Developing monoclonal antibodies for global health

Situation

One of the greatest challenges in creating new global health therapies is that they must be safe with few or no side effects. The treatment cannot be worse than the disease, and the low-income patients receiving these critical drugs often lack access to hospital care in the event they have a bad reaction to these medicines. Unfortunately, many promising new small molecule drugs have safety risks which rule them out for global health diseases.

Since the 2002 FDA approval of Humira for the treatment of rheumatoid arthritis, monoclonal antibodies (“mAb”) have consistently shown an excellent safety profile and clinical effectiveness against historically challenging diseases. Because these types of therapies are fairly new and have a high-risk of being ineffective, research and development for mAb has typically focused on high-reward cancer or autoimmune indications rather than infectious diseases in global health. Additionally, early mAb had poor “drugability” including short half-lives that required multiple expensive injections over the course of treatment. mAb have huge global health potential, but few companies are exploring them because of early limitations and the significant financial opportunity elsewhere.

Approach

In 2011, our colleagues on the HIV and Discovery & Translational Sciences teams identified Visterra as a very promising mAb design and engineering platform. The Company was quite young, having spun out of MIT in 2007, but it had a unique approach to identifying targets for mAb. Visterra explored the physics underlying disease targets and the interaction of their individual amino acid building blocks. This was orthogonal to many other mAb development platforms and had significant potential in identifying new targets for notoriously difficult to hit or highly resistant diseases like HIV. It also offered promise in designing mAb with improved drugability.

The Strategic Investment Fund participated in Visterra’s 2012 Series A financing alongside three very well-regarded biotech venture capitalist firms. The foundation’s $6.8 million investment supported the development of Visterra’s lead universal influenza therapeutic program and initiated a new research initiative to identify promising, previously unexplored drug targets against HIV. Unfortunately, despite diligent efforts by the Visterra team, the program was not successful against HIV; the foundation and the Company agreed to cease research into this area following completion of the agreed upon scope of work in 2015.

Luckily, great teams continue to innovate and move forward, and the foundation reinvested in Visterra’s v2.0 platform to close out the Company’s Series C financing in 2017. The goal of this $10.0 million reinvestment was to support the development of an antibody drug conjugate (imagine mAb targeted missiles combined with small molecule drug payloads) and develop Fc engineering to improve mAb half-life and drugability. The theory for the latter is that increasing the time mAb are circulating in the patient’s system from a couple of weeks to a few months could repurpose mAb developed as, for example, a flu or malaria therapy into a vaccine for these and other seasonal diseases.

Results

Visterra was acquired by Otsuka Pharmaceutical in September 2018, six years after the foundation’s initial investment. In between there were highs, including the U.S. Government Biomedical Advanced Research and Development Authority awarding Visterra with an up to $204.5 million grant for clinical trials of its promising flu monoclonal antibody therapy as well as strategic partnerships with A*STAR in Singapore, Serum Institute of India and Vir Biotechnology in San Francisco. There were also lows, including two failed initial public offerings and ongoing struggles accessing venture capital as an infectious disease-focused company. Through it all, Visterra’s management team, board and investors were steadfast foundation partners focusing on good science and working with world experts to systematically interrogate the potential of the Visterra platform for global health. As part of the $430 million Otsuka Pharmaceutical acquisition, the foundation has the right to bring highly promising mAb vaccine candidates to the Visterra team to attempt to increase their half-life. Additionally, the antibody drug conjugate development program will continue.

It is still early days – by decade-long drug development timeframes – in mAb development for global health. We hope that this partnership will one day pay off in safe, effective mAb featuring extended half-lives and/or novel targets, courtesy of Visterra. But this outcome is not certain; only about 1 in 8 new preclinical infectious disease drugs is approved for the mass market. The impact of the foundation’s investment in Visterra is that we have a chance to continue to work with a strong team that is aligned with the foundation’s goals even after the Company was acquired. With enough of these chances and great partners like Visterra, the foundation will create impactful new drugs against challenging global health diseases.