UBX1325 ASPIRE Study Results - UBX1325 showed a BCVA gain of 5.2 letters at week 24 and 5.5 letters at week 36[5] - Approximately 40% of UBX1325 patients did not require supplemental anti-VEGF treatment through week 36[5] - UBX1325 generally outperformed Aflibercept in subjects with less aggressive disease (baseline CST < 400 µm)[39] - Patients switching from Aflibercept to UBX1325 experienced consistent gains in BCVA and less variable CST[5, 39] - UBX1325 was non-inferior to Aflibercept at most time points through 36 weeks, but did not meet non-inferiority at the average of weeks 20 and 24 in the primary analysis[5] Market Opportunity and Unmet Needs in DME - The global Diabetic Macular Edema (DME) market is projected to reach $9.6 billion by 2031, with the US market reaching $5.5 billion[43] - Over 50% of patients discontinue anti-VEGF treatment by 6 months[43] - 58% of patients with DME exhibit suboptimal response to anti-VEGF therapies[43] - 28% of patients require frequent dosing (every 4 weeks) with current anti-VEGF treatments[43]

CHS-114 Overview - CHS-114 is a highly selective anti-CCR8 mAb with the potential to augment I-O therapy by depleting Treg-mediated tumor immune suppression[16] - CHS-114 specifically binds and preferentially depletes CCR8+ tumor Tregs, with no off-target binding[17,23] - Preclinical data shows that anti-CCR8 with anti-PD-1 treatment demonstrates antitumor activity and a significant increase in tumoral CD8+ T cells[27,29] - *In vitro* data shows CHS-114 demonstrates dose-dependent Treg depletion and activation of NK and myeloid cells[37] Clinical Trial Design and Results - The Phase 1/1b study is an open-label single-agent and combination dose trial evaluating CHS-114 in patients with advanced solid tumors and HNSCC, with safety and tolerability as the primary endpoint[50,63] - In the monotherapy dose escalation (Stage 1a), 20 patients with advanced solid tumors were enrolled and evaluated seven dose levels (5 mg – 1200 mg) of CHS-114[54] - In HNSCC patients, treatment-emergent adverse events (TEAE) were observed in 85.7% of patients receiving CHS-114 monotherapy (n=14) and 100% of patients receiving CHS-114 + Toripalimab (n=7)[68] - One heavily pretreated PD-1 refractory patient with HNSCC treated with CHS-114 (DL6) + Toripalimab achieved a confirmed partial response with a 40% reduction in target lesions[73,88] Biomarker Analysis and Conclusions - CHS-114 administration leads to a substantial increase in CD8+ T cells in the TME, providing a strong rationale for combining with other drugs such as T cell engagers and bispecifics[102] - In on-treatment tumor biopsies, CHS-114 depleted CCR8+ Tregs and increased CD8+ T cells in the TME, indicating favorable TME remodeling and establishing proof of mechanism[102]

Transaction Summary - Seanergy Maritime Holdings Corp计划发行 1 亿美元的高级无抵押债券[1,37] - 债券发行所得款项将用于一般公司用途，包括船舶收购和债务再融资[40,41] - Seanergy 在纳斯达克上市，股票代码为“SHIP”，市值约为 1.45 亿美元[30,37] Company Overview - Seanergy 是一家领先的 Capesize 型散货船船东和运营商，收购 Meiship 和 Blueship 后，拥有 21 艘船舶[30,40] - 该公司自 2008 年以来在纳斯达克上市，拥有丰富的资本市场经验，自 2020 年以来已筹集 1.8 亿美元的股权[31,42] - Seanergy 拥有高质量的船队，包括 19 艘 Capesize 型和 2 艘 Newcastlemax 型船舶，价值 6.6 亿美元[40,42] - 该公司采用混合运营模式，拥有低成本的内部技术管理和成熟的商业管理平台[42,65] - Seanergy 的船队 100% 采用期租方式，确保 100% 的利用率，平均高于波罗的海海岬型船指数的 105%[42,51] Financial Profile - Seanergy 拥有稳健的信贷指标，净贷款价值比为 45%，经预计债券发行调整后的净杠杆率为 2.7 倍[40,42] - 该公司拥有高效的运营模式，全面运营支出和资本支出盈亏平衡点约为每天 9,600 美元[70,60] - Seanergy 拥有良好的财务战略，过去 5 年在所有市场环境下均确保净贷款价值比低于 50%，交易完成后约为 45%[42,168]

