Fund Performance - The Patient Opportunity Equity Strategy achieved a total return of 14.1% net of fees in Q3 2025, outperforming the S&P 500 Index which returned 8.1% [2] - The portfolio's outperformance was driven by selection and interaction effects, while allocation effects partially offset these gains [3] Portfolio Composition - The strategy was overweight in sectors such as Consumer Discretionary, Communication Services, Financials, Energy, Industrials, and Health Care, while underweight in Real Estate, Utilities, Materials, Consumer Staples, and Information Technology [4] - The portfolio ended the quarter with 36 holdings, with the top 10 stocks representing 51.1% of total assets, indicating a high active share of approximately 92.5% [5] Market Context - The market's upward trend in Q3 was supported by resilient consumer spending, Federal Reserve rate cuts, and ongoing AI investments [6] - Long-held positions in the portfolio broke through multi-year resistance levels, contributing to overall performance [6] Key Contributors - Precigen (PGEN) was the top contributor, benefiting from the FDA approval of Papzimeos, which is expected to launch soon [10][15] - Alphabet Inc. (GOOGL) and Alibaba Group Holdings (BABA) also significantly contributed to performance, with GOOGL gaining regulatory clarity and BABA announcing aggressive AI investment plans [8][16][17] Key Detractors - Dave & Buster's Entertainment (PLAY) was the largest detractor due to disappointing results and leadership changes, although there is optimism for future recovery under new management [18] - QXO Inc. (QXO) faced concerns over weakening construction activity but continues to execute its acquisition strategy [19] - Crocs Inc. (CROX) declined following disappointing guidance and challenges with its HEYDUDE brand [20][21] Strategic Actions - The portfolio eliminated five positions during the quarter, reallocating capital towards higher conviction names [12] - The strategy continues to capitalize on market volatility, increasing positions in Delta Air Lines (DAL) and Norwegian Cruise Line Holdings (NCLH) during market pullbacks [9]

Core Insights - Precigen, Inc. announced long-term follow-up data showing durable responses to PAPZIMEOS (zopapogene imadenovec-drba) for adults with recurrent respiratory papillomatosis (RRP), presented at the AAO-HNSF 2025 Annual Meeting [1][3] - PAPZIMEOS is the first and only FDA-approved therapy for RRP, granted full approval in August 2025 [1][7] Efficacy and Safety - The pivotal study for PAPZIMEOS met primary safety and efficacy endpoints, with 51% of patients achieving complete response, requiring no surgeries in the 12 months post-treatment [2][5] - Long-term follow-up data indicated that 83% of complete responders maintained their response with a median follow-up of 36 months, and no new safety events were observed [5][6] Impact on Patients and Healthcare System - Durable responses from PAPZIMEOS lead to fewer surgical procedures, reducing complications and long-term healthcare burdens [3] - The percentage of patients experiencing a reduction in surgeries compared to the year prior to treatment was 86% in Year 1, 91% in Year 2, and 95% in Year 3 [5][6] Background on RRP - RRP is a rare disease caused by chronic HPV 6 or HPV 11 infection, leading to severe complications and requiring repeated surgeries, which can significantly impact patients' quality of life [4] - Approximately 27,000 adult RRP patients are estimated to be in the US, highlighting the unmet medical need for effective treatments [4]

Core Insights - Artificial intelligence (AI) is identified as the greatest investment opportunity of the current era, with a strong emphasis on the urgent need for energy to support its growth [1][2][3] - A specific company is highlighted as a key player in the AI energy sector, owning critical energy infrastructure assets that are essential for meeting the increasing energy demands of AI technologies [3][7][8] Investment Landscape - Wall Street is investing hundreds of billions into AI, but there is a pressing concern regarding the energy supply needed to sustain this growth [2] - AI data centers, which power large language models like ChatGPT, consume energy equivalent to that of a small city, indicating a significant strain on global power grids [2] - The company in focus is positioned to benefit from the anticipated surge in demand for electricity driven by AI advancements [3][6] Company Profile - The company is described as a "toll booth" operator in the AI energy boom, collecting fees from energy exports and playing a crucial role in U.S. LNG exportation [5][7] - It is noted for its debt-free status and substantial cash reserves, which amount to nearly one-third of its market capitalization, providing a strong financial foundation [8][10] - The company also holds a significant equity stake in another AI-related venture, offering investors indirect exposure to multiple growth opportunities in the AI sector [9][10] Market Positioning - The company is recognized for its capability to execute large-scale engineering, procurement, and construction projects across various energy sectors, including nuclear energy [7][8] - It is suggested that the company is undervalued, trading at less than seven times earnings, which presents a compelling investment opportunity [10][11] - The influx of talent into the AI sector is expected to drive continuous innovation, further solidifying the company's position in the market [12][13] Future Outlook - The article emphasizes the importance of investing in AI and energy infrastructure as the future is increasingly reliant on these technologies [13][14] - The potential for significant returns is highlighted, with projections of over 100% returns within 12 to 24 months for investors who act promptly [15][19]

