Aura Biosciences Reports Fourth Quarter and Full Year 2023 Financial Results and Business Highlights

On March 27, 2024 Aura Biosciences, Inc. (NASDAQ: AURA), a clinical-stage biotechnology company developing precision immunotherapies to treat solid tumors to preserve the function of the afflicted organ with cancer, reported financial results for the fourth quarter and year ended December 31, 2023, and provided recent business highlights (Press release, Aura Biosciences, MAR 27, 2024, View Source [SID1234641485]).

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"We’re excited to expand bel-sar into bladder cancer, as we leverage our therapy‘s unique mechanism of action in additional solid cancer indications with major unmet medical need," said Elisabet de los Pinos, Ph.D., CEO of Aura Biosciences. "Bel-sar is a potential vision-and-organ sparing therapy that we believe will change the standard of care in ocular oncology, in particular choroidal melanoma, where there are no treatment options except radiotherapy which leads to vision loss, or surgical removal of the eye. There is an urgent need to develop vision-sparing therapies, as all eye cancers represent an estimated 60,000 patients annually in the US and EU. This is a multi-billion dollar market, which includes choroidal melanoma, choroidal metastases, and ocular surface cancers. Our financial strength allows us to fund multiple clinical programs through major inflection points while enabling the flexibility to expand bel-sar into additional indications, starting with bladder cancer."

Recent Pipeline Developments

Global Phase 3 CoMpass trial actively enrolling patients for the treatment of small choroidal melanoma (CM) and indeterminate lesions (ILs).


The trial is a superiority trial comparing treatment with bel-sar versus a sham control arm. The trial is a global Phase 3, randomized, multi-center, masked study, and is intended to enroll approximately 100 patients randomized 2:1:2 to receive three cycles of treatment with either high or low doses of bel-sar, or a sham control.


The Company received written agreement from the U.S. Food and Drug Administration (FDA) under an SPA for the overall design, statistical analysis plan and clinical endpoints. The primary endpoint is time to tumor progression when the last patient completes 15 months of follow up.


The trial is actively enrolling in the U.S. with a strong endorsement from the ocular oncology community. The Company is on track to activate sites and enroll patients globally throughout 2024.

Positive Phase 2 data evaluating SC administration of bel-sar for patients with small CM and ILs was presented at the American Academy of Ophthalmology (AAO) 2023 Annual Meeting.

Results:


Patients who received the therapeutic regimen with three cycles of therapy showed a tumor control rate of 80% (8/10) and a visual acuity preservation rate of 90% (9/10), with most of the patients (>90%) being at 12 months of follow up. Final study results with all patients at 12 months will be presented by year end 2024.


The overall tolerability profile of bel-sar was favorable, with no dose-limiting toxicities, treatment-related serious adverse events (SAEs) or significant adverse events (AEs) reported as of August 3, 2023. There was no posterior segment inflammation and only mild anterior inflammation (Grade 1) in approximately 18% of the patients which was self-limited or resolved with a short course of topical steroids. Treatment-related AEs were predominantly mild and resolved without sequelae.


These patients match the criteria for enrollment in the ongoing Phase 3 trial which is highly powered based on the Phase 2 results.

Bel-sar is being evaluated in additional ocular oncology indications with a collective incidence of approximately 60,000 patients/year in the US/EU per year. The Company’s plan is to initiate clinical development in choroidal metastasis (Cmets), an indication with a high unmet medical need where bel-sar has the potential to be the first approved therapy that is vision and organ sparing. Cmets is the second potential ocular oncology indication for bel-sar affecting over 20,000 patients in the US/EU annually. The Company is on track to initiate a Phase 2 trial in 2024.

The Phase 1 trial of bel-sar for the treatment of non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) is currently ongoing, and the Company expects to report data in mid-2024. This represents an area of high unmet need with approximately 80,000 patients diagnosed in the U.S. every year where we have the possibility to selectively treat and induce a tissue and tumor specific immune response to prevent progression and recurrence of the disease. The Company received Fast Track Designation from the Oncology Division of the FDA for NMIBC in June 2022.


The ongoing Phase 1 multi-center, open-label clinical trial is expected to enroll approximately 21 adult patients. The trial is designed to assess the safety and tolerability of bel-sar as a single agent. The trial will provide histopathological evaluation after the local treatment to assess bel-sar’s biological activity which will include the evaluation of focal necrosis and immune activation.


The trial has completed enrollment of the cohort that received bel-sar injection without light activation. Protocol mandated safety review found no safety issues and the study has proceeded to the bel-sar injection plus light activation cohorts.


Preliminary data from the first patient in the light activated cohort of the trial, demonstrated a clinical complete response demonstrated by absence of cancer cells on histopathology with evidence of extensive necrosis and immune activation after a single administration of bel-sar followed by light activation.

Recent Corporate Events


Raised Gross Proceeds of $99.0 million in an underwritten public offering. In November 2023, the Company announced the pricing of an underwritten public offering of 11,000,000 shares of its common stock at a price to the public of $9.00 per share. The offering closed on November 9, 2023.