Efficacy Results - Atacicept demonstrated long-term stabilization of eGFR (estimated glomerular filtration rate) in IgAN patients over 96 weeks[31] - Atacicept treatment resulted in a sustained 66% reduction in Gd-IgA1 levels[20] - There was a notable 52% reduction in proteinuria (UPCR) with atacicept treatment over the 96-week study period[20] - Atacicept led to a 75% resolution of hematuria in treated participants[20] - The annualized eGFR slope with atacicept was -0.6 mL/min/1.73 m2 per year, comparable to the general population without kidney disease[20] Safety Profile - Atacicept was generally well-tolerated over 96 weeks, with an adverse event profile consistent with the initial 36-week randomized period[27] - During the double-blind phase, 73% of participants in the atacicept group experienced treatment-emergent adverse events (TEAEs)[27] - In the open-label extension (OLE) phase, 77% of participants experienced TEAEs[27] - Serious TEAEs were reported in 2% of participants during the double-blind phase and 11% during the OLE phase[27] - Discontinuation due to TEAEs occurred in 1% of participants during the double-blind phase and 2% during the OLE phase[27]

Pipeline and Drug Candidates - Revolution Medicines has a deep science-driven pipeline of targeted therapies for RAS-addicted cancers, with drug candidates expected to enter the clinic in 2022 [13, 14] - RMC-6236 is a first-in-class RASMULTI(ON) inhibitor with broad potential against RAS-addicted cancers [22] - RMC-6291 is a mutant-selective RAS(ON) inhibitor with best-in-class potential for KRASG12C cancers [44] - RMC-9805 is a mutant-selective RAS(ON) inhibitor with best-in-class potential for KRASG12D cancers [62] - RMC-8839 is a first-in-class mutant-selective RAS(ON) inhibitor for KRASG13C cancers [74] Clinical Priorities and Activities - Revolution Medicines plans to submit INDs for RMC-6236 and RMC-6291 in the first half of 2022 and initiate single-agent dose escalation studies [42, 60] - The company aims to complete enrollment in RMC-4630-03 and provide preliminary evaluation in the second half of 2022 [98] - Revolution Medicines anticipates submitting INDs for RMC-9805 in the first half of 2023 and RMC-8839 in the second half of 2023 [118] RAS-Addicted Cancers and Patient Numbers - RAS proteins drive 30% of human cancers [7, 122] - There are an estimated 137,000 new KRASG12X patients per year in the U S [23] - There are approximately 29,000 new KRASG12C patients per year in the U S [45] - There are approximately 55,000 new KRASG12D patients per year in the U S [63] - There are approximately 3,000 new KRASG13C patients per year in the U S [75] Financial Position - Revolution Medicines had $577.1 million in cash, cash equivalents, and marketable securities as of December 31, 2021 [120]

