Category: News Roundup

Icosavax launches to advance designer vaccines

Icosavax, Inc. today announced its launch with a $51 million Series A financing. The company was founded on computationally designed self-assembling virus-like particle (VLP) technology developed here at the IPD (Cell 2019, Preview).

The proceeds of the financing will be used to advance the company’s first vaccine candidate, IVX-121, for respiratory syncytial virus (RSV) for older adults through Phase 1b clinical studies. Icosavax also announced today its leadership team, board of directors and key scientific advisors.

“Icosavax’s vaccine technology solves the problem of constructing and manufacturing VLPs displaying complex antigens by utilizing computationally designed proteins that separate the folding of individual protein subunits from the assembly of the final macromolecular structure. The individual proteins are expressed and purified using traditional recombinant technologies, and then self-assemble into VLPs when mixed together,” said Icosavax co-founder Neil King, Ph.D.

VLPs are known to induce superior immunological responses compared to traditional soluble antigens, eliciting protective immune responses while reducing the need for strong adjuvants, which in some instances have been associated with side effects.

The company’s RSV vaccine candidate, IVX-121, incorporates a stabilized prefusion F antigen licensed from NIAID/NIH (DS-Cav1; Science 2019). Extensive preclinical studies conducted at IPD and Icosavax suggest that IVX-121 could increase the protective immunogenicity of RSV F compared to the DS-Cav1 antigen alone.


Read the full press release as well as coverage in GeekWire and EndPoints.

Neoleukin: from spinout to public company in 7 months

IPD-spinout Neoleukin Therapeutics announced this week a merger with Aquinox Pharmaceuticals, a publicly traded company. The combined company will change its name to Neoleukin Therapeutics, and will continue to advance its Rosetta-designed protein platform for cancer, inflammation, and autoimmune diseases.

Neoleukin was spun out of the IPD Translational Investigator Program in January. As a result of this exciting merger, it will be the first publicly traded company in history with a de novo designed protein as its core technology. The new stock ticker will be NASDAQ:NLTX after the deal closes.

As part of the deal, Neoleukin has also gained access to $65 million in capitalization.

“The merger with Aquinox is transformational for our company,” said Neoleukin CEO Jonathan Drachman, MD. “We believe that cytokine mimetics, or Neoleukins, have the potential to offer enhanced therapeutic effects with fewer toxic side effects.”

Senior leadership at Neoleukin still includes three IPD-trainees: Daniel Silva, PhD as VP, Head of Research; Umut Ulge, MD, PhD as VP, Translational Medicine; and Carl Walkey, PhD as VP, Corporate Development. Aquinox’s former stockholders own approximately 61% of the combined company’s capital stock.

To learn more about Neoleukin, visit: www.neoleukin.com

To learn more about their platform technology, see: https://www.nature.com/articles/s41586-018-0830-7

5 questions about LOCKR from our Reddit AMA

Researchers from the IPD and UCSF recently participated in a Reddit Ask Me Anything about LOCKR, our new de novo protein switch. Reddit users had dozens of fantastic questions — so many, in fact, that the team ran out of time before they could address them all.

“The questions were both insightful and interesting,” says Hana El-Samad, a co-senior author of the LOCKR reports. “I had so much fun answering them!”

Hana was joined by Bobby Langan from the IPD and Andrew Ng from UCSF, both co-first authors of the reports. Some participants asked pointed technical questions about concepts that our scientists are already grappling with. Others drew the lens back to ask about the medical and ethical ramifications of making proteins that can control the behavior of cells. (ICYMI: here’s the paper describing LOCKRs design, and here’s how the team turned it into a circuit for cellular feedback.)