Full Year and Fourth Quarter 2023 Financial Results


As of December 31, 2023, Aura had cash and cash equivalents and marketable securities totaling $226.2 million. The Company believes its current cash and cash equivalents and marketable securities are sufficient to fund its operations into the second half of 2026.


Research and development expenses increased to $20.3 million and $65.2 million for the three months and full year ended December 31, 2023, respectively, from $13.2 million and $42.2 million for the three months and full year ended December 31, 2022, respectively, primarily due to ongoing clinical costs associated with the progression of the Phase 2 study and contract research organization costs associated with the start of the Phase 3 global trial, and manufacturing and development costs for bel-sar.


General and administrative expenses increased to $4.5 million and $19.8 million for the three months and full year ended December 31, 2023, respectively, from $4.5 million and $18.1 million for the three months and full year ended December 31, 2022, respectively. General and administrative expenses include $1.2 million and $1.1 million of stock-based compensation for the three months ended December 31, 2023 and 2022, respectively. The increase was primarily driven by personnel expenses, as well as increases in travel expenses related to growth of the Company.


Net loss for the three months and full year ended December 31, 2023, was $22.1 million and $76.4 million, respectively, compared to $16.6 million and $58.8 million for the three months and full year ended December 31, 2022, respectively.

WuXi Biologics Reports Solid 2023 Annual Results

On March 26, 2024 WuXi Biologics, a leading global Contract Research, Development and Manufacturing Organization (CRDMO) service company offering end-to-end solutions for biologics discovery, development and manufacturing, reported its audited annual results for the year ended December 31, 2023 ("Reporting Period") (Press release, WuXi Biologics, MAR 26, 2024, View Source [SID1234644722]).

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2023 Financial Highlights

Revenue: The Group’s revenue increased to RMB17,034.3 million with an increase of 11.6% y-o-y. The increase was primarily attributed to: (i) the successful execution of the Group’s "Follow and Win the Molecule" strategies, coupled with the leading technology platform, best-in-industry timeline and excellent execution track record, contributing to the growth of the Group’s revenue; (ii) enlarged spectrum of services offered to the biologics industry, fast-growing technology platforms including ADCs and bispecific antibodies, contributing to the Group’s revenue stream; (iii) the growth of research services revenue generated from the Group’s various cutting-edge technologies; and (iv) the utilization of existing and newly expanded capacities, including ramp-up of the manufacturing sites in Europe and the U.S..

Gross Profit and Gross Profit Margin: The Group’s gross profit increased by 1.5% to RMB6,827.9 million, with a gross profit margin of 40.1%. The decrease of gross profit margin was mainly due to the expected ramp-up impact of new manufacturing facilities in Ireland, Germany, and the U.S., which was partially offset by the efficiency achieved from WBS and other continuous improvement initiatives.

Net Profit & Net Profit Attributable to Owners of the Company: Net profit and net profit attributable to owners of the Company for the Reporting Period amounted to RMB3,570.6 million and RMB3,399.7 million respectively, representing a 21.5% and 23.1% decrease compared to the same period last year. The decreases were mainly due to: (i) a decrease in gross profit margin due to the ramp-up impacts; (ii) a decrease in investment gains and losses due to the downturn in the capital market; (iii) a decrease in foreign exchange gains; (iv) increases in selling and marketing expenses, administration expenses and R&D expenses; and (v) the listing expenses associated with the separate listing of WuXi XDC.

Adjusted Net Profit: Excluding non-recurring investment gains and losses, foreign exchange impact, share-based compensation, and the WuXi XDC listing expenses, the Adjusted Net Profit for the period decreased by 2.0% y-o-y to RMB4,950.4 million. Margin of adjusted net profit was 29.1%.

Basic Earnings Per Share (EPS): Basic EPS and adjusted basic EPS were RMB0.82 and RMB1.13, respectively.

In 2023, the Group’s Free Cash Flow reached RMB0.6 billion, solidifying a strong financial foundation to support the Group’s ongoing capacity enhancement, globalization efforts, and continuous investment in cutting-edge technologies.

2023 Business Highlights

Amid a challenging macroeconomic environment post COVID-19, the Group maintained its stable growth trajectory, underpinned by its unique CRDMO business model and the successful execution of its "Follow and Win the Molecule" strategies.

The total number of integrated projects rose to a new height of 698 with 132 new integrated projects added to the pipeline, setting a historic record for non-COVID project additions within a fiscal year. 51 late-phase projects and 24 commercial manufacturing projects provided a solid foundation for the Group’s continued revenue growth.

The "Win-the-Molecule" strategy further propelled the growth of the project pipeline by contributing 18 external projects, including a record high of 9 late-phase and commercial manufacturing projects, which will boost near-term revenue growth and elevate long-term growth prospects.

As of Dec 31, 2023, the Group’s total backlog, which includes Services and Milestones, reached US$20,592 million. Of this total, Services accounted for US$13,398 million and Milestones contributed US$7,194 million, ensuring sustainable growth in both the short and long term.

Bolstered by a robust non-COVID pipeline, the Group’s non-COVID business maintained strong growth momentum with a notable 37.7% y-o-y revenue increase, reinforcing the Group’s outlook for sustained long-term growth.