Pipeline and Drug Candidates - Revolution Medicines is developing a deep pipeline of targeted therapies for RAS-addicted cancers, with the first two drug candidates expected to enter the clinic in 2022 [13] - RMC-6236 is a first-in-class RASMULTI(ON) inhibitor with potential against various RAS-addicted cancers, targeting approximately 137,000 new KRASG12X patients per year in the U S [19, 20] - RMC-6291 is a mutant-selective RAS(ON) inhibitor with best-in-class potential for KRASG12C cancers, addressing approximately 29,000 new KRASG12C patients per year in the U S [38, 39] - RMC-9805 is a first-in-class mutant-selective RAS(ON) inhibitor for KRASG12D cancers, targeting approximately 55,000 new KRASG12D patients per year in the U S [59, 60] - RMC-8839 is a first-in-class mutant-selective RAS(ON) inhibitor for KRASG13C cancers, addressing approximately 3,000 new KRASG13C patients per year in the U S [69, 70] Preclinical Data and Activity - RMC-6236 demonstrated robust anti-tumor activity in cancer models, with 44% ORR (8/18) in NSCLC, 53% ORR (8/15) in PDAC, and 61% ORR (11/18) in CRC [24] - RMC-6291 showed superior outcomes in a mouse clinical trial with KRASG12C NSCLC models, achieving 72% ORR (18/25) and 92% DCR (23/25) [43] - Preclinical research indicates that RMC-6236 and RMC-6291 exhibit anti-tumor immunity in vivo and strong additivity with checkpoint inhibitors [29, 52] Clinical Development and Strategy - Revolution Medicines plans to initiate single-agent dose escalation for RMC-6236 in patients with cancers harboring KRASG12X mutations, focusing on NSCLC, pancreatic cancer, and CRC [36] - The company also intends to start single-agent dose escalation for RMC-6291 in KRASG12C tumors, including expansion cohorts in select populations like NSCLC [58] - RMC-4630, a RAS companion inhibitor, is undergoing clinical combination studies, including with sotorasib and adagrasib, to address resistance mechanisms in KRASG12C tumors [91, 93] Financial Status - As of March 31, 2022, Revolution Medicines had approximately $518 8 million in cash, cash equivalents, and marketable securities [125] - The company anticipates a GAAP net loss of $260 million to $290 million for 2022, including $35 million to $40 million in non-cash stock-based compensation expense [125, 126]

Overview - Revolution Medicines is targeting RAS-addicted cancers, which are driven by RAS proteins and affect approximately 30% of human cancers[6, 8, 119] - The company is developing RAS(ON) inhibitors and RAS companion inhibitors to address this high unmet need[6, 11] RMC-6236 (RASMULTI Inhibitor) - RMC-6236 is a first-in-class RASMULTI(ON) inhibitor with potential against various RAS-addicted cancers, targeting approximately 137,000 new KRASG12X patients per year in the U S [17, 18] - Preclinical data shows robust anti-tumor activity in cancer models with common RAS variants, including KRASG12D, KRASG12V, KRASG12R, and KRASG12C[20] - In preclinical studies, RMC-6236 demonstrated a 44% Objective Response Rate (ORR) and 56% Disease Control Rate (DCR) in NSCLC models, 61% ORR and 89% DCR in PDAC models, and 53% ORR and 100% DCR in CRC models[24] RMC-6291 (KRASG12C Inhibitor) - RMC-6291 is a mutant-selective RAS(ON) inhibitor with best-in-class potential for KRASG12C cancers, addressing approximately 29,000 new patients per year in the U S [33, 34] - Preclinical studies in KRASG12C NSCLC models showed a 72% ORR and 92% DCR with RMC-6291, compared to 52% ORR and 72% DCR with Adagrasib[39] - RMC-6291 also demonstrated anti-tumor immunity in vivo and strong additivity with checkpoint inhibitors[48] RMC-9805 (KRASG12D Inhibitor) - RMC-9805 is a first-in-class mutant-selective RAS(ON) inhibitor for KRASG12D cancers, targeting approximately 55,000 new patients per year in the U S [51, 52] - Preclinical data shows rapid, deep, and sustained regressions in KRASG12D lung, pancreatic, and colorectal cancers[53] - In preclinical studies, RMC-9805 demonstrated a 64% ORR and 68% DCR across various KRASG12D cancer models[61] RMC-8839 (KRASG13C Inhibitor) - RMC-8839 is a first-in-class mutant-selective RAS(ON) inhibitor for KRASG13C cancers, addressing approximately 3,000 new patients per year in the U S [64, 65] - Preclinical data shows rapid, deep, and sustained regressions in KRASG13C lung cancers[66] Financial Status - As of September 30, 2022, Revolution Medicines had $655 million in cash, cash equivalents, and marketable securities, projecting funding for planned operations through 2024[116] - The company anticipates a 2022 GAAP net loss of $260 million to $280 million, including approximately $30 million to $35 million in non-cash stock-based compensation expense[116]

