Business
The Cures 2.0 Act: Transformative Investment in Early-Stage Biopharmaceutical Development & Commercialization
A bill that provides important frameworks for breakthrough products in the next three to five years
You may not have noticed the recent Cures 2.0 Act introduced to Congress by two U.S. Representatives, Diana DeGette (D-CO) and Fred Upton (R-MI).
As a follow-up bill to the bipartisan 21st Century Cures Act signed into law in 2016, which accelerated healthcare innovation, this 2.0 version is particularly interesting for biomedical researchers, industry, and investors because it has the latest details on the new Advanced Research Projects Agency for Health (ARPA-H). The 173-page bill is a bundle of proposed policies to plug into challenges facing healthcare technologies from bench to clinical, regulatory approval, and subsequent adoption.
The tone and tenor of national life sciences policy matters.
Not just from a funding standpoint, but also in the early stages of biopharmaceutical development when principal investigators (PIs) and research teams start to consider their work in the context of commercialization.
A path to market for early-stage research
Take biopharmaceuticals as an example and the focus of this analysis. Some of the most difficult challenges with their development occur in the pre-clinical domain (e.g., identification of novel composition of matter, construction of engineered cells with robust add-on features, conceptualization of specific indications for clinical validation, accumulation of in vivo data for a portfolio of outputs or derivatives). Frequently, a novel approach has been validated with a working definition of the ultimate product while the scientific data bear out. It is at this point that market opportunity questions emerge:
Who are the direct competitors?
Is there market interest?
What is the time and cost to market?
What is the appropriate IP strategy?
Has a business model been defined?
What channels of distribution are important?
Diligence in this manner often reveals significant risk, cost, and timing considerations, resulting in de-prioritization by investors. Thus, even getting to the clinical pipeline can be an ordeal. This is where the Cures 2.0 Act aims to offer solutions that will make it easier to translate science into business ventures with near-term commercial implications.
To be clear, biopharmaceutical research does not need commercialization to justify quality, applicability, or impact.
But for interested PIs, they can face a lot of market skepticism. Under ARPA-H, researchers would receive funding to tackle projects that may otherwise be considered too risky from a commercial standpoint. ARPA-H’s mantra is characterized as a relentless drive to take risks with sizable failure expected. For industry and investors, ARPA-H is a hub of high-risk, high-reward creativity to partner on commercialization, as well as access to aggregated top talent.
What ARPA-H may look like structurally
ARPA-H is tasked to deliver “transformational innovations in health and medical product development,” requesting $6.5 billion in the FY2022 budget. Similar in concept to the Defense Advanced Research Projects Agency (DARPA), ARPA-H would follow a “flexible and nimble” organizational strategy within the NIH under a five-year term-limited Director appointed by the President. A cohort of program managers (likely from industry or top research universities) hired for three years will have the independence and resources to deploy funding for “true breakthroughs” across public and private sectors.
See pages 142–163 of the bill for details on the authority, structure, personnel, and responsibilities of ARPA-H.
True breakthrough criteria in the near-term
So how would ARPA-H determine what research projects to fund? DARPA’s Heilmeier Catechism has been cited as a guiding analog, but these evaluation criteria are vague on critical proof points for both researchers and industry alike. National research directives in the Cures 2.0 Act provide some clues about prioritization for funding. Based on a close reading of the initial policy, the criteria below may better contextualize what it means to be a true breakthrough biopharmaceutical product under ARPA-H:
- Significant prospective disease burden demonstrated by a combination of factors including prevalence, total cost of care, subpopulation unmet need
- High level of current clinical and/or operational skepticism from key opinion leaders
- Clearly defined clinical milestones within 3 years
- Time to market 5+ years despite multi-stakeholder collaboration efforts
ARPA-H intends to accelerate research that is difficult to fit into existing support mechanisms from academia, industry, and investors. I’m an ex-life sciences consultant now working on business development at a university technology transfer office. Given my exposure to stakeholders involved with early- and late-stage technology, several approaches to determine biopharmaceutical research that likely meet initial qualifications for true breakthrough innovation under ARPA-H are outlined below.
