撰文丨王聪 编辑丨王多鱼 排版丨水成文 本周 （8 月 18 日- 8 月 24 日） ，国际顶尖学术期刊 Cell 共上线了 9 篇研究论文，其中 6 篇来自华人学者，这些研究分别是 ， 将 IscB 和 Cas9 转换为 RNA 编辑器、 世界首个维管植物整合细胞图谱、 修饰腺苷的解毒机制、 系统素拮抗肽调控番茄免疫系统的分子机制、 新型通用型 CAR-T 细胞疗法、 生物凝聚体调控神经系统。 将 IscB 和 Cas9 转换为 RNA 编辑器 2025 年 8 月 18 日，耶鲁大学 可爱龙 教授作为通讯作者，在 Cell 期刊发表了题为： Conversion of IscB and Cas9 into RNA-guided RNA- editors 的研究论文 【1】 。 该研究对 Cas9 的祖先 IscB 以及 Cas9 自身进行了工程化改造，删除了其 TID/PID 结构域， 将它们从原本的 RNA 引导的 DNA 编辑器转换为 RNA 引导的 RNA 编辑器 ，并展示其在可变剪切干扰、反式剪接及 RNA 碱基编辑中的应用潜力， 其性能可媲美甚至超越了 Cas13，且更具安全性，为 RNA 疗 ...

Financial Data and Key Metrics Changes - Research and development expenses increased to approximately $1,400,000 for Q2 2025 from approximately $800,000 in Q2 2024, and increased to approximately $2,900,000 for the six months ended June 2025 from $2,800,000 in the same period of 2024 [16] - Selling, general and administrative expenses decreased to approximately $700,000 in Q2 2025 from approximately $900,000 in Q2 2024, while remaining consistent at approximately $1,900,000 for the six months ended June 2025 compared to the same period in 2024 [16] - Net loss was approximately $2,000,000 for Q2 2025 compared to approximately $1,600,000 for Q2 2024, and approximately $4,800,000 for the six months ended June 2025 compared to approximately $3,900,000 for the same period in 2024 [17] - Cash and cash equivalents totaled $980,000 at the end of the quarter, with a current cash balance of approximately $1,100,000 after selling $769,000 in common stock [18] Business Line Data and Key Metrics Changes - The CardioAmp heart failure trial showed a lower incidence of all-cause death and non-fatal MACE in the treatment group compared to the control group, with a p-value of 0.17, and a statistically significant composite endpoint in patients with elevated NT proBNP with a p-value of 0.02 [6][9] - The CARDI Amp cell therapy in chronic myocardial ischemia (BCDO2) is expected to deliver final top-line data in Q4 2025 [14] - The Helix Biotherapeutic delivery system is anticipated to be submitted for FDA approval in Q3 2025 [15] Market Data and Key Metrics Changes - Japan's PMDA has shown interest in heart failure therapy, with the company expecting to align on pathways for therapy availability [7] - The company is preparing for a meeting with the FDA regarding the approvability of the CardiAmp system based on clinical data [9] Company Strategy and Development Direction - The company aims to partner its Helix delivery system for the cardiac electrophysiology market and is focused on creating value through partnerships across its four platforms: CardiAmp, CardiAllo, Helix, and MorphDNA [11][12] - The company is actively pursuing distribution partnerships in Japan and the U.S. for its therapies, emphasizing the cultural alignment of its autologous cell therapy with Japanese preferences [23][40] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism regarding the upcoming regulatory meetings with PMDA and FDA, highlighting the potential for approval based on compelling clinical data [35] - The company is focused on maintaining a low burn rate while advancing multiple trials and regulatory submissions, with an annual burn rate of approximately $6,000,000 [76] Other Important Information - The company is preparing a peer-reviewed manuscript based on the data presented at the American College of Cardiology, which will be accessible to the public [70] - The company is working on a financing event that aims to be beneficial for current shareholders, with a focus on minimizing dilution [73] Q&A Session Summary Question: Expectations regarding PMDA reviewing Cardium for heart failure as a medical device - Management indicated that the approval process is viewed as a lower hurdle for medical device approval, with a focus on the clinical consultation process [20][21] Question: Timing for the Cardium CMI program data - Management confirmed that the rolling cohort data related to primary endpoint results is expected in Q4 [26] Question: Timing of regulatory meetings and potential outcomes - If meetings go well, the approval process could take up to a year, with parallel efforts on reimbursement and distribution partnerships [32][34] Question: Status of FDA meeting type and HF2 trial screening - Management is contemplating the type of FDA meeting and confirmed that the HF2 trial is actively enrolling patients with a focus on compliance and stability [45][50] Question: Expectations following data readout for BCDA - Management stated that outcomes depend on PMDA and FDA responses, with potential for non-dilutive capital to accelerate the BCDA program [60] Question: Release of new data observations to the public - Management confirmed that a peer-reviewed manuscript will be prepared to share data observations, while also working on regulatory submissions [70] Question: Details on the upcoming financing event - Management emphasized the importance of a financing event that minimizes dilution and supports ongoing trials and partnerships [73][75]

