Pneumococcal Polysaccharide Conjugate Vaccine(Glaxosmithkline Plc)

Pneumococcal vaccines sales are dominated by Pfizer, and to a lesser extent, Merck, each company stepping up the competition with recent FDA approvals of shots that offer broader protection. GSK wants a bigger piece of this market so it’s committing $3.3 billion to acquire Affinivax, a clinical-stage vaccines developer with a Phase 3-ready vaccine candidate that could top the pneumococcal vaccines sold by its rivals. The deal announced Tuesday breaks down to a $2.1 billion upfront payment to Cambridge, Massachusetts-based Affinivax, whose most advanced product candidate is a pneumococcal vaccine for adults. Privately held Affinivax could earn $1.2 billion more from GSK depending on whether the biotech achieves two clinical milestones for its pediatric pneumococcal vaccine. Pneumococcal disease stems from Streptococcus pneumoniae. There are more than 100 strains of this bacteria, which can lead to sepsis, pneumonia, and meningitis among other infections. The pneumococcal vaccines market is dominated by Prevnar 13, a Pfizer shot that protects against 13 strains. Vaccine developers have been trying to top that number. Last year, Pfizer won FDA approval for Prevnar 20, a vaccine that protects against 20 pneumococcal strains. Merck followed with an approval for Vaxneuvance, which protects against 15 strains. Affinivax’s lead vaccine candidate, AFX3772, is designed to confer protection against 24 pneumococcal strains. A preclinical Affinivax vaccine candidate addresses more than 30 strains. The challenge of adding more strains to pneumococcal vaccines is capacity. The pneumococcal shots currently available are conjugate vaccines, which are made by bonding an antigen to a protein that carries it along. The antigen is a polysaccharide, a chain of sugar molecules from the bacteria’s outer coat. To protect against more strains, a vaccine needs to add more polysaccharides. It’s here that Affinivax’s conjugate vaccines could have an edge. Affinivax has developed a proprietary way of bonding polysaccharides to proteins. In a single vaccine, the Affinivax shot is capable of presenting more polysaccharide and protein combinations to the immune system compared to vaccines made by traditional conjugate chemistry. The biotech says those combinations induce a broad, protective immune response from both B cells and T cells. In addition to broader protection, Affinivax claims its technology offers the potential for a stronger immune response compared to currently available vaccines. The platform Affinivax technology is called MAPS, short for Multiple-Antigen Presenting System. Development of Affinivax’s pneumococcal vaccine candidate, formerly known as ASP3772, was funded by Astellas Pharma under a collaboration begun in 2017. In addition to the 24 strains, the vaccine also addresses two “conserved proteins,” meaning that they are found across different pneumococcal strains. Last July, the companies reported results from a Phase 2 study in nearly 800 adults showing antibody responses to each of the 24 polysaccharides of the vaccine, as well as an additional antibody response to the conserved pneumococcal proteins. The vaccine was well tolerated by patients and no serious adverse effects were reported. Earlier this year, Affinivax reacquired from Astellas global rights to the pneumococcal vaccine candidate, paying its former partner $65 million up front. Astellas is eligible for milestone payments tied to the progress of the vaccine, now renamed AFX3772, plus royalties from sales if it reaches the market. The Japanese pharmaceutical company is also eligible for royalties from next-generation pneumococcal vaccines based on the MAPS technology. GSK already has a pneumococcal vaccine, Synflorix. That product protects against 10 pneumococcal strains and it generated £357 million in 2021 sales (about $450 million), an 11% year-over-year decline that the company attributed to lower demand in emerging markets. The Prevnar family of products also saw an 11% decline in sales, but it’s still a much bigger franchise, accounting for more than $5.2 billion in global sales in 2021. In acquiring Affinivax, GSK will not only be able to better compete in the pneumococcal vaccines market, it also gains technology that could help it develop vaccines against other pathogens. Affinivax began in 2013, founded by CEO Steven Brugger and based on the research of Rick Malley, an infectious disease specialist at Boston Children’s Hospital and a professor of pediatrics at Harvard Medical School. Affinivax’s MAPS technology