AN9025 Key Features - AN9025 is a novel pan-RAS(ON) inhibitor developed by Adlai Nortye with improved potency and a favorable PK/PD profile[8, 16] - AN9025 strongly binds to cyclophilin A (CypA) with a dissociation constant (KD1) of 3.2 nM, exhibiting a 4-fold stronger binding affinity compared to RMC-6236[3, 4, 8] - AN9025 exhibits a 3- to 8-fold higher binding affinity for tri-complex formation compared to RMC-6236[5] - AN9025 demonstrates approximately 100-fold greater potency in inhibiting cell viability across RAS-mutant cell lines compared to RMC-6236[8] - AN9025 shows potent anti-proliferative activity in RAS-addicted cancer cell lines with picomolar IC50 values[7, 8] In Vivo Efficacy and PK/PD - In vivo studies show that AN9025 induces deep tumor regression, with efficacy comparable to or exceeding RMC-6236 in mouse CDX models[8, 9] - AN9025 demonstrates a favorable pharmacokinetic (PK) and pharmacodynamic (PD) profile in vivo[8] - AN9025 exhibits more sustained DUSP6 inhibition compared to RMC-6236 across all tested doses[8] Clinical Development - The prolonged tumor DUSP6 suppression following AN9025 administration suggests the potential for an intermittent dosing regimen to optimize tolerability and efficacy[8] - AN9025 is advancing through the IND-enabling stage[8] - Adlai Nortye is actively seeking strategic partnerships to advance the development of AN9025[18]

Company Strategy & Competitive Advantages - The company aims for a long-term Return on Equity (ROE) target of 15%[8] - The company operates where specialized knowledge provides a competitive edge[8, 11] - A decentralized structure enables quick responses to changing market conditions[11] - The company focuses on long-term risk-adjusted returns and shareholder value creation[7, 8] Financial Performance & Capital Management - In 2024, Insurance net premiums written were $10.5 billion, and Reinsurance & Monoline Excess net premiums written were $1.4 billion[20] - As of December 31, 2024, total debt was $2.841 billion, and common equity was $8.395 billion, resulting in a debt-to-capital ratio of 25.3%[42] - The company has returned $7.5 billion to shareholders through dividends and share repurchases since 2006, representing 55% of net income[49] - The company actively manages capital, including the issuance of subordinated debt in 2023 ($185 million at 5.700%), 2024 ($300 million at 5.100%), and planned issuances in 2025 ($250 million at 4.250%) and 2026 ($300 million at 4.125%)[46] Investment Portfolio - As of December 31, 2024, fixed maturity securities constituted 75.1% of the investment portfolio, totaling $22.397 billion[38] - Cash and cash equivalents represented 6.4% of the portfolio, amounting to $1.891 billion[38] - "Alternative" investments accounted for 18.5% of the portfolio, totaling $5.491 billion[38]

Pipeline and Milestones - Prothena has multiple clinical programs ongoing, including one partnered Phase 3 program, two partnered Phase 2 programs, one partnered Phase 1 program, and one wholly-owned Phase 1 program[13] - Prothena is eligible to receive up to $1.23 billion in total consideration from Novo Nordisk for coramitug and the broader ATTR amyloidosis program[13, 16] - Prothena anticipates up to $105 million in clinical milestones in 2026, including completion of Phase 3 development for prasinezumab and initial data from the Phase 1 ASCENT trial for PRX012[18] Partnerships and Financials - Prothena's partnerships are expected to generate meaningful value, with up to $755 million in total milestones and royalties for prasinezumab, up to $1.23 billion for coramitug, and up to $1.55 billion across two clinical-stage programs (BMS-986446 and PRX019)[20] - Bristol Myers Squibb (BMS) owns approximately 2.2% of Prothena's outstanding shares as of March 3, 2025[21] Alzheimer's Disease Programs - PRX012, Prothena's anti-Aβ candidate, has approximately 10X greater binding potency to fibrillar Aβ vs aducanumab and approximately 20X greater binding potency against protofibrils vs lecanemab[24] - BMS-986446 (formerly PRX005), an anti-tau candidate, has the potential to reduce pathogenic tau spread in Alzheimer's disease[27] - PRX123, a dual Aβ/tau vaccine candidate, is designed for both treatment and prevention of Alzheimer's disease, and its IND has been cleared[27] Parkinson's Disease Program - Roche will initiate Phase 3 development for prasinezumab in early-stage Parkinson's disease[15, 111] - The Parkinson's disease affects >10 million people worldwide and represents an overall economic burden of $52 billion in the US[5] ATTR Amyloidosis Program - Coramitug (formerly PRX004) is in Phase 2 development for ATTR amyloidosis with cardiomyopathy (ATTR-CM)[15, 142] - An estimated 450,000 patients worldwide have wtATTR or ATTRv[8]