Financial Data and Key Metrics Changes - CarVicti net trade sales reached approximately $439 million, representing a 136% increase year over year and a 19% increase from the first quarter [7][17] - Total revenues were RMB 255 million, driven by collaboration revenue growth of 136% year over year [30] - The company reported a net loss of RMB 10 million but achieved RMB 10 million in adjusted net income after excluding non-core items [30] - Operating loss improved from RMB 41 million in the same period last year to RMB 22 million [30] - Gross margin on net product sales was 57% [30] Business Line Data and Key Metrics Changes - CarVicti's U.S. net trade sales were $358 million, growing 114% year over year and 13% quarter over quarter [18] - Outside the U.S., sales were $81 million, which is four times the amount from the same period a year ago, representing a 59% increase quarter over quarter [19] Market Data and Key Metrics Changes - Over 60% of CarVicti utilization is now in earlier line settings [8] - The company has treated over 7,500 patients with CarVicti, marking it as the strongest CAR T launch to date [7][16] Company Strategy and Development Direction - The company aims to achieve operational breakeven for CarVicti by 2025 and company-wide profitability in 2026, excluding unrealized foreign exchange gains or losses [8][30] - The company is focused on solidifying its leadership in cell therapy and expanding into new indications such as solid tumor programs [14][15] - A new research facility is being built in Philadelphia to focus on in vivo delivery, enhancing innovation capabilities [15] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the FDA's decision to remove risk evaluation and mitigation strategies for approved CAR T therapies, which is expected to improve patient experience and access [8] - The company anticipates continued strong performance for CarVicti, driven by recent long-term survival data presented at ASCO [21][28] Other Important Information - The company has a cash position of approximately $1 billion, allowing for continued investment in core differentiators in cell therapy [16][32] - Manufacturing success rate remains at 97%, which is believed to be the highest in the CAR T industry [20] Q&A Session Summary Question: Update on interim readouts from CARDISUDE V and VI - Management is monitoring events closely and is in discussions with the FDA about using MRD as a dual primary endpoint [37][38] Question: Community oncology efforts and Virginia Oncology Associates - Virginia Oncology Associates is a key milestone for community adoption, having previously administered CAR T therapies and is part of the McKesson network [39] Question: Revenue contribution from community expansion efforts - Approximately 70% of patients come from the community setting, with over half of patients administered in outpatient settings [42][43] Question: Breakdown of treated patients in early line settings - Nearly 60% of orders are from the second through fourth line population, which is expected to grow significantly [48] Question: Impact of recent efficacy data from a competitor - Management emphasized that CarVicti is best in class with demonstrated overall survival benefits, differentiating it from competitors [63] Question: Future demand and supply dynamics - The company plans to drive both supply and demand simultaneously, with increasing contributions expected from Europe [83][85] Question: Novartis commercial supply ramp-up - Novartis is expected to reach full capacity by the end of the year, contributing to growth [107] Question: Impact of recent tariff changes - The company believes any potential exposure to tariffs will not be material based on current evaluations [103]

