LSI Medience Corp.

GERMANTOWN, Md., Nov. 07, 2024 (GLOBE NEWSWIRE) -- Senseonics Holdings, Inc. (NYSE American: SENS), a medical technology company focused on the development and manufacturing of long-term, implantable continuous glucose monitoring (CGM) systems for people with diabetes, today reported financial results for the third quarter ended September 30, 2024. Recent Highlights & Accomplishments: Eversense® 365 approved in the US as an integrated continuous glucose monitoring (iCGM) system for people with Type 1 and Type 2 diabetesCommercialization, now in process, driven by Senseonics’ global commercial partner, Ascensia Diabetes Care, a subsidiary of PHC Holdings CorporationMercy health system inserted the first commercial Eversense 365 patient and anticipates that up to 30,000 of Mercy’s patients could benefit from a CGM systemHosted KOL webinar on October 25th, highlighting clinicians’ perspectives on Eversense 365 and Mercy collaboration as a case study for other cost-conscious health systemsAcquired sensor insertion network assets of NPG to begin transitioning nurse practitioners to Eon Care business in order to support greater patient access and convenienceRaised gross proceeds of more than $20 million from equity offerings to strengthen the balance sheet and extend cash runwayExecuted a restructuring process with a target cash operating expense reduction of $10M in 2025Generated global revenue of $4.3 million in the third quarter and began U.S. winddown of Eversense E3 to prepare transition to Eversense 365 “We received FDA approval for Eversense 365 in the third quarter, and Mercy completed the first commercial patient insertion of our new sensor last month. This marks a significant achievement for Senseonics and establishes us as the world’s first and only 365-day CGM,” said Tim Goodnow, PhD, President and Chief Executive Officer of Senseonics. “In the first week after approval, we received the highest influx of inquiries in Senseonics’ history, and early feedback from clinicians has been extremely positive. While we are still in the early days of the launch, we are encouraged by the higher than expected number of healthcare provider leads and inbound interest from KOLs. Further, the recent financings and anticipated savings from restructuring lengthen our runway. Together, these accomplishments position us well for a transformational 2025.” Brian Hansen, President of CGM at Ascensia Diabetes Care, remarked, “Ascensia is strongly committed to providing customers with products that meet the highest standards of accuracy, precision, and reliability. Eversense 365 meets those criteria and provides a truly unique solution for patients with Type 1 and Type 2 diabetes. For our sales team, it’s easy to explain 365’s key points of differentiation- One year, One CGM. Removable transmitter with once a week calibration. We are working hand in hand with Senseonics management to ensure a successful launch of Eversense 365, and we are thrilled to see such strong early enthusiasm for this innovative and differentiated technology.” Third Quarter 2024 Results: Total revenue for the third quarter of 2024 was $4.3 million compared to $6.1 million for the third quarter of 2023. U.S. revenue was $2.4 million in the third quarter of 2024 compared to $3.9 million in the prior year period, and revenue outside the U.S. was $1.9 million in the third quarter of 2024 compared to $2.2 million in the prior year period. During the third quarter, inventory dynamics associated with the 365-day product launch impacted product sales, as we began reducing E3 inventory in anticipation of transition to 365-day insertions. Third quarter 2024 gross loss of $4.1 million compared to gross profit of $1.2 million for the third quarter of 2023. The decrease in gross profit was primarily driven by one time charges of $4.8 million associated with the transition from Eversense E3 to Eversense 365. Third quarter 2024 sales and marketing and general and administrative expenses increased by $0.9 million year-over-year, to $8.3 million. The increase was primarily driven by personnel and consultant costs. Third quarter 2024 research and development expenses decreased by $2.3 million year-over-year, to $10.5 million. The decrease was primarily due to a reduction in clinical studies and support services. Net loss was $24.0 million, or $0.04 per share, in the third quarter of 2024 compared to net loss of $24.1 million, or $0.04 per share, in the third quarter of 2023. Net loss decreased by $0.1 million due to lower research and development expenses offset by one-time charges associated with the transition from Eversense E3 to Eversense 365. Cash, cash equivalents, restricted cash and short-term investments were $74.8 million and outstanding indebtedness was $55.9 million as of September 30, 2024. Subsequent to the end of the third quarter of 2024, Senseonics received gross proceeds of $16.0 million from a recent financing. Full Year 2024 Financial Outlook Senseonics expects full-year 2024 global net revenue to be approximately $22 million as we begin to transition U.S. patients to Eversense 365 following approval in late Q3. The full-year 2024 financial outlook assumes more than doubling the U.S. new patient starts and increasing the global installed base by approximately 50% in 2024 compared to 2023. During the third quarter, inventory dynamics associated with the 365-day product launch impacted product sales, as we began reducing E3 inventory in anticipation of transition to 365-day insertions. Sales are expected to accelerate in the fourth quarter based on anticipated initial 365-day product demand and the initial ramp of the Mercy collaboration. Cash utilization in 2024 is expected to be consistent with 2023 at approximately $70 million. Conference Call and Webcast Information: Company management will host a conference call at 4:30 pm (Eastern Time) today, November 7, 2024, to discuss these financial