Welcome to the brainstorm episode 96, closing into our final 100th episode where Jake and I will make the determination whether to continue on or wrap it all up unless we get enough funny comments. So, please com comment away. We've got Shay Wilberg with us from our genomics team.Shay's first time joining us. Shay, do you want to give a a quick intro. >> Sure.So Shay Wilberg, I recently joined here at Arc Invest as a multiomics analyst on the team. Before this, I was working over on the cell side over at Ba ...

Core Insights - Cellectis reported financial results for Q2 2025, highlighting advancements in its gene editing platform and ongoing clinical trials for its therapies [1][11][34] - The company is preparing for a pivotal Phase 2 trial for lasme-cel (UCART22) in relapsed or refractory B-cell acute lymphoblastic leukemia (r/r B-ALL), expected to start in the second half of 2025 [3][6] - Cellectis will host an Investor R&D Day on October 16, 2025, to present Phase 1 data and discuss its late-stage development strategy [2][5] Financial Performance - As of June 30, 2025, Cellectis had $230 million in cash, cash equivalents, and fixed-term deposits, providing a financial runway into H2 2027 [11][38] - Consolidated revenues and other income for the first half of 2025 were $30.2 million, up from $16.0 million in the same period of 2024, primarily due to a $20 million increase from the AstraZeneca Joint Research Collaboration Agreement [16] - The net loss attributable to shareholders for the first half of 2025 was $41.9 million, compared to a net loss of $19.6 million in the same period of 2024 [21][27] Clinical Development - The company completed end-of-Phase 1 meetings with the FDA and EMA for lasme-cel in July 2025, marking a significant regulatory milestone [3][6] - Cellectis is also advancing the NatHaLi-01 study for eti-cel (UCART20x22) in relapsed or refractory B-cell non-Hodgkin lymphoma (r/r NHL), with a Phase 1 readout expected in late 2025 [4][5] - The company is engaged in ongoing R&D activities under its partnership with AstraZeneca, focusing on three cell and gene therapy programs [8][5] Corporate Updates - André Muller was appointed as a director to Cellectis' Board of Directors [5][13] - The company is involved in arbitration proceedings with Servier, with a decision expected by December 15, 2025 [9][5] - Cellectis continues to manage its operations and pipeline development, focusing on manufacturing and clinical trial expenses for its product candidates [15][11]

Core Insights - CRISPR Therapeutics is experiencing significant momentum in both commercial and clinical programs, particularly with the activation of over 75 authorized treatment centers for CASGEVY, which has led to approximately 115 patients having cells collected globally [1][2][3] - The company is advancing multiple clinical trials, including CTX310 targeting ANGPTL3, which has shown promising preliminary data with reductions of up to 82% in triglycerides and 86% in LDL [1][3][7] - CRISPR Therapeutics has a strong financial position with approximately $1.7 billion in cash and marketable securities as of June 30, 2025, despite a net loss of $208.5 million for the second quarter of 2025 [1][14][29] Commercial Programs - CASGEVY, a CRISPR/Cas9 gene-edited cell therapy, is approved in multiple regions including the U.S., EU, and Canada for treating sickle cell disease and transfusion-dependent beta thalassemia [3][12] - The company has achieved its target of activating 75 authorized treatment centers globally, with 29 patients having received infusions of CASGEVY, including 16 in the second quarter of 2025 [1][3] - Reimbursement agreements have been secured in 10 countries, enhancing patient access to CASGEVY [3] Clinical Trials - Ongoing clinical trials for CTX310™ are expected to present complete Phase 1 data in the second half of 2025, with preliminary results indicating significant reductions in triglycerides and LDL [1][3][7] - CTX320™ is in a Phase 1 trial targeting the LPA gene, with updates anticipated in the first half of 2026 [1][3] - CTX112™ and CTX131™ are also in clinical trials targeting CD19 and CD70, respectively, with broad updates expected in the second half of 2025 [1][3][7] Financial Performance - For the second quarter of 2025, CRISPR Therapeutics reported a net loss of $208.5 million, compared to a net loss of $126.4 million in the same period of 2024 [14][29] - Research and development expenses decreased to $69.9 million from $80.2 million year-over-year, primarily due to reduced employee-related costs [14][29] - The total operating expenses for the second quarter were $230.2 million, up from $151.8 million in the previous year, largely due to acquired in-process R&D expenses related to the Sirius Agreement [14][29] Strategic Collaborations - A strategic collaboration with Sirius Therapeutics was established to develop and commercialize small interfering RNA (siRNA) therapies, starting with SRSD107 for thromboembolic disorders [13][20] - The European Medicines Agency has authorized a Phase 2 clinical trial for SRSD107, which aims to evaluate its safety and efficacy in preventing postoperative venous thromboembolism [13][20]

