Immune globulin (Evolve Biologics)

Pictured: A volcano erupting of damaged and inflamed nerves/ Nicole Bean for BioSpace This quarter, Annexon Biosciences expects to release Phase III trial results from its flagship program for Guillain-Barre syndrome. At the same time, the company is looking beyond GBS and investigating the possibility of fighting other inflammation-driven diseases with the antibody, ANX005. Historically, GBS has been difficult to treat and understand due to a relative lack of understanding around the cause of the disease. With causative associations ranging from viral infections to surgeries, GBS is a rare autoimmune disease affecting approximately 12,000 people in the U.S. and Europe each year. It can debilitate patients by paralyzing peripheral nerves in the limbs. There is currently no curative or long-term treatment for GBS, although intravenous immunoglobulin (IVIg, available as a generic from multiple companies) and plasmapheresis are used for acute bouts of the disease. As a pooled antibody from human blood sources, IVIg does not lead to better outcomes in subsequent administrations for GBS after the first dose due to poor prognosis, a 2021 randomized controlled study found. The study found that compared with placebo, patients who received a second IVIg dose had more serious adverse events such as thromboembolic events. By contrast, plasmapheresis is a procedure that uses a machine to separate plasma from blood cells, then replaces the patient’s plasma before returning the blood to the body. In doing so, plasmapheresis removes antibodies in the plasma, easing the inflammation characteristic of GBS. But the procedure requires access to a central line via catheters and carries a risk of bleeding and infections. ANX005’s mechanism is different: it inhibits a protein complex called C1q that is part of the classical complement pathway, which is in turn a component of the innate immune system. ANX005 thus targets the classical complement pathway upstream while—unlike IVIg—leaving the lectin pathway and the alternative complement pathway intact. In other words, patients treated with ANX005 will still be able to activate C3 via the lectin pathway and the alternative complement pathway, but not the classical complement pathway. This mechanism likely leads to less immunosuppression than does IVIg, enabling the body to continue defending itself against pathogens. In Phase Ib trials, ANX005 was administered along with IVIg in an open-label treatment arm to GBS patients. But in Phase III trials, Annexon is betting on comparing two different ANX005 doses compared to placebo. As this trial’s primary endpoints measure the GBS Disability Score at eight weeks and look at the number of patients with adverse effects for six months, there is much at stake in terms of safety and efficacy. By targeting GBS from a new angle, ANX005 is offering hope in a therapeutic area where corticosteroids and interferon-beta 1a have failed in the past. Beyond GBS While Annexon continues to assemble data on its Phase III GBS trial for upcoming release, it is also moving toward testing C1q inhibition in other inflammatory diseases, and these trials provide additional information about its safety profile. Huntington’s disease, a progressive movement disorder, is also driven by the activation of the classical complement pathway. Based on Phase IIa safety data from its Huntington’s disease trial with ANX005, ANX005’s adverse effect pro limited to mainly infusion-site reactions that appear only upon the first dose, making it safer than IVIg for these patients. By contrast, with various side effects that appear even with the first dose such as chills, fever, flushing, flu-like muscle pains or joint pains, fatigue, nausea, vomiting, and rash, IVIg is only used when necessary to boost immune responses due to systemic adverse effects. With ANX005 also being investigated for use in amyotrophic lateral sclerosis (ALS), where the drugmaker aims to reduce disease progression, there are certainly exciting developments ahead for Annexon in the coming months. Jia Jie Chen writes analyses focusing on drug development in the biotech and pharma industries for BioSpace. He has a doctorate degree in pharmacy and experiences ranging from biotech equity research to business intelligence analysis. Follow him on LinkedIn.