Late-phase and commercial manufacturing revenue increased to RMB7,731.5 million, accounting for 45.4% of the total revenue in 2023, driven by the accelerated momentum of the Group’s late-stage and commercial manufacturing businesses. Excluding COVID-19 projects, revenue from late-phase and commercial manufacturing grew substantially by 101.7% y-o-y, showcasing the Group’s continued growth momentum in the post-COVID era.

Leveraging industry-leading technology platforms, the Group’s research business has flourished, establishing numerous drug discovery collaborations with a wide range of clients. Notable examples include a research service agreement with GSK plc (LSE/NYSE: GSK) for multiple novel bi- & multi-specific TCEs antibodies, and a research service agreement with BioNTech SE (NASDAQ: BNTX) for the discovery of investigational monoclonal antibodies (mAbs). These partnerships underscore the Group’s strong research capabilities – the "R" in its CRDMO business model.

The Group is devoted to providing a full range of CRDMO services through its industry-leading and globally accessible proprietary technology platforms. By the end of 2023, the Group boasted a diverse portfolio with 114 bispecific projects, including 45 WuXiBodyTM projects, 143 ADC projects, and 25 vaccine projects on its integrated platforms. These advanced platforms not only underpin the Group’s integrated CRDMO business model but are also pivotal in driving the Group’s ongoing growth.

To address burgeoning capacity demands and fulfill its "Global Dual Sourcing" strategy, the Group is enhancing its global footprint through capacity increases in Ireland, Germany, the U.S., and Singapore. With diversified manufacturing facilities in China, the U.S., Ireland, Germany, and Singapore, the Group offers a versatile and robust global supply chain network, ensuring it can meet the needs of its clients and partners around the world.

To maximize its business potential, the Group’s subsidiary, WuXi XDC Cayman Inc., a leading global CRDMO focused on ADC and the broader bioconjugate market, was listed on the Main Board of the Hong Kong Stock Exchange on November 17, 2023 (stock code: 2268.HK), embarking on a new chapter of growth and opportunity.

Excluding COVID-19 projects, the combined revenue from the North American and European markets grew strongly by 52.5% y-o-y. Furthermore, non-COVID revenue from Europe saw a significant surge of 172.4%, fueled by ongoing business momentum and enhanced global outreach.

The Group has consistently advanced its WBS initiatives, implementing over 370 WBS projects in 2023 and achieving cost savings exceeding RMB245 million across materials, capital expenditure, and operating expenses. Moreover, these initiatives have resulted in a significant reduction in inventory, equivalent to RMB270 million. The Group is committed to further developing WBS as a management system to drive continuous improvement and create value for its clients and partners.

The Group continues to adhere to the highest quality standards, and has completed 33 regulatory inspections conducted by the U.S. FDA, EU EMA, China NMPA and other global regulatory agencies since 2017.

As of Dec 31, 2023, the Group’s total staff reached 12,740, with a top-tier biologics development team of 4,432 scientists. The Group’s international hiring has been fruitful. Talent retention has remained robust, with a key talent retention rate of approximately 97%, surpassing the industry average.

The Group has incorporated Environmental, Social and Governance (ESG) as an essential part of its sustainable business growth strategies. The Group’s ESG performance has been evaluated by major ESG rating agencies and institutional investors, resulting in recognitions that include: listing on the Dow Jones SustainabilityTM World Index and Emerging Markets Index; an MSCI AAA Rating; the EcoVadis Platinum Medal; ranking as a Sustainalytics Industry and Regional Top-Rated Company; and scoring a CDP "A" rating for water security and "A-" for climate change.

Amidst an increasingly dynamic macroeconomic environment in 2023, the Group maintained its growth momentum supported by strong execution, advanced technologies, flexible manufacturing capacities, a premier quality system, and a persistent pursuit of operational excellence. Adhering to its "Follow and Win the Molecule" strategies and capitalizing on its distinctive CRDMO business model, the Group will continue to build momentum around its long-term growth and accelerate the empowerment of global partners for the benefit of patients worldwide.

Solid Business Performance Sustained Despite Macroeconomic Uncertainties

Throughout 2023, the Group adeptly navigated the global biopharmaceutical industry’s evolving dynamics and maintained strong business momentum by executing its "Follow and Win the Molecule" strategies and leveraging its unique CRDMO business model. The Group added 132 new integrated projects, reaching an all-time high (excluding COVID-19 projects) since its inception, which brought the total number of integrated projects to 698. In addition, 51 late-phase projects and 24 commercial manufacturing projects laid a solid foundation for the Group’s enduring revenue growth.

The Group’s revenue exceeded RMB17.0 billion in 2023, marking a 11.6% increase from 2022. This growth was propelled by a robust non-COVID pipeline, which resulted in a 37.7% y-o-y increase in non-COVID revenue. The booming development of the non-COVID business more than offset the sales decline in the COVID sector.

As of Dec 31, 2023, total backlog, service backlog and milestone backlog reached US$20,592 million, US$13,398 million and US$7,194 million respectively, providing high visibility of the Group’s sustainable growth. Backlog within three years increased to US$3,850 million, reinforcing stable short-term growth.