Core Insights - Cibus, Inc. is implementing a reduction in force (RIF) as part of its strategy to streamline operations and focus on commercial opportunities in rice and biofragrance products, aiming to reduce annual net cash usage to approximately $30 million by 2026 [1][2][3] Group 1: Business Strategy - The RIF is expected to incur one-time charges of approximately $0.5 million in Q3 2025, aligning with the company's focus on optimizing its Trait Machine gene editing processes [1][2] - Cibus is prioritizing the commercial advancement of its HT1 and HT3 weed management traits in rice, while also advancing sustainable ingredients and bio-based fermentation fragrance products [2][3] Group 2: Market Position and Opportunities - Cibus is positioned to pursue partner funding to support its advanced productivity trait portfolio, which includes traits for disease resistance in canola, winter oilseed rape (WOSR), and soybean [1][3] - The company emphasizes its role as a technology provider rather than a seed company, utilizing proprietary gene editing technology to develop traits more efficiently than conventional breeding methods [4]

Core Insights - Investing in biotechnology stocks involves long periods of inactivity followed by sharp movements, particularly in small-cap biotech stocks which often lack profitability and revenue [1][2] Group 1: Urogen Pharma - UroGen Pharma is focused on treating urologic cancers with its proprietary RTGel technology, enhancing drug efficacy by prolonging retention in the urinary tract [4] - UroGen stock has increased approximately 43% in 2025 due to an application to expand the Jelymyto label for low-grade bladder cancer, potentially increasing its market [5] - Analyst forecasts suggest a price target of $32.86 for URGN stock, indicating a potential gain of over 115% from its closing price on July 18, although short interest is high at over 42% [6] Group 2: Nektar Therapeutics - Nektar Therapeutics has seen a 78% gain in 2025 but remains down over 93% in the last five years due to several clinical trial failures [8] - Positive Phase 2b clinical trial results for a candidate treating systemic lupus erythematosus and ulcerative colitis have generated bullish sentiment, along with a Fast Track designation from the FDA [9] - The consensus price target for NKTR stock is $88.33, representing a 254% increase from its closing price on July 18, but a pullback is anticipated due to recent price surges [10] Group 3: Verve Therapeutics - Verve Therapeutics is pioneering gene editing to treat cardiovascular disease, currently in the clinical stage with revenue primarily from partnerships [12] - The company received approval for a Phase 1b U.S. clinical trial for its lead candidate, VERVE-102, targeting the PCSK9 gene associated with high cholesterol [13] - Analysts have set a price target of $14.57 for VERV stock, indicating a 33% upside, although this is lower compared to the other stocks mentioned [13]