Here is our pick for the top five LOCKR questions from our Reddit AMA:

1. How did you guys originally come up with the idea to design these proteins? Would a treatment using LOCKR still have side effects like drugs do? And you used the example of acute inflammation from a TBI; could these proteins be used for other kinds of inflammation as well, such as the chronic inflammation found in autoimmune diseases? – /u/raucous__raconteuse

The idea for LOCKR grew out of a 2016 paper (you may notice some authorship overlap 🙂 ) where we described how to create really well-behaved helical proteins. We wanted to add function into them, so after a couple whiteboard brainstorming sessions, we decided to try to get one part of the protein to switch in the way we published — and install function in such a modular way. Then, within the IPD and with Hana/Andrew, we developed the functions we’ve published and got it to work in living cells! There’s a lot of work still to do to determine if a cell that uses LOCKR will have any unintended side-effects. Of course, we are attempting to engineer the cells in a way to mitigate that in a predictable way.

TBI is an initial indication, but the field of engineering therapeutic cells — especially using LOCKR — is so new that working on other kinds of inflammation and autoimmune diseases is certainly on the table. What indications would you like to see researchers like us work on? – BL

2. Do you guys know yet when LOCKR could be in commercial use? Even a ballpark guestimation would be interesting. – /u/JustTheBP

There is a lot of work that still needs to be done to use LOCKR in a commercially viable product, and that work is starting! Since the biotech/FDA pipeline is (necessarily) long and rigorous, it’ll be many years before something using LOCKR is ready for use in humans. -BL

3. It sounds like the target for the artificial protein is different protein domains. Is there any risk of off-target binding? Does the “key” protein that allows the activity of the artificial protein need to be endogenous? I imagine there could be a situation where it would be desirable to have the artificial protein activated by a pharmaceutical, is that an area of interest for the research or is the focus more on utilizing existing pathways within the cell? – /u/senojsenoj

Because cells are like burritos where everything is mixed together, there is always a risk for off-target interaction, but part of the beauty of LOCKR is that since these proteins were completely designed in a computer, they will be far less likely to interact with other proteins in the cell compared to other engineered proteins that are directly taken from nature. Currently, the Key that activates the Switch is also a designer protein, but many others are interested in designing proteins that are activated by or interact with endogenous proteins. Designing proteins that can be activated by small molecules is also extremely useful, and many others are working on this! -AN

4. What advice do you have for an undergrad, looking to change the world someday? Have any living trials been conducted yet? Will there be any applications in an orthopedic surgical setting, like with joint replacements, to reduce post-op swelling? What about for chronic joint inflammation? Can this also be used in place of immuno suppressants after an organ transplant? – /u/whiskerbizkits

First piece of advice — keep up your passion for changing the world. Second, pursue studies in science and engineering, and think about engaging actively in research (ask professors what research opportunities are available). As to your questions about applications, we believe that live cell therapies (the ability to take cells out of a patient, engineer them and put them back to be “living medicine”) hold great promise for all the areas you mention. For these cells to be safe, effective and robust, they need to be “smart,” which means they need to be able to detect their local environment and react to it. We need to program them to do so. This is where LOCKR (and other synthetic proteins) and synthetic biology in general can help! And btw, these therapeutic cells could also be programmed to shut themselves off once their job is done, so this is not engineering the genetic code of a human, but rather giving them the equivalent of smarter “pills”! –HES

5. How many other names for the protein did you all consider? Did you have to stretch a bit to land on one as cool as LOCKR, or was that just totally serendipitous? – /u/DrColossusOfRhodes

I knew someone would comment on the name! Scott (another co-first author on this paper) and I went through several iterations over the span of a week — he came up with LOCK then I added the R from pRotein considering other, trendy, names in tech right now (CRISPR, tumblr, flickr, grindr, etc). I get a laugh every time I present the acronym. It’s a little stretched… but it works 🙂 -BL


Who’s who:

BL: Bobby Langan, co-first author, UW
AN: Andrew Ng, co-first author, UCSF
HES: Hana El-Samad, co-senior author, UCSF

How synthetic biology could treat celiac disease

Dr. Ingrid Pultz, an IPD Translational Investigator and Chief Scientific Officer at PvP Biologics, has written a special report for the American Council on Science and Health about how protein design is being used to help fight celiac disease. Pultz describes how an international competition, a video game, and venture capital all aligned to help enable this exciting work.