Group 1 - Precigen, Inc. (NASDAQ: PGEN) shares have significantly increased following the FDA's full approval of its recurrent respiratory papillomatosis therapy, Papzimeos, on August 14th, marking the first-ever approval for this indication [2] Group 2 - The Biotech Forum, led by Bret, offers a model portfolio featuring 12-20 high upside biotech stocks, along with live chat discussions on trade ideas and weekly market commentary [2]

Group 1: AI Investment Opportunity - Artificial intelligence is identified as the greatest investment opportunity of our lifetime, with a strong emphasis on the urgency to invest now [1] - Wall Street is investing hundreds of billions into AI, but there is a critical question regarding the energy supply needed to support this technology [2] - AI data centers consume massive amounts of energy, comparable to the energy needs of small cities, leading to concerns about power grid strain and rising electricity prices [2] Group 2: Company Overview - A specific company is highlighted as a key player in the AI energy sector, owning critical energy infrastructure assets that are essential for meeting the increasing energy demands of AI [3][7] - This company is positioned to benefit from the surge in demand for electricity driven by AI data centers, making it a potentially valuable investment in the digital age [3] - The company is debt-free and has a significant cash reserve, amounting to nearly one-third of its market capitalization, which provides financial stability and growth potential [8] Group 3: Market Position and Strategy - The company plays a crucial role in U.S. LNG exportation, which is expected to grow under the current administration's energy policies [7] - It is capable of executing large-scale engineering, procurement, and construction projects across various energy sectors, including oil, gas, and renewable fuels [7] - The company also holds a substantial equity stake in another AI-related venture, providing investors with indirect exposure to multiple growth opportunities in the AI sector [9] Group 4: Investment Appeal - The stock is described as undervalued, trading at less than 7 times earnings, which presents a compelling investment opportunity compared to other energy and utility firms [10] - The company is not just a speculative investment; it generates real cash flows and owns critical infrastructure, making it a solid choice for investors looking to capitalize on the AI and energy convergence [11] - The influx of talent into the AI sector ensures continuous innovation, further solidifying the investment case for companies involved in AI infrastructure [12]

Group 1 - Precigen, Inc. has signed a credit facility agreement worth up to $125 million to support its commercialization efforts for PAPZIMEOS and expand into international markets [2][3][4] - The credit facility consists of two tranches: the first tranche of $100 million was funded at closing, while the second tranche of $25 million can be drawn at the company's discretion until March 21, 2027 [2][4] - The funding aims to bolster the company's position in the U.S. market and pursue pediatric and other HPV-related indications, indicating potential for near-term revenue growth [3][4] Group 2 - Precigen is a biopharmaceutical company focused on the discovery and clinical-stage development of gene and cell therapies targeting diseases in immuno-oncology, autoimmune disorders, and infectious diseases [5]

Group 1 - Precigen Inc. (NASDAQ:PGEN) is recognized as a promising multibagger stock, particularly due to its UltraCAR-T platform which aims for faster manufacturing and improved safety profiles in CAR-T treatments [1] - The company's stock has surged over 300% year-to-date, with a notable doubling of share price since mid-August following the FDA approval of its Papzimeos therapy, the first approved treatment for adults with recurrent respiratory papillomatosis [2] - Analysts have reacted positively to the FDA approval, with JPMorgan upgrading the stock to Neutral from Underweight, and Cantor Fitzgerald and H.C. Wainwright reaffirming their Buy ratings [3] Group 2 - The FDA approval of Papzimeos is seen as favorable, covering a broad indication for approximately 27,000 U.S. adults, with projected sales of $15 million by Q4 2025 [4] - Precigen focuses on developing gene and cellular therapies, particularly in the fields of immuno-oncology, autoimmune disorders, and infectious diseases [5]