Financial Data and Key Metrics Changes - In Q2 2025, total revenue was reported at $60 million, representing a 22% growth over the previous quarter [9] - The company reiterated its full-year 2025 revenue guidance of $250 million to $300 million, which includes sales from Ampagni in the US and Prolupine globally [10][18] - Gross margin was reported at 31%, excluding non-cash items, with expectations for improvement due to strategic restructuring [10][11] Business Line Data and Key Metrics Changes - Product revenue from US Ampagni sales was approximately $54 million in Q2 2025, reflecting a 24% quarter-over-quarter growth [15] - Prolupine revenue was approximately $6 million, showing a 2% increase quarter-over-quarter [15] - The number of patients treated with Ampagni reached 102 in Q2, up from 85 in Q1, indicating strong adoption [40][41] Market Data and Key Metrics Changes - The company is focused on expanding its market presence, with plans to onboard large community practices to enhance patient access [8] - There is potential for US peak sales of Ampagni to exceed $1 billion, with significant opportunities in international markets [10][19] Company Strategy and Development Direction - The company is committed to improving profitability through a strategic restructuring that includes a workforce reduction of approximately 19%, expected to generate over $100 million in annual cost savings [12] - The focus remains on expanding the product pipeline and achieving multiple clinical milestones in the second half of 2025 [9][31] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the ongoing demand for Ampagni and the potential for continued growth in the second half of the year [43] - The company is optimistic about its cash position, expecting it to fund operations into 2026, despite a projected net cash burn of less than $245 million [13] Other Important Information - The company withdrew its submission from the European Medicines Agency due to a need for additional analysis, with plans to resubmit [62] - The new Chief Financial Officer, Corleen Roche, joined the team and will cover financial results in future calls [14] Q&A Session Summary Question: Can you talk about the patient number from Q1 to Q2? - The number of infusions increased from 85 in Q1 to 102 in Q2, with a price increase to $562,000 effective April 1 [40][41] Question: What gives you confidence around Prolupin's performance? - Prolupin is expected to see continued orders from wholesalers, reflecting increased utilization alongside Ampagni [51] Question: Can you elaborate on the decision to withdraw the marketing authorization application in Europe? - The withdrawal was due to the need for additional analysis, and the company plans to resubmit without requiring additional clinical trials [62][63] Question: How do you see infusions tracking for Ampagni quarter to date? - Strong demand is noted, but specific infusion numbers cannot be disclosed [68] Question: Can you provide an update on patient drop-offs and manufacturing success rates? - Manufacturing success rates improved in Q2, with lower patient drop-off rates compared to Q1 [78]

Financial Overview - Arovella Therapeutics Limited (ASX:ALA) has a market capitalization of $136.7 million[16] - The company has 1,188.6 million shares on issue[16] - Arovella's cash balance as of June 30, 2025, was $20.9 million[16, 20] - Biotech Capital Management Pty Ltd holds 108,526,184 shares, representing 9.17% ownership[16] ALA-101 Clinical Development - ALA-101, a potential treatment for CD19-positive blood cancers, is progressing to phase 1 clinical trials, expected to commence in early 2026[8, 96] - The company completed a $15 million placement to fully fund enrollment and report initial safety and efficacy data for the phase 1 trial for ALA-101[21] - Arovella is conducting IND-enabling non-clinical safety and efficacy studies to support regulatory approval for ALA-101[64] Cell Therapy Market and Technology - The cell therapy market is expected to reach $61.2 billion by 2030[25] - 40-60% of patients relapse post-CAR-T therapy[25] - Recent cell therapy acquisition deals for in vivo CAR therapies in Phase 1 reached up to $2,100 million[18]

