The Antibody Society

the official website of the antibody society

An international non-profit supporting antibody-related research and development.

EUA issued for anti-SARS-CoV-2 sotrovimab

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On March 27, 2021, the U.S. Food and Drug Administration issued an emergency use authorization (EUA) for sotrovimab (VIR-7831; GSK4182136) for the treatment of mild-to-moderate COVID-19 in adults and pediatric patients with positive results of direct SARS-CoV-2 viral testing and who are at high risk for progression to severe COVID-19, including hospitalization or death. The EUA was issued to GlaxoSmithKline.

Sotrovimab, a human anti-SARS-CoV2 antibody, is being evaluated in a Phase 1/2/3 randomized, double-blind, placebo-controlled clinical trial in non-hospitalized adults with mild-to-moderate COVID-19 symptoms and a positive SARS-CoV-2 test result. The EUA is based on an interim analysis of results for 583  patients in the study, 291 and 292  of whom received sotrovimab or placebo, respectively, within five days of onset of COVID-19 symptoms. The primary endpoint was progression of COVID-19 (defined as hospitalization for greater than 24 hours for acute management of any illness or death from any cause) through day 29. Hospitalization or death occurred in 21 (7%) patients who received placebo compared to 3 (1%) patients treated with sotrovimab.

Sotrovimab is administered as a 500 milligram single dose given intravenously over 30 minutes by health care providers.

Prior to the authorization of sotrovimab, FDA issued EUAs for the treatment of mild-to-moderate COVID-19 for two combinations of anti-SARS-CoV-2 monoclonal antibodies. The combination of casirivimab and imdevimab was authorized in November 2020 and the combination of bamlanivimab and etesevimab was authorized in February 2021. In addition, Celltrion’s anti-SARS-CoV-2 antibody regdanvimab (CT-P59; Regkirona) received authorization in South Korea in February 2021.

More than 20 additional anti-SARS-CoV-2 monoclonal antibodies are undergoing evaluation in clinical studies. Of these, 7 monotherapies or combinations are in late-stage clinical studies, including ADG20 (Adagio Therapeutics) and AZD7442 (AstraZeneca). The Antibody Society will continue to track these investigational antibodies and report progress in the future.

Funding the Development of Antibody Innovations, Part 2: Business Angels and Venture Capitalists

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By Tom Burt (Partner, Sofinnova Partners) & Nick Hutchinson (BSG Lead, Mammalian Cell Culture, FUJIFILM Diosynth Biotechnologies)

Antibody scientists with exciting technologies typically require substantial amounts of capital to develop their ideas and turn them into products that can be marketed. In the case of therapeutic antibodies, this can take many years and cost millions if not billions of dollars. In our first post on raising finance to support antibody innovations, we described why scientists are excited about raising finance at the current time (1). In this second post, we explore possible sources of funding for newly formed antibody companies at the very beginning of the funding cycle.

Venture capitalist (VCs) firms have traditionally been significant sources of funding for start-up biotech companies because they are undeterred by the risk that an individual company may not generate a return due to the challenges of product development in this sector. In order to generate a return on their investments, VCs back numerous start-ups in the hope that a minority will win big. However, for most scientists attempting to commercialize the fruits of their research labors, VCs are probably not the first port of call when attempting to raise funds. Biotech start-ups commonly rely on pre-seed funding in the form of government grants, bank loans, technology transfer funding from universities and even family or friends.

Business Angels are also sources of early finance. These are often individual, or syndicates of wealthy, private individuals that invest their own money in sectors that they know and understand. They typically make smaller investments than VC, usually up to $2 million, but small companies can often obtain the funds sooner. Angel investors are often interested in being involved in the project and are able to provide mentoring and access to useful networks in addition to the funding they bring.

Start-up biotechs use this seed funding to protect their intellectual property and progress their idea sufficiently such that VCs or other partners will become interested in the technology. Fortunately, in the past few years the cost of research infrastructure has gone down, allowing start-up companies to make greater progress with their ideas prior to reaching out to the VC community. Low rent lab-space is now more commonly available, suppliers provide more convenient ways to access equipment, and entrepreneurial scientists can outsource more routine studies and testing to contract research organizations.

Antiverse, a UK-based biotech start-up, recently announced it had raised £1.4 million [US$2m] to fund the development of its Artificial Intelligence-powered antibody discovery technology for accelerating antibody drug development by accurately predicting antibody-antigen binding. The company believes their platform will enable the development of antibody drugs for difficult targets associated with cancer, and heart and lung diseases. It will use the money to further develop the platform, to build a new laboratory in Cardiff, Wales, and to recruit specialist machine-learning engineers, laboratory scientists and structural biologists. The funding was raised from The Development Bank of Wales and a syndicate of Angel Investors.

