Denali Therapeutics FY Conference Summary Company Overview - **Company**: Denali Therapeutics (NasdaqGS:DNLI) - **Industry**: Biotechnology, focusing on biotherapeutics for neurological diseases Key Messages and Core Points 1. **Transport Vehicle Technology**: Denali emphasizes its transport vehicle technology as a validated and clinically proven platform for delivering biotherapeutics across the blood-brain barrier (BBB) [3][4][12] 2. **Market Potential**: The company anticipates capturing a market exceeding $1 billion with upcoming launches for treatments targeting rare diseases such as Hunter syndrome and Sanfilippo [3] 3. **Clinical Programs**: Denali is advancing multiple clinical programs, including: - TIVI for Hunter syndrome, with a BLA filing and a PDUFA date set for April 5, 2026 [16][33] - OTV MAPT and ATV A beta for Alzheimer's disease, with clinical studies expected to start soon [4][27] - DNL126 for Sanfilippo, aiming for accelerated approval by 2027 [18][44] Financial and Market Strategy 1. **Launch Strategy for TIVI**: The company plans a seamless transition for patients currently on standard care, focusing on engaging centers of excellence and ensuring payer coverage [34][38] 2. **Revenue Expectations**: Minimal revenues are expected in 2026 due to the nature of rare disease launches, with a significant increase anticipated in 2027 as coverage expands [37] 3. **Pricing Strategy**: Denali aims to price TIVI at a premium compared to current treatments, ensuring broad access and affordability for patients [38] Clinical Data and Safety 1. **TIVI Clinical Data**: Safety data shows a decline in infusion-related reactions over time, with normalization of biomarkers indicating efficacy in halting neurodegeneration [15][16] 2. **Sanfilippo Program**: The ongoing phase one-two study for DNL126 is designed to leverage learnings from TIVI, with a focus on CSF heparan sulfate as a surrogate biomarker [41][44] 3. **Alzheimer's Programs**: ATV-A shows promise in reducing amyloid-related imaging abnormalities (ARIA) and improving plaque reduction compared to standard treatments [23][25] Research and Development Focus 1. **Broad Portfolio**: Denali is expanding its portfolio to include treatments for lysosomal storage diseases and common neurodegenerative diseases, with a focus on both enzyme replacement and oligonucleotide therapies [6][22] 2. **Innovative Approaches**: The company is committed to advancing its transport vehicle technology to enhance drug delivery across the BBB and improve treatment outcomes [11][52] Competitive Landscape 1. **Market Position**: Denali acknowledges the competitive nature of the field but believes its unique technology and clinical validation position it favorably [2][3] 2. **Future Opportunities**: The company is exploring additional indications for its transport vehicle platform, prioritizing diseases with well-understood biology and significant unmet needs [52] Conclusion Denali Therapeutics is poised for significant growth with its innovative transport vehicle technology, targeting both rare diseases and common neurodegenerative conditions. The company is strategically positioned to launch its products, engage with the medical community, and ensure patient access while navigating the complexities of the biotechnology market.

Denali Therapeutics Investor Day Summary Company Overview - **Company**: Denali Therapeutics (NasdaqGS:DNLI) - **Event**: 2025 Investor Day - **Date**: December 04, 2025 Key Messages 1. **Biotherapeutics Delivery**: Denali aims to deliver biotherapeutics to the entire body, including the brain, utilizing their transferrin receptor-enabled technology, which enhances delivery to hard-to-reach tissues [2][3] 2. **Market Opportunity**: The company is poised to capture a billion-plus opportunity in enzyme replacement therapies with their ETV franchise, addressing a significant unmet need in the market [4][5] 3. **Focus on Alzheimer's**: Denali is focusing on Alzheimer's disease, leveraging their transport vehicle technology to enhance treatment efficacy [5][6] 4. **Execution Strategy**: The company emphasizes efficient execution and capital allocation to expand their programs quickly and cost-effectively [6][9] Transport Vehicle Technology - **Innovation**: Denali's transport vehicle technology allows for the delivery of enzymes, oligonucleotides, and antibodies across the blood-brain barrier and to other tissues [6][11] - **Clinical Validation**: The technology has been validated through clinical data, demonstrating its ability to enhance delivery to the brain and other tissues [12][14] - **Competitive Landscape**: Denali is positioned as a leader in transferrin receptor-enabled therapeutics, with multiple clinical stage programs and a robust pipeline [15][16] Enzyme Replacement Therapy (ERT) Franchise 1. **Market Potential**: The combined market opportunity for Hunter syndrome (MPS II) and Sanfilippo syndrome (MPS III) is estimated at around $1 billion [16][17] 2. **Patient Population**: Over 30,000 individuals are living with lysosomal storage disorders, with a significant portion experiencing CNS manifestations [17][18] 3. **Regulatory Updates**: Denali has signed a deal with Royalty Pharma potentially worth up to $275 million, contingent on the approval of their drug tividenofusp alfa (TIVI) [6][7] 4. **Clinical Progress**: The company has made significant progress with TIVI, including a late-cycle meeting with the FDA and ongoing label negotiations [8][58] Clinical Data Highlights - **TIVI Efficacy**: Clinical data show greater than 90% reduction in cerebrospinal fluid heparan sulfate levels, indicating effective treatment for MPS II [54][55] - **Safety Profile**: The primary adverse events associated with TIVI are infusion-related reactions, which are generally mild to moderate and decrease over time with continued treatment [56] - **Ongoing Studies**: The COMPASS study is a pivotal trial comparing TIVI to the current standard of care, idursulfase, focusing on both neurological and peripheral outcomes [57][58] Future Outlook - **D3 Strategy**: Denali's strategy focuses on discovering, developing, and delivering innovative therapies, with a goal of launching multiple clinical stage programs in the next few years [9][10] - **Long-term Vision**: The company aims to build a strong portfolio of clinical and commercial products, addressing both immediate and long-term patient needs in lysosomal storage disorders [10][11] Additional Insights - **Unmet Needs**: There is a significant unmet need in treating neurodegenerative aspects of lysosomal storage disorders, particularly in MPS II and MPS III, where current therapies do not adequately address CNS manifestations [33][41] - **Patient Advocacy**: The involvement of patient advocates and experts in the field highlights the importance of addressing the needs of individuals affected by these disorders [19][20] This summary encapsulates the key points discussed during Denali Therapeutics' Investor Day, focusing on their innovative approaches, market opportunities, and the clinical landscape surrounding their therapies.

