DUBLIN--(BUSINESS WIRE)---- $PRTA #Prothena--Prothena partners presented clinical data updates for prasinezumab for Parkinson's and BMS-986446 for Alzheimer's disease at AD/PDâ"¢ 2026. ...

Summary of Prothena's Conference Call Company Overview - Prothena is a biotechnology company focused on diseases characterized by dysfunctional proteins, established in 2012 as a spin-out from Elan Pharmaceuticals. The company has a diverse portfolio of partnered and unpartnered programs, including multiple phase 3 studies in collaboration with major pharmaceutical companies like Roche and Novo Nordisk [6][7][8]. Key Programs and Partnerships - **Parkinson's Disease**: Prothena has a partnership with Roche for a molecule targeting alpha-synuclein, which has advanced to phase 3 studies based on promising phase 2 data [7]. - **ATTR Cardiomyopathy**: A partnered program with Novo Nordisk is also in phase 3, focusing on a disease caused by transthyretin deposition in the heart [7]. - **Tau Protein Program**: In collaboration with Bristol Myers Squibb, Prothena is developing a molecule targeting the tau protein, which has received Fast Track designation from the FDA. The phase 2 study has been fully enrolled, with data expected in the first half of next year [8][9]. - **PRX-019**: Another program with Bristol Myers Squibb is completing phase 1 studies, with a decision on moving to phase 2 expected by year-end [9][10]. Financial Highlights - Prothena anticipates generating over $100 million in milestone payments from partner programs this year, including a recent $50 million milestone from Novo Nordisk [17][18]. - The company has announced a share repurchase program of up to $100 million for 2026, which is not included in the year-end guidance of $255 million [18][19]. - The total deal with Roche includes $755 million in milestones and royalties, with $135 million received to date [36]. Market Opportunities - The peak sales potential for the partnered programs is projected at over $3.5 billion, with significant milestone payments still to be received [36][68]. - The company is actively exploring business development opportunities to expand its proprietary pipeline and leverage its CYTOPE technology for previously undruggable targets [73][74]. CYTOPE Technology - CYTOPE technology aims to target previously undruggable proteins within cells, exemplified by the TDP-43 approach, which is significant in the context of ALS [14][79]. - The technology allows for specific targeting and clearance of cytosolic aggregates without disrupting normal protein functions, demonstrating potential in both CNS and peripheral applications [81][84]. Upcoming Data Releases - Roche is expected to present additional data on the prasinezumab program at the upcoming ADPD 2026 conference, including long-term extension data from previous trials [26][28]. - Prothena is looking forward to data releases from its partnered programs, particularly the phase 2 study with Bristol Myers Squibb and the phase 3 studies with Roche and Novo Nordisk [23][41]. Conclusion - Prothena is positioned as a science-focused, pipeline-rich company with significant partnerships and a robust portfolio. The company is strategically balancing capital allocation to maximize future opportunities while advancing its proprietary technologies [68][74].

Core Insights - The article emphasizes the expertise of Terry Chrisomalis in the Biotech sector, highlighting his background in Applied Science and his focus on generating long-term value in Healthcare investments [2]. Group 1 - The Biotech Analysis Central service offers a comprehensive analysis of pharmaceutical companies, including a library of over 600 articles and a model portfolio of more than 10 small and mid-cap stocks [2]. - A two-week free trial is currently available for new subscribers, with a monthly subscription priced at $49, and an annual plan offering a 33.50% discount at $399 [1]. Group 2 - The service includes live chat features and a range of analysis and news reports aimed at assisting Healthcare investors in making informed decisions [2].

Group 1 - Prothena (PRTA) closed at $9.4, with a 5.5% gain over the past four weeks, and a mean price target of $20.5 suggests an 118.1% upside potential [1] - The mean estimate includes six short-term price targets with a standard deviation of $10.65, indicating variability; the lowest estimate is $8.00 (14.9% decline), while the highest is $36.00 (283% increase) [2] - Analysts show strong agreement on PRTA's ability to report better earnings, with a positive trend in earnings estimate revisions indicating potential upside [4][11] Group 2 - Over the last 30 days, the Zacks Consensus Estimate for the current year has increased by 73.3%, with three estimates moving higher and no negative revisions [12] - PRTA holds a Zacks Rank 2 (Buy), placing it in the top 20% of over 4,000 ranked stocks based on earnings estimates [13] - While the consensus price target may not be a reliable indicator of potential gains, it does provide a directional guide for price movement [14]