Even with the strong backlog and a record number of projects, the Group is still able to start any new project within four weeks, supported by its strong capabilities and ample capacity.

Late-Phase and Commercial Manufacturing Projects Drive Future Growth

With the execution of its proven "Follow and Win the Molecule" strategies, the Group accelerated business momentum in late-stage and commercial manufacturing projects. By the end of the Reporting Period, the number of late-phase and commercial manufacturing projects had increased to 51 and 24 respectively. Late-phase and commercial manufacturing revenue increased by 12.8% y-o-y to RMB7,731.5 million, accounting for 45.4% of the total revenue in 2023. Excluding COVID-19 projects, late-phase and commercial manufacturing revenue saw a remarkable 101.7% y-o-y increase, indicating strong future growth potential.

During the Reporting Period, one of the Group’s strategic partners, Amicus Therapeutics, Inc. (NASDAQ: FOLD), received the U.S. FDA, the U.K. MHRA and the European Commission’s approval for PombilitiTM, a long-term enzyme replacement therapy used in combination with miglustat therapy for adults with late-onset Pompe disease. PombilitiTM was initiated within the Group in 2012, starting from a mere concept and has since achieved commercialization. This success was made possible through the Group’s proprietary integrated technology platform and extensive manufacturing capabilities. Such an achievement truly attests to the effectiveness of the Group’s long-standing "Follow the Molecule" strategy, which turns concepts into commercialized biologics therapeutics.

Leveraging its track record of reliable execution, swift timelines and cutting-edge technology, the Group has forged an outstanding reputation for its capabilities and scale in commercial manufacturing, garnering widespread recognition from global customers. During the Reporting Period, the Group’s "Win-the-Molecule" strategy continued to accelerate pipeline expansion by adding 18 external projects, including a record-breaking 9 late-phase and commercial manufacturing projects. This strategy will continue to spur the rise of late-phase and commercial revenues and contribute to the Group’s long-term growth.

CRDMO Platform – Research (R):
Thriving Research Business Achieved Remarkable Success

The Group continuously focuses on enhancing its capabilities in innovative biologics generation and optimization, as well as enriching and optimizing its existing technological platforms. These efforts are integral to its CRDMO business model and have fostered the prosperous development of its research business.

In addition to the partnership with GSK plc (LSE/NYSE: GSK), the Group’s research capability was further showcased through a research service agreement with BioNTech SE (NASDAQ: BNTX), where the Group used its proprietary antibody discovery platforms to discover two undisclosed targets for BioNTech’s preclinical investigational monoclonal antibodies. In return, the Group received a US$20 million upfront payment from BioNTech for exclusive rights to these antibodies, and will receive potential additional payments for research, development, regulatory, and commercial milestones, plus tiered royalties.

During the Reporting Period, the Group also opened its Boston Research Service Center in the United States. The facility is the Group’s third research service center globally and the first in the U.S. to offer discovery services to clients of all sizes, complementing the full range of services the Group offers within the U.S. and around the world.

CRDMO Platform – Development (D):
New Premier Technology Platform Launched to Boost Development Strength

With the goal of enabling its global partners to bring more high-quality and affordable biologics to patients worldwide, the Group’s industry-leading biologics development team strives for innovation with the mission of "Turning Ideas into Life-Improving Biologics and Vaccines". During the Reporting Period, the Group enabled 110 INDs and provided research and development services for over 670 different molecules.

As part of its drive to foster innovation, the Group launched a new advanced technology platform during the Reporting Period — WuXiUITM, a novel proprietary bioprocessing platform that significantly boosts productivity and quality for various cell lines and product modalities. This ultra-intensified fed-batch solution aims to revolutionize upstream processing by enhancing productivity by 3-6 times and reducing manufacturing costs substantially compared to traditional processes. WuXiUITM offers exceptional flexibility and competitiveness in meeting different commercial market supply and manufacturing needs. The Group’s continual launch of new technology platforms empowers its clients to embrace the wave of next-generation innovative drugs, while achieving a balance of quality, speed, and cost.

CRDMO Platform – Manufacturing (M):
Expanding Capacities to Strengthen Manufacturing Capabilities

To accommodate the ever-changing needs of its worldwide customers, the Group is continuously enhancing its "Global Dual Sourcing" strategy and increasing its global capacity to ensure supply chain resilience.

During the Reporting Period, the Group’s manufacturing facility in Dundalk, Ireland, received the 2023 Facility of the Year Award ("FOYA") in the Operations category from the International Society for Pharmaceutical Engineering ("ISPE"). The Ireland facility has been ramping up rapidly and efficiently since its GMP release in Q4 2022, supported by substantial commercial manufacturing demand from global clients.

The Group plans to enhance its manufacturing presence in Germany, installing a new drug product fill-and-finish line at its Leverkusen site and doubling the Wuppertal site’s capacity from 12,000L to 24,000L. These enhancements, along with the drug product facility in Leverkusen, will boost the Group’s clinical and commercial manufacturing capacities in Europe.

