$50M Program in Human Organs, Physiology, and Engineering (HOPE)

$50M Program in Human Organs, Physiology, and Engineering (HOPE)

We need better models of human physiology – the mouse is not a human and dialysis is not a kidney.

In the past 15 years, even as the number of new drug candidates in development nearly doubled, 90% of those that succeeded in preclinical animal studies failed in human trials. This high attrition rate – approximately 50% of failures for lack of efficacy and 30% for toxicity – raises the cost per new drug up to $2.8 billion according to recent estimates. In the current pandemic, mRNA vaccines went from virus sequence to first dosing in humans in an unprecedented 63 days – but the clinical trials will take more than a year. Even a single month saved in clinical trials would have meant trillions of dollars in global economic damage avoided. 

For patients with organ failure, allograft donor transplant is often the only option. Worldwide, millions of patients on dialysis await a kidney transplant, for example. In the United States, alone, about 5,000 people die each year while waiting, making kidney disease a top ten killer – responsible for more deaths each year than breast cancer and more than $100B in Medicare costs. Of the more than 2 million patients with late-stage chronic kidney disease receiving dialysis replacement therapy, only 35% will survive the wait.

What do these challenges have in common?  An inability to replicate human physiology; in particular, functional organs and immunological responses.

It’s time to bioengineer a change.

Indeed, if we are to build new solutions that catalyze a Health Age, we need 10x, scalable, transformations in the underlying time, cost, and efficiency of finding new solutions. Historically, fundamental advances in these parameters have exploded the number of innovators and the pace of innovation in fields as diverse as semiconductors, software, and genome sequencing.

Program goals.

In this program, we aim to leverage the power of bioengineering to advance stem cells, organoids, and whole organ systems and connections that recapitulate human physiology in vitro and restore vital functions in vivo. We have two goals:

1. Bioengineer a multiorgan platform that recreates human immunological responses with sufficient fidelity to double the predictive value of a preclinical trial with respect to efficacy, toxicity and immunogenicity for therapeutic interventions targeting cancer, autoimmune and infectious diseases.

1a. The platform should represent tissue-resident and lymphatic immune systems and recreate immunological mechanisms involved in pathologies and drug-induced reactions (including effects on target and non-target organs), as demonstrated in retrospective studies of a statistically relevant number of immunomodulator drugs.

1b. The platform should predict the wanted immunogenic activity of vaccines and the unwanted immunogenic risks of therapeutics, especially to inform the design principles for an immunologically tolerated transplantable organ.

2. Demonstrate the advances necessary to restore organ functions using cultivated organs or biological/synthetic hybrid systems that would result in a doubling of the 5-year survival rate of patients on replacement therapy or awaiting organ transplantation and point to a fully transplantable, non-rejected, human organ within 10 years.

2a. In the program we expect to produce the first hypo-immunogenic living functional unit at human scale, for example a kidney nephron with a filtration rate at least equivalent to moderate CKD stage and an immunogenicity profile in the range of an autologous graft.

2b. Advances are expected to contribute to the physiological relevance and robustness of organ system platforms for in vitro applications such as drug testing.

Call for abstracts and proposals.

We are soliciting abstracts and proposals for work over 3 years (with a potential additional one-year option) in one or more of 5 thrust areas, which are described in detail in the full program announcement. Proposers should clearly relate work in these thrust areas to one or more of the program goals.

Program Director.

Annie Moisan, PhD. Annie’s expertise is in the mechanistic biology of drug targets and preclinical safety strategies of novel therapeutics. She has worked at Idorsia Pharmaceuticals, Roche Innovation Center Basel, and as a postdoctoral fellow in genetics and stem cell biology at Harvard Medical School. She earned her Ph.D. in molecular and cell biology from University of Sherbrooke, Canada.

Send inquiries to HOPE@wellcomeleap.org

Process and timeline

Program announcement.

30 DAYS FOR PREPARATION AND SUBMISSION OF ABSTRACT

15-Day Abstract review round.

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Day 1

Submission deadline: 1 Dec 2020

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Day 1

Submission deadline: 1 Dec 2020

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Day 1

Submission deadline:

1 Dec 2020

7-page abstracts submitted (from individual organizations or teams) that address one or more thrust areas of the program.

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Day 15

Abstract feedback sent: 15 Dec 2020

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Day 15

Abstract feedback sent: 15 Dec 2020

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Day 15

Abstract feedback sent:

15 Dec 2020

All submissions will receive technical and/or programmatic feedback as well as a recommendation to submit or not submit a full proposal.

30 DAYS FOR PREPARATION OF FULL PROPOSALS AFTER ABSTRACT FEEDBACK

30-Day Full proposal review round.

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Day 45

Submission deadline: 13 Jan 2021

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Day 45

Submission deadline: 13 Jan 2021

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Day 45

Submission deadline:

13 Jan 2021

25-page full proposals including technical approach, milestones, costs, and key personnel submitted. Proposals should specifically address abstract feedback.

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Day 75

Proposal decision sent: 11 Feb 2021

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Day 75

Proposal decision sent: 11 Feb 2021

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Day 75

Proposal decision sent:

11 Feb 2021

All submissions will receive a ‘selected for funding’ or ‘not selected for funding’ decision. Those selected will proceed to contract signature as the final gate with work expected to commence within approximately 30 days.

Mechanics of applying

Who is eligible?

Performers from universities and research institutions: small, medium and large companies (including venture-backed); and government or non-profit research organizations are invited to propose. We encourage individuals, research labs, companies, or small teams to apply in the thrust areas best aligned with their expertise and capabilities. It is not necessary to form a large consortium or team a priori to address all thrusts or an entire goal in a single abstract or proposal. Indeed, we intend to facilitate synergies dynamically among HOPE performers as we make progress together toward the program’s goals.
 

To submit an abstract, proposers will be asked to agree to the following:

I understand that the information being disclosed will be reviewed and evaluated independently on behalf of Leap. I am submitting information with the intention that it imposes no confidentiality obligations on Leap. Furthermore, my submission does not breach any confidentiality obligations that I owe to others; there is no legal reason why I cannot submit information; and I am not underage or otherwise legally incompetent. By submitting, I am not granting, other than for the purpose of evaluation, any rights in relation to any patent, copyright or design. I am not relying upon Leap in any way for legal advice, including (but not limited to) whether the contents of my submission can be protected under IP law. I recognize that Leap may already be aware of or funding the same or related efforts as described by my submission. I agree that no contractual obligation or working relationship is being created between myself and Leap by submitting this information. If the submission is deemed of interest, I may be required to sign a further Agreement with Leap so that any confidential information, that is subsequently shared, is protected.

Abstract application steps.

  1. Download abstract template
  2. Download guidelines
  3. We’ll remind you when the application portal is open 48 hours before the submission deadline.
  4. Upload your abstract and submit your application before midnight, 1 Dec 2020, at 12:00am EST.

More details will be provided for the proposal round of submissions.

Frequently Asked Questions.

If you have questions, please review our FAQ section.

References

1 Wouters OJ, McKee M, Luyten J. Estimated Research and Development Investment Needed to Bring a New Medicine to Market, 2009-2018. JAMA. 2020;323(9):844–853. doi:10.1001/jama.2020.1166

2 DiMasi JA, Grabowski HG, Hansen RW. Innovation in the pharmaceutical industry: new estimates of R&D costs. J Health Econ. 2016;47:20- 33. doi:10.1016/j.jhealeco.2016.01.012