Pipeline and Therapeutic Development - Prothena's pipeline includes therapeutic candidates for diseases such as Parkinson's disease, ATTR amyloidosis, Alzheimer's disease, and ALS, leveraging proprietary CYTOPE® technology[20] - The company is currently advancing four therapeutic antibody programs in active clinical development, including prasinezumab for Parkinson's disease and coramitug for ATTR amyloidosis[42] - Prasinezumab is being evaluated in the Phase 3 PARAISO clinical trial, while coramitug is in the Phase 3 CLEOPATTRA clinical trial, both in collaboration with major pharmaceutical partners[25] - Prothena has received FDA clearance for an investigational new drug application for PRX123, an Alzheimer's disease vaccine program, which has also been granted Fast Track designation[43] - The company is focusing on diseases that lack effective therapies, particularly in neurodegenerative and rare peripheral amyloid diseases[33] - Prothena's diverse pipeline includes antibody, small molecule, and vaccine approaches, positioning it to impact a broad spectrum of diseases[43] - Prothena's research includes the development of an anti-pTDP-43 CYTOPE for ALS, addressing the core molecular pathology associated with the disease[36] Clinical Trials and Results - Prasinezumab is currently in Phase 3 PARAISO trial for early Parkinson's disease, with approximately 900 participants enrolled[49] - In the Phase 2b PADOVA trial, prasinezumab showed a hazard ratio (HR) of 0.84 for time to confirmed motor progression, with a nominal p-value of 0.0657[50] - The Phase 2 PASADENA trial indicated a 35% reduction in motor function decline for prasinezumab-treated patients compared to placebo after one year[54] - In the Phase 1 clinical trials, prasinezumab demonstrated a mean concentration of 0.3% in cerebrospinal fluid relative to serum, exceeding expectations[59] - The ongoing Phase 3 trial aims to evaluate the efficacy and safety of prasinezumab over a minimum of 104 weeks[49] - The Phase 2b PADOVA trial included 586 participants treated for a minimum of 18 months, showing significant effects in a subgroup treated with levodopa (HR=0.79, nominal p=0.0431)[50] - The Phase 2 PASADENA trial's primary endpoint was the change in MDS-UPDRS total score at 52 weeks, with pooled dose levels showing a reduction of 14.0%[55] - Prasinezumab was found to be generally safe and well tolerated, with most adverse events reported as mild or moderate[58] - The Phase 2 trial of coramitug showed a statistically significant reduction in NT-proBNP levels by 48% compared to placebo over 52 weeks[76] - The Phase 3 CLEOPATTRA trial for coramitug is set to evaluate approximately 1,280 participants with ATTR-CM, focusing on cardiovascular deaths and events over a four-year period[75] Collaborations and Partnerships - The company is collaborating with Roche for the development of prasinezumab, focusing on its potential in treating synucleinopathies[45] - Prothena has earned $135.0 million of a total $755.0 million in potential clinical, regulatory, and sales milestones from Roche, including $30.0 million upfront and $60.0 million for the PADOVA trial initiation[63] - The Phase 2 clinical trial of prasinezumab in early Parkinson's disease, PADOVA, began in May 2021, triggering a $60.0 million milestone payment from Roche[61] - Coramitug, an investigational antibody for ATTR amyloidosis, has a potential total milestone payment structure of up to $290.0 million for development and regulatory achievements, plus tiered royalties based on annual net sales[67] - In July 2023, the company entered into an exclusive global license agreement for BMS-986446, receiving an option exercise fee of $55 million and being eligible for up to $563 million in regulatory and sales milestone payments[87] - The company is developing PRX123, a dual vaccine targeting both Aβ and tau proteins, with preclinical studies showing promising immune responses against both targets[103] - The company plans to explore partnership opportunities to advance PRX012 and the preclinical PRX012-TfR antibody programs[97] Financial Performance and Capital Requirements - The company incurred net losses of $244.1 million, $122.3 million, and $147.0 million for the years ended December 31, 2025, 2024, and 2023, respectively, with an accumulated deficit of $1.3 billion as of December 31, 2025[151] - As of December 31, 2025, the company had cash and cash equivalents of $307.5 million, which is expected to be sufficient to meet obligations for at least the next twelve months[153] - The company anticipates requiring additional capital to continue research and development and eventual commercialization of drug candidates, with future capital requirements dependent on various unknown factors[157] - The company may need to raise substantial additional funds through public or private equity or debt financings, which could result in dilution to existing shareholders or unfavorable terms[157] Regulatory and Compliance Challenges - The regulatory approval process for drug candidates is lengthy and unpredictable, typically taking many years, and there is no guarantee of approval for any existing or future candidates[196] - If regulatory approval is obtained, it may be for fewer indications than requested, which could limit the commercial prospects of the drug candidates[198] - Ongoing regulatory requirements must be met post-approval, and failure to comply could result in sanctions or suspension of product sales[202] - The acceptance of clinical trial data from international studies by the FDA or other regulatory authorities may be subject to strict conditions, potentially leading to additional trials[200] - Adverse side effects identified during development or post-approval could necessitate further trials or product withdrawals, significantly impacting revenue generation[204] - Regulatory compliance is critical, as failure to adhere to healthcare laws can result in legal actions, fines, and delays in product approvals[127] Operational Risks and Workforce Management - The company is dependent on third-party manufacturers for clinical supplies of its drug candidates, including collaborations with Roche and Novo Nordisk[139][140] - The company faces significant competition from larger pharmaceutical companies and generic drug manufacturers, which may adversely affect its revenues and results[136][138] - The company is highly dependent on key personnel, including the President and CEO, and the loss of such personnel could impede research and development objectives[159] - The company announced a 63% reduction in workforce in June 2025 to lower operating costs and support remaining programs and business development activities[107] - The company expects to reduce its headcount by 17 employees in 2026, primarily in research and development roles[143] Cybersecurity and Data Protection - Cybersecurity risks are increasing, and breaches of information technology systems could disrupt development programs and business operations[165] - Changes in privacy and data protection laws may increase compliance costs and expose the company to liability, impacting business operations and financial performance[168] - Compliance with privacy and data security laws is a rigorous process that may increase operational and compliance costs, potentially impacting business practices[169] - The EU GDPR imposes fines for breaches up to €20 million or 4% of total annual global turnover, which could significantly affect the company's financial condition[172] - The UK GDPR has similar penalties, with fines up to £17.5 million or 4% of total annual global turnover, indicating substantial compliance costs[173]