results and recent business developments. Investors interested in listening to the conference call may do so by accessing a live and archived webcast of the event at this link. Individuals interested in participating in the call via telephone may access the call by dialing +1-800-445-7795 (+1-203-518-9856 for those outside the U.S.) and referencing Conference ID SENSQ3. A replay of the call can be accessed on Senseonics’ website http://www.senseonics.com under “Investor Relations.” About SenseonicsSenseonics Holdings, Inc. ("Senseonics") is a medical technology company focused on the development and manufacturing of glucose monitoring products designed to transform lives in the global diabetes community with differentiated, long-term implantable glucose management technology. Senseonics' CGM systems Eversense® 365 and Eversense® E3 include a small sensor inserted completely under the skin that communicates with a smart transmitter worn over the sensor. The glucose data are automatically sent every 5 minutes to a mobile app on the user's smartphone. About EversenseThe Eversense® Continuous Glucose Monitoring (CGM) Systems are indicated for continually measuring glucose levels for up to 365 days for Eversense® 365 and 180 days for Eversense® E3 in persons with diabetes age 18 and older. The systems are indicated for use to replace fingerstick blood glucose (BG) measurements for diabetes treatment decisions. Fingerstick BG measurements are still required for calibration primarily one time per week after day 14 for Eversense® 365 and one time per day after day 21 for Eversense® E3, and when symptoms do not match CGM information or when taking medications of the tetracycline class. The sensor insertion and removal procedures are performed by a health care provider. The Eversense CGM Systems are prescription devices; patients should talk to their health care provider to learn more. For important safety information, see https://www.eversensediabetes.com/safety-info/. About Ascensia Diabetes CareAscensia Diabetes Care is a global company focused entirely on helping people with diabetes. Our mission is to empower those living with diabetes through innovative solutions that simplify and improve their lives. We are home to the world-renowned CONTOUR® portfolio of blood glucose monitoring systems and the exclusive global distribution partner for the Eversense® Continuous Glucose Monitoring Systems from Senseonics. These products combine advanced technology with user-friendly functionality to help people with diabetes manage their condition and make a positive difference to their lives. As a trusted partner in the diabetes community, we collaborate closely with healthcare professionals and other partners to ensure our products meet the highest standards of accuracy, precision and reliability, and that we conduct our business compliantly and with integrity. Ascensia is a member of PHC Group and was established in 2016 through the acquisition of Bayer Diabetes Care by PHC Holdings Corporation. Ascensia products are sold in more than 100 countries. Ascensia has around 1,400 employees and operations in 29 countries. For further information, please visit the Ascensia Diabetes Care website at: http://www.ascensia.com. About PHC Holdings CorporationPHC Holdings Corporation (TSE 6523) is a global healthcare company with a mission of contributing to the health of society through healthcare solutions that have a positive impact and improve the lives of people. Its subsidiaries (referred to collectively as PHC Group) include PHC Corporation, Ascensia Diabetes Care Holdings AG, Epredia Holdings Ltd., LSI Medience Corporation, Mediford Corporation, and Wemex. Together, these companies develop, manufacture, sell and service solutions across diabetes management, healthcare solutions, life sciences and diagnostics. PHC Group’s consolidated net sales in FY2023 were JPY 353.9 billion with global distribution of products and services in more than 125 countries. www.phchd.com ©2024 Ascensia Diabetes Care Holdings AG. All right reserved. Ascensia, the Ascensia Diabetes Care logo and Contour are trademarks and/or registered trademarks of Ascensia Diabetes Care Holdings AG. About MercyMercy, one of the 20 largest U.S. health systems and named the top large system in the U.S. for excellent patient experience by NRC Health, serves millions annually with nationally recognized care and one of the nation’s largest and highest performing Accountable Care Organizations in quality and cost. Mercy is a highly integrated, multi-state health care system including more than 50 acute care and specialty (heart, children’s, orthopedic and rehab) hospitals, convenient and urgent care locations, imaging centers and pharmacies. Mercy has over 900 physician practice locations and outpatient facilities, more than 4,500 physicians and advanced practitioners and 50,000 co-workers serving patients and families across Arkansas, Kansas, Missouri and Oklahoma. Mercy also has clinics, outpatient services and outreach ministries in Arkansas, Louisiana, Mississippi and Texas. In fiscal year 2023 alone, Mercy provided more than half a billion dollars of free care and other community benefits, including traditional charity care and unreimbursed Medicaid. Forward Looking Statements Any statements in this press release about future expectations, plans and prospects for Senseonics, including the revenue and cash projections, assumptions related to U.S. new patient starts and the global installed base under the heading “Full Year 2024 Financial Outlook,” statements regarding plans, timing and success of the commercial launch of the 365-day system, statements regarding increasing patient access and convenience, statements regarding potential users of CGM at health systems, statements regarding the attributes experienced by people with diabetes and differentiating the system from short-term CGM, statements regarding the integration of