Core Insights - Prime Medicine has secured up to $24 million in additional funding from the Cystic Fibrosis Foundation to accelerate the development of Prime Editors for cystic fibrosis (CF) [1][2][3] - The funding aims to enhance Prime Editing technology, which has the potential to correct a wide range of genetic mutations affecting over 93% of individuals with CF [1][2] - The initial focus will be on the G542X mutation, a prevalent CF-causing mutation with no current therapies available [2] Company Overview - Prime Medicine is a biotechnology company dedicated to developing one-time curative genetic therapies using its proprietary Prime Editing platform, which allows precise and efficient gene editing [5][6] - The company is advancing a diversified portfolio of therapeutic programs targeting liver, lung, immunology, and oncology diseases [6][7] - Prime Editing technology is designed to minimize unwanted DNA modifications while effectively repairing various genetic mutations across different tissues and organs [5] Funding Details - The CF Foundation's investment builds on an earlier agreement from January 2024 and will be provided in two tranches, with the first tranche including a $6 million equity investment [2][3] - The funding is contingent upon meeting certain scientific milestones and closing conditions [3] Disease Context - Cystic fibrosis is a serious genetic disease caused by mutations in the CFTR gene, affecting approximately 100,000 people globally, including over 40,000 in the United States [4] - Current disease-modifying therapies are not curative and may be ineffective for certain mutations, highlighting the need for innovative treatments [4]

Group 1: CRISPR Therapeutics - CRISPR Therapeutics has developed Casgevy, the first gene-editing medicine approved using the CRISPR technique, but the stock has been on a downward trend since 2021 due to clinical progress, complexity of therapy administration, and unprofitability [3][4] - The company is targeting challenging areas such as type 1 diabetes and hard-to-treat cancers, with expected data readouts for ongoing clinical trials as early as this year, which could positively impact stock performance [5] - Casgevy has significant financial implications, with a treatment cost of $2.2 million in the U.S. and an estimated 60,000 patients in target geographies, indicating blockbuster potential [9] Group 2: Viking Therapeutics - Viking Therapeutics gained attention after strong phase 2 results for VK2735, an investigational weight management therapy, but has seen stock performance decline as investors took profits [10] - The anti-obesity therapy market is rapidly growing, and Viking's VK2735 has shown promising mid-stage data, with an oral formulation currently in Phase 2 studies [11] - Viking Therapeutics has a robust pipeline, including VK2809 for metabolic dysfunction-associated steatohepatitis entering phase 3 studies and VK0214 for X-linked adrenoleukodystrophy, which has received orphan drug designation [12][13]

Core Insights - CRISPR Therapeutics has been recognized in the TIME 100 Most Influential Companies list for its pioneering work in gene editing [1][2][3] - The company is expanding its focus beyond sickle cell disease and beta thalassemia to address significant unmet medical needs in cardiovascular and autoimmune diseases [2][4] - The recognition by TIME reflects the company's commitment to transforming medicine through innovation and collaboration [3] Company Overview - CRISPR Therapeutics has evolved from a research-stage company to a leader in gene editing, celebrating the approval of the first-ever CRISPR-based therapy [4] - The company has a diverse portfolio targeting various disease areas, including hemoglobinopathies, oncology, regenerative medicine, cardiovascular, autoimmune, and rare diseases [4] - The first CRISPR/Cas9 gene-edited therapy was advanced into clinical trials in 2018, with CASGEVY (exa-cel) approved in several countries starting late 2023 for treating eligible patients [4] Strategic Partnerships - To enhance its capabilities, CRISPR Therapeutics has formed strategic partnerships with leading companies, including Vertex Pharmaceuticals [4] Recognition and Impact - TIME's selection process involved evaluating companies based on impact, innovation, ambition, and success, highlighting CRISPR Therapeutics' role in shaping the future of business and society [3]

Industry Overview - The field of genomics has rapidly evolved over the past decade, focusing on the complete set of genes and their interactions rather than individual genes [1] - Genomics is pivotal for developing targeted therapies, leading to a revolutionary era in genetic medicine, attracting significant attention from pharmaceutical and biotech companies [2] Technological Innovations - Synthetic biology, which applies engineering principles to biology, has emerged as a key concept within genomics, aiding in drug discovery, disease detection, and gene editing [3] - The cost, accuracy, and time required to map an individual's genome have drastically reduced, enhancing the spotlight on genomics companies [4] Market Potential - The genomics market is projected to reach $157.47 billion by 2033, while the global synthetic biology market was valued at $16.22 billion in 2024, with a projected CAGR of 17.30% from 2025 to 2030 [6] Company Highlights - MeiraGTx Holdings plc is focused on genetic medicine with a pipeline addressing conditions like Parkinson's disease and retinal dystrophy, showing promising efficacy data [8][9] - Beam Therapeutics is advancing base editing programs for genetic diseases, with FDA orphan drug designation for its BEAM-101 treatment for sickle cell disease [12][13] - Krystal Biotech received FDA approval for Vyjuvek, the first gene therapy for dystrophic epidermolysis bullosa, and is advancing a pipeline in various therapeutic areas [14][15]