In response to rising contract manufacturing demand, the Group will also increase its Worcester, Massachusetts facility’s capacity to 36,000L, up from the initially planned 24,000L. With the Worcester facility’s commencement, the Group will be well positioned to provide full-spectrum integrated services in the U.S., encompassing biologics discovery, development, and both clinical and commercial manufacturing.

The Group’s Singapore CRDMO Center Project is also gaining momentum. In coordination with local authorities, land acquisition has been completed and the Group is making progress with various applications. Groundbreaking has recently taken place and the design and construction of the site are progressing as planned. Furthermore, the Group has entered into a strategic partnership with Pharmadule Morimatsu to provide modular facilities for two production facilities at the Singapore site.

With these developments, the Group reinforces its global presence in China, the U.S., Ireland, Germany, and Singapore, enabling it to offer enhanced service to its global customers with greater proximity and agility.

Microbial and New Modalities to Be Next Growth Engines

The Group has strategically leveraged its capabilities and capacity to establish integrated platforms for various new modalities. These platforms have seen rapid success and expansion, significantly broadening the Group’s service spectrum, and emerging as key drivers for future growth.

With its extensive antibody development knowledge and skilled scientific team, the Group had accumulated 114 bispecific projects with different formats by the end of the Reporting Period. The Group’s proprietary bispecific antibody platform, WuXiBodyTM, known for its flexibility and capability to combine almost any mAb pair, continued to earn global recognition, with rights to 45 projects granted to external partners. WuXi XDC achieved remarkable progress as well, securing 143 integrated projects for ADCs and other bioconjugates globally, with 21 in phase II/III, which further reinforced its leading position in the global ADC and broader bioconjugates outsourcing services market. During the Reporting Period, WuXi Vaccines also experienced consistent growth and prosperity, with the number of projects increasing to 59, including 25 integrated projects. This underscores its superior technical and quality strengths, CMC, and regulatory capabilities, alongside its growing reputation in the industry.

Additionally, the Group has established comprehensive capabilities to provide end-to-end services for next-generation biological products that are based on microbial fermentation technologies. The incorporation of the use of microbial expression systems such as E. coli and yeast into the Group’s integrated technology platforms allows faster, more efficient and cost-effective production across multiple modalities, including enzymes, antibody fragments, recombinant proteins, and virus-like particles (VLP).

Successful Listing of WuXi XDC on the Hong Kong Stock Exchange

In July 2023, the Group announced the spin-off and separate Hong Kong Stock Exchange listing of its subsidiary, WuXi XDC Cayman Inc., which was successfully listed on the Main Board of HKEX on November 17, 2023, under the stock code 2268.HK. WuXi XDC remains a subsidiary of the Group, ensuring full consolidation. The separate listing allows WuXi XDC to develop as a unique global leading CRDMO, focusing initially on ADCs and expanding to all bioconjugates, and bring a more defined business focus and strategy to support the growth of the Group. This, in turn, will lead to a more organized and efficient allocation of capital and resources for the Group as a whole, and benefit the Group through continued consolidation of financials, as well as improved governance, market communication, and operational and financial transparency, thereby creating value for the Group and its shareholders.

World-Class Quality System Underpins Future Growth

The Group remains dedicated to meeting the highest industry quality standards. With its world-class quality system, the Group has completed 33 regulatory inspections conducted by the U.S. FDA, EU EMA, China NMPA, and other global regulatory agencies since 2017 with no critical issues identified and zero data integrity findings, which distinguishes the Group as the first and only biologics company certified by these regulatory agencies for commercial manufacturing in China. The Group has completed more than 1,200 GMP audits by global clients, and more than 120 audits by EU Qualified Persons. These audits and certifications demonstrate to clients that the Group’s quality system adheres to global standards, ensuring the provision of the highest quality biologics to patients worldwide.

Seasoned Talent Team

The Group emphasizes workforce development, implementing a strategic human resources strategy to attract, train, and retain global talent. As of Dec 31, 2023, the Group’s total employee count had reached 12,740, including a top-tier biologics development team with 4,432 scientists. The Group’s global recruitment efforts have successfully enhanced its operations and competencies at all of its facilities, enabling the Group to maintain a solid growth trajectory and efficiently meet its project commitments. Furthermore, the Group’s talent retention remained strong, with a key talent retention rate of approximately 97%, which is markedly higher than the average in the sector.

ESG as a Long-Term Business Strategy

The Group regards sustainability as the cornerstone of its business development strategy, aligning it with its vision and mission to drive long-term success. It embraces social, environmental and governance responsibilities, actively working to maintain a strong ESG performance for the benefit of all stakeholders and the broader good of society. During the Reporting Period, the Group’s ESG targets and metrics were prioritized and monitored in the focus areas, including Diversity, Equity and Inclusion ("DEI"), climate change and energy saving, and resource efficiency.