was co-invented by Fan Zhang and Yingjie Lu, professors of pediatrics at Harvard who are also scientific co-founders of the startup. Though pneumococcal vaccines are Affinivax’s initial focus, the platform technology is also being applied to other targets. The biotech, which received its seed funding in 2014 from the Bill & Melinda Gates Foundation, has raised $346 million in the past two years as it expanded its scope to healthcare-associated infections such as Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus, and Clostridium difficile. Those programs are preclinical. The company also has exploratory programs in SARS-CoV-2 and melanoma. GSK’s Affinivax acquisition comes at a key time for the biotech, which was looking ahead to a pivotal test of its pneumococcal vaccine in adults and a pediatric clinical trial, and it needed to finance both without the deep pockets of Astellas. GSK is taking on that responsibility, and it said that a Phase 3 clinical trial is expected to start soon. A Phase 1/2 pediatric clinical trial is planned to start later in the year. “The proposed acquisition further strengthens our vaccines R&D pipeline, provides access to a new, potentially disruptive technology, and broadens GSK’s existing scientific footprint in the Boston area,” Hal Barron, GSK’s chief scientific officer and president of R&D said in a prepared statement. “We look forward to working with the many talented people at Affinivax to combine our industry-leading development, manufacturing, and commercialization capabilities to make this exciting new technology available to those in need.” Public domain image by the CDC

Q1, 2021 saw both winners and losers in the biopharma space. While the COVID-19 pandemic has dominated – and highlighted – the industry for the past year, some companies have made significant progress against the copious other diseases that refuse to let up. BioSpace takes an in-depth look at the Top 25 of Q1. Johnson & Johnson $435.77 billion The recent snag in J&J’s COVID-19 journey was resolved on April 23rd as the FDA and CDC determined that the benefits outweighed the risks for its single-shot vaccine. The agencies had paused the vaccine a week earlier over six cases of serious blood clots. Despite this minor blip, J&J announced Q1 earnings of $12.19 billion in revenue for its pharmaceutical business, a 9.6% year-over-year increase. Sales were driven by multiple myeloma drug, Darzalex, which brought in $1.37 billion, along with inflammatory disease treatment, Stelara, which netted $2.15 billion. The single-shot vaccine brought in $100 million for the quarter. Roche $287.85 billion When Switzerland’s representative to the pharmaceutical world announced its Q1 earnings on April 21st, there were both victories and failures. On the COVID-19 front, Roche pulled two more programs, a monoclonal antibody licensed from Amgen called astegolimab (RG6149), and IL-22 inhibitor, RG7880 (efmarodocokin alfa). Both were being studied for the treatment of pneumonia related to the coronavirus. However, Roche scored a major victory in the diagnostics space with its $1.8 billion acquisition of GenMark Diagnostics in March. GenMark was one of the first companies to receive emergency use authorization (EUA) from the FDA for its ePlex SARS-CoV-2 Test. This boosts Roche’s own portfolio, which includes the Elecsys IL-6 test and Elecsys Anti-SARS-CoV-2 antibody test. Pfizer $220.56 billion Co-developer and owner of the COVID-19 market’s “it” vaccine, Pfizer is sitting atop of the world. On April 9th, Pfizer & development partner, BioNTech went for another first, asking the FDA to approve its shot for use in adolescents 12-15 after preliminary data showed it to be 100% effective in preventing illness in this cohort. The agency is currently reviewing the request. Pfizer expects to bring in $15 billion from the vaccine in 2021, which would greatly contribute to the $59 billion to $61 billion it expects to earn overall for the year. Abbott $213.19 billion The pharma giant of the Midwest kicked off 2021 strong, announcing $10.5 billion in sales, a growth rate of 35.3 percent in Q1. Global sales from Abbott’s COVID-19 rapid testing platforms, BinaxNOW™, Panbio™ and ID NOW™, accounted for roughly 1/5 of the total, reeling in $1.8 billion or a total $2.2 billion in this space. On the home healthcare front, Abbott launched NeuroSphere™ Virtual Clinic, a novel technology allowing patients with chronic pain or movement disorders to communicate with physicians, ensure proper settings and functionality, and adjust treatment settings remotely. AbbVie $202.25 billion