Clene Inc. Conference Call Summary Company Overview - **Company Name**: Clene Inc. - **Ticker Symbol**: CLNN - **Industry**: Biopharmaceuticals - **Focus**: Improving mitochondrial health and protecting neuronal function to treat neurodegenerative diseases, particularly ALS (Amyotrophic Lateral Sclerosis) [1] Core Points and Arguments - **Regulatory Engagement**: Clene is actively engaging with the FDA to seek regulatory flexibility for ALS treatments, emphasizing the urgent need for effective therapies in light of recent tragedies involving ALS patients [6][30]. - **Product Description**: The primary product, CNM-Au8, is described as a nanotherapeutic suspension that can cross the blood-brain barrier, aiming to enhance neuronal housekeeping functions [7][8]. - **Biomarker Significance**: Neurofilament levels are highlighted as critical biomarkers for assessing neurodegenerative diseases, particularly ALS. Elevated neurofilament levels correlate with disease progression and shorter survival [9][11]. - **Clinical Trial Results**: Clene's clinical trials have shown a 94% risk reduction in clinical worsening as a secondary endpoint in the HEALEY study. However, the primary endpoint (ALSFRS) was not met [13][14]. - **FDA Feedback**: The FDA has requested additional evidence regarding neurofilament data and its correlation with survival benefits. Clene is preparing to provide this data [25][26]. - **Future Plans**: Clene plans to file a New Drug Application (NDA) by mid-2026, with potential commercialization by early 2027, contingent on FDA approval [29][40]. Financial Overview - **Funding**: Clene raised $6 million at $6.50 per share, with additional tranches of $7 million and $13 million tied to regulatory milestones, ensuring financial stability through key upcoming events [34][35]. - **Cash Runway**: The company has sufficient cash to navigate through critical milestones, including the FDA Type C meeting and NDA filing [33][34]. Upcoming Milestones - **FDA Type C Meeting**: Expected by the end of March 2026, which will determine the next steps for the NDA submission [36][39]. - **NDA Filing**: Anticipated by the end of the second quarter of 2026, with a potential PDUFA date in the third quarter [40][41]. Additional Insights - **Market Need**: Clene emphasizes the urgent need for ALS therapies, highlighting the devastating impact of the disease and the importance of early diagnosis and treatment [30]. - **Broader Applications**: While the focus is on ALS, Clene also has plans for multiple sclerosis (MS) treatments, indicating a broader pipeline potential [31][32]. - **Regulatory Flexibility**: The company is advocating for regulatory flexibility from the FDA, particularly for orphan diseases like ALS, which have limited treatment options [30][43]. This summary encapsulates the key points discussed during the Clene Inc. conference call, focusing on the company's strategic direction, product development, regulatory interactions, and financial health.

Core Insights - Clene Inc. is focused on developing treatments for neurodegenerative diseases, particularly ALS, through its investigational drug CNM-Au8, with key regulatory and clinical milestones anticipated in 2026 [1][2] Financial Position - The company completed an oversubscribed registered direct offering of over $28 million in January 2026, providing sufficient cash to fund operations into the fourth quarter of 2026 [4][7] - Additional financing tranches totaling over $22 million are structured to align with NDA acceptance and FDA approval milestones, expected to support operations into 2027 [4] Regulatory Steps and Clinical Milestones - Clene has engaged with the FDA regarding CNM-Au8, with an in-person Type C meeting scheduled by the end of Q1 2026 to discuss data submitted in late 2025 [5][7] - The company plans to submit a New Drug Application (NDA) for CNM-Au8 via an accelerated regulatory pathway in Q2 2026, with potential FDA acceptance and PDUFA date issuance in the second half of 2026 [5][7] Clinical Data and Efficacy - CNM-Au8 has shown prolonged survival in ALS patients, with a median life expectancy of 2-4 years post-diagnosis, and demonstrated statistically significant reductions in mortality risk and clinical worsening [6][8] - The treatment has also shown favorable safety and tolerability, with no serious adverse events reported across over 1,000 patient years of treatment [9] Future Trials - A confirmatory Phase 3 RESTORE-ALS trial is planned to begin later in 2026 to further evaluate the survival benefit of CNM-Au8 [10] Broader Pipeline - CNM-Au8 is also being explored for potential benefits in multiple sclerosis (MS) and Parkinson's disease, with plans to finalize Phase 3 clinical trial designs for MS in 2026 [12]

