Summary of Travere Therapeutics (TVTX) FY Conference Call - August 13, 2025 Company Overview - **Company**: Travere Therapeutics - **Focus**: Development of therapies for rare diseases, particularly in rare nephrology and rare metabolics [3][4] Core Products - **Filspari**: - Approved for IgA nephropathy and in development for FSGS (Focal Segmental Glomerulosclerosis) - Unique as the only dual endothelin angiotensin receptor antagonist approved for these conditions [3][4] - **Pegtobatinib**: - Enzyme replacement therapy for classical homocystinuria (HCU) - Phase III study expected to begin enrollment next year [4][56] Commercial Performance - **Filspari Commercial Uptake**: - Accelerated approval received in February 2023, with a focus on becoming foundational care for IgA nephropathy [5][6] - Initial uptake was consistent with expectations, outperforming benchmark launches in the renal space [6] - Demand increased from approximately 500 patient start forms (PSFs) to around 700 PSFs following full approval in September [7][8] - 96% payer coverage achieved, with improvements in reimbursement timelines from 20-60 days to the lower end of that range [11][12] Regulatory Updates - **Supplemental NDA (sNDA)**: - Filed to modify Risk Evaluation and Mitigation Strategy (REMS) to remove embryo-fetal toxicity monitoring and adjust liver monitoring requirements [13][14] - Expectation for approval by PDUFA date of August 28 [17] Market Dynamics - **IgA Nephropathy Landscape**: - Recent approvals in the space (e.g., Tepalta, Venrafia) have not negatively impacted Filspari's market approach [23][24] - Over 70,000 addressable patients in the IgA nephropathy market, with KDIGO guidelines emphasizing ambitious treatment goals [25][26] - Filspari's unique position as the only non-immunosuppressive therapy approved for all patients at risk of progression [31] FSGS Market Potential - **FSGS Market Size**: - Potential to be larger than IgA nephropathy, with approximately half the patient population [47] - Nephrologists are more aware of the need for early treatment in FSGS, leading to a motivated patient and physician group [48] - Anticipated strong uptake due to existing experience with Filspari among nephrologists [49] Sales Strategy - **Sales Force Expansion**: - Incremental increase in sales force to maintain market share in IgA nephropathy and target pediatric nephrologists for FSGS [51][55] - Over 80% overlap in physicians treating both IgA nephropathy and FSGS patients [54] Future Outlook - **PDUFA Date for FSGS**: January 2026, with expectations for a strong narrative based on clinical data and alignment with recent Parasol workshop findings [35][42] - **Pegtobatinib**: Anticipated enrollment in Phase III study for HCU, targeting a patient population of 7,000-10,000 in the US [56] Conclusion - Travere Therapeutics is positioned for significant growth with Filspari and pegtobatinib, leveraging strong clinical data and market dynamics to enhance patient care in rare diseases [57][58]

Core Viewpoint - The article discusses the advancements in gene therapy for congenital deafness, highlighting its superiority over traditional cochlear implants in restoring natural hearing and improving speech perception [2][12]. Group 1: Overview of Hearing Loss - Hearing loss is one of the most common sensory disabilities globally, affecting 20% of the population, with 5% experiencing disabling hearing loss [2]. - Approximately 2-3 out of every 1000 newborns are born with congenital hearing impairment, with 60% of cases linked to genetic factors [2]. Group 2: Traditional Treatments and Limitations - Cochlear implants have been the gold standard for severe hearing loss for nearly half a century, but they do not fully restore natural hearing and have low acceptance due to external device maintenance [2][12]. - There has been no clinical treatment available for congenital deafness until the emergence of gene therapy [2]. Group 3: Gene Therapy Advancements - A study led by Fudan University found that gene therapy significantly outperformed cochlear implants in restoring hearing function and speech perception in children with congenital deafness [3][6]. - The study included 11 children who received gene therapy and compared them with 61 children who received cochlear implants, assessing multiple dimensions of auditory perception over a year [6]. Group 4: Results of Gene Therapy - Among the 11 patients treated with gene therapy, 9 showed stable hearing recovery and improved speech abilities after one year [8]. - The gene therapy group scored significantly higher in various auditory perception tests compared to the cochlear implant group, indicating better auditory processing capabilities [9][10]. Group 5: Clinical Implications - The research provides evidence that gene therapy can lead to faster recovery and better quality of auditory perception compared to cochlear implants, marking a new era in precise auditory medicine [12][26]. - The findings suggest that even patients with prior cochlear implants can benefit from subsequent gene therapy, enhancing their auditory capabilities [10]. Group 6: Future Directions - The success of gene therapy for congenital deafness may pave the way for advancements in treating other rare genetic diseases, as the techniques developed can be applied to broader genetic conditions [24][25]. - A new laboratory focused on rare disease gene editing and cell therapy has been established to further research in this area, aiming to develop effective treatments for various genetic disorders [24][25].