Clinical Trial Results - MeiraGTx's rAAV8.hRKp.AIPL1 gene therapy has shown efficacy in all 11 children (aged 1-4 years) treated for AIPL1 Retinal Dystrophy (LCA4) [3] - In the unilateral treatment group (4 patients), durable efficacy has been observed for up to 4 years [3] - In the unilateral treatment group, visual acuities of treated eyes improved to a mean of 0.9 LogMAR, while untreated eyes showed no improvement [6] - All 7 bilaterally-treated children showed meaningful improvements in functional vision, visual acuity, and neurophysiology [14] - Binocular visual acuities in bilaterally-treated children improved to a mean of 1.0 LogMAR after a mean follow-up of 5 months [14] Regulatory Status - MeiraGTx was granted an Innovation Passport designation in the UK for rAAV8.hRKp.AIPL1 [16] - MeiraGTx has been advised to file for 'Marketing Authorization Under Exceptional Circumstance' in the UK based on data from 11 children [16] - AAV-AIPL1 has orphan status in the US and EU and Rare Pediatric Disease Designation in the US, making it eligible for a PRV voucher upon approval [16] Overall Impact - Treatment with rAAV8.hRKp.AIPL1 has resulted in improvements in visual function, retinal function, and visual behavior in treated children [15] - These visual improvements have led to life-changing benefits in communication, behavior, schooling, mood, psychological well-being, and social integration [15]

Clinical Pipeline and Regulatory Milestones - The company has 3 late-stage clinical programs in pivotal/Phase 3 trials for prevalent non-inherited indications[4,7,30,36,42,90] - Potential global filings are anticipated in 2025, 2026, and 2027[7,30,36,42,90] - The company has a deep pre-IND pipeline targeting conditions like ALS, MC4R obesity, and metabolic disease[7,8,32,38,45,93] Manufacturing and Technology - The company operates 2 GMP facilities at commercial scale[5,9,33,39,46,94] - Proprietary vectorization technology increases potency by 2-10x from the same promoter[5,9,34,40,47,95] - AI-driven improvements are based on over 20 vectors and more than 50 GMP runs[5,9,33,39,46,94] Partnerships and Financials - MeiraGTx will receive up to $415 million from Janssen through an asset purchase agreement[11] - Sanofi made a $30 million strategic investment through the sale of 4 million ordinary shares at $7.50 per share[11] AAV-AQP1 for Radiation Induced Xerostomia - There are 170,000 Grade 2/3 RIX patients in the US[13] - There are 15,000 new cases of grade 2/3 RIX annually in the US[13] AAV-GAD for Parkinson's Disease - There are 10 million Parkinson's patients worldwide[18,28] - The estimated economic burden of Parkinson's Disease in the US is $52 billion[19]

PYX-201 Mechanism and Target - PYX-201 is a first-in-concept extracellular-cleaving ADC targeting EDB+FN, a non-cellular component of the tumor extracellular matrix [6, 7] - EDB+FN is highly overexpressed in various solid tumors, releasing the payload extracellularly for direct tumor killing, bystander effect, and immunogenic cell death [10, 11] - PYX-201's unique mechanism of action (MOA) may address a primary cause of drug resistance by altering the ECM [16] Clinical Trial and Tolerability - Phase 1 dose escalation study included 80 patients with 10 solid tumor types [29] - PYX-201 demonstrated a favorable tolerability profile with a low treatment discontinuation rate of 1% [6, 39] - The identified dose range for further evaluation is 3.6 - 5.4 mg/kg [6, 34] Efficacy and Responses - An overall response rate (ORR) of 26% was observed in 6 responding tumor types (n=31) at the identified dose range of 3.6-5.4 mg/kg [6, 43] - In HNSCC patients within the 3.6 – 5.4 mg/kg dose range, a 50% ORR and 100% disease control rate (DCR) were observed [6, 54] - Median time on study in Phase 1 Part 1 was approximately 12 weeks [50, 51] Future Development and Catalysts - A clinical trial collaboration will evaluate PYX-201 in combination with KEYTRUDA® (pembrolizumab) [18] - Multiple clinical catalysts are expected in the next 6-18 months, including readouts from HNSCC monotherapy and early line combination studies [6, 65] - As of Q3 2024, the company has $146 million in cash, providing runway into 2H 2026 [87]

Company Overview - enCore Energy aims to produce 3 million pounds of U3O8 per year by the end of 2026 and 5 million pounds of U3O8 per year by the end of 2028 [26] - The company has a market capitalization of $835,566,936 USD as of February 12, 2024 [34] Production and Operations - Rosita Central ISR Uranium Processing Plant (CPP) restarted production in November 2023 and is expected to produce approximately 200,000 pounds of U3O8 per year [65, 92] - The Rosita CPP has a licensed production capacity of 800,000 pounds of U3O8 per year, with the potential to double capacity within existing licenses [67] - Alta Mesa CPP is planned for production in 2024, with an initial production target of approximately 500,000 pounds [16, 96] - The combined capacity of the company's three fully licensed CPPs (Rosita, Kingsville Dome, and Alta Mesa) is 3.6 million pounds of U3O8 per year [82] Resource Estimates - Alta Mesa and Mesteña Grande have total Measured and Indicated Mineral Resources of 1,570,000 tons at 0.109% U3O8, containing 3.41 million pounds of U3O8 [95] - Alta Mesa and Mesteña Grande have total Inferred Mineral Resources of 6,996,000 tons at 0.120% U3O8, containing 16.793 million pounds of U3O8 [95] - Dewey-Burdock Project has Measured and Indicated ISR Resources of 7,388,222 tons at an average grade of 0.116% U3O8, containing 17.12 million pounds [102] - Gas Hills Project has Measured & Indicated ISR mineral resources of 3.83 million tons at 0.101% eU3O8, attributable to 7.71 million pounds U3O8 [111] - Crownpoint & Hosta Butte Project has total Indicated Mineral Resource of 10.96 million tons at Grade eU3O8 0.117 %, attributable U3O8 is 25.70 million pounds [124] Market and Strategy - The company has four uranium sales agreements in place [23, 87] - The company is pursuing a non-core asset divestment strategy [25, 136] - The company is investing in new technologies like Prompt Fission Neutron (PFN) technology [25, 58, 137]