AbbVie announced Q1 results on April 30 that chairman and chief executive officer, Richard A. Gonzalez, described as “ahead of our expectations.” Blockbuster drug, Humira, led the way with global net revenues of $4.867 billion. The company recently took a hit as the suddenly cautious FDA extended its review of JAK inhibitor, Rinvoq (upadacitinib) for atopic dermatitis, requesting an updated assessment of its benefit-risk profile. This follows the news of a delay in the approval of Rinvoq for psoriatic arthritis. Rinvoq, which brought in $303 million globally this quarter, is one of the drugs AbbVie is counting on to allay the loss when patent protection for Humira expires in 2023. Novartis $194 billion Novartis struggled to stay ahead of the COVID-19 pandemic, with Q4 2020 revenues of $12.8 billion missing the popular Zacks Consensus Estimate of $13 billion. The company’s dermatology, ophthalmology and Sandoz retail businesses were the hardest hit by disruptions in hospitals. But the Swiss pharma began the quarter with a big win as the FDA granted Entresto® expanded indication in heart failure. Novartis, along with collaboration partner, Genentech (Roche), recently won FDA approval for a prefilled syringe of Xolair® (omalizumab). Merck & Co. $191.89 billion Last week, Merck reported that sales had stayed almost exactly the same as Q1, 2020, helped in large part by the strong performance of KEYTRUDA. Amidst a series of setbacks in the COVID-19 space, Merck announced on April 15th that it was discontinuing development of CD24Fc (MK-7710), the Phase III therapeutic asset it acquired along with OncoImmune in November. This only compounded the company’s COVID-19 woes after it shuttered its pandemic vaccine program in January due to poor responses in Phase I studies. Merck will now focus its attention on advancing molnupiravir (MK-4482 and EIDD-2801), an oral antiviral candidate it is developing with Ridgeback Biotherapeutics, and producing J&J’s vaccine. Eli Lilly and Company $178.13 billion Eli Lilly announced a revenue increase of a healthy 16% on April 27th, 7% excluding the $810.1 million brought in by COVID-19 antibodies. Lilly recently made news on this front, requesting that the FDA revoke the EUA for its single antibody therapy, bamlanivimab, which is less effective against the variants than the combination antibody therapy of bamlanivimab and etesevimab. Lilly enjoyed a recent oncology win, announcing positive Phase III results of TYVYT® (sintilimab injection), which is being studied as a second-line treatment for squamous non-small cell lung cancer. Novo Nordisk $173.37 billion Diabetes drug, Ozempic® injection, won the year for Novo in 2020, bringing in $3.4 billion in sales. So it was a surprise to the company when the FDA slapped it with a Refusal to File letter for its request to expand the label to double the dose to 2 mg for type 2 diabetes. But the future appears bright for Novo with Ozempic®, a glucagon-like peptide 1 (GLP-1) receptor, which showed promise as an obesity remedy, significantly reducing weight in patients over the course of 68 weeks. The data was published in the New England Journal of Medicine. The company filed an NDA with the FDA in December for this indication. AstraZeneca $141.88 billion The saga of the AstraZeneca-Oxford vaccine (AZD1222) would make for good day-time TV. After multiple European and Asian countries suspended the use of the vaccine, co-developed with Oxford University, due to incidences of potentially-related blood clots, the jury remains out on whether or not the thrombosis is connected to the vaccine. The vaccine is still yet to be approved in the U.S. after a lengthy pause in its phase III trial and the submission date has now been pushed back to mid-May. In other therapeutic news, AstraZeneca announced on Friday that it had halted development of promising anti-BCMA antibody-drug conjugate, MEDI2228, citing safety and efficacy concerns. The drug was also facing an uphill competitive battle, primarily from GSK’s Blenrep. Bristol Myers Squibb $141.65 billion BMS enjoyed an astronomical 63% revenue boost, with sales totaling $42.5 billion in 2020 as the fruits of the Celgene megamerger began to emerge. Its CEO and board chair, Giovanni Caforio, M.D., enjoyed a 7% salary raise, taking home an astronomical $20.15 million. BMS is not without its challenges, however, as blockbuster multiple myeloma drug, REVLIMID®, will lose some of its exclusivity in 2022. The company hopes to combat any losses with drugs like multiple sclerosis drug Zeposia, which received the first FDA approval after the Celgene