the Eversense CGM solution within the Mercy health care system and the adoption and/or growth of Eversense, and other statements containing the words "believe," “expect,” “intend,” “may,” “projects,” “will,” “planned,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: uncertainties inherent in the execution of the independent business unit of Ascensia Diabetes Care, the Company’s commercialization partner for Eversense, and other commercial initiatives, uncertainties in insurer, regulatory and administrative processes and decisions, uncertainties inherent in the development and registration and roll-out of new technology and solutions, uncertainties inherent in finalizing integration and commercial terms and coordinations with health systems and other new collaboration partners and third parties, uncertainties inherent in the ongoing commercialization of the Eversense product and the expansion of the Eversense product and Senseonics’ activities, uncertainties relating to the current economic environment and such other factors as are set forth in the risk factors detailed in Senseonics' Annual Report on Form 10-K for the year ended December 31, 2023 and subsequent quarterly reports on Form 10-Q filed with the SEC under the heading "Risk Factors." In addition, the forward-looking statements included in this press release represent Senseonics’ views as of the date hereof. Senseonics anticipates that subsequent events and developments will cause Senseonics’ views to change. However, while Senseonics may elect to update these forward-looking statements at some point in the future, Senseonics specifically disclaims any obligation to do so except as required by law. These forward-looking statements should not be relied upon as representing Senseonics’ views as of any date subsequent to the date hereof. Senseonics Investor Contact Jeremy FefferLifeSci Advisorsinvestors@senseonics.com Senseonics Holdings, Inc.Condensed Consolidated Balance Sheets(in thousands, except share and per share data) September 30, December 31, 2024 2023 (unaudited) Assets Current assets: Cash and cash equivalents$27,106 $75,709 Restricted cash 315 — Short term investments, net 47,375 33,747 Accounts receivable, net 1,523 808 Accounts receivable, net - related parties 2,507 3,724 Inventory, net 3,207 8,776 Prepaid expenses and other current assets 5,665 7,266 Total current assets 87,698 130,030 Deposits and other assets 5,209 7,006 Property and equipment, net 3,424 1,184 Total assets$96,331 $138,220 Liabilities and Stockholders’ (Deficit) Equity Current liabilities: Accounts payable$2,107 $4,568 Accrued expenses and other current liabilities 12,578 11,744 Accrued expenses and other current liabilities, related parties 1,448 945 Notes payable, current portion, net 19,376 — Total current liabilities 35,509 17,257 Long-term debt and notes payables, net 34,448 41,195 Derivative liabilities — 102 Other liabilities 5,899 6,214 Total liabilities 75,856 64,768 Preferred stock and additional paid-in-capital, subject to possible redemption: $0.001 par value per share; 12,000 shares authorized and 12,000 shares issued and outstanding as of September 30, 2024 and December 31, 2023 37,656 37,656 Total temporary equity 37,656 37,656 Commitments and contingencies Stockholders’ (deficit) equity: Common stock, $0.001 par value per share; 1,400,000,000 shares and 900,000,000 shares authorized as of September 30, 2024 and December 31, 2023; 545,612,780 shares and 530,364,237 shares issued and outstanding as of September 30, 2024 and December 31, 2023 546 530 Additional paid-in capital 914,637 904,535 Accumulated other comprehensive income (loss) 34 (11)Accumulated deficit (932,398) (869,258)Total stockholders’ (deficit) equity (17,181) 35,796 Total liabilities and stockholders’ equity$96,331 $138,220 Senseonics Holdings, Inc.Unaudited Condensed Consolidated Statements of Operations and Comprehensive Loss(in thousands, except share and per share data) Three Months Ended Nine Months Ended September 30, September 30, 2024 2023 2024 2023 Revenue, net$955 $426 $2,322 $1,176 Revenue, net - related parties 3,308 5,671 11,853 13,184 Total revenue 4,263 6,097 14,175 14,360 Cost of sales 8,314 4,925 17,593 12,358 Gross (loss) profit (4,051) 1,172 (3,418) 2,002 Expenses: Research and development expenses 10,546 12,769 31,784 38,003 Selling, general and administrative expenses 8,250 7,425 25,369 22,598 Operating loss (22,847) (19,022) (60,571) (58,599)Other (expense) income, net: Interest income 1,010 1,460 3,584 3,879 Exchange related (loss) gain, net — (4,569) — 14,207 Interest expense (2,133) (2,425) (6,266) (9,388)Gain on change in fair value of derivatives — 438 102 6,505 Other (expense) income (6) 15 11 194 Total other (expense) income, net (1,129) (5,081) (2,569) 15,397 Net Loss (23,976) (24,103) (63,140) (43,202)Other comprehensive loss Unrealized gain on marketable securities 41 61 45 619 Other comprehensive gain 41 61 45 619 Total comprehensive loss$(23,935) $(24,042) $(63,095) $(42,583) Basic net loss per common share$(0.04) $(0.04) $(0.10) $(0.08)Basic weighted-average shares outstanding 620,897,955 592,452,262 617,370,311 552,703,546 Diluted net loss per common share$(0.04) $(0.04) $(0.10) $(0.08)Diluted weighted-average shares outstanding 620,897,955 592,452,262 617,370,311 552,703,546