Strong CSL Behring portfolio growth especially Ig FINANCIAL HIGHLIGHTS 4 Revenue $8.05 billion, up 11% at CC3 NPAT $1.90 billion1, up 17% NPAT $1.94 billion1 at CC3, up 20% NPATA $2.02 billion1,2 , up 11% NPATA $2.06 billion1,2 at CC3, up 13% NPATA1,2 earnings per share $4.182, up 11% NPATA1,2 earnings per share $4.26 at CC3 up 13% Interim dividend 5 of US$1.19 per share Converted to Australian currency, the interim dividend is approximately A$1.81 per share, up 12% Guidance reaffirmed – FY24 NPATA2,4 anticipated to be in the range of approximately $2.9 billion to $3.0 billion2 at CC3 MELBOURNE, Australia, Feb. 13, 2024 /PRNewswire/ -- CSL Limited (ASX:CSL; USOTC:CSLLY) today announces a reported net profit after tax of $1.90 billion1 for the 6 months ended 31 December 2023, up 20% on a constant currency basis3. Underlying profit (NPATA) was $2.02 billion1,2, up 13% on a constant currency basis to $2.06 billion1,2,3. Dr. Paul McKenzie, CSL's Chief Executive Officer and Managing Director said, "Our strong first-half result for the 2024 financial year was driven by CSL Behring's exceptional performance across its portfolio, especially immunoglobulins. The plasma initiatives we have implemented are starting to drive gross margin recovery. "CSL Seqirus achieved solid growth in a challenging season. Its portfolio of differentiated products outperformed the market. "For CSL Vifor we are well prepared for the transitioning iron market." PERFORMANCE CSL Behring Total revenue was $5,238 million, up 14%3 when compared to the prior comparable period. Immunoglobulin (Ig) product sales of $2,757 million, increased 23%3 with strong growth recorded across all geographies driven by global plasma supply and patient demand. PRIVIGEN® / INTRAGRAM® (Immune Globulin Intravenous (Human), 10% Liquid) sales grew 27%3 as the momentum from the prior year continued in improving product availability and patient diagnosis rates. HIZENTRA® (Immune Globulin Subcutaneous (Human), 20% Liquid) sales were up 18%3 driven by patient diagnosis rates. HIZENTRA® continues to be the clear market leader for subcutaneous immunoglobulin. Underlying demand for Ig continues to be strong due to significant patient needs in core indications – namely Primary Immune Deficiency, Secondary Immune Deficiency and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). Albumin sales of $613 million, were up 8%3. Sales were strong in emerging markets with solid growth in the US and Europe. Growth in China was modest, tempered by competitive pressure. Haemophilia product sales of $662 million increased 8%3. IDELVION®, CSL Behring's novel long-acting recombinant factor IX product achieved growth of 7%3 and continues to be the market leader in key markets. HEMGENIX®, the first and only gene therapy for haemophilia B was successfully launched in the US in FY23 and patient referrals have been accelerating. The haemophilia A market continued to be competitive resulting in a modest decline in sales for AFSTYLA®, a novel recombinant factor VIII product. Plasma-derived haemophilia products, however, achieved growth of 8% driven by HUMATE® / HAEMATE®, therapies for the treatment of patients with von Willebrand disease. Specialty products sales of $976 million, were up 6%3 led predominately by demand for KCENTRA® and HAEGARDA®. KCENTRA® (4 factor prothrombin complex concentrate) recorded sales growth of 12%3, as it continues to further penetrate the warfarin reversal market in the US. HAEGARDA®, our therapy for patients with Hereditary Angioedema, increased 9%, driven by the continued shift from on-demand to prophylaxis treatment and a strong performance in the UK and Europe. Garadacimab (Anti-FXIIa) for HAE, was filed for regulatory approval in the US and EU. Plasma Collections Plasma collections remain strong. The cost of collections, which includes donor compensation and labour, continued to trend down. A new roll out plan for the RIKA plasmapheresis devices was developed. Deployment across the US fleet is expected over the next 18 months. In addition, results from an individualised nomogram trial conducted by our supplier have been submitted for regulatory approval. CSL Seqirus Total revenue of $1,804 million, was up 2%3 driven by the adjuvanted influenza vaccine FLUAD®, which increased by 14%3. This growth was achieved against a backdrop of reduced rates of immunisation and highlights the strength of CSL Seqirus' differentiated product portfolio. During the period: Self-amplifying mRNA vaccine for COVID was approved by Japan's Ministry of Health, Labour and Welfare aQIVc, a next generation influenza vaccine combining adjuvant technology with cell-based manufacturing, enrolled its last patient in the Phase III clinical study in January 2024. CSL Vifor Total revenue was $1,011 million. The prior comparable period included only 5 months revenue following the acquisition of Vifor Pharma in August 2022. During the period: Preparations were made for the transitioning iron market There was strong performance from the long-acting erythropoiesis-stimulating agent, MIRCERA® TAVNEOS® was successfully launched in multiple European countries While the strategic potential of the business remains strong, we have dampened our near-term growth aspirations for CSL Vifor. Expense Performance Research and development (R&D) expenses were $669 million8 , up 11%3 when compared to the prior comparable period. The increase in expenses reflects higher costs associated with the progression of the R&D portfolio and investment in R&D infrastructure. Selling and marketing expenses (S&M) were $707 million8, up 2%3 in comparison to the prior comparable period. An additional month of CSL Vifor and an increase in labour costs accounts for the increase in S&M expenses while other S&M expenses were held in line with the prior comparable period. General and administrative (G&A) expenses were $323 million8, down 7%3 due to favourable foreign exchange differences and efficiencies generated from the centralisation of