merger, in March 2020. Zeposia is estimated to reap $1.598 billion by 2024. BMS took a hit on Friday as Opdivo failed to maintain accelerated approval in liver cancer. Amgen $140.75 billion It’s been a season of big acquisitions for Amgen, as the biotech giant kicked off March by picking up Five Prime Therapeutics for $1.9 million in cash along with its Phase III ready anti- FGFR2b antibody, Bemarituzumab, for gastric cancer. Amgen quickly followed this with the purchase of Seattle-based Rodeo Therapeutics to finish the month. Rodeo's 15-PGDH program, with which it is developing small-molecule therapies designed to promote regeneration and repair of multiple tissues, will add value to Amgen's inflammation portfolio. Amgen will have to hope the fruit of these acquisitions comes to bear soon, as the pandemic has hit the company hard. Total Q1 revenues for the company are down 4% over Q1, 2020, reflecting the negative impact of COVID-19 on patient visits. Sanofi $127.55 billion As Sanofi continues to work with partner, GSK, to refine its adjuvanted recombinant protein-based COVID-19 vaccine candidate, it is hoping for positive results from a phase II study meant to finalize a formulation that is effective for all adults. The vaccine ran into trouble in December due to an insufficient response in older trial participants. If positive, Sanofi and GSK will head to Phase III in Q2 2021. Elsewhere on the therapeutic spectrum, checkpoint inhibitor Libtayo (cemiplimab), which Sanofi co-markets with Regeneron Pharmaceuticals, performed so well in its phase III trial in cervical cancer, the trial was halted early. The pair plan to use the data for regulatory submission at some point in 2021.. GlaxoSmithKline $94.57 billion GSK, which made the decision to take a supporting role in the COVID-19 fight, signed its most notable deal with Sanofi, adding its pandemic adjuvant technology to the latter’s S-protein COVID-19 antigen in the hopes of creating an effective vaccine. The two hit a snag in December due to an insufficient immune response in older trial patients, delaying the projection for the vaccine candidate until the end of 2021. Meanwhile, GSK will need to hope for a better year with its established vaccines. In 2020, fewer people risked visiting the doctor’s office for its hepatitis, and DTPa-containing vaccines, Synflorix and Bexsero. Gilead Sciences Inc. $81.75 billion On the strength of a certain antiviral medication called Veklury®, better known as remdesivir, Gilead posted a 16% year-over-year product sales increase in Q1. Remdesivir, which is indicated for adults and children 12 and over with COVID-19, was the first drug approved by the FDA for treating the SARS-CoV-2 virus. Another exciting medicine on the horizon for Gilead is Trodelvy, which on April 8 received full approval from FDA for adults with unresectable locally advanced or metastatic triple-negative breast cancer (TNBC). Moderna, Inc. $74.98 billion While Moderna is not expected to report Q1 earnings until May 6, Zacks Investment Research estimates that the mRNA vaccine king will finish the quarter trading at $2.64 per share – an astronomical catapult from the reported $-0.35 in Q1, 2020 almost entirely the product of its mRNA-1273 vaccine for COVID-19 which won Emergency Use Approval in November. The past 12 months have clearly been transformative for Moderna, which on March 16th, became the first of the “big 4” to launch trials of its vaccine in children between 6 months and 12 years of age. Bayer $63.89 billion The German pharmaceutical and chemical behemoth continues to be dragged down by litigation over allegations that Roundup, the popular weedkiller it picked up in its acquisition of Monsanto, causes cancer. In early February, Bayer announced a $2 billion proposal to establish a fund for future claimants who allege that Roundup caused their non-Hodgkin’s lymphoma. The company is also facing challenges with its pharma pipeline, as patent protection for its star drugs, Xarelto and Eylea, will both run out within the next few years. Illumina Inc. $56.89 billion On April 5, Illumina announced preliminary Q1 revenue of approximately $1,085 million, compared to the $859 million it achieved during the first quarter of 2020, representing a hearty 26% year-over-year growth for the quarter. This should come as no surprise, given Illumina’s transmission tracking and surveillance capabilities. The genomic sequencing leader received record orders of approximately $1.4 billion with COVID-19 surveillance revenues for sequencing consumables comprising around $20 million of this. Some of