Core Insights - Prothena Corporation reported a fourth-quarter 2025 adjusted loss per share of 45 cents, consistent with Zacks Consensus Estimate, compared to a loss of $1.08 per share in the same quarter last year [1] - Revenues for the quarter were $0.02 million, falling short of the Zacks Consensus Estimate of $3.0 million, and down from $2.1 million in the year-ago quarter [1] - The company experienced a significant decline in total revenues for 2025, reporting $9.7 million, a 93% decrease year over year [4] Financial Performance - Research and development expenses decreased by 71% year over year to $14.6 million, attributed to lower clinical trial, manufacturing, personnel, and consulting costs [3] - General and administrative expenses were reported at $12.6 million, down 25% year over year [3] - As of December 31, 2025, Prothena had $308.4 million in cash and equivalents, a decrease from $331.7 million as of September 30, 2025, with no debt [3] Future Guidance - For 2026, Prothena anticipates a net cash burn of $50 million to $55 million and projects year-end cash to be approximately $255 million [7] - The projected net loss for 2026 is estimated to be between $67 million and $72 million [7] - The company expects to earn up to $105 million in milestone payments related to clinical advancements in 2026 [6][7] Pipeline Developments - Prothena is collaborating with Roche on prasinezumab for Parkinson's disease, with peak sales potential exceeding $3.5 billion [8] - Novo Nordisk is evaluating Prothena's Coramitug for ATTR amyloidosis, with the study expected to complete by 2029 [9] - Prothena's pipeline includes several neurological programs in collaboration with Bristol Myers Squibb, including BMS-986446 for Alzheimer's disease, which has received Fast Track designation from the FDA [12][13]