Eversense 365 cleared in the U.S. as an integrated continuous glucose monitoring (iCGM) system for people with diabetes With a single sensor, the Eversense 365 system provides one year of use, versus 10-14 days with short-term CGM’s for minimal life disruption Launch expected early in the fourth quarter of 2024 GERMANTOWN, Md. and PARSIPPANY, N.J., Sept. 17, 2024 (GLOBE NEWSWIRE) -- Senseonics Holdings, Inc. (NYSE American: SENS), a medical technology company focused on the development and manufacturing of long-term, implantable continuous glucose monitoring (CGM) systems for people with diabetes and Ascensia Diabetes Care, a global diabetes care company, today announced that the U.S. Food and Drug Administration (FDA) has cleared the next-generation Eversense® 365 CGM system for people with Type 1 and Type 2 diabetes aged 18 years and older. Eversense 365 is the world’s first One Year CGM system, representing a significant breakthrough in diabetes technology and management. “The approval of Eversense 365 represents a significant leap in CGM innovation. Extending sensor longevity to a full year, coupled with seamless device connectivity and a high level of accuracy, provides both freedom and peace of mind to patients living with diabetes,” said Tim Goodnow, PhD, President and Chief Executive Officer of Senseonics. “Eversense 365 was ‘designed for real life’ and is optimally suited to help people with diabetes increase time in range of desired glucose levels and lower A1c. The delivery of the world’s first 365-day sensor is a seminal event for Senseonics and we’re excited to bring it to people with diabetes.” “Managing diabetes can be stressful and it is important for technology to disrupt life as little as possible to limit this burden,” said Brian Hansen, President of CGM at Ascensia Diabetes Care, a subsidiary of PHC Holdings Corporation (TSE 6523). “Eversense 365 allows people with diabetes to focus on living their lives, rather than managing the limitations that many experience with short-term CGMs. We are very excited about Senseonics’ ability to once again bring true innovation to the CGM space and are working closely with our partner to make Eversense 365 commercially available as soon as possible. In parallel, our partnership discussions with various pump manufacturers continue to progress, as we look to leverage Eversense 365’s unique potential to simplify life with integrated automated insulin delivery (AID) systems.” Eversense 365 is supporting people with diabetes to live life uninterrupted, as a fully-implantable, long-term CGM option that is highly-differentiated from short-term CGMs: Longest lasting CGM: The only CGM with a 365-day sensor means no frequent sensor changes, and only one insertion and one “Day 1” every year, compared to every 10-14 days with short-term CGM systemsMost dependable CGM: Sensor survivability across 12 months reduces the burden of data interruptions from frequent short-term CGM sensor failures or changes1, 2, 3No more wasted sensors: A tiny sensor that rests comfortably under the skin means that it cannot be knocked off, minimizing the inconvenience and cost of regular replacementsAlerts that can be trusted: Exceptional accuracy consistently for one year4 and almost no false alerts from compression lows during the night5Maximum comfort: A gentle silicone-based adhesive that can be changed daily and causes almost no skin reactions6More freedom: The only CGM with a removable transmitter which can be easily taken on and off† without wasting a sensor or adding a warm up periodImproved discretion: On-body vibration alerts keep patients notified even when their mobile phone is out of sight Ascensia expects to initiate the U.S. launch of Eversense 365 U.S. in the fourth quarter of 2024, with work ongoing to transition coverage availability in order to facilitate immediate access to as many users as possible. Eversense 365 has been cleared as an integrated CGM (iCGM) system, indicating that it can integrate with compatible medical devices, including insulin pumps as part of an automated insulin delivery (AID) system. Eversense 365 is exceptionally well suited to address common limitations7 of AID systems and the companies are advancing partnership discussions with various pump manufacturers. To learn more about Eversense 365 and for additional information about when the system will be available, go to www.eversensecgm.com. Physicians, nurse practitioners and physician assistants who are interested in prescribing the Eversense CGM System can sign up at www.ascensiadiabetes.com/eversense/become-a-provider/. Alternatively, contact 1-844-SENSE4U (1-844-736-7348) to learn more about the first and only long-term implantable CGM system. † There is no glucose data generated when the transmitter is removed 1 Senseonics. (2024) Eversense 365 User Guide. 2 Abbott. (2024) Freestyle Libre 3 User Guide ART49385-001 Rev. A 04/24 3 Dexcom (2024) G7 User Guide AW00078-10 Rev 003 MT-00078-10 4 Data on file 5 Christiansen MP, Klaff LJ, Brazg R, et al. A Prospective Multicenter Evaluation of the Accuracy of a Novel Implanted Continuous Glucose Sensor: PRECISE II. Diabetes Technol Ther. 2018;20(3):197-206. doi:10.1089/dia.2017.0142 6 Deiss, D. et al. (2020). Real-world safety of an implantable continuous glucose sensor over multiple cycles of use: A post-market registry study. Diabetes Technology & Therapeutics, 22(1), 48–52. 7 Sherr JL, Heinemann L, Fleming GA, et al. Automated insulin delivery: benefits, challenges, and recommendations. A Consensus Report of the Joint Diabetes Technology Working Group of the European Association for the Study of Diabetes and the American Diabetes Association. Diabetologia. 