Illunina’s customers built additional capacity and boosted the purchase of instruments, equaling approximately $35 million in instrument revenue. Vertex Pharmaceuticals $56.76 billion Vertex, which recently expanded its collaborative partnership with CRISPR Therapeutics, enjoyed a year-over-year Q1 revenue increase of 14%. This biopharma juggernaut nestled in the heart of Genetown, has enjoyed tremendous success out of the gate in 2021. Vertex, which expects to control the Cystic Fibrosis market well into the 2030s with TRIKAFTA®, is developing a number of other investigational therapies including VX-880, a novel investigational cell therapy for Type 1 Diabetes, the first pancreatic islet replacement therapy to receive Fast Track Designation from the FDA on March 10th. Takeda Pharmaceutical $52.99 billion The Japanese juggernaut’s Q3 2020 results, announced on February 4th, boasted a 24% revenue growth for ulcerative colitis and Chron’s disease drug, ENTYVIO, a 38.1% boost for hereditary angioedema (HAE) prevention therapy, TAKHZYRO, and 13.7% growth for Immunoglobulin. Takeda has been investing in more physical space of late, opening a 24,000-square-foot R&D cell therapy manufacturing facility in Boston, Massachusetts, at the site of its R&D headquarters. Regeneron Pharmaceuticals, Inc. $52.30 billion Regeneron, of COVID-19 antibody cocktail fame, is another new household name. On April 12, Regeneron reported results from its Phase III trial REGEN-COV (casirivimab with imdevimab) in recently infected asymptomatic COVID-19 patients. The data showed that the cocktail decreased the overall risk of patients progressing to symptomatic COVID-19 by 31% and decreased the risk of progression by 76% after the third day. While the SARS-CoV-2 virus continues to ravage the world, Regeneron continues to succeed with eczema drug, Dupixient, which brought in $1.17 billion in Q4, 2020, while macular degeneration drug, Eylea, contributed $1.34 billion in the 4th quarter. BioNTech $49.56 billion When BioNTech, Pfizer’s partner in the most coveted COVID-19 vaccine, announced its Q4 2020 earnings on March 30, the results were so astronomical (to the tune of a 1,134% year-over-year increase), the German biotech’s stock jumped more than 3% in early market trading. Emblematic of rapidly changing fortunes, after posting a net loss of $58.2 million euros in the prior year period, BioNTech boasted a net profit of $366.9 million euros in Q4 2020. Much more than a one-trick pony, BioNTech has mRNA-based medicines in many oncological pursuits including melanoma, non-small cell lung cancer (NSCLC), ovarian and breast cancer at various stages of development. The company plans to announce Q1 2021 results on May 10. Biogen $41.03 billion The neuro leader has had a promising quarter on multiple fronts. Biogen recently announced that SAGE-324, the investigational therapy it is developing with Sage Therapeutics, significantly reduced tremor score in a phase II study of adults with essential tremor. Biogen has invested a lot in this collaboration, paying Sage $1.52 billion upfront to jointly develop and commercialize both SAGE-324, and zuranolone (SAGE-217) for major depressive disorder (MDD), postpartum depression (PPD) and other psychiatric disorders. Biogen also announced positive results from its overall MS portfolio at the American Academy of Neurology (AAN) 2021 Virtual Annual Meeting, for TYSABRI® and VUMERITY®. Alexion Pharmaceuticals, Inc. $37.42 billion Alexion finished Q1 on a strong note, reporting a 13% increase in total revenue over the same period in 2020. The strong results were led by superstar drugs, Soliris and Ultomiris. Soliris, a first-in-class C5 complement inhibitor for rare paroxysmal nocturnal hemoglobinuria (PNH) is facing steep competition from Apellis Pharmaceuticals’ C3 drug pegcetacopla, which demonstrated superiority in a head-to-head comparison recently published by the New England Journal of Medicine (NEJM). BeiGene Co. Ltd. $32.38 billion The lone China-based biopharma to crack the top 25, BeiGene is quickly becoming a leader in the immuno-oncology space. The commercial-stage company recently presented interim analysis results of its Phase III RATIONALE 303 trial of anti-PD-1 antibody tislelizumab. Compared to docetaxel as a second or third-line treatment for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC), the data showed that the drug significantly improved overall survival. And tislelizumab will be manufactured in style at BeiGene’s recently approved one million square foot plus state-of-the-art biologics facility in Guangzhou, China.