NASDAQ: OTLK outlooktherapeutics.com Redefining the Treatment of Retinal Disease Corporate Presentation July 2025 This presentation contains forward-looking statements about Outlook Therapeutics, Inc. ("Outlook Therapeutics" or the "Company") based on management's current expectations, which are subject to known and unknown uncertainties and risks. Words such as "expect," "explore," "initiate," "intend," "may," "plan," and "potential," and variations of these words or similar expressions are intended to ide ...

Obicetrapib Clinical Development and Market Opportunity - Obicetrapib is designed to address the significant unmet need for oral LDL-C lowering therapy as an adjunct to statins, targeting over 30 million patients in the US who are not achieving LDL-C lowering goals[7, 11] - Obicetrapib demonstrated a 43% mean LDL-C lowering as monotherapy and a 59% mean LDL-C lowering in combination with ezetimibe, observed on top of high-intensity statins[8] - The lipid-lowering therapy market is a growing opportunity, with over 250 million prescriptions written in the past 12 months and a market growth of over 4% in the last 2 years[16] - Approximately 75% of ASCVD patients are not at their risk-based LDL-C goal, highlighting the need for more effective treatments[23] PREVAIL CVOT Trial Design and Potential Benefits - The PREVAIL CVOT is designed to apply lessons learned from previous CVOTs to reduce risk and demonstrate Obicetrapib's full benefit, targeting higher baseline LDL-C patients and a longer duration of follow-up[32] - Phase 2 efficacy data applied to PREVAIL baseline data predicts at least a 20% MACE benefit projection across multiple biomarkers[34, 35, 37, 40] - The PREVAIL study inclusion criteria requires high baseline LDL-C (also translates to high ApoB) and risk enhancers will increase high-risk patient populations[62] Upcoming Milestones and Data Readouts - Multiple potential pivotal data readouts are expected in the next 12 months from Phase 3 BROADWAY, BROOKLYN, and Phase 2b Japan trials[42, 43] - Enrollment is complete for the BROOKLYN Phase 3 trial, and topline results are expected in Q4 2024, while BROADWAY Phase 3 topline results are expected in Q3 2024[65] Addressing Limitations of Existing Therapies - Obicetrapib program is designed to overcome limitations of prior CETP inhibitors, with a 97% CETP inhibition at a 10mg dose, and demonstrated Lp(a) lowering of 47-57%[28]

Clinical Program and Trial Results - NewAmsterdam Pharma completed enrollment for BROOKLYN, BROADWAY and PREVAIL Phase 3 studies[5] - The BROOKLYN Phase 3 trial, involving 354 participants with HeFH and LDL-C ≥70 mg/dL, has primary endpoint of LDL-C reduction at 12 weeks[46, 49] - The BROADWAY Phase 3 trial, involving 2,532 participants with ASCVD or HeFH and LDL-C ≥55 mg/dL, also has primary endpoint of LDL-C reduction at 12 weeks[46, 53] - The PREVAIL CVOT, involving 9,541 participants with ASCVD and LDL-C ≥55 mg/dL, has primary endpoint of 4-Point MACE+ with a minimum 30-month follow-up[46, 61] - Initial data from an Alzheimer's Disease sub-study showed that obicetrapib 10mg decreased 24s- & 27s-hydroxycholesterol in both plasma and cerebrospinal fluid in a phase 2a study (n=13)[55] Obicetrapib's Potential Benefits - Obicetrapib observed to lower small LDL-P by 90%+ and total particles by over 70% in combination with ezetimibe[24] - Obicetrapib 10 mg on top of high-intensity statins significantly lowered Lp(a) by 57% vs placebo, in ROSE[80] - Obicetrapib monotherapy observed a 43% mean LDL-C lowering[30] - Obicetrapib in combination with ezetimibe observed a 59% mean LDL-C lowering on top of high-intensity statins[31] Commercial Opportunity - Approximately 30 million+ patients in the US are not achieving LDL-C lowering goals despite standard-of-care[30] - The lipid-lowering therapy market has over 250 million prescriptions annually[164] - The market is growing at over 4% over the last 2 years, with the non-statin market growing at high double digits[164] Financial Position - NewAmsterdam Pharma had $481 million in cash as of 1Q24[225]