Clene Inc. Conference Call Summary Company Overview - Clene Inc. is a clinical stage biopharmaceutical company focused on improving mitochondrial health and protecting neuronal function to treat neurodegenerative diseases, including ALS (Amyotrophic Lateral Sclerosis) and MS (Multiple Sclerosis) [1] Key Accomplishments and FDA Interactions - Clene has achieved an in-person meeting with the FDA this quarter, marking the fifth meeting in 14 months to discuss extensive biomarker and survival data [2] - The company presented significant biomarker analyses showing reductions in neurofilament and GFAP (glial fibrillary acidic protein), which are associated with longer survival in ALS patients [3][4] - Clene aims to file a new drug application (NDA) under the accelerated approval pathway, utilizing biomarker data as a surrogate endpoint due to missed primary endpoints in previous studies [5][6] Biomarker Data and Clinical Evidence - The company has demonstrated that reductions in neurofilament levels are quantitatively associated with improved survival, with a noted reduction of 9%-10% linked to lower mortality risk [8] - Clene is pursuing a three-pronged approach to validate the biomarker benefits, including proving substantial biomarker benefit, establishing an independent association with mortality, and demonstrating consistent clinical benefits [7][9] Future Plans and Timeline - The FDA meeting is scheduled for later this quarter, with the intent to file the NDA in the second quarter of 2024 if the FDA concurs with the data presented [11][12] - If accepted, commercialization could begin by early 2025, with aspirations to approve CNM-Au8 for ALS patients [13] Financing and Cash Runway - Clene raised approximately $6 million at a price of $6.50 per share through a tranche financing, extending its cash runway by an additional quarter [17] - Future tranches are planned, with potential raises of $7 million at $7 per share and $15 million at a $12.50 strike price upon approval [18] Industry Context and Need for New Treatments - There are over 30,000 ALS patients in the U.S., with a uniform mortality rate of 2-4 years without treatment, highlighting the urgent need for new drugs [19] - Clene is also working to reauthorize funding for ALS research at the Congressional level, emphasizing the critical need for advancements in treatment options [19] Conclusion - Clene Inc. is positioned to make significant strides in ALS treatment through its ongoing FDA interactions and biomarker research, with a clear plan for future drug application and funding strategies [20]

Core Viewpoint - Clene Inc. has received an in-person Type C Meeting from the FDA to discuss its biomarker and survival data related to its investigational treatment CNM-Au8 for neurodegenerative diseases, particularly ALS [1][8][13] Group 1: FDA Interaction and Meeting - The FDA has granted Clene an in-person Type C meeting scheduled for the first quarter of 2026 to review evidence supporting the use of neurofilament light chain (NfL) as a candidate biomarker for accelerated approval [1][8] - Clene has submitted a pre-meeting briefing package to the FDA, addressing previous requests regarding the clinical significance of NfL declines and their reproducibility [2][4] Group 2: Biomarker Evidence and Analysis - Clene's analyses indicate that longitudinal changes in NfL are associated with survival outcomes in ALS patients, independent of baseline disease severity [3][5] - Statistically significant reductions in NfL levels were observed in patients treated with CNM-Au8, demonstrating consistent pharmacodynamic effects across multiple studies [6][9] Group 3: Clinical Outcomes and Survival Benefits - Modest reductions in NfL (approximately 9-10%) were associated with an 8-13% lower risk of death in ALS patients, highlighting the potential clinical relevance of NfL as a surrogate endpoint [7][9] - In responders with IGFBP7 biomarker decline, CNM-Au8 treatment was associated with a 78% reduced mortality risk, indicating a strong link between biomarker changes and survival [8][10] Group 4: Mechanistic Insights and Future Directions - IGFBP7 has been identified as a key pharmacodynamic biomarker, with its decline correlating with improved survival and other disease-relevant biomarkers [11][12] - The findings suggest a mechanistic pathway linking CNM-Au8's action to neuroprotection, supported by genetic evidence related to IGFBP7 expression [12]