Company Overview - Beihai Kangcheng Pharmaceutical Co., Ltd. (stock code 01228.HK) is a leading global biopharmaceutical company in China, focusing on rare diseases and dedicated to the research, development, and commercialization of innovative therapies [2] - The company has a portfolio of 10 drug assets with significant market potential, including 2 approved products and 8 in development, targeting common rare disease indications such as Hunter syndrome and other lysosomal storage diseases, complement-mediated diseases, hemophilia A, metabolic disorders, rare cholestatic liver diseases, and neuromuscular diseases [2] Research and Development - The company is developing new and potentially curative gene therapies for rare genetic diseases, including Pompe disease, Fabry disease, Duchenne muscular dystrophy (DMD), and other neuromuscular diseases at its next-generation gene technology R&D center [2] - Beihai Kangcheng collaborates with leading researchers and biotechnology companies globally, including Apogenix, GCPharma, Mirum, WuXi Biologics, Privus, Washington University School of Medicine, and ScriptrGlobal [2] Management Team - The company is led by a management team with extensive experience in the rare disease sector, covering R&D, clinical development, regulatory affairs, business development, and commercialization [3] - 42% of the employees hold PhDs and/or MDs, and over 70% have experience working in multinational biopharmaceutical companies [3] - The management team has a strong track record of successfully obtaining approvals and commercializing rare disease therapies in major markets, including China and the United States [3] Industry Context - As of the latest data, the average price-to-earnings (P/E) ratio for the pharmaceutical and biotechnology industry is 3.78 times, with a median of 6.52 times [1] - Beihai Kangcheng's P/E ratio is -0.28 times, ranking 155th in the industry, indicating a significant undervaluation compared to peers such as Jingxin Pharmaceutical (0.85 times) and King’s Ray Biotechnology (1.44 times) [1]

Core Viewpoint - The launch of Luwo Meitini tablets marks a significant advancement in the treatment of rare diseases in China, specifically targeting LCH and NF1, providing new therapeutic options for patients [1][2][3]. Group 1: Product Overview - Luwo Meitini tablets are the first and only targeted drug approved in China for both adult LCH and NF1 in children aged 2 and above [1]. - The drug is an innovative small molecule developed by Fosun Pharma, selectively inhibiting MEK1/2 protein activity to block the abnormal activation of the MAPK signaling pathway, thereby suppressing tumor cell proliferation and inducing apoptosis [2]. Group 2: Clinical Data and Efficacy - Clinical trial data shows a median follow-up time of 15.1 months, with a best objective response rate (ORR) of 60.5% and a median time to response (TTR) of 4.7 months, indicating effective and controllable safety [2]. - NF1 is a rare autosomal dominant genetic disorder, with a significant disease burden that can lead to pain, mobility issues, and disfigurement, necessitating the development of targeted therapies [2]. Group 3: Future Prospects - In addition to the current indications, Luwo Meitini is undergoing clinical trials for low-grade gliomas, extracranial arteriovenous malformations, and pediatric LCH, with the potential to expand its application to more disease areas [4].