2023;66(1):3-22. doi:10.1007/s00125-022-05744-z About SenseonicsSenseonics Holdings, Inc. (“Senseonics”) is a medical technology company focused on the development and manufacturing of glucose monitoring products designed to transform lives in the global diabetes community with differentiated, long-term implantable glucose management technology. Senseonics' CGM systems Eversense® 365 and Eversense® E3 include a small sensor inserted completely under the skin that communicates with a smart transmitter worn over the sensor. The glucose data are automatically sent every 5 minutes to a mobile app on the user's smartphone. About Eversense The Eversense® Continuous Glucose Monitoring (CGM) Systems are indicated for continually measuring glucose levels for up to 365 days for Eversense® 365 and 180 days for Eversense® E3 in persons with diabetes age 18 and older. The systems are indicated for use to replace fingerstick blood glucose (BG) measurements for diabetes treatment decisions. Fingerstick BG measurements are still required for calibration primarily one time per week after day 14 for Eversense® 365 and one time per day after day 21 for Eversense® E3, and when symptoms do not match CGM information or when taking medications of the tetracycline class. The sensor insertion and removal procedures are performed by a health care provider. The Eversense CGM Systems are prescription devices; patients should talk to their health care provider to learn more. For important safety information, see https://www.eversensediabetes.com/safety-info/. About Ascensia Diabetes Care Ascensia Diabetes Care is a global company focused entirely on helping people with diabetes. Our mission is to empower those living with diabetes through innovative solutions that simplify and improve their lives. We are home to the world-renowned CONTOUR® portfolio of blood glucose monitoring systems and the exclusive global distribution partner for the Eversense® Continuous Glucose Monitoring Systems from Senseonics. These products combine advanced technology with user-friendly functionality to help people with diabetes manage their condition and make a positive difference to their lives. As a trusted partner in the diabetes community, we collaborate closely with healthcare professionals and other partners to ensure our products meet the highest standards of accuracy, precision and reliability, and that we conduct our business compliantly and with integrity. Ascensia is a member of PHC Group and was established in 2016 through the acquisition of Bayer Diabetes Care by PHC Holdings Corporation. Ascensia products are sold in more than 100 countries. Ascensia has around 1,400 employees and operations in 29 countries. For further information, please visit the Ascensia Diabetes Care website at: http://www.ascensia.com About PHC Holdings Corporation PHC Holdings Corporation (TSE 6523) is a global healthcare company with a mission of contributing to the health of society through healthcare solutions that have a positive impact and improve the lives of people. Its subsidiaries (referred to collectively as PHC Group) include PHC Corporation, Ascensia Diabetes Care Holdings AG, Epredia Holdings Ltd., LSI Medience Corporation, Mediford Corporation, and Wemex. Together, these companies develop, manufacture, sell and service solutions across diabetes management, healthcare solutions, life sciences and diagnostics. PHC Group’s consolidated net sales in FY2023 were JPY 353.9 billion with global distribution of products and services in more than 125 countries.www.phchd.com ©2024 Ascensia Diabetes Care Holdings AG. All right reserved. Ascensia, the Ascensia Diabetes Care logo and Contour are trademarks and/or registered trademarks of Ascensia Diabetes Care Holdings AG. Forward Looking Statements Any statements in this press release about future expectations, plans and prospects for Senseonics, including statements regarding plans and timing for the commercial launch of the 365-day system, statements regarding the attributes experienced by people with diabetes and differentiating the system from short-term CGM, statements regarding the potential integration with insulin pump systems, statements regarding the transition of insurer coverage, and other statements containing the words “believe,” “expect,” “intend,” “may,” “projects,” “will,” “planned,” and similar expressions, constitute forward-looking statements within the meaning of The Private Securities Litigation Reform Act of 1995. Actual results may differ materially from those indicated by such forward-looking statements as a result of various important factors, including: uncertainties inherent in the execution of the independent business unit of Ascensia Diabetes Care, the Company’s commercialization partner for Eversense, and other commercial initiatives, uncertainties in insurer, regulatory and administrative processes and decisions, uncertainties inherent in the development and registration of new technology and solutions, uncertainties inherent in finalizing integration and commercial terms with new partners and other third parties, uncertainties inherent in the ongoing commercialization of the Eversense product and the expansion of the Eversense product, uncertainties relating to the current economic environment and such other factors as are set forth in the risk factors detailed in Senseonics' Quarterly Report on Form 10-Q for the quarter ended June 30, 2024 and Senseonics' other filings with the SEC under the heading “Risk Factors.” In addition, the forward-looking statements included in this press release represent Senseonics’ views as of the date hereof. Senseonics anticipates that subsequent events and developments will cause Senseonics’ views to change. However, while Senseonics may elect to update these forward-looking statements at some point in the future, Senseonics specifically disclaims any obligation to do so except as required by law. These forward-looking statements should not be relied upon as representing Senseonics’ views as of any date subsequent to the date hereof. Senseonics Investor Contact Jeremy FefferLifeSci Advisorsinvestors@senseonics.com Ascensia Communications Contact Lorraine ChandlerHead of Corporate CommunicationsLorraine.chandler@ascensia.com

