthrough Therapy Designation - The Breakthrough Therapy Designation is based on promising data from the Phase I/II EVICTION trial, which showed high response rates in patients treated with IPN60340 and Ven-Aza [2][3] - The trial demonstrated a near doubling of complete response rates compared to historical standard care data, particularly in molecular subtypes less responsive to standard treatments [2][3] Group 2: EVICTION Trial Details - The EVICTION trial is a first-in-human study that includes dose-escalation and cohort-expansion phases for patients with advanced cancers, including newly diagnosed AML [3] - The trial aims to evaluate the safety and efficacy of IPN60340 in patients who have exhausted standard treatment options [3] Group 3: Mechanism of Action - IPN60340 is designed to enhance the immune response by promoting the recognition and elimination of tumor cells by γ9δ2 T cells [4] - The therapy targets BTN3A, which is overexpressed in various solid tumors and hematologic malignancies, facilitating the activation of anti-tumor immune responses [4] Group 4: Company Overview - Ipsen is a global biopharmaceutical company focused on developing transformative medicines in oncology, rare diseases, and neuroscience [5] - The company has nearly 100 years of development experience and operates in over 40 countries, bringing medicines to patients in more than 100 countries [5]

Core Viewpoint - AB Science reports a fourth consecutive positive response in a Phase 1 study for the combination of AB8939 and venetoclax in treating refractory or relapsed acute myeloid leukemia (AML) with a very unfavorable genetic profile [2][3]. Summary by Sections Clinical Trial Results - The fourth patient treated with AB8939 (21.3 mg/m²) plus venetoclax for 14 days achieved a partial response, consistent with previous results from three other patients [2][3]. - The combination treatment has shown a 100% response rate (4 out of 4 patients), including one complete remission, one near complete response, and two partial responses [5]. Patient Profile and Treatment Context - The fourth patient had a complex karyotype with a monosomy of chromosome 5 and a TP53 mutation, indicating a very adverse risk profile [5][6]. - All four patients had difficult-to-treat cytogenetic profiles, which typically correlate with poor prognosis due to aggressive disease and treatment resistance [5]. Mechanism of Action - AB8939 destabilizes microtubules and targets cancer stem cells by inhibiting ALDH1A1 and ALDH2, which are essential for cancer cell survival [7][13]. - The combination of AB8939 and venetoclax is expected to have additive or synergistic effects, enhancing treatment efficacy against AML [17]. Future Development Plans - The next steps include completing the Phase 1 trial and launching an expansion study involving approximately 15 AML patients eligible for the AB8939 and venetoclax combination [14]. - AB Science is in discussions with the European Medicines Agency (EMA) and the US Food and Drug Administration (FDA) regarding potential registration studies for AB8939 in relapsed/refractory AML, with a market size potential exceeding EUR 2 billion annually [15][21]. Market and Competitive Landscape - The estimated market size for treatments targeting relapsed or refractory AML is projected to be over EUR 2 billion per annum, highlighting a significant unmet medical need [15]. - The combination of AB8939 and venetoclax is anticipated to be less toxic than existing treatments, positioning it favorably in the competitive landscape of AML therapies [17]. Intellectual Property and Regulatory Status - AB8939 has secured intellectual property rights until 2036, with potential extensions through additional patent applications [20]. - The drug has received orphan drug designation from both the EMA and FDA, granting it marketing exclusivity for 10 years in Europe and 7 years in the US [21].