Company Overview - Kopin is a leading provider of specialized application-specific optical solutions for high-performance and mission-critical AR and VR applications[7] - The MicroDisplay market is forecasted to reach $6 billion in 2028 with a 20% CAGR[9] - Kopin is the 1 MicroDisplay provider for attractive end markets in defense, enterprise & industrial, and consumer sectors[9] - Kopin has deeply ingrained, long-tenured relationships with global market leaders with strategic focus on existing and emerging high-performance defense (90%), enterprise & industrial and consumer applications (10%)[9] Market Opportunity - The Department of Defense budget request for 2025 is $849.8 billion[17] - The global AR/VR market is expected to reach $71.2 billion in 2029, with AR at $29.6 billion (18% CAGR) and VR at $12.9 billion (23.2% CAGR)[52] - The global MicroDisplay market is projected to reach $9.2 billion in 2030 with a 17.6% CAGR[51] Technology and Products - Kopin offers a proprietary MicroDisplay portfolio including OLED, LCOS, µLED, and AMLCD MicroDisplays[19] - Existing programs in production & development represent approximately $70 million in revenue potential[40] - Kopin's µLED MicroDisplay has the potential for significantly higher brightness than OLED (up to 40x higher)[49] Intellectual Property and Manufacturing - Kopin has an extensive IP portfolio with over 200 pending or issued patents[57] - Kopin has manufacturing facilities in the United States and the United Kingdom[24]

Alzheimer's Disease Burden and Current Treatments - Alzheimer's accounts for 60-80% of dementia cases[6] - It affects 6.9 million Americans[6] - Alzheimer's is the 5th leading cause of death for those aged 65+[6] - The U.S annual financial impact of Alzheimer's and other dementias is $360 billion[6] - Current treatments primarily target amyloid-beta plaques but have limitations, including limited therapeutic effects and side effects[14, 15] INM-901: A Multifactorial Approach - INM-901 is an orally available small molecule drug candidate that can cross the blood-brain barrier[8, 21, 48] - It acts as a preferential signaling agonist for CB1/CB2 receptors and impacts the PPAR signaling pathway[8, 18, 21] - In vitro studies show INM-901 demonstrates neuroprotective effects and increased neurite outgrowth, signifying enhanced neuronal function[8, 27, 28, 29, 32] - Preclinical in vivo studies suggest INM-901 improves behavior and cognitive function, reduces neuroinflammation, and enhances neuronal function[8, 39, 42, 44] - Molecular data indicates INM-901 reduces pro-inflammatory genes and elevates neuronal function genes[42]

Icotrokinra (JNJ-2113) - Oral IL-23 Receptor Antagonist - Icotrokinra has the potential for NDA filings in 2025 for psoriasis[5, 8] - JNJ collaboration includes $3375 million upfront and milestones achieved to date, with $630 million in future potential milestones and royalties ranging from 6% to 10%, reaching 10% at ≥ $4 billion net sales[13] - Phase 3 ICONIC-LEAD study showed that 65% of patients achieved an IGA score of 0/1 (clear or almost clear skin) and 50% achieved a PASI 90 response at Week 16[121] - In adolescents receiving Icotrokinra, skin response rates increased through Week 24, with 86% achieving IGA 0/1 and 89% achieving PASI 90[76] - In the ICONIC-TOTAL study, Icotrokinra demonstrated significantly higher rates of IGA 0/1 vs placebo at Week 16[95] - Clinical response rates of up to 635% and clinical remission rates up to 302% at week 12 were observed in the phase 2b ANTHEM-UC study for ulcerative colitis[58, 149] Rusfertide - SC Hepcidin Mimetic - Rusfertide also has the potential for NDA filing in Q4 2025 for Polycythemia Vera (PV)[6, 8] - Takeda partnership includes $300 million upfront received in January 2024[16] - In the VERIFY Phase 3 study, 769% of patients on rusfertide achieved clinical response compared to 329% on placebo (p<00001)[178] - The VERIFY study also met all four key secondary endpoints, including phlebotomy rate (p<00001), hematocrit control, and patient-reported outcomes[185] - Rusfertide may provide consistent hematocrit control and reduce treatment burden to achieve peak revenue potential of $1-2 billion[191, 192] PN-881 - Oral IL-17 Antagonist - Phase 1 study initiation for oral IL-17 antagonist PN-881 is expected in Q4 2025[8, 26] - IL-17 inhibitors are expected to capture 31% of the psoriasis (PsO) market by 2031, generating $93 billion[26]