成立于1897年，百年以来，龙沙的主要业务经历了能源发电→基础化工→精细化工→合同开发和生产（CDMO）的变迁。本文根据公开资料梳理，水平有限不能保证无错，具有时效性不能保证及时，不构成任何投资依据。01电气时代的先驱19世纪，人类社会正经历着“电气时代”这一生产力发展的重大飞跃。电不仅带来了光明，更是作为一种能源被用于改变物质，催生了电化学以及电化学品。世纪之初，瑞典化学家贝采尼乌斯（Jons Jakob Berzelius）与英国化学家汉弗里·戴维（Humphry Davy）就已经开始进行电解试验并成功分离出多种化学成分。19世纪中晚期，随着发电机与可负担电能的出现，电化学迎来了真正的发展。1880年，人们建立起了将盐溶液分离为氯和苛性钠的工厂。同一时期，电解法被成功用于从无水熔融矿石中分解铝，成为1889年巴黎世博会上的轰动展示之一。1892年，法国化学家亨利·莫瓦桑（Henri Moissan）对碳化钙（Calcium carbide）又称电石，的科学研究，标志着欧洲电化学工业的诞生。电石灯是当时工业化国家普遍采用的照明方式。通过碳化钙与水的剧烈反应产生乙炔（Acetylene），被点燃后形成明亮的火焰【CaC2 + 2H20 -> C2H2 + Ca(OH)2 + 34 kcal/Mol】，电石灯在各个街角发出耀眼光芒，甚至一度被用作自行车的安全灯。与今天一样，将最新的研发成果转化落地，并进行商业化是一项非常艰巨的任务，不仅需要耐心，更是一种风险极高的冒险。而在那个遥远的世纪之交（1897年），一群“具有冒险及先驱精神”的投资人及企业家以80万瑞士法郎的初始股本在瑞士瓦莱州（Valais）甘培尔（Gampel）小镇的龙沙河畔（Lonza River）建立了一座水利发电站——Elektrizitätwerks Lonza和配套的电化学工厂生产碳化钙。龙沙第一座水力发电厂，摄于1915年将科学层面的Know-how付诸实践是极其困难的，而龙沙在一开始就展现出了这方面的坚韧和能力。碳化钙的生产是一种强吸热反应【CaO + 3C -> CaC2 + CO】对炉温有着较高要求。工厂建成后的第二年，龙沙在熔炉技术发展方面取得重大进展，成功将炉温提升至大约2000℃，极大改善了原有工艺中原材料和电力的浪费情况。自此，龙沙开启了一段不断追求突破性创新并将其付诸实践，从而改变人类生活方式的百年传奇。碳化物产业的兴盛与扩张同时带来了机遇与危机。随着大量资金涌入行业，无数工厂如雨后春笋般建立起来，1909年龙沙菲斯普（Visp）工厂的建成。然而，交流电的使用极大推进了电气工程技术发展，电石灯与电灯之间的竞争逐渐尘埃落定。同行竞争和外部冲击之下，龙沙的碳化物业务亟需转型。转机很快到来，1899年德国化学家阿道夫·弗兰克（Adalf Frank）与海因里希·卡罗（Heinrich Caro）通过试验将氮气导向发光的电石，发明了一种生产石灰氮（氰氨化钙CaCN2）的工艺【CaC2 + N2-> CaCN2 + C + 69 kcal/Mol】。石灰氮可以中和酸性土壤并缓慢为植物提供氮，是人类的首个合成肥料。而龙沙凭借其对新兴技术的敏锐嗅觉，再次抓住了机会。1915年，龙沙完成了工艺放大，开始用碳化钙规模化生产石灰氮。进入化肥产业，也标志着龙沙业务多元化的开始和向工业集团的转型。随着一战进行，国际碳化物交易量从战前的16万吨飙升至战争结束时的130万吨。由于战争所导致的封锁，煤炭短缺导致碳化钙作为一种替代燃料的需求猛增。对于战争国来说，氰氨化钙作为一种制作火药与爆炸物的基本材料有着很大用量。此外龙沙还利用氰氨化钙生产氨（ammonia），用于支持瑞士军方部门。同时，战争所带来的可发酵农产品短缺，导致瑞士在酒精生产方面困难重重，而龙沙的碳化钙可以用来生产酒精。由于战前碳化钙市场已经开始波动，龙沙开始寻找乙炔使用的新方法开始了乙醛（Acetaldehyde）【C2H2 + H20 -> C2H4O】和乙酸（Acetic acid）【C2H4O + ½O2 -> C2H2O2】的工业化生产。很快，战争结束后的产能过剩危机迫使龙沙将甘培尔和菲斯普的碳化钙产量减半，还关闭了早些时候在日内瓦周边收购的工厂。而酒精业务也由于关键设备的延迟，直到1918年底才开始运行，并由于高企的煤价，最终只生产了100吨酒精。不过，这一挫折反而给龙沙的发电业务带来新的机遇，周边工厂的关闭导致龙沙发电量超过使用量，为了解决这一问题，龙沙在上瓦莱州和位于瑞士南部的Gesellschaft für Chemische Industrie company（汽巴精化前身）之间修建了100公里长的高压线路。这次扩展还使得龙沙得以收购其他数座发电厂，逐渐接管了瓦莱州下游的总体电力供应。同一时期，法国公司Societe L’Air Liquide - Paris开发的一种低温蒸馏分离空气的方法立刻挑动了龙沙敏感的技术神经。很快，以该技术发明人Georges Claude为名的工厂在甘培尔建立，龙沙开始规模化生产氮和氧。同一时期，龙沙工程师Pechkranz开发出了可用于工业化规模使用的水电解槽，率先开启了氢气的工业生产。低温蒸馏，电解技术与高温高压技术一起，为龙沙的基本化学业务打下了坚实基础。自此，龙沙开始有能力处理几乎所有的化学过程。碳化钙市场的崩溃也让龙沙见到了产品单一所带来的风险，也意识到了基础化学品并不能带来高利润。于是，凭借着氨和乙炔两大支柱，龙沙开始开发新的产品，逐渐向更加附加值的化学品领域进发。02能源&化工互补发展事实上此时的龙沙已经成为两个业务互补的企业集团，一个是提供电力的公共事业公司，一个是专注于化工的化学品制造企业。化学品业务方面，通过在甘培尔工厂生产的氰氨化钙和硝酸钙，龙沙成功在化肥行业站稳了脚跟。1930年，龙沙通过向化肥中添加更多活性成分，进一步提升工艺，推出了一系列富肥产品。1968年，龙沙开设了一家新的化肥厂，配有自动化生产线和储存设施以应对季节性需求。龙沙的化肥产量在1980年代达到顶峰。不过，由于化肥行业的竞争压力和种植技术的发展，1993年开始龙沙的化肥业务开始缩减，并退出了这些产品的市场营销。该业务后来被交予龙沙旗下一家合资企业负责。前文提到一战以来，龙沙开始探索乙炔使用的新方法，此举也开启了龙沙有机化学的尝试。随后该探索逐渐集中在碳化钙制成乙酸（acetic acid）中间体乙醛（Acetaldehyde）上。乙醛在龙沙的有机化学业务中扮演了重要角色，是许多龙沙明星产品工艺过程的重要基础，例如多聚乙醛（Metaldehyde）【4C2H4O -> C8H16O4】，三聚乙醛（paraldehyde）【3C2H4O -> C6H12O3】，乙酸，乙酸乙酯（ethyl acetate）等。其中最出名的是多聚乙醛品牌Meta®。Meta®诞生于对乙醛的固体化研究。Meta®曾经是世界领先的固体燃料品牌之一，其结晶是在低于0℃温度下，利用催化剂将四个乙醛分子键合，并在离心机中从液体副产物中分离而成。此后经过惰性气体干燥，加入稳定剂，龙沙会将Meta®粉末压成较大体积的砖块状进行存储，或压成细长小片作为燃料销售。不过到70年代，由于毒物管理法规变化，Meta®只能在药店售卖，直到1985年Meta®被放弃作为燃料销售，压片厂也被关闭。1923年，龙沙开始生产多聚乙醛，商品名Meta®，作为引燃剂和燃料二战期间，龙沙的工作受控于政府，被优先安排了化肥制造以促进粮食生产。之后，研发重心逐渐转移到替代燃料，溶剂，橡胶，合金成分和用于生产清漆，油漆，染料，农药，纺织品和药品的原材料及中间体。战后，龙沙保持住了化肥和替代燃料制造商的地位。战时任务的影响是深远的，不仅是有些战争合同一直延续到1950年代，更是推动了龙沙技术的进一步发展，例如为了满足战时对替代燃料的需求，龙沙开发了一种制备与苯混合的三聚乙醛燃料成分的工艺。从1941年2月第一船燃料交付到运输停止，龙沙已很好的了解三聚乙醛。作为合成5-乙基-2-甲基吡的基础材料，未来，三聚乙醛也将龙沙带入了吡啶化学领域。半个世纪以来，碳化物一直是龙沙运营的核心。不过这一情况在20世纪50年代发生了改变。彼时，市场对有机产品需求大增，加之人们对环保的重视，龙沙的以碳化物为化学基础的技术开始落后于行业。与依然使用煤炭作为化学基础材料的龙沙不同，国际上其他工业中心已经转向使用石油与天然气。为了应对挑战，1959年的股东大会上，龙沙董事会宣布将龙沙的化学基础从煤炭转化为石油。尽管转型规模巨大，龙沙仍然迅速做出反应，与技术发展和市场步伐保持一致。1964年，龙沙选择了来自于意大利蒙特卡蒂尼（Montecatini Co.）公司贾科莫·福瑟（Giacomo Fauser）的工艺，在菲斯普建成了全世界最小的工业石脑油裂解装置，成本达1.3亿瑞士法郎。事实上，龙沙在建立该设施时遇到了许多困难，比如在试运行期间忽略了煤烟和焦油混合物的影响，导致其快速堵塞了许多管道。面对难题，龙沙员通过一些自制的改进和补救，成功让工厂在6个月内准备好投入生产。龙沙利用该设施把天然气和石油分解成乙烯和氢等石油化工基础化学品，极大的扩展了产品组合。该工厂在精心维护下连续运转了数十年，为龙沙提供了从有机物起始物质到中间体的一系列产品，也为龙沙的后来的业务结构奠定了基础。菲斯普的石脑油裂解设施1966年，龙沙的化学品业务迎来了彻底性重组，新的业务板块被划分为四个基本独立部门，包括无机化学品，肥料和农用化学，化学品和塑料。1972年，龙沙菲斯普工厂最后一次生产碳化物，结束了近75年的碳化物为基础的化学工业史。以下是龙沙化学品业务的主要产品：乙烯酮ketene乙烯酮（ketene），一种沸点在-45°的气体，通过在600-700°下加入酸性催化剂磷酸三乙脂催化裂解乙酸后分离而得。1928年，龙沙建立乙烯酮生产线，乙烯酮及其衍生产品并逐渐成为瓦莱州工厂第二重要的产品系列。最初，龙沙生产乙烯酮是希望将其作为人造丝（尼龙）的原料进行销售。但是由于市场表现不及预期，龙沙决定自行生产人造丝。1928年，龙沙在菲斯普建立了一座纺纱厂，一直持续运行到1932年。之后，龙沙研发了一套专有的醋酸人造丝（acetate silk）工艺，并借助德国的有利市场条件，开始建厂并大规模工业化生产。双烯酮diketene1947年以前乙烯酮几乎全部被用于生产乙酸酐（acetate anhydride），之后龙沙扩张产能开始使用乙烯酮生产双烯酮（diketene）。双烯酮是一种高度活跃的无色液体，其低稳定性很低，在室温下只能保持几天，无法通过公路或铁路大量转运。所以龙沙直接在自己德瓦莱州工厂中将双烯酮转化为更稳定的衍生物，包括各种乙酰乙酸乙酯（acetoacetic esters），芳基化物（arylides），丙烯酰胺（alkylamides）和脱氢乙酸（dehydroacetic acid）。所有的这些产品都作为中间原材料进行销售，其中一小部分由龙沙自用，更多则是卖给市场上的其他化工企业用以生产终端产品。1993年龙沙再度扩大了乙烯酮生产，建立了一座先进的乙烯酮/双烯酮露天工厂，该设施可年产乙烯酮18000吨。龙沙的瑞士菲斯普工厂和美国贝波特工厂一度满足了全球四分一的双烯酮需求。2004年，龙沙剥离了美国贝波特工厂，并重新命名为Gulf Bayport Chemicals LP。1993年建立的乙烯酮/双烯酮露天工厂吡啶pyridine起源于龙沙对碳二化合物的研究，吡啶（pyridine）化学是今天龙沙各产品系列中最成功的，是生产高附加值产品的基础。最初，龙沙使用碳化钙反应生成乙炔来生产吡啶，1960年后，随着石脑油裂解设施建成，龙沙使用乙炔和乙烯进行合成。对于龙沙来说，吡啶化学中最重要的产品是5-乙基-2-甲基-吡啶，该产品可以由乙醛直接生产或经由三聚乙醛得到。1956年，龙沙围绕其最初的工艺，建立了一座由2000米管道和12个加热模块组成的反应装。管道中，氨气（ammonia）和乙酸在20℃和100bar压力下连续反应。该装置分别在1972年和1993年进行了扩建。烟酸nicotinic acid18到19世纪，在欧洲和北非的人群与动物中出现了一种名为“糙皮病（pellagra）”的流行病，该病表现为皮肤炎症和腹泻，有人甚至因此患上精神问题。人们发现糙皮病的流行区域与玉米种植区高度重合，原因是与其他主粮相比，玉米不提供任何可被人体吸收的烟酸，而烟酸又是人体所必须的一种维生素——烟酰胺（niacinamide）的基础。烟酰胺是烟酸的酰胺化合物，当人和动物摄入烟酸后可以在体内合成烟酰胺，发挥实际的维生素作用。因此两种形式的维生素效果是一样的。1937年，科学家开始研究烟酸的合成制造办法，而龙沙最大优势是拥有大量合成烟酸的关键基本物质，包括三聚乙醛，氨和硝酸（nitric acid）。1940年，龙沙进行了一次非加压催化工艺的试运行。1956年，龙沙采用高压灭菌器中直接将5-乙基-2-甲基-吡啶转化为烟酸【C8H11N+6HNO3-> C6H5NO2+6NO+6H2O+2CO2】的工艺进行生产，产量达几百吨。1963年，龙沙开始使用连续工艺生产烟酸。工艺和产品质量的改善使龙沙始终处于市场领先地位。龙沙一度在该领域拥有全球60%的市场份额，生产的大约10%烟酸会被转化为烟酰胺。这两种形式的产品都被用作食品，复合维生素和药物中的添加剂使用。1995年，龙沙在中国广州合资建立了一座烟酸/烟酰胺工厂。氢氰酸hydrocyanic acid除了双烯酮和吡啶外，龙沙第三大产品系列是氢氰酸（hydrocyanic acid），又称普鲁士酸（prussic acid）或氰化氢（hydrogen cyanide），是一种带有少许杏仁味的无色剧毒液体。1950年末，研究人员开始寻找一种利用碳氢化合物与氨气生产氢氰酸的方法。1963年龙沙的第一座氢氰酸工厂投产，日产量达1.5吨。不过，由于氢氰酸是当时合成丙烯晴所产生的副产物，导致市场上充斥着大量廉价氢氰酸，巨大的竞争压力导致龙沙氢氰酸厂在1966年停产。直到1976年丙烯晴制成工艺改善后，副产物氢氰酸大量减少。重新释放出的市场促使龙沙引进德国德固赛（Degussa）的工艺在瓦莱州建设了一座全新的氢氰酸工厂。氢氰酸生产中，最令人关注的是如何处理这种剧毒物质有关的卫生和安全问题。具体来说，甲烷和氨气可以在合适的条件下被转化为氢氰酸，这两种气体在1350°的高温下在耐热管中发生反应，管壁内部涂有一层含有贵金属基底的催化剂。该反应管束状悬挂在陶瓷炉中，由天然气进行加热。经过多级精炼工艺，可以获得氢氰酸含量为25%的水溶液以进行储存和出售。对于龙沙来说，氢氰酸是公司化学合成业务的重要组成部，约80%的氢氰酸产量被转化为氯化氢（cyanogen chloride）。1950年，瑞士汽巴精化（Ciba Specialty Chemicals）要求龙沙提供三聚氯氰（cyanuric chloride）用以生产添加在洗涤剂中的增白剂。为此龙沙开发了自己的专有工艺，既在420℃-450℃下将氯化氰转化为三聚氯氰，这也给龙沙掌握更多化学衍生物打下了坚实基础。包括，丙二腈（malononitrile）,氰化钠（sodium dicyanamide）以及各种氰基乙酸脂类物（cyanoacetic esters）和丙二酸（malonic acid）。丙二腈主要用于生产维生素B1（thiamine），染料和农用化学品。各种氰基乙酸脂类物被用于制药，染料，香水，特殊塑料和影像化学品。氰基乙酸脂的一种衍生物还可以制成多功能粘合剂，可以用作二次粘合剂和粘合伤口。能源发电业务方面，龙沙持续新建电站和收购其他水力发电公司，扩大发电业务。