While the levels of pre-seeding funding might not match that provided by VCs, some founding scientists see a benefit in taking maximum advantage of investments that allow them to retain greater control.

Tom Burt of Sofinnova Partners says, “To truly scale a start-up requires quantums of growth capital that can really only feasibly be provided by VCs. Beyond the necessary capital, VCs are also helpful to emerging companies in more qualitative ways, given their accumulated experience of financing other similar enterprises. VCs can contribute by attracting talent to Board and Management-level positions who increase the probability of success through sage advice on all areas of development.”

“In addition, the VC’s network can be invaluable in forging connections with potential pharma and biotech partners as well as investors and bankers for assistance with further financings. While the founder can expect some loss of control, VCs are typically minority investors looking to work collegially with other stakeholders to improve outcomes,” he continues.

In our next post, we’ll look at the first two rounds of financing that VCs provide to antibody start-up companies and we’ll introduce the concept of the cross-over fund, a relatively new concept by which VCs invest in promising companies that have the near-term potential to list their shares on a stock exchange.

Look for the third post in the series next week.

(1)    Burt T. & Hutchinson N. Funding the Development of Antibody Innovations. Part 1: Entrepreneurial Antibody Scientists.

 

Join us for “Fundamentals of the Immune System”, Parts I & II

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Part I:  Organization of the immune system.
Thursday June 3, 2021, 11am – 1pm ET. 

Part II:  The immune system in action.
Tuesday June 15, 2021, 11am – 1pm ET.

In this 2-part workshop on the fundamentals of the immune system, Dr. Jamie Scott, Professor Emerita, Simon Fraser University, Canada, will first provide an overview of humoral and cellular immunity, and the basic structure of the immune system, including its cells, tissues and compartments, along with the “superhighway” of the immune system: the circulatory and lymphatic systems. In that context, innate and adaptive immune systems and their interaction, and the general timing and dynamics of immune responses will be presented.

The processes of lymphocyte development, including the various B- and T-cell subsets, positive and negative selection, and the genetic basis of B-cell and T-cell receptor diversification, will be presented to provide a clear idea of what adaptive-immune receptor repertoires (AIRRs) are, and in general terms, how they are currently assessed via high-throughput sequencing. Dr. Scott will then cover the signaling, activation, proliferation and differentiation of T-cell and B-cell clones in the context of lymphoid compartments where antigen is concentrated and presented to naïve and memory B and T cells. The role of co-stimulation in determining the type immune response generated will be emphasized.

In Part II, Dr. Scott will review the orchestration of systemic and mucosal immune responses, including the roles of tolerance and inflammation in these processes. Examples of immune responses to vaccines, chronic viral infection, and/or cancer, as well as autoimmunity, will be presented as variations on a common theme, reiterating the dynamics of the immune response. Some engineered immunotherapies, such as therapeutic antibodies, CAR-T cells and dendritic-cell vaccines, will be introduced as well.

The importance of AIRR-sequencing data to our understanding of immune responses will be emphasized throughout the latter half of this workshop.

Click here to register for Part I

Click here to register for Part II

Amivantamab granted FDA approval for non-small cell lung cancer

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On May 21, 2021, U.S. Food and Drug Administration approved Rybrevant (amivantamab-vmjw) as the first treatment for adult patients with non-small cell lung cancer (NSCLC) whose tumors have specific types of genetic mutations: epidermal growth factor receptor (EGFR) exon 20 insertion mutations. Rybrevant received Priority Review and Breakthrough Therapy designation for this indication.

Amivantamab (JNJ-61186372; Janssen Pharmaceutical Companies of Johnson & Johnson) is a human, low-fucose IgG1-based bispecific antibody targeting EGFR and mesenchymal epithelial transition factor (MET) that was created using Genmab’s DuoBody technology. Amivantamab has been shown to function through multiple mechanisms of action in preclinical models of NSCLC with EGFR exon 20 insertion driver mutations, which cause tumor cells to be insensitive to EGFR tyrosine kinase inhibitors.

The efficacy of amivantamab was evaluated in a study of 81 patients with non-small cell lung cancer and EGFR exon 20 insertion mutations whose disease had progressed on or after platinum-based chemotherapy. In the trial population in which all patients received the drug, the overall response rate was 40% and the median duration of response was 11.1 months, with 63% of patients having a duration of response of 6 months or more.

FDA’s review was conducted under Project Orbis, an initiative of the FDA Oncology Center of Excellence. Project Orbis provides a framework for concurrent submission and review of oncology drugs among international partners. For review of amivantamab, the FDA collaborated with the Brazilian Health Regulatory Agency and United Kingdom’s Medicines and Healthcare products Regulatory Agency.