Core Viewpoint - Clene Inc. has announced a registered direct offering priced above market, raising over $28 million from new and existing investors to support its clinical-stage biopharmaceutical efforts in treating neurodegenerative diseases, particularly ALS and MS [1][2][3] Financing Details - The offering includes an oversubscribed registered direct offering to new, existing, and insider investors, with an initial financing tranche of over $6 million expected to fund operations into Q3 2026 [3] - Two additional financing tranches totaling over $22 million are contingent on the acceptance and approval of the New Drug Application (NDA) by the FDA, providing sufficient capital into early 2027 for potential commercialization of CNM-Au8 in ALS [3] - The gross proceeds from the offering are expected to be approximately $28 million, with BTIG, LLC acting as the sole placement agent [7] Warrant Details - The offering includes Series A Warrants and Series B Warrants, both with an initial exercise price of $6.00 per share, which can increase based on specific conditions related to the company's stock price and FDA announcements [4][5][6] - The potential gross proceeds from the exercise of the Series A Warrants total approximately $6.7 million, while the Series B Warrants could generate around $15.6 million, expected to fund commercialization efforts [5][6] Company Overview - Clene Inc. is a late clinical-stage biopharmaceutical company focused on improving mitochondrial health and protecting neuronal function to treat neurodegenerative diseases, including ALS, Parkinson's disease, and MS [10] - CNM-Au8 is an investigational therapy designed to enhance neuronal health by increasing energy production and reducing oxidative stress [11]

Company Overview - Clene Inc. (NASDAQ: CLNN) is a biotechnology company focused on developing innovative treatments for neurodegenerative diseases, particularly through nanotherapeutics [1] - The company competes with other biotech firms such as Biogen and Novartis in the same therapeutic area [1] Shareholder Activity - On January 7, 2026, significant shareholder Ugwumba Chidozie sold 3,938 shares at $6.29 each, following a previous sale of 4,138 shares on December 30 at $6.03, totaling approximately $24,952 [2] - After the January 7 transaction, Chidozie holds 753,562 shares, a decrease from 783,590 shares held after the December 30 sale, but he remains a major shareholder with holdings valued at around $4.7 million [3] Stock Performance - The current price of CLNN is $6.28, reflecting a 2.28% increase, with intraday fluctuations between $6.06 and $6.56 [4] - Over the past year, CLNN's stock price ranged from a high of $13.50 to a low of $2.28, and the company's market capitalization is approximately $58.4 million [4] - The trading volume on the NASDAQ exchange is 51,957 shares [4]