Company Overview - Beihai Kangcheng Pharmaceutical Co., Ltd. is a leading global biopharmaceutical company in China, focusing on rare diseases and dedicated to the research, development, and commercialization of innovative therapies [2] - The company has a portfolio of 10 drug assets with significant market potential, including 2 approved products and 8 in development, targeting common rare disease indications such as Hunter syndrome and other lysosomal storage diseases [2] Research and Development - The company is developing new and potentially curative gene therapies for rare genetic diseases, including Pompe disease, Fabry disease, Duchenne muscular dystrophy (DMD), and other neuromuscular diseases [2] - Beihai Kangcheng collaborates with leading researchers and biotechnology companies globally, including Apogenix, GCPharma, Mirum, WuXi Biologics, Privus, Washington University School of Medicine, and ScriptrGlobal [2] Management Team - The company is led by a management team with extensive experience in the rare disease sector, covering R&D, clinical development, regulatory affairs, business development, and commercialization [3] - 42% of the employees hold PhDs and/or MDs, and over 70% have experience working in multinational biopharmaceutical companies [3] - The management team has a strong track record of successfully obtaining approvals and commercializing rare disease therapies in major markets, including China and the United States [3]

Summary of Amicus Therapeutics (FOLD) FY Conference Call - June 10, 2025 Company Overview - **Company**: Amicus Therapeutics - **Core Business**: Development of therapies for rare diseases, primarily focusing on Galafold for Fabry disease and Pombility for Pompe disease - **Sales Projections**: Expected to surpass $500 million in sales for Galafold and $100 million for Pombility in 2025 [3][4] Key Points and Arguments Financial Performance and Growth - **Galafold**: - Projected to achieve $1 billion in peak sales with a growth rate of 10% to 15% in 2025 [4] - Currently in a $2 billion global market, expected to grow to $3 billion over the next decade [8][9] - **Pompe Disease Therapies**: - Pombility and Upholda projected to achieve $100 million in sales with a growth rate of 50% to 65% [4] - Anticipated to reach $1 billion in sales in the future [4] - **New Asset - DMX200**: - Licensed from Dimerix for FSGS, a rare kidney disease, with potential blockbuster status [5] - Expected to contribute to significant revenue growth by 2028 [5] Market Position and Competitive Landscape - **Macro Environment**: - Company believes it is well-positioned to navigate macroeconomic challenges affecting the sector [7][8] - Emphasizes the undervaluation of Galafold and the potential for increased diagnoses in the Fabry disease space [8][9] - **Launch Dynamics**: - Initial launch delays due to COVID-19 impacted market entry for Pompe therapies [37] - Positive trends observed in the U.S. market with increasing patient switches from competitors [39][41] Regulatory and Operational Considerations - **Impact of Tariffs and Regulations**: - Minimal impact from tariffs due to low cost of goods for Galafold, which is manufactured in Switzerland [16][18] - Company is adapting to regulatory changes and believes it is insulated from potential negative impacts [20][22] - **FDA Dynamics**: - New leadership at the FDA is expected to support rare disease regulatory reforms, potentially benefiting Amicus [23][24] Guidance and Future Outlook - **Profitability Expectations**: - Guidance for GAAP profitability in the second half of 2025, with revenue growth projected at 15% to 22% [25][26] - Operating expenses expected to remain flat or increase slightly, allowing for positive free cash flow [27][29] - **Long-term Strategy**: - Focus on maintaining financial discipline while expanding the product portfolio [6][12] - Plans to leverage cash flow for new development opportunities in rare diseases [80] Additional Important Insights - **Market Dynamics**: - The company is seeing strong uptake in initial launch countries, with market shares reaching 20-30% in key markets [47] - New countries like the Netherlands are expected to significantly contribute to revenue through patient switches [50][52] - **Patient Diagnosis Trends**: - Increased diagnosis rates for Fabry disease due to lower costs of genetic testing and newborn screenings [64][66] - Potential for significant patient population growth as awareness and testing improve [67][70] Conclusion Amicus Therapeutics is positioned for strong growth in the rare disease market, with a focus on financial discipline and strategic expansion. The company anticipates achieving profitability in the near term while navigating macroeconomic challenges and regulatory changes. The potential for increased patient diagnoses and successful product launches underpins a positive outlook for future revenue growth.