Also during the Reporting Period, the Group committed to the Science-Based Targets initiative ("SBTi"), established a dedicated DEI Committee, and became a signatory to the United Nations Global Compact. With its many ESG initiatives and achievements, the Group has received recognition from various major ESG rating agencies and institutional investors, including: a listing on the Dow Jones SustainabilityTM World Index and Emerging Markets Index; an MSCI AAA Rating; the EcoVadis Platinum Medal; ranking as a Sustainalytics Industry and Regional Top-Rated Company; and scoring a CDP "A" rating for water security and "A-" for climate change.

Management Comment

Dr. Chris Chen, CEO of WuXi Biologics, said, "Despite challenges from an uncertain macroenvironment, our unique CRDMO business model and the successful implementation of ‘Follow and Win the Molecule’ strategies led to new opportunities and stable growth in 2023. With a notable recovery in the second half, 132 new integrated projects were added during the year, including a record increase in non-COVID projects. The total number of integrated projects grew to 698, featuring 51 in late-phase and 24 in commercial manufacturing, underscoring our continued strong growth momentum. The ‘Win-the-Molecule’ strategy introduced 18 external projects, including a record 9 late-phase and commercial manufacturing projects, reflecting increased recognition from global customers. Powered by a robust pipeline, the non-COVID sector remained a pivotal growth driver, with overall non-COVID revenue increasing by 37.7% y-o-y and revenue from non-COVID late-phase and commercial manufacturing surging by 101.7% y-o-y. With active business development and enhanced global presence, non-COVID revenue from North America and Europe witnessed a rapid 52.5% y-o-y growth, fueled by deeper collaboration and strong industry trust."

Dr. Chris Chen added, "In 2023, we achieved positive advancements across our Research, Development, and Manufacturing segments. In Research, we secured service agreements with GSK and BioNTech, demonstrating the capabilities of our integrated discovery platforms in enabling global partners to develop new modalities. In Development, we facilitated 110 INDs for global clients, and launched new technology platforms such as WuXiUITM and WuXiHighTM. We will continue to invest in cutting-edge technologies and enhance our R&D capabilities to maintain our position at the technological forefront, ensuring the delivery of high-quality results to our customers. In Manufacturing, with 24 ongoing projects and an expected rise in commercial projects and potential blockbusters, we anticipate a bright future for growth. To support this accelerated momentum, we have furthered our ‘Global Dual Sourcing’ strategy and increased global capacity with solid free cash flow, laying the groundwork for a comprehensive global biomanufacturing network with major operations in China, the U.S., Ireland, Germany, and Singapore.

In the face of uncertainties, we are dedicated to finding certainty and stability through our strategic initiatives. Looking ahead to 2024, we are committed to serving and contributing to the global healthcare community, adhering to the highest standards of compliance and the legal requirements of all jurisdictions where we operate. In our pursuit to deepen trust with our customers and enhance collaboration, we will continue to improve operational efficiency through additional WBS efforts, while steadfastly upholding global ESG and quality standards. Our ongoing investments in capabilities, capacity, and innovative technology platforms will drive the acceleration and transformation of biologics discovery, development, and manufacturing processes worldwide, benefiting global partners and patients alike."

Dr. Ge Li, Chairman of WuXi Biologics, concluded, "WuXi Biologics continued to achieve consistent and steady business growth, driven by our distinctive CRDMO business model and a steadfast commitment to meeting our customers’ needs. Looking ahead, we will adhere to our end-to-end CRDMO model, further improve our execution capabilities, enhance our global footprint, and strive for operational excellence, all while maintaining a customer-centric approach. We remain dedicated to delivering groundbreaking therapies to patients and fulfilling our vision that ‘every drug can be made and every disease can be treated’."

Key Financial Ratios
(For the Twelve Months Ended Dec 31)

Key Financial Ratio

2023

2022

Change

Revenue (In RMB million)

17,034.3

15,268.7

11.6%

Gross Profit (In RMB million)

6,827.9

6,724.0

1.5%

Margin (%)

40.1%

44.0%

Net Profit (In RMB million)

3,570.6

4,549.9

(21.5%)

Margin (%)

21.0%

29.8%

Net Profit Attributable to Owners of the Company (In RMB million)

Margin (%)

3,399.7

20.0%

4,420.3

29.0%

(23.1%)

Adjusted Net Profit (In RMB million)

4,950.4

5,053.9

(2.0%)

Margin (%)

29.1%

33.1%

EBITDA (In RMB million)

5,613.2

6,353.4

(11.7%)

Margin (%)

33.0%

41.6%

Adjusted EBITDA (In RMB million)

6,993.0

6,857.4

2.0%

Margin (%)

41.1%

44.9%

Adjusted Basic EPS (In RMB)

1.13

1.18

(4.2%)

Entry into a Material Definitive Agreement

On March 26, 2024 (the "Closing Date"), Castle Biosciences, Inc., a Delaware corporation (the "Company"), entered into a Loan and Security Agreement (the "Loan Agreement"), by and between the Company, its wholly owned subsidiary, Castle Narnia Real Estate Holding 1, LLC ("Narnia") and Silicon Valley Bank, a division of First-Citizens Bank & Trust Company (the "Lender") (Filing, Castle Biosciences, MAR 26, 2024, View Source [SID1234641487]). The Loan Agreement provides for (i) on the Closing Date, $10.0 million aggregate principal amount of term loans, and (ii) from the Closing Date until March 31, 2025, an additional $25.0 million term loan facility available at the Company’s option (collectively, the "Term Loans"). The Company drew $10.0 million in Term Loans on the Closing Date. The Company expects to use the proceeds from the Term Loans for the purpose of developing a commercial office building to be used as the Company’s future corporate headquarters, and the remainder for working capital and other general corporate purposes.