由于瑞士在二战期间保持了中立，基础工业设施完好无损，瑞士工业化快速发展进一步促进了电力的需求和电网规模的扩大。这一时期龙沙的发电能力已经难以满足需求，但由于水力发电业务投入太大，龙沙开辟了新的经营模式，即通过收购与合作，成立新的合资企业和子公司建造电站和大坝。例如，1948年收购Salanfe SA一半股份，合作修建了Salanfe水库，同期成立Aletsch AG，建成Aletsch-Mörel电站和Ackersand 二号电站；1965年与其他五家公司成立财团，共同修建了瑞士第一座火力发电站位于武夫里（Vouvry）的查瓦隆热电厂（Chavalon Thermal Power Plant），该设施在2000年最终关闭前依然是瑞士唯一的燃油发电站；1971年与铝生产商Alusuisse共同成立了Lötschen AG，三年后发电厂竣工。此外，随着龙沙向石油化工转型，能源的使用得到缓解，相比过去的碳化物生产，石油裂解设施使得龙沙菲斯普工厂节约了三分之一的能源。1974年，龙沙与Alusuisse整合，以应对70年代石油禁运所导致能源供应问题。03精细化工“Leave it to Lonza”一方面，石油危机迫使西方重新审视对中东能源的依赖，转而能耗高的从重工业向服务业和高附加值制造业转型。另一方面，战后经济繁荣促使龙沙大力拓展国际市场，将业务拓展到美国。龙沙一直以来都明白产品多样性和高附加值的重要性，面对国际上其他化学品制造商的激烈竞争，很早就开始探索将基础化学品进一步加工成具有高附加值的精细化工品。这一趋势的早期表现是龙沙美国德克萨斯州贝波特工厂的开业，这是龙沙在美国的第一家精细化工品工厂。70年代还发生了一件不起眼但对龙沙产生极大影响的事件。彼时葛兰素史克开发了一种革命性药物组胺受体（H2）阻滞剂西米替丁，可以减少胃酸分泌，有助于消化性胃溃疡的愈合，减少手术。该产品取得了巨大成功，但葛兰素史克自己的工厂难以满足需求。这时龙沙正好拥有闲置产能，可以用于该产品的早期生产。虽然这段合作并没有持续多久，但这段经历给龙沙进军精细化工提供了极大动力，也为龙沙未来的发展埋下了进军CDMO行业的韵脚。精细化工业务的挑战不仅体现在研发能力上，更在生产领域中。一方面，这些高附加值，产量相对较小的精细化工品，大部分是给单个用户提供的独家产品。这些独家产品不仅对龙沙的技术和工艺能力提出了更高要求，还需要龙沙能满足更苛刻的时间表。另一方面，这些独家产品在定价方面比普通化工品高出数倍，但需求更加不稳定。多数情况下，一种精细化工品的订单会在数年内归零。因此，无论从时间还是成本上，都不可能为其专门建立工厂。同时，这也意味着龙沙需要建立起一种模块化的多用途工厂，这些模块可以根据特定需求进行互联组和。1990年，龙沙更名为“Alusuisse-Lonza Holding AG”，并通过提前储备与灵活调用闲置产能，提出了“Leave it to Lonza”理念，帮助诸如制药公司在内的客户把精力集中在独家产品的研发与营销上，而不用发愁实际生产，减少企业负担。这也标志着龙沙合同制造业务（CMO）的开始。为此龙沙在菲斯普建立了一个全新的精细化工综合体（Fine Chemicals Complex，FCC）。1998年工程完成时，该设施已经成为一座由数个防火大厅组成的5层楼高建筑，可以容纳6个多用途工厂，并且有着一系列完整配套设施，包括一座用于生产冷却及压缩空气的厂房，加热与冷却系统，测控系统和先进废物处理系统。除此之外，龙沙还开发了“LONZADATA分析系统”，该系统可以用来测定土壤中的养分需求，以确保肥料得到最好利用，而龙沙的化肥业务也在这个时候达到了一个高峰。龙沙精细化工综合体（FCC）这一时期，龙沙不断将其基础化学和精细化工业务扩张到世界其他地区，分别在美国，英国，中国，捷克和意大利进行了重大并购，获得了生产脂肪酸，脂类，甘油，乙酰胆碱和特殊表面活性剂的工厂。能源业务方面，随着环保理念的兴起和精细化工与生物化工业务的壮大，世纪之交龙沙开始梳理其发电业务。为了满足环保要求，龙沙开始治理菲斯普电厂的废气排放，并通过回收废气作为燃料预热蒸汽厂用水，节约能源的同时还可以减少空气污染。04生命科学的世纪，转型CDMO上世纪80年代开始，生命科学与制药技术取得重要进展，由此掀起的资本狂潮不仅加快了制药行业的发展，更加剧了企业间的竞争，倒逼着参与者们不断在药物研发效率，时间和成本上进行优化。除此之外，行业的快速发展也促使政府在推出支持政策的同时，不断完善监管措施，这也使得新药研发，申报，生产逐渐成为一类高度复杂与专业化的工作。由此，当代意义的合同研发服物和药品委托生产（CRO/CMO）行业随即诞生，此后随着市场需求升级，一些具有创新能力的CMO公司开始尝试“定制研发+定制生产”模式，为客户提供更加全面的合同开发与生产服务，被称作CDMO公司。如同对能源，电化学和精细化工的敏锐嗅觉一样，龙沙对即将迎来爆发的生物技术给予了足够重视。早在1982年，龙沙就在菲斯普组织了一个8人生物技术工作小组。该小组的目标是将龙沙在精细化学和有机物方面积累的专业知识应用到生物技术领域，了解客户需求的同时通过跨学科合作，推动创新。基于在化学领域的丰富积累和化学与生物技术的协同效果，龙沙通过外部并购，内部扩产和剥离旧业务三种策略，一边纵向整合创新技术，填补空白领域，一边建设产能，横向扩大生产规模，逐步转型CDMO并确立了公司在该领域的领先地位。纵向并购通过收并购，龙沙从最初的API业务开始，逐渐向产业链上下游延伸，打造CDMO一站式服物业务模式。以下表格为龙沙的主要收并购活动：不难发现，龙沙的并购历史几乎是这一时期生物技术产业发展的缩影。80年代开始，美国迎来了生物技术产业的“黄金十年”，大量初创企业如雨后春笋般出现，随之而来的需求骤增也让从事合同外包服物的企业迎来大发展。与众不同的是，龙沙并没有参与90年代末的并购狂潮。在仔细跟踪制药公司管线后，龙沙认为一些产品很可能遭遇挫折。保守的态度使得龙沙在这一阶段坚守瑞士和美国资产，只进行了规模有限的并购，1996年，龙沙以8000万美元相对温和的对价收购了英国Celltech Biologics，获得了位于美国朴次茅斯（Portsmouth）和英国斯洛福（Slough）的两座主要设施，打入细胞培养和单抗市场。事实证明龙沙的选择十分明智，随着90年代生物技术泡沫的破灭，“闪崩”成为当时生物技术公司常态，由此引发的需求下降很快传递到下游的合同服物公司。在此背景下，龙沙不得不削减部分产能，裁员以及关闭加州工厂。此后十年，龙沙没有进行过显著的并购活动。然而，泡沫破裂无法阻止生物技术的快速发展，经历过大浪淘沙的企业和管线逐渐在新世纪迎来收获，需求重新繁荣叠加08年金融危机给初创型制药企业带来的资金压力，医药行业再次出现了新一轮并购热潮。与上一轮资本泡沫不同的是，这一轮整合受到技术发展的支撑，更多是为下一个十年的行业繁荣蓄积力量。而龙沙敏锐把握住机会，也在这一阶段开始了并购动作。一方面，龙沙通过收购产业链上游的创新企业，建立自身的技术优势。比如2006年，龙沙收购了优时比生物制造部门，获得了其液相多肽合成技术，成为首个同时拥有三种多肽合成技术（液相多肽合成，固相多肽合成与重组技术）的服物提供商。同年10月，龙沙收购Cambrex的研究用生物制品和微生物制药部门，直接收获了细胞培养业务的骨架品牌，包括Clonetics原代细胞及培养基系统，Biowhittaker培养基与内毒素检测产品和FMC天然聚合物琼脂糖电泳介质。2007年收购Amaxa，获得Nucleofection电穿孔细胞核转染技术，巩固了公司在细胞发现领域的能力。2009年，连续收购两家CRO公司Simbiosys和AlgoNomics，扩大了细胞生物学产品组合与免疫原性分析平台。2010年收购MODA Technology Partners，建立了自动化，无纸化质量控制与信息平台。同年，收购Vivante GMP Solutions，获得了其腺病毒载体，AAV载体和慢病毒载体，扩大了在病毒疫苗和基因治疗领域的服务能力。2023年龙沙收购Synaffix，通过整合该公司的有效载荷与定点偶联技术，龙沙强化了偶联技术对外许可业务。另一方面，龙沙还通过收购向产业链下游延伸。2016年，龙沙收购Capsugel获得了其独特口服给药胶囊技术。2017年收购Micro-macinazione获得了其微粉化技术。结合此前收购Capsugel，龙沙强化了满足下游制剂，剂型和包装方面的能力，填补了其向寻求外包生产制药商直接提供药品的空白。横向扩产龙沙通过收购，新建和升级现有工厂等方式，逐步在全球范围内建立起了庞大的CDMO产能。其中一些主要的基地与产能布局如下：1996年通过收购Celltech，龙沙获得了位于美国朴次茅斯（Portsmouth）和英国斯洛福（Slough）的两座主要设施，这就是日后的美国朴次茅斯基地和英国斯洛福基地，为CDMO业务打下了坚实基础。此后十年间，龙沙实施内部战略，专注于完善和升级现有资产。2000年，龙沙扩建朴茨茅斯工厂，增建了三座20000升的生物反应器并于2004年完成，耗资超2亿美元，成为当时龙沙最大的一笔投资。2006年，该设施的第四座20000升生物反应器投入使用。2018年龙沙决定增强该设施的中等规模生产能力，新建4座新一代6000升生物反应器，以满足更灵活的需求，此外该基地还扩建了多套细胞治疗产能。朴茨茅斯工厂的20000升生物反应器2007年，龙沙与基因泰克达成合作协议收购了其西班牙工厂，这就是日后龙沙西班牙波里尼奥基地，该设施拥有4座10000升生物反应器。此外，根据协议龙沙在新加坡建立一座新的工厂用以生产贝伐单抗（Avastin）原料药，该设施拥有80000升产能。2008年基因泰克行使优先选择权购买了该工厂。此后，龙沙又在新加坡建设了自己的大型哺乳动物生物制品工厂，既今天的龙沙新加坡大士基地，该基地拥有4座20000升生物反应器，2016年龙沙对该基地进行扩建，增加了4个2000升一次性生物反应器。2017年，龙沙收购了Shire位于美国加州海沃德的哺乳动物生物制造设施（于2024年关闭），该设施拥有1000升和2000升一次性生物反应器与相应的下游能力。2018年，龙沙在中国广东新建一家生物技术工厂（于2024年关闭），这是龙沙进入中国以来的第三家工厂，总投资超1亿美元，此前两家工厂分别是位于苏州的胶囊工厂和位于广州南沙的小分子与原料药工厂。2021年，龙沙宣布将投资6.5亿瑞士法郎，在菲斯普工厂扩建6个20000升生物反应器，预计在2024年完工。转型剥离随着公司业务转向精细化工和生物化学领域，龙沙的一些老旧业务被认为不再匹配公司战略。90年代末龙沙从Alusuisse-Lonza集团中分离出来并在瑞士证券交易所独立上市，完成冶金业务剥离。2001年，龙沙将能源业务（Energy Business）出售给EnBW Energie Baden-Württemberg AG，完成发电业务剥离，重命名为EnAlpin Wallis AG。2006年，龙沙以在意大利IPO的方式将其聚合物中间体部门（Polymer Intermediates Business）Lonza SpA进行剥离，公司更名为Polynt SpA。2017年，龙沙将肽业务（Peptides Business）剥离给肽制造公司PolyPeptide Laboratories。2019年，龙沙以6.3亿美元价格将水处理业务（Water Care Business）剥离给投资公司Platinum Equity，成为名为Innovation Water Care的独立公司，之后在2019年改名为Sigura。2021年，龙沙以45亿美元价格将特种原料业务（Specialty Ingredients Business，LSI）剥离给投资公司Bain Capital和Cinven，成为一家名为Arxada的独立企业。剥离前，LSI与制药、生物技术和营养品（Pharma Biotech & Nutrition）分列公司两大主要业务板块。LSI业务主要分为微生物控制解决方案（Microbial-Control Solutions）和特种化工服物（Specialty Chemical Services）两部分。根据龙沙2019年和2020年财报显示，该业务板块表现喜忧参半，其中兽医、生物安全、食品服务和个人及家庭消毒护理表现强劲，但特种化工业务持续受到地缘局势紧张、原材料供应和终端市场周期性动荡的负面影响。与当初剥离传统的冶金与能源业务类似，此次决定剥离LSI再度凸显了龙沙的与时俱进和战略聚焦。自此，龙沙完成了能源化工到制药，生物技术和营养保健的转型。而这一系列并购，投资和剥离动作也缔造了如今龙沙覆盖世界范围的CDMO业务网络。05今天的龙沙：“Enabling a Healthier World”如今，龙沙集团的目标是“打造更健康的世界（Enabling a Healthier World）”，愿景为“将任何疗法变为现实（Bring any therapy to life）”。公司拥有五大关键优先事项作为战略重点，指导业务活动和实践，包括：服物：卓越的制造和运营能力，（为客户）提供质量，价值和正确的时机。范围：在服务和模式方面，拥有无与伦比的广度。可持续性：在经济，环境和社会方面提供长久的价值。解决方案：凭借专业的科学，法规和制造知识，解决客户所面对的挑战。速度：拥有加速化商业进程的能力。龙沙在全球拥有超过18000名员，由四大核心价值观团结在一起，这些价值观定义了企业文化，指导龙沙员工如何对待彼此，如何与客户，供应商和合作伙伴开展业务：正直：有责任心，诚实和勇气，敢于发生和做正确的事。包容：支持和尊重他人并对他人负责。创新：保持专注，好奇与探究，找到最佳解决方案。倡议：自我驱动，积极进取，致力于专注与交付。为了满足客户的复杂需求，龙沙聚焦四大业务板块——生物制品（Biologics），小分子（Small Molecules），细胞与基因（Cell & Gene）和胶囊和保健原料（Capsules & Health Ingredients），拥有遍及五大洲的20多处主要基地和30多个咨询办事处，可提供的服物和产品涵盖了早期发现，定制开发与生产制造全流程阶段，以及为制药，消费健康和营养品行业提供创新剂型。