Core Viewpoint - CRISPR Therapeutics (CRSP) and Intellia Therapeutics (NTLA) are leading companies in the CRISPR/Cas9 gene editing space, with CRSP being the first to market a CRISPR-based therapy, while NTLA focuses on late-stage in vivo therapies [1][10]. Group 1: CRISPR Therapeutics (CRSP) - CRSP achieved a significant milestone by securing approval for Casgevy (exa-cel) for treating sickle cell disease (SCD) and transfusion-dependent beta thalassemia (TDT) in late 2023/early 2024, marking the first-ever approval for a CRISPR/Cas9 therapy globally [2][3]. - The commercial uptake of Casgevy has been slow due to the complexity of the treatment process, although VRTX has activated over 65 authorized treatment centers globally, with nearly 90 patients having completed cell collection as of May 1 [4]. - CRSP has multiple other CRISPR candidates in its pipeline, including two CAR-T therapy candidates, CTX112 and CTX131, which are in early-stage studies, with updates expected this year [5]. - Encouraging initial data from an early-stage study on CTX310, an in vivo CRISPR-based gene therapy targeting ANGPTL3 for atherosclerotic heart disease, has raised excitement for CRSP's in vivo programs [6][7]. - Despite the progress, CRSP's pipeline is still in early-stage development, and Casgevy faces competition from chronic therapies like Bristol Myers' Reblozyl and Novartis' Adakveo [8]. Group 2: Intellia Therapeutics (NTLA) - NTLA has shown potential in the biotech space by focusing on in vivo therapies, with two late-stage candidates: lonvo-z for hereditary angioedema (HAE) and nex-z for transthyretin (ATTR) amyloidosis [9][11]. - The pivotal phase III HAELO study for lonvo-z is underway, with enrollment expected to complete by Q3 2025, and regulatory filing planned for the second half of 2026 [12]. - Nex-z is being developed in collaboration with Regeneron Pharmaceuticals and is evaluated in two late-stage studies for ATTR amyloidosis [13]. - NTLA initiated a strategic reorganization to prioritize late-stage candidates, resulting in the cessation of some research programs and a planned workforce reduction of nearly 27% [14]. - A recent setback in the nex-z development due to liver safety concerns has raised questions about the therapy's long-term safety [15]. Group 3: Financial Estimates and Performance - The Zacks Consensus Estimate for CRSP's 2025 sales implies a 7% year-over-year increase, while loss estimates per share are expected to widen by about 28% [16]. - NTLA's 2025 loss per share is expected to improve nearly 20%, with loss estimates for 2025 and 2026 having narrowed over the past 60 days [17]. - Year-to-date, CRSP shares have risen by 19%, while NTLA shares have declined by 18%, compared to a 4% decline in the industry [19]. - CRSP's shares trade at a price/book (P/B) ratio of 2.21, higher than NTLA's 1.27, indicating that CRSP appears more expensive from a valuation standpoint [20]. Group 4: Investment Considerations - Both companies hold a Zacks Rank 3 (Hold), making it challenging to choose one over the other [24]. - CRSP is viewed as a safer investment due to its marketed product and a strong cash balance of $1.9 billion as of March 2025, while NTLA's cash balance was $707 million, raising concerns due to the lack of a stable revenue stream [25]. - Despite setbacks, CRSP's broader pipeline across in vivo and ex vivo therapies offers greater diversification, suggesting potential growth driven by solid fundamentals and positive stock price movement [26].