Core Viewpoint - The healthcare sector is experiencing significant stock price increases, with some stocks more than doubling in value since the end of July, indicating potential for further gains despite recent surges [1][2]. Group 1: Precigen - Precigen's shares increased by 155% from the end of July to September 5, following FDA approval for its first treatment, Papzimeos, which is aimed at recurrent respiratory papillomatosis (RRP) [4][5]. - Papzimeos is the first and only FDA-approved treatment for approximately 27,000 patients with RRP, with a notable response rate in clinical trials where 18 out of 35 patients avoided surgery for at least 12 months post-treatment [5][6]. - Analysts, including Swayampakula Ramakanth from HC Wainwright, have set a price target of $8.50 for Precigen, suggesting a potential 95% increase in the next year [6]. Group 2: Mineralys Therapeutics - Mineralys Therapeutics saw a 146% rise in stock price from the end of July to September 5, driven by a successful funding round for the development of its lead candidate, lorundrostat [7][8]. - The company raised $287.5 million through a secondary offering, which followed the suspension of an at-the-money equity offering [8]. - In a phase 3 trial, lorundrostat demonstrated a significant reduction in systolic pressure, outperforming a placebo [9]. - Following AstraZeneca's less favorable data for a competing product, Bank of America analyst Greg Harrison raised the target price for Mineralys to $43 per share, indicating a potential 24% gain [11]. - Despite the positive outlook, the company ended June with $325 million in cash, sufficient to last until 2027, raising concerns about the urgency of submitting for approval [12]. - Mineralys has a market cap of $2.7 billion, which could be affected by the timing of lorundrostat's approval compared to competitors [14]. Group 3: Market Potential - Precigen's market cap is approximately $1.3 billion, with expectations for Papzimeos potentially underestimated, as it is set to launch in a niche market without competition [15]. - Papzimeos could generate over $1 billion in annual sales at peak pricing, with a list price exceeding $200,000 per patient per year [16].

Core Insights - Precigen is a biopharmaceutical company focused on innovative precision medicines for difficult-to-treat diseases with high unmet needs [1] - The company has received FDA approval for PAPZIMEOS, the first drug approved for treating recurrent respiratory papillomatosis in adults [2] - PAPZIMEOS is a nonreplicating adenoviral vector-based immunotherapy targeting HPV 6 and 11, which are believed to cause the disease [2] - The FDA granted full approval on August 15, ahead of the PDUFA date of August 27, and the drug is set to launch in early Q4 of this year [2]

Summary of Precigen (PGEN) Fireside Chat - September 02, 2025 Company Overview - **Company**: Precigen (PGEN) - **Industry**: Biopharmaceuticals - **Focus**: Development of innovative precision medicines for difficult-to-treat diseases with high unmet needs - **Recent Achievement**: Approval of PapSimios, the first drug for recurrent respiratory papillomatosis (RRP), a rare and potentially fatal disease caused by HPV types six and eleven [1][11] Core Points and Arguments Drug Approval and Launch - **Approval Date**: FDA granted full approval for PapSimios on August 15, 2025, ahead of the PDUFA date of August 27 [1] - **Launch Timeline**: Management plans to launch the drug in early Q4 2025 [1] - **Significance**: PapSimios is the first FDA-approved treatment targeting the root cause of RRP, addressing a significant unmet medical need [12] Business Strategy and Platforms - **Business Plan**: Focus on innovative platforms, specifically the AdenoVerse platform and overnight CAR T cell therapy [4][5] - **Development Speed**: The company demonstrated rapid drug development, achieving full approval in four years, which is noted as unprecedented in the industry [5] - **CAR T Platform**: Autologous CAR T therapy developed with a non-viral platform, allowing for rapid patient treatment [9] Patient Population and Disease Impact - **RRP Patient Population**: Estimated 27,000 adults in the U.S. with RRP, with potential extrapolation to 100,000-120,000 patients in top markets outside the U.S. [20][22] - **Disease Characteristics**: RRP is debilitating, often requiring multiple surgeries, leading to irreversible damage to vocal cords or trachea [12][14] - **Treatment Necessity**: Patients can receive PapSimios immediately upon diagnosis, regardless of disease severity [32][33] Clinical Data and Efficacy - **Clinical Trial Results**: 51% of patients did not require surgery for at least one year post-treatment, with 86% showing overall response [24][25] - **Durability of Response**: Some patients have maintained responses for over three years [24][47] Commercialization Strategy - **Sales Strategy**: Activation of sales teams across 18 territories covering over 90% of identified patient potential [38][42] - **Payer Mix**: Expected payer distribution is 60-65% commercial, 30-35% Medicare, and the remainder Medicaid [42] - **Patient Support**: Initiatives in place to assist patients with financial aid and access to treatment [46] Future Plans and Pipeline - **Expansion Plans**: Focus on expanding indications for PapSimios to include genital warts and pediatric populations [51] - **Additional Products**: Development of PRGN 2009 for HPV-related cancers, with promising initial data [52] Financial Position - **Cash Position**: As of the last quarter, the company reported a cash runway of $59 million, sufficient to support the commercial launch and manufacturing [58] - **Funding Strategy**: Plans to avoid equity dilution while exploring non-dilutive funding options [59] Other Important Content - **Patient Advocacy**: Close collaboration with patient advocacy groups to ensure patient needs are met and to promote awareness of PapSimios as a standard of care [40] - **Regulatory Insights**: The FDA's decision for full approval was influenced by robust clinical data demonstrating safety and efficacy [25] This summary encapsulates the key points discussed during the fireside chat, highlighting the company's strategic direction, product development, and market potential.