Summary of Chimeric Therapeutics (CHM) 2025 Extraordinary General Meeting Company Overview - **Company**: Chimeric Therapeutics (CHM) - **Meeting Date**: July 22, 2025 - **Location**: Online meeting hosted from Victoria, Australia Key Points and Arguments Financial Performance - **Fundraising**: Raised $16.6 million during FY 2025, including $5.6 million from a US Family Office [7] - **Debt Management**: The Lindt facility will be fully paid out, marking a significant financial milestone [7] Clinical Development Updates - **CHM CDH 17**: - Trial commenced late last year with five patients treated. - Best result: One patient with stable disease after six months [9] - Manufacturing success: Eight out of eight successful runs, indicating strong operational capabilities [10] - **CHM CoreNK**: - Transitioned to frontline setting for the ADVENT AML study. - Achieved two complete responses with no signs of leukemia in patients [10][14] Resolutions and Voting Outcomes - **Resolution 1**: Ratification of the issuance of 164.3 million first tranche placement shares. - Proxy votes: 86% in favor, 14% against [18] - **Resolution 2**: Approval to issue up to 1.485 billion second tranche placement shares. - Proxy votes: 85% in favor, 15% against [20] - **Resolution 3**: Approval to issue up to 1.65 billion attaching options. - Proxy votes: 79% in favor, 21% against [22] - **Resolution 4**: Approval to issue 25 million adviser options for professional services. - Proxy votes: 79% in favor, 21% against [24] - **Resolution 5A and 5B**: Approval to issue 141.25 million shares and options to Lind. - Proxy votes: 73% in favor, 27% against [26] Meeting Logistics - **Voting Process**: Conducted via a poll, with results to be announced on the ASX later that day [6][30] - **Q&A Session**: No questions were raised during the meeting, indicating either satisfaction with the presented information or a lack of engagement from attendees [29] Additional Important Information - **Management Acknowledgment**: The meeting included acknowledgments of traditional custodians of the land, reflecting the company's commitment to cultural respect [1] - **Operational Efficiency**: Significant headcount and cost reductions were noted, contributing to improved business operations [8] This summary encapsulates the critical aspects of the meeting, highlighting the company's financial health, clinical advancements, and shareholder engagement through resolutions and voting outcomes.

Core Viewpoint - Osteoarthritis (OA) is a degenerative joint disease primarily affecting the elderly, characterized by the degradation of articular cartilage and subsequent joint pain and limited mobility. Current treatments include non-steroidal anti-inflammatory drugs and, in severe cases, total joint replacement [2]. Group 1: Treatment Innovations - The FDA has recently approved Matrix-associated Autologous Chondrocyte Implantation (MACI) for repairing isolated cartilage injuries in patients aged 18-55, indicating that cell therapy may become an effective treatment for osteoarthritis [3]. - Procr chondroprogenitors, identified in a study published in Cell, are sensitive to mechanical stimuli and play a crucial role in maintaining and regenerating articular cartilage, presenting a promising cell source for treating degenerative orthopedic diseases like osteoarthritis [4][9]. Group 2: Research Findings - The study found that mechanical stimulation from forced running significantly increased the number of Procr+ cells, while mechanical unloading decreased their numbers. OA activates Procr+ cells to repair cartilage erosion, and their genetic knockout accelerates OA progression [6]. - Inhibition of the mechanosensor Piezo1 significantly impairs the cartilage repair function of Procr+ cells, while intra-articular injection of Piezo1 agonists improves OA symptoms [6]. - Purified Procr+ superficial cells, after expansion and in vivo transplantation, can effectively repair cartilage defects, highlighting their potential as a reliable cell source for treating knee joint diseases like osteoarthritis [9].

Core Viewpoint - Capricor Therapeutics Inc. received a Complete Response Letter (CRL) from the FDA regarding its Biologics License Application (BLA) for Deramiocel, indicating that the application cannot be approved in its current form due to insufficient evidence of effectiveness and the need for additional clinical data [1][2]. Group 1: FDA Response and Requirements - The FDA stated that the BLA does not meet the statutory requirement for substantial evidence of effectiveness and that additional clinical data is needed [2]. - The CRL referenced outstanding items in the Chemistry, Manufacturing and Controls (CMC) section, which Capricor claims to have addressed in prior communications, but the FDA did not review these materials due to the timing of the CRL issuance [3]. Group 2: Next Steps and Company Plans - The FDA confirmed that it will restart the review clock upon resubmission and offered Capricor the opportunity to request a Type A meeting to discuss the path forward [4]. - Capricor plans to submit data from the Phase 3 HOPE-3 clinical trial to provide additional evidence of effectiveness, with topline results expected in the third quarter of 2025 [5]. Group 3: Market Reaction - Following the news, CAPR stock is down 37.4% at $7.14 during the premarket session [6].