Core Insights - Roche has advanced prasinezumab into the phase 3 PARAISO trial for early Parkinson's disease, aiming to enroll approximately 900 participants with primary completion expected in 2029 [2] - Prothena highlighted significant progress in its clinical pipeline during 2025, with two partner programs moving into phase 3 trials [3] - Prothena's cash burn guidance for 2026 has been sharply reduced, with an expected net cash use of $50–55 million and an anticipated year-end cash balance of approximately $255 million [6][18] Group 1: Clinical Trials and Pipeline Developments - Roche's prasinezumab showed a 40% relative reduction in progression on MDS-UPDRS part 3 versus placebo at 24 months in a subset of participants on stable levodopa, with a nominal p-value of 0.0177 [1] - Prothena's partner programs, including Roche's prasinezumab and Novo Nordisk's coramitug, have advanced to late-stage trials, with primary completions expected around 2029 [7] - The phase 2 trial of coramitug demonstrated a 48% reduction in NT-proBNP versus placebo, with a p-value of 0.0017 [8] Group 2: Financial Performance and Guidance - Prothena reported a net cash used in operations of $163.7 million for 2025, which was favorable compared to its guidance range of $170 million to $178 million [17] - The company ended 2025 with $308.4 million in cash and no debt, and it expects to maintain a cash balance of approximately $255 million by the end of 2026 [6][18] - Prothena's 2026 guidance excludes up to $105 million of potential clinical milestone payments related to coramitug and PRX019 [19] Group 3: Research and Development Focus - Prothena's CYTOPE platform is showing promising preclinical CNS activity, particularly in targeting intracellular disease pathways [5][14] - The company is advancing its anti-amyloid beta antibody program, with prior phase 1 results indicating significant amyloid reductions [16] - Prothena is also conducting a phase 1 trial for PRX019 under its agreement with Bristol Myers Squibb, with completion expected in 2026 [12]

Core Insights - Prothena reported a quarterly loss of $0.44 per share, slightly better than the Zacks Consensus Estimate of a loss of $0.45, and an improvement from a loss of $1.08 per share a year ago, resulting in an earnings surprise of +1.12% [1] - The company generated revenues of $0.02 million for the quarter ended December 2025, missing the Zacks Consensus Estimate by 99.3%, and a significant decline from year-ago revenues of $2.12 million [2] - Prothena's stock has underperformed, losing about 4.8% since the beginning of the year, while the S&P 500 has gained 0.5% [3] Earnings Outlook - The future performance of Prothena's stock will largely depend on management's commentary during the earnings call and the company's earnings outlook, including current consensus earnings expectations for upcoming quarters [4] - The estimate revisions trend for Prothena was mixed ahead of the earnings release, resulting in a Zacks Rank 3 (Hold), indicating expected performance in line with the market [6] - Current consensus EPS estimate for the next quarter is -$0.39 on $5 million in revenues, and for the current fiscal year, it is $0.20 on $148.76 million in revenues [7] Industry Context - The Medical - Biomedical and Genetics industry, to which Prothena belongs, is currently in the top 36% of over 250 Zacks industries, suggesting a favorable outlook compared to lower-ranked industries [8] - Compugen, another company in the same industry, is expected to report quarterly earnings of $0.05 per share, reflecting a year-over-year change of +171.4%, with revenues anticipated to be $17.87 million, up 1115.7% from the previous year [9]

Financial Data and Key Metrics Changes - In 2025, Prothena reported a net cash used in operating and investing activities of $163.7 million, which was favorable compared to the guidance range of $170 million to $178 million [37] - The net loss for 2025 was $244.1 million, aligning with the guidance range of $240 million to $248 million [37] - As of December 31, 2025, Prothena had $308.4 million in cash, cash equivalents, and restricted cash, exceeding the guidance of $298 million [38] Business Line Data and Key Metrics Changes - Prothena's clinical pipeline saw significant progress, with two partnered programs, prasinezumab and coramitug, advancing into phase 3 clinical trials [6][7] - The phase 2 clinical trial for BMS-986446 in early Alzheimer's disease was fully enrolled in 2025, with completion expected in the first half of 2027 [8] - The company introduced its CYTOPE technology, demonstrating potential for precise targeting of intracellular disease pathways [9][30] Market Data and Key Metrics Changes - The phase 3 PARAISO trial for prasinezumab is expected to enroll approximately 900 participants, with primary completion anticipated in 2029 [16] - The phase 3 CLEOPATTRA trial for coramitug is intended to enroll about 1,280 ATTR-CM patients, with primary completion also expected in 2029 [23] - Prothena's partnered clinical programs have the potential to deliver up to approximately $3 billion in future milestone payments [12] Company Strategy and Development Direction - Prothena aims to capture value from clinical partnerships, with potential clinical milestone payments of up to $105 million in 2026 [10][40] - The company plans to implement a share redemption program and invest in its preclinical portfolio to support ongoing partnering efforts [40] - Prothena is focused on advancing its knowledge of the preclinical portfolio to explore research collaborations and licensing agreements [11] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the robust pipeline addressing significant unmet needs for millions of patients [40] - The company highlighted the importance of upcoming milestones and the potential for significant medical advances in areas with high unmet needs [45] - Prothena remains well-capitalized with a strong cash position, focusing on delivering long-term shareholder value [41] Other Important Information - Prothena's collaborations with Bristol Myers Squibb progressed, with BMS-986446 receiving Fast Track designation from the U.S. FDA for Alzheimer's treatment [8] - The company is engaged in research collaborations exploring multiple approaches for applying its CYTOPE technology [11] Q&A Session Summary Question: Key milestones for partnered program trials for PARAISO and CLEOPATTRA - Management outlined expectations for sharing more information on CYTOPE activities and data from the tau program with Bristol Myers Squibb in 2027, along with the phase 3 readouts expected in 2029 for coramitug and prasinezumab [42][44] Question: Keeping the amyloid beta story alive against competitors - Management discussed the advantages of the PRX012 transferrin-based approach, emphasizing its potential for improved amyloid removal and reduced ARIA rates compared to competitors [51][55] Question: Data sharing from the phase one study of PRX019 - Management confirmed that data from the PRX019 study will be shared with Bristol Myers Squibb, who holds global rights to the program [62][68] Question: Data necessary to secure a partnership for the CYTOPE platform - Management highlighted the importance of demonstrating robust CNS activity and specificity in targeting TDP-43 aggregates, which could facilitate partnerships [71][75]