Financial Data and Key Metrics Changes - For the first nine months of 2025, total revenues were $43.6 million, a 24% increase compared to the same period last year [4] - Total revenues for the third quarter were $17.9 million, reflecting a decrease of 1% compared to the same period in 2024 [4] - The net loss for the nine-month period ended September 30, 2025, was $1.1 million, or $0.01 per share, compared to a net loss of $3.6 million, or $0.05 per share for the same period in 2024 [17] - For the three months ended September 30, 2025, net income was approximately $2.4 million, or $0.03 per share, compared to net income of $3.2 million, or $0.04 per share for the same period in 2024 [18] Business Line Data and Key Metrics Changes - Total revenues from selling goods for the nine months ended September 30, 2025, were $43.1 million, an increase of $8.3 million, or 24%, compared to $34.8 million for the same period in 2024 [10] - Revenues consisted of $18.6 million in sales of Elefabrio to Chiesi, $15.4 million in sales of Elelyso to Pfizer, and $9.1 million in sales of Elelyso to Fiocruz in Brazil [10] - For the three months ended September 30, 2025, total revenues from selling goods were $17.7 million, a decrease of $0.1 million, or 1%, compared to $17.8 million for the same period in 2024 [10] Market Data and Key Metrics Changes - The company recognizes revenues from sales to partners, and individual purchases vary from quarter to quarter as each partner controls its own inventories [11] - The company anticipates a significant increase in the overall gout market in the next five to six years, particularly for uncontrolled gout patients requiring uricases [22] Company Strategy and Development Direction - The operating strategy focuses on three pillars: driving commercial success with Elefabrio, advancing PRX-115 and other early-stage pipeline programs, and maintaining financial discipline [7] - The company is preparing for the phase two clinical trial of PRX-115, which is viewed as a strategic investment in the pipeline and long-term growth [13] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in Elefabrio's long-term potential and is working closely with Chiesi to support the re-examination of the once-in-four-weeks dosing regimen [6] - The company believes that the achievements in 2025 position it for long-term growth and value creation [19] Other Important Information - Research and development expenses for the nine months ended September 30, 2025, totaled $13.9 million, an increase of 58% compared to the prior year period [13] - Selling general and administrative expenses for the nine months ended September 30, 2025, were $8.2 million, down 11% from the same period last year [14] - The company had $29.4 million in cash and cash equivalents at September 30, 2025, sufficient to satisfy capital needs for at least 12 months [18] Q&A Session Summary Question: Timeline for the re-examination of the CHMP opinion on Elefabrio - The company expects to have an answer in Q1 of 2026 regarding the re-examination request [22] Question: Comments on the competitive landscape in treatment refractory gout - The company foresees a significant increase in the overall gout market and believes that if the phase two trial is successful, it could capture a substantial market share [22] Question: Predictability of royalty-based revenue recognition related to Elefabrio sales - The company continues to recognize what it sells to Chiesi's inventory and is optimistic about future revenue [23][24] Question: Cash runway guidance - The cash runway guidance is based on both operating expenditures and continued receipt of royalty-based revenue on Elefabrio [25][26] Question: Anticipated R&D growth during the phase two of PRX-115 - The company is taking into account the expenses associated with the phase two trial and has sufficient cash for more than 12 months to fund this trial [45]

Core Insights - Protalix BioTherapeutics reported total revenues of $43.6 million for the first nine months of 2025, a 24% increase compared to the same period in 2024, while third-quarter revenues were $17.9 million, reflecting a 1% decrease year-over-year [2][13] - The company is advancing its recombinant PEGylated uricase candidate, PRX-115, for uncontrolled gout, with plans to initiate a phase 2 clinical trial later this year based on promising phase 1 data [2][5] - Protalix's financial results indicate a net income of approximately $2.4 million for the third quarter of 2025, down from $3.2 million in the same quarter of 2024 [6] Financial Highlights - Total revenues for the nine months ended September 30, 2025, were $43.1 million, up from $34.8 million in 2024, with significant contributions from sales of Elfabrio, Elelyso, and alfataliglicerase [13] - Cost of goods sold increased by 10% to $22.4 million for the nine months ended September 30, 2025, primarily due to increased sales to Chiesi and Pfizer [13] - Research and development expenses rose by 58% to approximately $13.9 million for the nine months ended September 30, 2025, driven by preparations for the phase 2 clinical trial of PRX-115 [13][18] Operational Updates - The company submitted an Investigational New Drug (IND) application to the FDA for PRX-115, which became effective after the standard 30-day review period [5] - Protalix is collaborating with Chiesi Global Rare Diseases to address a negative opinion from the EMA regarding Elfabrio's dosing regimen, while the currently approved regimen remains unaffected [5] - As of September 30, 2025, Protalix had $29.4 million in cash and cash equivalents, sufficient to meet capital needs for at least the next 12 months [8]