Summary of Conference Call for Clene Inc. and Faraday Future Intelligent Electric Inc. Clene Inc. (Ticker: CLNN) Industry Overview - Clene is a clinical stage biopharmaceutical company focused on improving mitochondrial health and protecting neuronal function to treat neurodegenerative diseases, specifically ALS (Amyotrophic Lateral Sclerosis) [1][2]. Core Points and Arguments - Clene has released biomarker data requested by the U.S. FDA, which is crucial for the accelerated approval pathway for its lead asset, CNMA-08 [2]. - The FDA has outlined a path for Clene to use biomarker data as part of the commercialization process, with a meeting scheduled for the first quarter of the upcoming year [2][3]. - Clene is pursuing three methods to validate biomarker data: finding additional biomarkers, verifying existing data, and obtaining new data from the Healy Harvard program [3]. - The two key biomarkers discussed are neurofilament light chain and glial fibrillary protein (GFAP), both of which showed statistically significant data in Clene's studies [5][6]. - Clene is preparing a New Drug Application (NDA) to be submitted in the first half of the year, with the possibility of commercialization by late 2026 or early 2027 [9][10]. - The accelerated approval process allows for conditional market entry based on surrogate endpoints, with a confirmatory phase 3 study to follow [12][13]. - The current market for ALS treatments is limited, with only a few drugs available, highlighting the significant opportunity for Clene if approved [14][15]. - Previous approvals in the ALS space have led to substantial market caps for companies, indicating a potential for Clene's market cap to grow significantly upon FDA approval [16]. Other Important Information - The FDA's accelerated approval process is particularly relevant for uniformly fatal diseases like ALS, allowing for quicker access to treatments based on biomarker data [13]. - Clene's approach to treatment and data collection is critical for establishing a correlation between biomarker changes and survival benefits [10][11]. Faraday Future Intelligent Electric Inc. (Ticker: FFAI) Industry Overview - Faraday Future is a California-based company focused on creating a user-centric electric vehicle (EV) ecosystem, aiming to disrupt the automotive industry [19][20]. Core Points and Arguments - The company has invested $3.5 billion in R&D and CapEx, resulting in over 600 patents and a unique business model that partners with Chinese OEMs [20][21]. - Faraday Future's vehicle lineup includes the ultra-premium FF91 and the more affordable FX Super 1, with plans for a lower-priced FX4 model [22][23]. - The FX Super 1 is priced at $84,000 and is designed for high performance, featuring advanced technology and luxury elements [23][24]. - The company has a manufacturing site in Hanford, California, with an initial capacity of 10,000 vehicles annually, which can ramp up to 30,000 [21]. - Faraday Future's business model includes advantages such as lower tariffs on parts due to local assembly, proprietary software development, and an established dealership network [26][27]. Other Important Information - The company has received 11,000 pre-orders for the FX Super 1, indicating strong market interest [29]. - Recent partnerships, including one with Tesla for access to their supercharging network, enhance Faraday Future's competitive position in the EV market [29]. - Upcoming milestones include the production of pre-production vehicles and further announcements from the manufacturing site [30].

Summary of Clene Nanomedicine's ALS Program Update Conference Call Company and Industry - **Company**: Clene Nanomedicine - **Industry**: Amyotrophic Lateral Sclerosis (ALS) treatment and research Key Points and Arguments Overview of CNM-Au8 and ALS Program - Clene has been developing CNM-Au8 for ALS treatment for 12 years, with significant data supporting its efficacy [3][4] - The company has conducted randomized double-blind clinical trials and expanded access protocols for ALS patients [3] FDA Interaction and Data Requirements - The FDA indicated that if Clene can substantiate the effects on neurofilament light (NFL), they would consider the 24-week data from the Healey trial for accelerated approval [4] - Clene is focusing on three areas: neurofilament change analysis, biomarker change analysis, and supportive ALS disease-specific biomarkers [6] Biomarkers and Clinical Relevance - Neurofilament light chain (NFL) and glial fibrillary acidic protein (GFAP) are key biomarkers for ALS, with NFL being a structural protein in neurons and GFAP indicating astrocytic activity [8][9] - Higher baseline NFL levels correlate with faster disease progression and higher mortality risk [10] Expanded Access Program Findings - The NIH Expanded Access Program provided a dataset of 291 participants, showing significant reductions in neurofilament levels across matched participants [12][14] - Bulbar onset patients showed a stronger reduction in neurofilament levels, indicating a clinically meaningful effect [16] Survival Analysis and Efficacy - CNM-Au8 demonstrated a 73% reduction in mortality risk at 12 months in the full analysis set and a 77% reduction in a comparable risk set [30] - Participants transitioning from placebo to CNM-Au8 showed a 51% reduction in mortality risk at 12 months [32] Future Steps and Regulatory Considerations - Clene plans to submit a new drug application to the FDA, with a focus on the totality of data supporting CNM-Au8's efficacy [36] - The upcoming phase 3 RESTORE-ALS trial will have survival as the primary endpoint, with ALSFRS as a secondary exploratory endpoint [66] Additional Insights - The data from the Expanded Access Program supports the hypothesis that CNM-Au8 can provide benefits even in more advanced ALS patients [60] - The relationship between neurofilament and GFAP changes and survival strengthens the case for CNM-Au8's clinical impact [27][33] Other Important Content - The call included discussions on the challenges of using matched controls in the Expanded Access Program and the importance of ensuring comparability in patient characteristics [55] - There was a focus on the potential implications of the findings for other neurodegenerative diseases, such as multiple sclerosis [75]