the group's Enabling Functions. Depreciation and amortisation (D&A) expense (excluding acquired intellectual property) was $297 million, up 1%3. Net finance costs were $234 million9, up 32%3. The increase in net finance costs was due to the debt associated with the acquisition of Vifor Pharma and higher interest rates. Financial position Cashflow from operations was $1,069 million, up 9%. The increase was driven by higher profitability and overall growth in sales. This was partly offset by higher payments for income tax and interest. Cash outflow from investing was $702 million, down significantly when compared to the prior comparable period as payment for the acquisition of Vifor Pharma was made in the prior period. CSL's balance sheet remains in a strong position with net assets of $19,162 million. Current assets increased by 10% to $10,146 million. The main driver was an increase in receivables due to the increase in sales and the seasonality of CSL Seqirus. Non-current assets increased by 1% to $27,158 million in comparison to the previous year. Current liabilities increased by 2% to $4,718 million. The increase in interest-bearing liabilities and borrowings (bank debt) was offset by the decrease in trade and other payables and current tax liabilities. Non-current liabilities decreased by 3% to $13,424 million. The decrease was due to the reclassification of certain bank borrowings as current, coupled with repayment across the Group's debt portfolio including the private placement senior notes. Outlook (at FY23 exchange rates) Commenting on CSL's outlook, Dr. McKenzie said, "For FY24, I am pleased to reaffirm our previous guidance. CSL's underlying profit, NPATA is expected be in the range of approximately $2.9 billion to $3.0 billion at constant currency3, representing growth over FY23 of approximately 13-17%[6]" "CSL is in a strong position to deliver annualised double-digit earnings growth over the medium term. "The strong growth in our immunoglobulins franchise is expected to continue as patient demand remains strong. "We have a number of initiatives underway in plasma collections that are improving efficiencies and processing times, supporting continued expansion in CSL Behring's gross margin. "Our transformational gene therapy product for haemophilia B patients, HEMGENIX®, is attracting significant interest from patients and health care professionals and patient referrals have accelerated. We expect more patients dosed in the second half of this financial year. "CSL Seqirus has performed well in a challenging season. However, due to the seasonality of this business we anticipate it to post a loss in the second half of the fiscal year. "For CSL Vifor, we are operating within an evolving iron market. While there are challenges for near-term growth, we are well positioned for iron competition in the EU and further geographic expansion. Our focus remains on unlocking value by leveraging capabilities across the CSL group", Dr. McKenzie concluded. In compiling the company's financial forecasts for FY24, a number of key variables that may have a significant impact on guidance have been identified and these have been included in the endnote[7]. FURTHER INFORMATION Additional details about CSL's results are included in the company's 4D statement, investor presentation slides and webcast, all of which can be found on CSL's website A glossary of medical terms can also be found on the website. 1 Attributable to CSL shareholders 2 Statutory net profit after tax (NPAT) before impairment and amortisation of acquired intellectual property, business acquisition and integration costs and the unwind of the inventory fair value uplift. 3 Constant currency (CC) removes the impact of exchange rate movements, facilitating the comparability of operational performance. For further detail refer to CSL's Financial Statements for the Half Year ended December 2023 (Directors Report). 4 All figures are expressed in US dollars unless otherwise stated. 5 For shareholders with an Australian registered address, the interim dividend of US$1.19 per share (approximately A$1.81) is expected to be paid on 3 April 2024. For shareholders with a New Zealand registered address the interim dividend of US$1.19 per share (approximately NZ$1.94) is expected to be paid on 3 April 2024. The exchange rates will be fixed at the record date of 12 March 2024. All other shareholders will be paid in US$. CSL also offers shareholders the opportunity to receive dividend payments in US$ by direct credit to a US bank account. 6 % growth rates excludes the one-off gain from the sale of property in FY23 (NPATA $44m). 7 Key variables that could cause actual results to differ materially include: the success and timing of research and development activities; decisions by regulatory authorities regarding approval of our products as well as their decisions regarding label claims; competitive developments affecting our products; the ability to successfully market new and existing products; difficulties or delays in manufacturing; ability to collect plasma; trade buying patterns and fluctuations in interest and currency exchange rates; legislation or regulations that affect product production, distribution, pricing, reimbursement, access or tax; acquisitions and divestitures; research collaborations; litigation or government investigations; and CSL's ability to protect its patents and other intellectual property. 8 Underlying results are adjusted to exclude amortisation of acquired intellectual property ($132 million), business acquisition and integrations costs and the unwind of the inventory fair value uplift. 9 At reported currency For further information, please contact: Investors: Bernard Ronchi Director, Investor Relations CSL Limited P: +61 3 9389 3470 E: [email protected] Stephen McKeon Director, Investor Relations CSL Limited P: +61 402 231 696 E: [email protected] Media: Jimmy Baker Communications CSL Limited P: +61 450 909 211 E: [email protected] SOURCE CSL Limited