Financial Data and Key Metrics Changes - In 2025, Prothena reported a net cash used in operating and investing activities of $163.7 million, which was favorable compared to the guidance range of $170 million to $178 million [37] - The net loss for 2025 was $244.1 million, aligning with the guidance range of $240 million to $248 million [37] - As of December 31, 2025, Prothena had $308.4 million in cash, cash equivalents, and restricted cash, exceeding the guidance of $298 million [38] - For 2026, the expected net cash used in operating and investing activities is projected to be between $50 million and $55 million, with an estimated net loss of $67 million to $72 million [38][39] Business Line Data and Key Metrics Changes - Prothena's clinical pipeline saw significant advancements, with two partnered programs, prasinezumab and coramitug, moving into phase III clinical trials [6][7] - The phase II TargetTau-1 clinical trial for BMS-986446 in early Alzheimer's disease was fully enrolled in 2025, with completion expected in the first half of 2027 [8] - The company introduced its CYTOPE technology, demonstrating potential for precise targeting of intracellular disease pathways [9][30] Market Data and Key Metrics Changes - The phase III PARAISO trial for prasinezumab is expected to enroll approximately 900 participants, with primary completion anticipated in 2029 [16] - The phase III CLEOPATRA trial for coramitug is set to enroll around 1,280 ATTR-CM patients, with primary completion also expected in 2029 [23] - Prothena's partnered clinical programs have the potential to deliver up to approximately $3 billion in future milestone payments, in addition to any royalties [12] Company Strategy and Development Direction - Prothena aims to capture value from clinical partnerships, with potential clinical milestone payments of up to $105 million in 2026 [10][41] - The company plans to implement a share redemption program and invest in its preclinical portfolio to support ongoing partnering efforts [10][41] - Prothena is focused on advancing its knowledge of the preclinical portfolio to explore research collaborations and licensing agreements [11] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the robust pipeline addressing significant unmet needs for millions of patients [40] - The company highlighted the importance of upcoming milestones and the potential for significant medical advances in areas with high unmet needs [46] - Management emphasized the strategic importance of the share redemption program and the potential for clinical milestone payments from partners [47][48] Other Important Information - Prothena's cash position as of year-end 2025 was $308.4 million, allowing for prudent capital utilization to support future potential economics from partner programs [11] - The company is engaged in research collaborations exploring multiple approaches for applying its CYTOPE technology [10] Q&A Session Summary Question: Key milestones for partnered program trials for PARAISO and CLEOPATRA - Management outlined that significant activities are expected in 2026 and 2027, including data from the CYTOPE activities and the phase II tau program with Bristol Myers Squibb [44][46] Question: Keeping the amyloid beta story alive against competitors - Management discussed the advantages of the PRX-012 transferrin-based approach and the potential for improved profiles compared to existing therapies [51][55] Question: Data sharing from the phase I study of PRX-019 - Management indicated that data will be shared with Bristol Myers Squibb, who holds global rights to the program, and will decide on public dissemination [62][68] Question: Data necessary for securing a partnership for the CYTOPE platform - Management highlighted the importance of robust in-vivo data demonstrating the technology's ability to target intracellular disease pathways effectively [71][75]