Summary of BeOne Medicines Conference Call Company Overview - **Company**: BeOne Medicines (ONC/688235.SS) - **Industry**: Oncology - **Headquarters**: Switzerland - **Focus**: Discovering and developing innovative cancer treatments, with a portfolio in hematology and solid tumors, including products like Brukinsa and Tevimbra [7][10] Key Points from the Conference Call Approval and Market Entry - **Sonro Approval**: On January 5th, 2025, the China NMPA approved sonrotoclax (BCL2 inhibitor) for relapsed/refractory chronic lymphocytic leukemia (R/R CLL) and mantle cell lymphoma (R/R MCL) [1] - **Approval Timeline**: The NDA review took only eight months, which is considered quick compared to the typical 12-18 months for new drug approvals, indicating a significant unmet need for BCL2 inhibitors in China [1] Market Dynamics - **Sales Ramp-Up**: There is a focus on tracking the sales ramp-up of venetoclax and lisaftoclax, as well as feedback from physicians and patients regarding the new BCL2 inhibitors [2] - **Differentiation Potential**: Sonrotoclax and lisaftoclax are expected to disrupt the market due to: 1. **Better Tolerability**: Both drugs showed lower rates of neutropenia and discontinuation compared to venetoclax, with sonrotoclax showing a lower rate than lisaftoclax [2] 2. **Quicker Dose Ramp-Up**: Lisaftoclax has a 4-6 days daily dose ramp-up scheme, while sonrotoclax and venetoclax follow a weekly ramp-up [2] Financial Projections - **Earnings Adjustments**: FY2025-2027 earnings estimates were adjusted, with EPS revised from US$3.78/US$6.26/US$6.64 to US$3.59/US$4.65/US$4.46 [6] - **Sales Estimates**: Near-term sales estimates for sonro were fine-tuned with increased SG&A investment, and R&D spending was increased due to multiple pipeline assets entering the proof of concept stage [6] - **Target Prices**: The 12-month target prices were updated to US$385.79 for ONC and Rmb345.86 for the A-share [6] Risks and Challenges - **Key Risks**: 1. Uncertainties in R&D and regulatory approvals, especially for the early-stage solid tumor franchise [7][10] 2. Competition from BTK and PD-1 inhibitors [7][10] 3. Development risks for clinical-stage assets [7][10] 4. Market access bottlenecks [7][10] Investment Rating - **Current Rating**: The company maintains a "Buy" rating, with shares trading at a modest discount due to broader macroeconomic factors and concerns around its product pipeline [7][10] Additional Insights - **Clinical Development Team**: BeOne Medicines has a growing internal clinical development team, which may provide cost savings and advantages in product launch times compared to peers [7] - **Market Position**: The company is well-positioned to grow and bring additional therapies to both the local Chinese market and the global pharmaceutical stage [7] This summary encapsulates the critical insights from the conference call regarding BeOne Medicines, its market strategies, financial outlook, and associated risks.

Core Insights - Resistance to venetoclax, a $2.5 billion therapy for Chronic Lymphocytic Leukemia (CLL), is becoming a significant therapeutic challenge as leukemic cells persist despite combination therapies [1][3] - New in vivo studies indicate that the addition of opaganib, a potent sphingosine kinase 2 (SPHK2) inhibitor, to venetoclax can reduce CLL cell counts by 50% compared to controls, suggesting its potential as an add-on therapy for venetoclax-resistant CLL [1][2] - Opaganib has demonstrated a favorable safety and tolerability profile in over 470 clinical trials and is being evaluated for multiple indications, including oncology and viral infections [1][9] Company Overview - RedHill Biopharma Ltd. is a specialty biopharmaceutical company focused on the development and commercialization of drugs for gastrointestinal diseases, infectious diseases, and oncology [12] - The company promotes the FDA-approved drug Talicia for treating Helicobacter pylori infections and is advancing several late-stage clinical programs, including opaganib [12][13] - Opaganib is currently undergoing a Phase 2 clinical trial in combination with darolutamide for advanced prostate cancer, highlighting its broad therapeutic potential [1][7] Product Insights - Venetoclax, approved by the FDA in 2016, is a first-in-class BCL-2 inhibitor that has become a cornerstone of CLL therapy, achieving sales of approximately $2.5 billion in 2024 [3] - Opaganib is a first-in-class, orally administered drug with anticancer, anti-inflammatory, and antiviral activities, targeting multiple indications including various cancers and viral diseases [6][10] - The drug has received orphan-drug designations from the FDA for cholangiocarcinoma and neuroblastoma, indicating its potential in treating rare diseases [7]

Core Insights - 100% of patients in Cohorts 1-3 remain free of cytokine release syndrome, indicating a strong safety profile for the CD3 design used in the study [1] - The study evaluates mipletamig, a CD123 x CD3 bispecific molecule, in combination with azacitidine and venetoclax for newly diagnosed acute myeloid leukemia patients unfit for intensive chemotherapy [1] - Preliminary results were presented at the American Society of Hematology Annual Meeting, highlighting the potential of the ADAPTIR™ and ADAPTIR-FLEX™ platform technologies developed by the company [1] Company Summary - Aptevo Therapeutics Inc. is a clinical-stage biotechnology company focused on developing novel immune-oncology therapeutics [1] - The company utilizes proprietary ADAPTIR™ and ADAPTIR-FLEX™ platform technologies in its research and development efforts [1] Industry Context - The ongoing Phase 1b/2 RAINIER study is significant for the treatment of acute myeloid leukemia, particularly for patients who cannot undergo intensive chemotherapy [1] - The combination of mipletamig with standard treatments like azacitidine and venetoclax represents a potential advancement in the therapeutic options available for AML [1]