The Antibody Society

the official website of the antibody society

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

Funding the Development of Antibody Innovations: Part 3: Crossover Investors

by

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

The development of antibody therapeutics requires large amounts of cash to sustain nascent companies while they demonstrate the safety and efficacy of their products in clinical trials. It is estimated that it takes over a billion dollars to bring an antibody therapeutic to market. In our last post (1) we described how biotech firms use pre-seed and seed funding to get their ideas off the ground, but following these, they typically rely on VCs for their next rounds of finance. The first round of VC funding or Series A funding can run into tens of millions of dollars.

Ori Biotech, a company developing a manufacturing platform for cell and gene therapies, raised $30 million of additional funds from a group of VCs, having initially raised $10 million in seed funding. The team believe the Series A funding is sufficient to develop a minimum viable product, the earliest version of the technology that can be released to the first customers for them to provide feedback and allow subsequent improvement cycles.

In an interview published in March 2021, Ori Biotech CEO, Jason Foster, advised start-up companies seeking Series A investment to start by developing a comprehensive understanding of the market for the technology and how to pitch effectively to potential investors. Secondly, he recommended firms target the right investors, as different investors specialize in different sectors and investment stages. Finally, he emphasized that fundraising is a full-time job, so companies should ensure they have sufficient support and time allocated to this critical activity (2).

Series B Venture Capital funding

AgomAb, is a Belgium start-up that is working on regenerative pathway modulators in inflammatory, metabolic and fibrotic diseases. It has raised two rounds of VC funding. Scientists at the company have drawn upon research from the 1990s that suggested hepatocyte growth factor (HGF) and the HGF-MET pathway might have regenerative potential. Founded in 2017, the company raised $25 million in 2019 in a Series A funding round, which it used to perform research on a set of full and partial MET agonists.  These had been discovered through a partnership with argenx, which gave AgomAb access to the SIMPLE antibodyTM technology platform that raises antibodies with variable regions derived from the immune systems of ‘outbred’ llamas.

AgomAb’s Series A funding allowed it to progress its lead antibody candidate, AGMB-101, into Investigational New Drug-enabling toxicology studies, but the company needed additional funding to enter the clinic and so raised a further $74 million in Series B funding. Significantly, AgomAb considers that AGMB-101 could be efficacious in a range of disorders and represent a pipeline-in-a-product; however, it is also seeking to expand its pipeline beyond this lead candidate (3).

So, what’s the difference between Series A and Series B funding? Tom Burt of Sofinnova Partners points out, “The AgomAb example highlights that the amount of capital raised in Series B is larger, which in this case this is helpful because of the high costs of clinical development activities, and that the scope of what the business must achieve has evolved. In many instances, the two rounds of funding might seem similar and represent a continuum, with the Series B round being led by the same Series A investors. Redmile and Cormorant, two well-known US-based crossover funds, led this funding round.”

“Crossover investors can be considered as VCs that invest in promising companies that have the near-term potential to list their shares on a stock exchange in a financing round known as an Initial Public Offering [IPO]. They are a relatively new addition to the venture capital continuum. While a crossover investor will still need to be convinced of the potential in the company’s pipeline, they also have a focus on the public markets,” he says.

Cross-over investors can be more flexible around the clinical stage of development and can finance preclinical to Phase 3 clinical-stage companies if they believe that sufficient appetite exists amongst public market investors for the IPO candidate. Typically, the crossover investor[s] will seek to raise a significant amount of funds in a Series B [and sometimes Series A round] with the committed intention of supporting any IPO round alongside traditional institutional investors.

In our final post of this 4-part series, we will look at the final stages of the financing cycle, including how crossover investing has altered valuations of early-stage biotech companies. We’ll examine the case of EpiMab and discuss how investors in  a company like this might look to exit and generate a return on their investments.

We hope you’ll join us next week for the final post in this series, Exit Strategies for Investors in Antibodies.

(1)    Burt T. & Hutchinson N. (2021). Funding the Development of Antibody Innovations. Part 2: Business Angels and Venture Capitalists.

(2)    Finerva (2021). Ori Biotech – Fundraising & Growth. March 12, 2021.

(3)    Taylor, P. T. (2021) AgromAb raises $74M to develop regenerative pathway modulators. Fierce Biotech. March 10, 2021.

COVID-19 AIRR-seq Vaccine Data Available!

by

The first AIRR-seq dataset from people who have been vaccinated against COVID-19 is now available in the AIRR Data Commons, accessible through the iReceptor Gateway. As more vaccination studies are made available, researchers will be able to compare these antibody/B-cell and T-cell receptor (BCR/TCR) sequences to the over 1 billion such sequences from studies of COVID-19 patients. Vaccines are designed to elicit the same immune response as that caused by natural infection, and the availability of data from vaccinated individuals will enable direct comparisons between these two types of responses. Such comparisons can determine the effect of different vaccine technologies, measure level of protection against circulating variants, and identify immune pressures leading to future variants. For example, this first vaccination study (Goel et al.) that is now curated in the AIRR Data Commons presents data from five recovered donors at three time points: before vaccination and after the first and second vaccinations, and the comparison suggests that COVID-19 recovered individuals may only require a single vaccine dose to achieve peak immune response. Similar comparisons as new vaccination studies become available will help inform public health decisions such as vaccine dosing and booster schedules.

The AIRR Community encourages and supports researchers in sharing their COVID-19 AIRR-seq data from natural infection and vaccination through the AIRR Data Commons. Now more than ever, access to curated, ready-to-analyze antibody and BCR/TCR sequence data will contribute to rapid health insights and public health strategies worldwide as we work to move through and beyond the COVID-19 global pandemic.

For an overview of the AIRR Data Commons, including demos on how to find and share data, see our recent webinar, The AIRR Data Commons: 4 billion reasons to store, analyze and share antibody/B-cell and T-cell receptor repertoire data.

EUA issued for anti-SARS-CoV-2 sotrovimab

by

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

by

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

by

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