Read her full report here: How Synthetic Biology Could Treat Celiac Disease

 

September IPD News Roundup

P-icon-color

RESEARCH

IPD Translational Investigator, Dr. Ingrid Pultz, published a paper in JACS  this month titled ‘Engineering of Kuma030: A Gliadin Peptidase That Rapidly Degrades Immunogenic Gliadin Peptides in Gastric Conditions‘.Kuma030 Using Rosetta to redesign the active site of the gliadin protease KumaMax – an enzyme computationally designed to break down gluten in the stomach – Dr. Pultz and collaborators show that the new variant Kuma030 degrades >99% of the gluten peptide that triggers inflammation in celiac disease patients. This work brings us even closer to arriving at an oral therapeutic for celiac disease.

IN THE NEWS

Dr. Pultz was interviewed by MyNorthwest.com on her work developing a pill that celiac patients can take before consuming gluten. Read and hear more at the link:

http://mynorthwest.com/874/2814454/A-gluten-fighting-pill-for-Celiac-disease-is-on-its-way-thanks-to-UW-Medicine-researchers

INSTITUTE

The IPD hosted its second Scientific Council meeting this month, chaired by David Urdal, PhD, MS. The council is made up of UW and Fred Hutch faculty from a variety of departments (Oncology, Genome Sciences, Immunology, Allergy & Infectious Diseases, Biochemistry, and Pharmacology). The goal of the IPD Scientific Council is threefold:
1. Identify new opportunities, targets, and applications to which protein design can be applied
2. To strategize on how best to balance core technology development with translational projects of value today and translational projects with important impacts 5 to 10 years down the road
3. Provide feedback on current projects

IPD Director Dr. David Baker was the Keynote speaker at the 13th Annual NanoDDS (International Nanomedicine and Drug Delivery) symposium, held at the UW this year. Dr. Baker gave a talk entitled ‘Engineering Protein Nanocarriers: Deisgn of protein interaction inhibitors and self-assembling nanocages’.

Dr. Baker also spoke on a panel at the Washington State Academy of Sciences 8th Annual Symposium on “Accelerating Science’s Impact: Translating Discoveries Into Solutions”. Held at the Museum of Flight, the panel was moderated by UW CoMotion Executive Director Vikram Jandhlaya and panelists discussed various topics under the theme of “Translational Science for Health and Disease Barriers and Solutions”.

August IPD News Roundup

P-icon-color

RESEARCH

Following the groundbreaking 2014 Nature paper describing the development of a computational method to design multi-component coassembling protein nanoparticles, comes a publication in Protein Science from Baker lab graduate student Jacob Bale and collaborators. Titled “Structure of a designed tetrahedral protein assembly variant engineered to have improved soluble expression“, the paper reports a variant of a previously low yielding tetrahedral designed material for which structure determination was difficult. The new variant described in the paper had a much improved yield after redesign and the structure obtained agreed with the computational model with high atomic-level accuracy. The methods used here to improve soluble protein yield will be generally applicable to improving the yield of many designed protein nanomaterials.

Bale_improvedTetr

INSTITUTE

Congratulations to newly minted PhDs and graduates of the Baker lab Dr. Shawn Yu and Dr. Ray Wang! Both defended their dissertations this month. Dr. Yu gave a talk on “Computational design of interleukin-2 mimetics” and Dr. Wang spoke about “Protein structure determination from cryoEM density maps”. We wish them the best of the luck in their next steps!

The annual RosettaCON meeting was held July 29-Aug1 at the beautiful Sleeping Lady Mountain Resort in Leavenworth, WA. Many IPD scientists attended the conference, heard talks from researchers in Rosetta labs across the country, presented posters on their own research, and socialized with the larger Rosetta community.