CNM-Au8 & ALS Biomarkers - Clene announced statistically significant ALS biomarker results supporting an accelerated approval pathway for CNM-Au8® [1] - High NfL and GFAP levels are associated with mortality risk in ALS [21] - Substantiation of NfL biomarker effect may support acceptance of survival analyses [7, 28] - FDA guidance suggests that substantiation of NfL effects may allow 24-week data from the HEALEY platform trial and post-hoc analyses on long-term survival to provide evidence of clinical benefit [9, 10] - In the HEALEY ALS platform trial, CNM-Au8 demonstrated consistent effects on NfL and GFAP biomarkers [67] - In HEALEY trial, Plasma NfL W24 LS Mean GMR was 0.905 (95% CI: 0.822 – 0.996, p = 0.0403) and W24 AUC GMR was 0.901 (95% CI: 0.845 – 0.959, p = 0.0013) [69] - In HEALEY trial, Plasma GFAP W24 LS Mean GMR was 0.891 (95% CI: 0.798 – 0.995, p = 0.0401) and W24 AUC GMR was 0.913 (95% CI: 0.841 – 0.990, p = 0.0278) [72, 73] - In NIH-EAP trial, NfL and GFAP AUC decline is also consistent [75] Survival Analysis - NfL change significantly impacts ALS survival, with a joint-model hazard ratio of 1.40 (95% CI: 1.31 – 1.51) [108, 110] - Long-term survival evidence from the HEALEY ALS Platform Trial shows a 73% risk reduction at Month 12 in the Full Analysis Set and a 77% risk reduction in the Comparable Risk Set [113, 130, 133] - Improved long-term survival in ex-placebo to CNM-Au8 group, with a 51% risk reduction at 12-months post-CNM-Au8 treatment initiation [139, 140]

Core Insights - Clene Inc. has completed FDA-recommended biomarker analyses for CNM-Au8 in ALS patients, showing significant reductions in neurofilament light (NfL) and glial fibrillary acidic protein (GFAP), indicating a potential link between biomarker decline and improved survival [1][2][3] Biomarker Analyses - The FDA recommended three specific analyses to strengthen the evidence for CNM-Au8's effect on NfL and its relationship to clinical benefit, including evaluations in the NIH-sponsored Expanded Access Program (NIH-EAP) [3] - Statistically significant reductions in NfL and GFAP were observed in participants treated with CNM-Au8, with improvements strongly associated with longer survival [3][4] - The analyses confirmed the robustness of findings across various pre-specified supportive analyses, with significant effects noted in specific participant subgroups [4][5] Survival Benefit - Updated survival analyses indicate that CNM-Au8 treatment demonstrated a statistically significant survival benefit compared to controls, with a 73% reduction in the risk of death in the full analysis set and a 77% reduction in a risk-balanced population [6][7] - Even among a small cohort of participants who switched from placebo to CNM-Au8, a significant survival benefit was observed, with an average increase of 30.7 days in survival [7] Safety Profile - CNM-Au8 has shown a strong safety profile across over 1,000 patient years of exposure, with no serious adverse events related to the treatment identified [8] Regulatory Pathway - Clene has requested a Type C meeting with the FDA to present the completed analyses and plans to submit a New Drug Application (NDA) under the accelerated approval pathway in early 2026 [11][12]