Core Viewpoint - Fosun Pharma has received approval from the National Medical Products Administration for its self-developed drug, Luwo Meitini tablets, making it the first drug in China for the treatment of adult patients with Langerhans cell histiocytosis (LCH) [1][3] Group 1: Drug Approval and Indications - Luwo Meitini tablets are approved for two indications: treatment of adult patients with LCH and treatment of symptomatic, inoperable plexiform neurofibromas (PN) in children and adolescents aged 2 years and older with Neurofibromatosis Type 1 (NF1) [3] - LCH and Erdheim-Chester disease (ECD) are rare hematological tumors, with over 80% of patients affected by multi-system involvement, leading to severe symptoms and poor prognosis due to limited effective treatment options [1] Group 2: Mechanism of Action - Luwo Meitini tablets act as a highly selective MEK1/2 inhibitor, blocking the abnormal activation of the MAPK signaling pathway, thereby inhibiting tumor cell proliferation and inducing apoptosis [1] Group 3: Ongoing Clinical Trials - Fosun Pharma is expanding the indications for Luwo Meitini tablets, with ongoing Phase III clinical trials for adult NF1 in China and Phase II trials for low-grade gliomas, extracranial arteriovenous malformations, and pediatric LCH [3]

Core Viewpoint - The approval of the injection drug Velaglucerase beta (brand name: Gorynin) by the National Medical Products Administration (NMPA) marks a significant milestone as it is the first domestically developed enzyme replacement therapy for Gaucher disease in China, targeting adolescents and adults aged 12 and above with Type I and III Gaucher disease [1][2]. Group 1: Product Approval and Significance - Velaglucerase beta is the only locally developed enzyme replacement therapy for Gaucher disease in China, making it a unique addition to the treatment options available [1]. - The drug is noted for having the broadest range of indications among Gaucher disease treatments currently available [1]. Group 2: Disease Background and Treatment - Gaucher disease is a rare genetic lysosomal storage disorder, with clinical manifestations including hepatosplenomegaly, anemia, bone pain, and neurological complications, potentially leading to life-threatening conditions [2]. - The global prevalence of Gaucher disease is estimated at 0.7 to 1.75 cases per 100,000 people [2]. - Enzyme replacement therapy (ERT) has been the standard treatment for Gaucher disease for 30 years, showing significant efficacy in improving non-neurological symptoms and enhancing the quality of life for patients [2]. Group 3: Development and Technology - The development of Gorynin was facilitated by collaborative efforts with partners like WuXi Biologics, which helped reduce development costs and ensure the drug is safe and effective for patients [2]. - The drug's development utilized second-generation innovative technology, resulting in over a 110-fold increase in production yield and more than a 50% enhancement in enzyme activity, significantly lowering production costs [2]. - WuXi Biologics also developed a cell-based activity assay for quality control, addressing the unique challenges of testing enzyme-based drugs [2].

Financial Data and Key Metrics Changes - At the end of Q1 2025, the company had over $172 million in cash and short-term investments [23] - A $200 million debt facility was executed with Hercules, providing a cash runway into the second half of 2027 [23] Business Line Data and Key Metrics Changes - The company is focused on a single development program for a rare disease called autoimmune pulmonary alveolar proteinosis (APAP) [2] - The Phase III pivotal clinical trial IMPALA two showed statistically significant improvement in DLCO compared to placebo at week 24, with sustained improvement at week 48 [7][8] - 97% of patients completed the double-blind treatment period, with no withdrawals due to drug-related adverse events [8] Market Data and Key Metrics Changes - The diagnosed prevalence of APAP in the U.S. is estimated at approximately 3,600 patients, with an additional 3,700 likely undiagnosed patients [13][14] - The potential market opportunity in the U.S. is significant, with a total of over 7,000 patients identified [15] Company Strategy and Development Direction - The company aims to establish relationships with pulmonologists and treatment centers to gain visibility into the patient population before the launch of Molbrevi [17] - A U.S. commercial team is being built prior to approval, consisting of 25 to 30 individuals responsible for patient profiling and disease awareness campaigns [22] - The pricing power for Molbrevi is projected between $300,000 and $500,000 per patient per year, aligning with other orphan drug analogues [24] Management's Comments on Operating Environment and Future Outlook - Management expressed confidence in the potential of Molbrevi, highlighting the lack of approved medicines for APAP in the U.S. and Europe [4][11] - The company anticipates a potential PDUFA date around November if priority review is granted by the FDA [11] - There is a strong interest from U.S. pulmonologists and payers regarding Molbrevi, with 83% of pulmonologists likely to prescribe it [18][19] Other Important Information - The company launched a free blood antibody test called APAP ClearPath to facilitate quicker diagnosis of APAP [20] - The test has been piloted at an interstitial lung disease clinic, aiming to identify undiagnosed APAP patients [21] Q&A Session Summary Question: What is the current status of the regulatory submission for Molbrevi? - The company completed the submission of the BLA to the FDA and is awaiting feedback within a 60-day window [11] Question: How many patients does the company aim to reach by launch? - The company aims to have line of sight to 1,000 known APAP patients by launch, with a goal to confirm the total of 3,600 patients [15][17] Question: What are the expectations regarding payer coverage for Molbrevi? - 87% of payers indicated they intend to provide coverage with simple pre-authorization criteria, recognizing the disease burden of APAP [19]