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The obligations under the Loan Agreement are secured by a perfected security interest in substantially all of the Company’s and Narnia’s assets except for intellectual property, the real property held by Narnia and certain other customary excluded property pursuant to the terms of the Loan Agreement.

The interest rate applicable to the Term Loans is the greater of (a) the WSJ Prime Rate plus 0.25% or (b) 6.00% per annum. The Term Loans are interest only from the Closing Date through November 30, 2025, which may be extended at the Company’s option through November 30, 2026 as long as no event of default under the Loan Agreement has occurred. After the end of the interest only period, the Company is required to pay equal monthly installments of principal through November 1, 2028, the maturity date.

The Term Loans may be prepaid in full through the first anniversary of the Closing Date with payment of a 1.50% prepayment premium, after which they may be prepaid in full through the second anniversary of the Closing Date with payment of a 1.00% prepayment premium, after which they may be prepaid in full with no prepayment premium. An additional final payment of 2.00% of the amount of Terms Loans advanced by the Lender will be due upon prepayment or repayment of the Term Loans in full.

The Loan Agreement contains customary representations and warranties and customary affirmative and negative covenants, including, among other things, restrictions on indebtedness, liens, investments, mergers, dispositions, prepayment of other indebtedness and dividends and other distributions. The Company must also comply with a financial covenant which requires that the Company maintain either a minimum liquidity ratio or minimum EBITDA as more fully described in the Loan Agreement.

The Loan Agreement also includes customary events of default, including failure to pay principal, interest or certain other amounts when due, material inaccuracy of representations and warranties, violation of covenants, specified cross-default and cross-acceleration to other material indebtedness, certain bankruptcy and insolvency events, certain undischarged judgments, material invalidity of guarantees or grant of security interest, material adverse change, involuntary delisting from the Nasdaq Global Market and change of control, in certain cases subject to certain thresholds and grace periods. If one or more events of default occurs and continues beyond any applicable cure period, the Lender may terminate the commitments to make further loans and declare all of the obligations of the Company under the Loan Agreement to be immediately due and payable.

The foregoing description of the Loan Agreement is not intended to be complete and is qualified in its entirety by reference to the Loan Agreement, a copy of which is attached hereto as Exhibit 10.1 and incorporated herein by reference.

UPDATE ON AMPLIA’S ACCENT TRIAL IN PANCREATIC CANCER

On March 26, 2024 Amplia Therapeutics Limited (ASX: ATX), ("Amplia" or the "Company"), reported an update on its Phase 1b/2a trial (the ACCENT trial) of narmafotinib in combination with standard-of-care chemotherapy gemcitabine and Abraxane in first-line patients with advanced pancreatic cancer (Press release, Amplia Therapeutics, MAR 26, 2024, View Source [SID1234641474]). Narmafotinib is the company’s best-in-class inhibitor of the protein FAK, a drug target gaining increasing attention in the treatment of solid tumours.

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Completion of the Phase 1b stage of the trial was announced in November 2023.

• Fourteen (14) patients were dosed over three dose levels,
• A safe and well-tolerated dose of 400 mg narmafotinib once-a-day was identified that provided the drug levels to significantly inhibit FAK.
• Of these fourteen patients seven (7) patients remained on trial for >6 months, with two (2) patients being on trial for more than 10 months. By contrast, the median progression free survival for advanced pancreatic cancer patients treated with gemcitabine and Abraxane alone is 5.5 months.
• Six (6) patients have now recorded a partial response as best response, with the remaining eight (8) recording stable disease.
• These response rates are substantially higher than predicted from historical studies of gemcitabine and Abraxane treatment alone.
• Three (3) patients remain on trial from the Phase 1b cohort. The Phase 2a trial will initially enrol 26 patients over the coming months. Recruitment into this next stage of the trial is progressing well recruiting patients through six trial sites in Australia and five trial sites in South Korea.
• Currently eleven patients have now been recruited.
• Seven patients in Australia and four patients in Korea.

An interim analysis of efficacy will then be conducted around Q3 2024. An efficacy assessmentshowing six or more partial or complete responses out of the 26 patients will be sufficient to continue the trial. An additional 24 patients will then be enrolled to give a total of 50 patients.

Amplia CEO and MD Dr Chris Burns commented: "The clinical responses we are seeing in patientsfrom the Phase 1b stage is very promising. The duration on trial, given the aggressiveness of the disease inthese patients, is also extremely encouraging. As reported at the end of our Phase 1b trial, the drug safety and tolerability also appears to be very acceptable for this patient group. We look forward to reporting on further data from the trial as the Phase 2a patients are assessed."