Need help keeping up to date on US and EU approvals?

The Antibody Society maintains a comprehensive table of approved monoclonal antibody therapeutics and those in regulatory review in the EU or US. The table, which is located in the Web Resources section of the Society’s website, can be downloaded in Excel format.

Funding the Development of Antibody Innovations, Part 1: Entrepreneurial Antibody Scientists

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By Tom Burt (Partner, Sofinnova Partners) & Nick Hutchinson (BSG Lead, Mammalian Cell Culture, FUJIFILM Diosynth Biotechnologies)

The Antibody Society has partnered with Tom Burt, Partner at Sofinnova Partners, a leading European venture capital firm in life sciences, specializing in healthcare and sustainability to produce a 4-part series of articles explaining the basics of financing a start-up biotech company. Our aim is to support and inspire researchers working in labs with a passion for their science and the drive to push their ideas as far as they will go. In Part 1, we discuss the characteristics of the entrepreneurial antibody scientist.

As of 2021, the pipeline of therapeutic antibodies is strong and the biopharmaceutical industry is enjoying unprecedented success in bringing new products to market (1). The launch of new antibody drugs can have a tremendous impact on the lives of patients suffering from diseases for which there are either no existing treatments or current treatments are lacking. Technological developments, such as Fc engineering, bi- and multi-specific antibody formats and antibody-drug conjugates will lead to improved antibody treatments in the future. Not all advances in antibody science are new drugs, however, and many are leading to new enabling research tools and novel diagnostics. The amount of innovation in the sector, driven by creative scientists working in labs around the world, is startling.

Scientists developing antibody therapeutics must progress the idea through discovery and development phases, including preclinical and clinical testing, with various regulatory hurdles that must be navigated before commercial launch can take place. Large pharma and biotech companies are well versed in managing the complexity and costs of antibody development and commercialization, but there is always room in the market for smaller, more agile players who can compete on an equal footing with these giants.

Entrepreneurial scientists are eschewing the traditional career pathways of staying in academia or joining large pharma companies (2) in favor of establishing their own companies. They are raising money to finance discovery and development, while managing their biotech businesses in order to turn their ideas into a reality. By adopting this approach, founders can retain much greater control of their inventions, can align the development of their technology with their own values, and furthermore, stand to benefit financially if their candidate is shown to be successful.

“It’s an excellent time to be considering raising finance for biotech start-ups. Investors have lots of capital that is waiting to be deployed and society is re-considering how it values medtech innovations in light of the pandemic,” explained Tom.

Investors’ attitudes to these different types of start-up will vary depending on the size of the investment that the company will need, the level of risk associated with the investment, the size of the likely return and the time it will take to see a return. Raising finance for different types of antibody start-up companies will depend on the business model and the nature of the innovation being commercialized. A technology for antibody discovery embedded in a piece of equipment will differ from an amino acid sequence that can be licensed, which will differ from an antibody therapeutic requiring ten years and hundreds of millions if not billions of dollars before any revenues are generated.

“Investors in therapeutics are very wary of “one-trick ponies” with only a single drug candidate,” says Tom. “We look for companies with innovative technologies that might be applied to a number of candidates for multiple disease targets. This reduces risks by ensuring the start-up can have multiple shots on goal.”

One such example is the start-up antibody company Gigagen, which was recently acquired by Grifols, a specialist in plasma-derived medicine. Gigagen’s Magnify Platform enables the identification of rare novel targets within the tumor microenvironment, which in turn can be fed into its Surge Platform, allowing the production of recombinant polyclonal antibodies derived from mammalian repertoires. The company has an oncology pipeline containing monoclonal and bispecific antibodies and a recombinant polyclonal immunoglobulin pipeline, which includes treatments for COVID-19 and other infectious diseases.

Like other start-up biotechs, Gigagen had licensed these platforms technologies to other antibody discovery and development companies in order to generate early revenues, before using them as a springboard to launch their own candidate development programmes.

In the next three posts in this series, we’ll explain the start-up financing cycle and how it relates to antibody companies, especially those developing antibody products for therapeutic use. We’ll use industry examples to describe different types of investors in antibody innovations, what they look for in a company or idea, and their expectations as to how the funding is utilized. We will also explain how the funding cycle is changing, which will help inventors fund the clinical journey more easily.

Watch for our second post next week!

1.       Kaplon H & Reichert JM (2021) Antibodies to watch in 2021. mAbs.

2.       Friedman J. How Biotech Startup Funding Will Changing in the Next 10 Years.