Financial Data and Key Metrics Changes - In Q1 2025, the company reported net revenue of $20.4 million, with $17.1 million from MyPlifa, $0.1 million from Olpruva, and $2.3 million in net reimbursements from the French EAP for Aramcholamol [29][30] - Operating expenses for Q1 were $22.8 million, a decrease of $0.6 million compared to the same quarter last year [30] - The net loss for Q1 2025 was $3.1 million, compared to a net loss of $16.6 million in the same quarter a year ago [30][31] - Total cash, cash equivalents, and investments as of March 31, 2025, were $68.7 million, a decrease of $6.8 million from December 31, 2024 [30][31] Business Line Data and Key Metrics Changes - MyPlifa's launch has exceeded expectations, with 122 prescription enrollment forms received since launch, indicating that approximately one-third of diagnosed NPC patients in the U.S. have been enrolled [20][21] - Olpruva received a total of 28 prescription enrollment forms since its initial availability, with five forms received in Q1 2025 [12][27] - The company has achieved 38% of covered lives for MyPlifa, which is in line with expectations at this stage of the launch [21][22] Market Data and Key Metrics Changes - The company is focusing on expanding MyPlifa's availability outside the U.S., with plans for a marketing authorization application in Europe in the second half of the year [11] - The European market for NPC is well established, with approximately 1,100 people estimated to be living with the disease [11] Company Strategy and Development Direction - The company is executing on four strategic pillars: commercial excellence, pipeline and innovation, talent and culture, and corporate foundation [5][8] - The focus is on bringing innovative therapies to patients with rare diseases, with a strong emphasis on MyPlifa as a cornerstone treatment for NPC [17][33] - The company is also assessing strategic alternatives for its Phase III ready asset KP1077 for rare sleep disorders [6] Management's Comments on Operating Environment and Future Outlook - Management expressed optimism about the early success of MyPlifa and the refined marketing strategy for Olpruva, indicating a strong position for future growth [33] - The company believes it is well positioned to support its strategic priorities and execute on its long-term vision, independent from capital markets [31][32] Other Important Information - The company has successfully monetized its Pediatric Rare Disease Priority Review Voucher, adding $148.3 million of non-dilutive capital to its balance sheet [8][31] - The company is committed to patient access and comprehensive patient services through its in-house program, Amplify Assist [27] Q&A Session Summary Question: Details on the number of patients on MyPlifa and reimbursement status - The company received 122 enrollments since launch, with the majority of patients actively on the drug, while some are in the benefits investigation process [36] Question: Reasons for reimbursement denials for MyPlifa - Initial denials are common for rare disease products, primarily due to prior authorization requirements, but the company has been successful in securing coverage through medical exception processes [39][40] Question: Visibility on patient cohorts and enrollment cadence - The company estimates around 600 undiagnosed patients and 300 diagnosed patients, with ongoing efforts to raise awareness and facilitate treatment [47][59] Question: Inventory levels at the end of the quarter - The company is managing inventory closely and maintaining target levels as it supports patient needs during the early launch phase [50] Question: Qualitative metrics on refill rates and patient retention - The majority of patients receiving active drug have continued to refill, reflecting the clinical benefit and durability of MyPlifa [54] Question: Coverage details and impact on patient access - 38% of covered lives have access to MyPlifa, with ongoing efforts to increase this percentage as more plans evaluate the product [63][64]