Vertex Pharmaceuticals (VRTX) Conference Summary Company Overview - **Company**: Vertex Pharmaceuticals - **Event**: Conference at the American Diabetes Association 85th Scientific Sessions - **Date**: June 20, 2025 Key Industry and Company Insights Type 1 Diabetes (T1D) Landscape - T1D is caused by the destruction of insulin-producing beta cells in the pancreas, leading to a lifelong dependency on insulin therapy, which has not significantly changed since 1921 [7][9] - Approximately 4 million people are diagnosed with T1D in North America and Europe, with an estimated 60,000 patients experiencing severe hypoglycemic events [11][42] - Severe hypoglycemic events can lead to serious complications, including seizures and increased mortality rates, with those affected having a fivefold increased risk of death [12] Zamyla Cell Overview - **Zamyla Cell**: An investigational islet cell therapy derived from stem cells, designed to replace destroyed islet cells in T1D patients [13] - Administered via infusion into the hepatic portal vein, protected from immune destruction through a steroid-free immunosuppressive regimen [14] - The pivotal Phase 1/2/3 study is progressing, with enrollment expected to complete in summer 2025 [15] Clinical Trial Data - The FORWARD study has transitioned to a Phase 3 pivotal study, focusing on patients with severe hypoglycemia and impaired awareness [20] - Primary efficacy endpoints include freedom from severe hypoglycemia and achieving a hemoglobin A1c (HbA1c) of less than 7% [20] - Data from 12 participants showed restored endogenous insulin production and significant reductions in HbA1c, with 10 out of 12 participants eliminating insulin requirements by 12 months [23][25] Regulatory and Market Potential - Vertex has received several regulatory designations, including RMAT and fast track designations in the US, and PRIME designation in Europe, highlighting the high unmet need for T1D therapies [15] - Anticipated regulatory submissions for Zamyla Cell are expected in 2026, with preparations for commercialization underway [42] Additional Insights Patient Population and Treatment Considerations - Ideal candidates for Zamyla Cell therapy are adults with long-standing T1D and impaired awareness of hypoglycemia [64] - The therapy is expected to significantly improve the quality of life for patients, addressing the burdens of daily diabetes management [39] Future Innovations - Vertex is exploring next-generation therapies, including gene editing and novel immunotherapies, to enhance treatment options for T1D [60] - Manufacturing capabilities are being expanded to meet anticipated demand, with partnerships established to support production [61] Challenges and Considerations - Continuous glucose monitoring has reduced severe hypoglycemic events, but a significant portion of patients still experience these events, indicating a continued need for therapies like Zamyla Cell [49] - The potential for redosing Zamyla Cell exists, as it is an off-the-shelf therapy that can be supplied on demand [54] Conclusion - Zamyla Cell represents a transformative potential for T1D treatment, addressing a significant unmet medical need for patients suffering from severe hypoglycemia [42] - Vertex Pharmaceuticals is positioned to lead advancements in T1D therapies, with ongoing research and development efforts aimed at improving patient outcomes and quality of life [60]

Core Viewpoint - China Resources Sanjiu (华润三九) and Nanjing Ai'erpu Regenerative Medicine have announced a joint development agreement for HiCM-188, an iPSC-derived cardiac cell therapy aimed at addressing the unmet clinical needs of heart failure patients in China [1][2]. Group 1: Company Collaboration - The collaboration between China Resources Sanjiu and Ai'erpu Regenerative Medicine is seen as a significant milestone, leveraging China Resources Sanjiu's strong marketing network and innovative drug promotion experience [2]. - The partnership aims to accelerate the development and commercialization of HiCM-188, which is the first iPSC-derived cardiac cell therapy approved for clinical trials in both China and the U.S. [1][2]. Group 2: Market Context and Clinical Need - According to the "China Heart Failure Center Work Report," there are approximately 12.1 million heart failure patients aged 25 and above in China, with around 3 million new cases each year [1]. - The five-year survival rate for heart failure patients is only 56.7%, and the survival rate for end-stage heart failure patients is less than 60% after two years, highlighting the urgent need for effective treatments [1]. Group 3: Innovation and Future Prospects - HiCM-188 is positioned to meet the significant clinical demand for end-stage heart failure treatments, as no effective drugs have been developed for this condition to date [1]. - The collaboration is expected to contribute to the rapid development of the cell therapy industry in China, aligning with the trend of regenerative medicine for aging and difficult-to-treat diseases [2].