Potential use cases
Diseases with standard of care limitations
One strategy is to examine disease indications where the standard of care is limited (e.g., few FDA-approved options, low overall survival, insufficient durable response). Some therapeutic areas have no disease-modifying treatments on the market to-date (e.g., NASH) while others have many options with no recent clinical innovation (e.g., ADHD). There are also diseases like acute myeloid leukemia (AML) and myelodysplastic syndromes (MDS) where overall survival is frequently <4 months. Specific subpopulations like higher-risk vs. intermediate or newly diagnosed vs. relapsed / refractory can also be considered, such as in multiple myeloma (MM) where patients progress into late-line settings. This represents a nuanced approach to identify priority disease indications instead of over-indexing on traditional metrics like prevalence.
Multi-indication biopharmaceutical modalities
A second approach is to look at various modalities. This wishlist of “what-if” research projects can easily be filled up. Allogeneic cell therapeutics, bi-specific T-cell engagers, microbiome gene therapies, protease-activated antibiotics, and cancer vaccines are a few top-of-mind examples. Each of these has sparked a notable level of optimism or skepticism during my in-depth discussions with healthcare stakeholders. It is a common refrain to hear that the data are immature, and we must wait for more robust clinical outcomes. With ARPA-H, it will be possible to embrace the upside scenarios and fast-track biomedical research. No longer will the sentiment be one of hesitation.
New cost-sensitive, patient-centered clinical paradigms
Beyond disease reversal, a third approach is to support new clinical paradigms — particularly in a cost-sensitive, patient-centered manner. ARPA-H projects can improve existing classes of therapeutics (e.g., less toxic chemotherapies), advance statistical analyses given patient dropout from clinical trials, study surrogate endpoints (e.g., MRD negativity in multiple myeloma), develop scalable manufacturing processes for T / NK cells, and revisit definitions of patient progression (e.g., triple-exposed vs. third-line). In fact, clinical treatment paradigms can be updated — for example, movement of CAR T-cell therapies into early lines or re-treatment with the same modality — that will influence corresponding therapeutics’ reimbursement opportunity. Ultimately, evolving cost sensitivity and clinical benchmarks will be key drivers for ARPA-H funding in a competitive biopharmaceutical ecosystem.
The future of Cures 2.0
Other noteworthy provisions in the Cures 2.0 Act cover digital health regulation, formalizing the Medicare Coverage of Innovative Technology pathway for breakthrough devices, clinical trial design optimization (e.g., real-world evidence, patient enrollment diversity), antimicrobial development incentives (e.g., novel subscription model), two new FDA Centers of Excellence, and national pandemic preparedness (e.g., study on long COVID, testing and vaccine distribution strategy).
If the Cures 2.0 Act passes like its predecessor, the Director of ARPA-H must provide a report to the U.S. Senate within 180 days after becoming law on the guiding principles for funding over the next three fiscal years. It remains to be seen whether this bill can move the needle on bringing transformative products to market by leveraging exciting mechanisms to advance innovation.
About the author
Anna Du is a Manager, Business Development & Engagement and Opportunity Development at University of California, San Francisco Innovation Ventures. She evaluates market opportunities for novel technologies identified through research conducted at UCSF. Anna works closely with UCSF faculty and staff on commercialization activities, including start-up incubation and IP licensing. Her role helps determine the viability of emerging innovations for partners across academia, industry, and early-stage investors.
Prior to UCSF, Anna was a life sciences consultant at CBPartners focused on clinical trial design optimization, go-to-market, and market access strategy for high unmet need pipeline therapeutics — with expertise in oncology and neurological disorders. Anna graduated with honors from Johns Hopkins University where she earned a B.A. in Public Health Studies.
Anna’s LinkedIn profile and contact information are here.