About the ACCENT Trial

The protocol for the ACCENT trial is entitled ‘A Phase 1b/2a, Multicentre, Open Label Study of the Pharmacokinetics, Safety and Efficacy of AMP945 in Combination with Nab-paclitaxel and Gemcitabine in Pancreatic Cancer Patients’. The trial is a single-arm open label study conducted in two stages. The first stage (Phase 1b) determined an optimal dose of AMP945 by assessing the safety, tolerability, pharmacokinetics, pharmacodynamics and preliminary efficacy of AMP945 when dosed in combination with gemcitabine and Abraxane in first-line patients with advanced pancreatic cancer.

This second stage (Phase 2a), of the trial is designed to assess efficacy in combination with gemcitabine and Abraxane. The primary endpoints are Objective Response Rate (ORR) and Duration on Trial (DOT) with secondary endpoints being Progression Free Survival (PFS) and Overall Survival (OS). Safety and tolerability will continue to be assessed.

More information about the ACCENT trial, including a list of participating sites, can be found via the Amplia Therapeutics website and at ClinicalTrials.gov under the identifier NCT05355298.

The Company will provide further updates on the trial as recruitment proceeds.

Aptamer Sciences Inc. Files IND Application for Innovative Liver Cancer Treatment AST-201: A Promising Approach to Address Under Medical Needs

On March 26, 2024 Aptamer Sciences Inc. (KOSDAQ, 291650) reported the filing of an Investigational New Drug (IND) application for the phase 1 clinical trial of AST-201 with the Korean Ministry of Food and Drug Safety on March 12th, 2024 (Press release, Aptamer Sciences, MAR 26, 2024, View Source [SID1234641473]).

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AST-201, the company’s pioneering candidate in its pipeline, is an ApDCTM (Aptamer-Drug Conjugate) designed to target GPC3 protein, which exhibits high expression levels in specific cancer cells, notably liver cancer. It comprises gemcitabine as the payload and an aptamer that selectively binds to GPC3 protein. Gemcitabine, a proven systemic anticancer agent, is widely utilized in treating various cancers, including ovarian, breast, non-small cell lung, and pancreatic cancer. The choice of gemcitabine as the payload was deliberate, owing to its moderate toxicity profile, particularly suitable for liver targeting, given the organ’s susceptibility to drug toxicity. Additionally, gemcitabine’s nature as a DNA analogue facilitates its synthesis within the aptamer DNA sequence. The company’s strategic focus on liver cancer addresses significant unmet medical needs, as evidenced by AST-201’s superior efficacy over sorafenib in animal models and its synergistic effect when co-administered with anti-PD-1 therapy.

Liver cancer poses a significant health challenge, particularly in East Asia, with a dismal survival rate. While combination therapies such as atezolizumab and bevacizumab have emerged as standard treatments for advanced liver cancer, recent findings published in Nature Medicine suggest their limited efficacy in certain liver cancer populations with high GPC3 expression levels, highlighting substantial unmet medical needs. In this context, AST-201 offers a promising therapeutic approach by specifically targeting GPC3.

The planned phase 1 trial seeks to evaluate the safety, pharmacokinetic profile, and preliminary efficacy of AST-201 in patients with GPC3-positive advanced solid tumors. Notably, Dr. Hong Jae Chon from CHA Bundang Medical Center, a prominent medical oncologist in South Korea, will serve as the coordinating investigator. The trial will be conducted across four hospitals, including CHA Bundang Medical Center, Samsung Medical Center, Severance Hospital, and the National Cancer Center in South Korea.

Dr. Chon remarked, "GPC3 has garnered considerable attention in liver cancer therapeutic development among biopharmaceutical companies," expressing optimism that "AST-201 may emerge as a novel treatment option for liver cancer patients."

Aptamer Sciences Inc. aims to showcase the clinical benefits of AST-201 and the technological value of its ApDCTM platform through this trial. Moreover, the company anticipates that this milestone will propel its research and development efforts, enhancing the competitiveness of its subsequent hemato-oncology pipeline products, including AST-202 targeting CD25, ApRC (Aptamer Radioligand Conjugate), ApIS (Aptamer Immune Stimulator Conjugate), and so on.

Dr. Dong-il Han, CEO of Aptamer Sciences Inc., emphasized, "Since the second aptamer drug Izervay approved by FDA last year, aptamer technology has garnered significant attention in the pharmaceutical market," highlighting, "The AST-201 clinical trial will showcase the technological capabilities of the ApDCTM platform and expedite ongoing technology transfer discussion with multiple partners. This milestone underscores Aptamer Sciences Inc.’s commitment to advancing innovative therapies and addressing critical unmet needs in oncology."

Fig 1. AST-201 structure (Among the sequence of GPC3 aptamer, the payload of gemcitabine is conjugated as the part of sequence.)

Fig 2. AST-201 mechanism of action

1. AST-201 targets and binds to the GPC3 protein located on the surface of cancer cells.

2. The drug undergoes internalization into the cancer cell by endocytosis.

3. After the lysosomal degradation, gemcitabine monophosphate (dFdCMP), the active form of gemcitabine, is released within the cell leading to programmed cell death of the tumor cell (apoptosis).