凭借着公司庞大的规模和丰富资源，龙沙有能力为客户提供一站式解决方案。生物制品Biologics作为生物制药领域的领先CDMO，龙沙为客户提供从临床前开发，临床阶段研发，到上市及商业化供应的全周期服物。公司拥有完整的服物与产品组和，涵盖了各类分子形式，包括哺乳细胞和微生物表达系统，生物偶联物和mRNA制造能力。公司目前还在增强和扩大药物配方和药物产品开发与制造能力，为客户提供简化和去风险的供应链。1. 哺乳动物生物制药服物根据客户的分子需求和在时间，工艺和风险方面的不同优先安排，龙沙可以为客户提供定制计划，加速临床和上市速度。为此，龙沙打造了IbexTM Solutions一站式解决方案，该方案主要分为三个环节：Ibex® Design：为药物开发的临床前和第一阶段提供固定价格的产品包装和快速交付选项，并为临床再供应预留生产位置。Ibex® Develop：为需要生物制剂许可申请批准和营销的后期临床试验而设计。该解决方案使公司能够在短时间内建立产能以满足不断增长的需求。它还消除了技术转让的需要，并允许流程优化，同时提高运营效率。Ibex® Design和Ibex® Develop可以在开发的各个阶段实现无缝转换，切入和操作。Ibex® Dedicate：一种创新性的定制化供应解决方案，可在产品进入市场之前加速开发过程。该解决方案管理与投资相关的风险和投资决策。其灵活的运营模式为哺乳动物和微生物疫苗、细胞和基因疗法的生产提供定制解决方案。2017年龙沙投资4亿瑞士法郎在瑞士菲斯普基地建立了一座全新的生物制造综合体——Ibex® Biopark，以容纳IbexTM Solutions。基于此，龙沙可以提供各类哺乳动物细胞分子的早期设计服物，包括单克隆抗体，双特异性抗体，支架和其他重组蛋白，Fabs和Fc融合蛋白。Ibex® Design mAbsIbex® Design mAbs 是一个综合方案，集速度、内容和质量于一体，只需要11 个月即可将单克隆抗体从DNA推进到IND。如果客户需要更快获得关于产品的信息，仅需5个月即可提供毒理学研究样本。在此期间，细胞系和原料药工艺的平行开发是速度的关键。此外，该计划还为客户的临床再供应保留了位置，灵活的药物生产可以进一步减少时间成本，提高材料供应的可预测性。 Ibex® Design BispecialsIbex® Design Bispecials是一个综合方案，该方案通过优化平台，工艺和分析的工作流程，采用基于风险的跟踪方法来监测DNA到IND过程中的各项并行活动，在不增加风险的情况下减少时间成本。龙沙表示只需要13个月，该方案就可以将双抗从DNA推进到IND，如果需要更早进行毒理学研究，只需要7个月即可交付毒理学研究样本。Ibex® Design Scaffolds and other Recombinant ProteinsIbex® Design Scaffolds and other Recombinant Proteins是一个集成了原料药/药品的综合性方案，可以为支架和其他重组蛋白提供量身定制的解决方案。这类产品通常不适于为单抗产品开发的平台，而且有着影响开发策略的特定需求。龙沙在这类分子的研究中有着丰富的经验和技术，只需要10个月即可将这类分子从DNA转化为毒理学研究样本，并在15个月内推向IND。Ibex® Design Fabs and Ibex® Design Fc-Fusion Proteins诸如抗原结合片段（Fab）和Fc融合蛋白，新的分子形式变化多样，对工艺开发和生产提出了独特挑战。为了满足这类产品的需求并加速IND进程，该方案紧密集成交付各项CMC职能，并且在开发的早期阶段就启动关键项目。龙沙还会使用合适的平台工艺和可用的替代工具箱以实现对特定产品的定制化解决。只需9个月即可将分子从DNA转化为毒理学研究样本，并在14个月内获得IND。服物内容：哺乳动物细胞系开发哺乳动物工艺开发哺乳动物分析开发哺乳动物原料药制造肠胃外药物配方开发非GMP生产 Light PathTM Discovery大规模生产专有技术：GS Xceed®基因表达技术GS piggyBac®转座子技术GS Effex®细胞系GS Discovery®瞬时表达平台bYIok®双特异性配对技术2. 微生物发酵服物基于在微生物发酵方面拥有的30多年经验和BLA规划及执行的良好记录。龙沙在设计可扩展及商业上可行的工艺（临床前开发到商业化规模生产）方面拥有强大能力，并且可以根据客户需求变化调整计划，为每个项目定制解决方案。服物内容：微生物菌株开发微生物工艺开发微生物分析开发微生物原料药制造肠胃外药物配方开发非GMP生产 Light PathTM Discovery大规模生产专有技术：XS® Pichia & E. coli表达技术3. 生物偶联物服物从开发与生产角度来看ADCs和生物偶联物十分复杂。龙沙可以提供全方位的端到端解决方案，简化价值链并加快临床或商业化进程。基于此，龙沙可以提供针对各类生物偶联物的技术支持，包括ADC，AOC（抗体寡核苷酸偶联），抗体与纳米颗粒（TNP）和非细胞毒药物（肽和聚合物）偶联，双抗偶联，放射免疫偶联（单抗与螯合剂偶联），疫苗（与载体蛋白偶联的半抗原），PEGylation和cross-linking。Ibex® Design ADCIbex® Design ADC是一个集速度，质量和效率于一体的综合解决方案，可以在15个月内帮助客户通过CMC获得IND。该解决方案将龙沙在哺乳动物细胞和生物偶联方面的专业知识和高效罐装与表面处理方面的丰富经验相结合，降低了供应复杂性。服物内容：早期生物偶联物开发|ADCADC工艺开发药物分析及ADC分析开发ADC原料药制造靶向剂和载体蛋白服物4. 肠外药物产品（注射用药物产品）服物由于生物制品的复杂性不断增加和监管环境的变化，肠外药物的开发越来越具有挑战性。目前85%的药品召回是由于颗粒和无菌问题造成，而龙沙提供的开发策略和制造工艺可以防止这种情况发生。服物内容：生物制品候选物选择/配方研究药品分析开发药品配方开发药品工艺开发可提取物和可浸出物测试容器密闭完整性测试临床使用兼容性研究QC放行和稳定性研究5. mRNA/LNP产品将一款mRNA产品成功推向大规模生产需要多环节的无缝集成，包括可靠的DNA模板（DNA template），采用智能加帽技术的稳定有效的mRNA体外转录工艺，脂质纳米颗粒（LNP）的稳定封装以及后续的无菌灌装。而龙沙有能力将以上环节整合在一起，并且管理生产和供应链方面有着丰富经验。2022年9月，龙沙宣布与Touchlight达成合作协议，获得了该公司doggybone DNA（dbDNA）技术的许可。相比其传统的细菌发酵制造质粒DNA耗时，昂贵且不稳定的缺点，Touchlight的dbDNA技术是一种线性，共价闭合的DNA载体，可以编码长的，复杂的或不稳定的DNA序列（28bp），无需来自细菌的序列。该技术采用酶促制造工艺，两次层析净化除去加工酶和其他杂质，能够以前所未有的50天速度完成规模化的高纯度GMP生产。服物内容：mRNA/LNP工艺开发mRNA/LNP分析服物mRNA制造脂质纳米颗粒封装作为全球领先的CDMO公司，2023年龙沙拥有世界第二大规模的生物大分子产能约45万升。不过在2024年，龙沙宣布关闭了在美国海沃德和中国广州的基地。具体产能布局如下图与表格：小分子Small Molecules小分子代表了最大的单一药物类别，按收入计算占全球制药市场的40%以上，临床管道的一半以上。如今，小分子药物开发出现了新趋势，一方面，小型和创新公司是研发主力军，拥有84%的小分子药物管线。另一方面，过去二十年中小分子药物的合成路径增长了75%，极大提高了该类药物的复杂性。这些新趋势要求企业对复杂供应链，广泛资产和产品工艺有着深入了解，而这是大部分小型公司难以顾全的。所以选择合适的CDMO伙伴成为必要。龙沙可以提供药物原材料到产品的全面整合方案，涉及小分子产品设计，开发和制造全流程，提供原料药、颗粒工程和药物产品开发与制造等服物。这项服务通过简化流程对接，降低成本和加快时间表，为客户的药物开发流程提供助力。凭借在复杂小分子领域的深厚积累，龙沙成熟和差异化的服物可以满足客户多样化的需求，在高效活性药物成分（HPAPIs）和特殊成分处理（例如，生物偶联物的payload）方面拥有领先地位。与生物制品业务一样，在横跨欧洲、美国和中国的全球网络中，龙沙的小分子服物布局与生物制药行业的主要增长市场保持一致。1. 原料药API原料药服物高效API技术ADC有效载荷开发固体形态服物2. 颗粒工程喷雾干燥分散技术固体分散技术微粉化和喷射研磨生物利用度优化3. 药品服物口服药物产品服物吸入制剂开发服物定制药品设计服物细胞与基因Cell and Gene细胞和基因治疗（CGT）在过去几年中出现了巨大的增长，新的分子和工具不断出现，包括外泌体、诱导多能干细胞( iPSC )为基础的免疫治疗、同种异体CAR-T细胞、NK细胞和体内基因编辑。开发和制造方面的持续创新对CGT疗法的成功和商业化至关重要。在此背景下，CDMO将在商业化的道路上发挥更加重要的作用，帮助客户得到强大的质量体系、专业知识和可扩展的制造方法的支持。作为该领域领先的CDMO公司，龙沙可以提供包括工艺开发，cGMP制造，监管策略支持，质量属性检测，组织采购物流等全流程服物，涵盖了细胞和基因治疗中的多个领域，包括自体细胞，同种异体通用型细胞，病毒载体和外泌体和诱导多功能干细胞。无论在分子形式还是服物内容上，龙沙相比对手拥有更为全面服物能力。龙沙的细胞与基因业务被进一步细分为三个板块，分别为细胞与基因疗法技术，个性化药物和生物科学。1. 分子形式自体同种异体病毒载体外泌体诱导多功能干细胞2. 服物内容工艺开发cGMP制造监管服物生物测定服物3. 技术支持Cocoon®平台Nucleofector®技术TheraPEAK®产品MODA®平台内毒素和热源测试解决方案胶囊&营养保健成分Capsules & Health Ingredients2016年龙沙接连收购了营养成分公司InterHealth Nutraceuticals和创新剂型公司 Capsugel S.A. 。通过将其与龙沙的专业知识相结合，龙沙在营养品成分和胶囊封装技术方面享誉全球，可以满足产品开发周期中的各种需求，帮助客户设计，优化和生产具有差异化的各类剂型。该业务主要服务于医药和营养保健品市场。1. 胶囊“Made Better. By Science.TM”基于Capsugel®胶囊技术，龙沙提供多样的胶囊封装服物包括：在此基础上，龙沙还提供一系列相关支持服务，这些服务可以高效缩短产品开发时间，例如：快速研发胶囊产品，包括完整的研发胶囊样品库以及用于研发稳定性试验的定制胶囊快速制造提供一款名为“Build your own capsule”的颜色编辑工具来帮助定制胶囊颜色文档可立即在客户端获取专有实验室规模的设备适用于粉末和液体配方专门且可定制的胶囊旨在让研发按时按时进行专业的一线科学家对囊壳选择和兼容性、粉末混合物理化特性以及基于胶囊的干粉吸入优化进行评估专业工程师帮助将配方与设备相匹配2. 营养品成分 凭借端到端的产品，服务和全球网络，龙沙可以为营养保健品客户提供从剂型开发到市场研究的全面服务。龙沙的技术可以从提高生物利用度，靶向递送，吞咽性，味道，气味遮蔽，外观，干净配料表，胶囊及封装等方面帮助客户创造独特的解决方案。龙沙主要通过营养胶囊，保健成分和市场调研来实现上述承诺。胶囊服务保健成分市场服务龙沙的胶囊及营养保健品业务为超过2000家客户提供服务，加之专业的第三方市场及消费者研究，龙沙可以提供丰富的市场见解和想法，支持营养品创新开发。市场服务内容包括，市场趋势调研，消费者研究，定制化调查，产品概念品牌推荐及本地化监管。06结 束 语根据2023年公司年报（Annual Report）统计的十年关键指标来看，龙沙经历了长足发展，在此期间内，虽然陆续剥离了水处理和特种原料业务，但公司在销售额和员工规模上几乎实现翻翻，而在利润方面更是翻了近3倍。这一趋势也正好反映了近十年来CXO行业的兴起与发展。龙沙作为该领域内的龙头企业之一，十分具有代表性。如今，药品生命周期和产业链各环节已经高度专业化和复杂化，CXO发展趋势持续看好。短期来看，随着大流行影响褪去，日渐紧张的地缘政治，全球生物制药行业从顶峰下滑，投融资活动冷却，导致的许多企业不得不重新审视产品管线，降本求活。制药企业紧缩的局面很快传导到下游CXO。2023年龙沙全年表现强劲，销售额达67亿瑞士法郎，按CER/AER(固定/实际汇率)计算同比增长10.9%/7.9%，税息折旧及摊销前利润（EBITDA）为20亿瑞士法郎，利润率29.8%。稳健的财务表现主要受生物制品和小分子业务部推动，而细胞与基因及胶囊&营养品保健成分部门表现疲软。包括龙沙在内，CDMO巨头们这两年一边关厂一边收购新厂，体现了复杂国际形式下，制药行业全球供应链深度重构。2024年，龙沙开始梳理产能，陆续终止了美国海沃德和中国广州两处基地。但也宣布将收购罗氏位于美国加利福尼亚州瓦卡维尔（Vacaville）的大规模生物制药工厂，交易总额达12亿美元。龙沙董事会主席兼临时CEO Albert M. Baehny在年报开头的致信中写道：“无论对世界还是对龙沙来说，2023年都是充满挑战和变化的一年。我们目睹了高利率、持续通胀、供应链中断、乌克兰与中东战争、地缘政治紧张局势加剧和气候变化的持续挑战。然而，企业投资依然稳固，利用创新和技术应对未来挑战......展望未来，我们看到医疗和保健行业的巨大潜力，市场增长强劲，新药渠道丰富，不断出现的新的分子和新的给药方法。”参考来源：1. Lonza.com2. 100 years of progress with Lonza3. https://www.lonza.com/about-us/our-history4. https://en.wikipedia.org/wiki/Lonza_Group本周好文推荐如需转载请联系佰傲谷并在醒目位置注明出处········