Transforming the way diseases are detected, tracked, treated, and understood.
Overview:
Glympse Bio was founded in 2015 when it was spun-out of Dr. Sangeeta Bhatia’s lab at MIT. Dr. Bhatia is a world renowned bioengineer whose research focuses on the measurement of disease progression in vivo using noninvasive biosensors. The company is trying to pull us forward to a future where these biosensors can detect diseases such as Cancer, NASH, and other infectious diseases way before one might develop symptoms or otherwise know they might be sick. This transition to a world of diagnosing disease proactively instead of reactively is one discussed in depth by Dr. Eric Topol, and Glympse Bio brings us into this new world.
Technology and Pipeline:
A better alternative to biopsies
Due to the miniaturization of transistors, computers that once took the space of entire rooms can now fit into our pockets, and this forever changed our world as you already know. What if you had a detector in your body that was so small it could circulate in your body, find the tumor by itself (or disease site), and then send a signal to the outside world confirming or denying disease? That is what Glympse Bio is doing. It’s possible to shrink the parts that make up the detector to 100 nanometers, which is 1,000X smaller than the width of a human hair. At this nanometer scale, the properties of the materials change as do the way they travel through the body. The blood vessels of many tumors (disease site) are leaky, and so nanoparticles can leak out from the bloodstream into the tumor. Whether they leak out depends on their size, which can be achieved by how big or small the material is made. These nanoparticles then are activated by proteases to release a small molecule (the signal). One protease can activate 1,000 of these chemical reactions in an hour, which makes this detector ultra-sensitive.
Now to how these molecules (the signals) reach the outside world. The Kidney is responsible for filtering out the blood and for putting waste into the urine. Coincidentally, what the Kidney filters is also dependent on size. These small molecules (the signals) are then able to filter through the kidney as waste (because of their size) and into the urine. Since the molecules are completely synthetic, they can be customized to be analyzed with almost any tool of choice, be it a mass spectrometer (expensive) or paper (think pregnancy test; inexpensive; paper diagnostics). From intake of the biosensors, it can take roughly an hour to obtain actionable results.
For those ignorant such as myself, a protease is an enzyme that catalyzes proteolysis, which is the breakdown of proteins into smaller polypeptides or single amino acids. Proteases are involved in many biological functions, and this technology can be applicable with any protease mediated disease. There are 570 different native proteases found within the body (Source: Biotech 2050 podcast).
PEG synthetic biomarkers are made of nanoparticles conjugated with protease-cleavable peptides. Polyethylene glycol (PEG) is widely utilized in drug delivery and nanotechnology due to its reported “stealth” properties and biocompatibility, therefore evading the immune system and prolonging circulation lifetime (PEG source).
This platform allows the company to measure unique parts of biology that no other technology can, and can be combined with other research to create a data engine that can drive insights into drug target validation, responders and non-responders, and earlier and improved outcomes for patients. Gilead is an investor in the company which gives them the opportunity to watch the development of the platform. This partnership aligns with Gilead’s therapeutic strategy around NASH as they are the leading player in that indication. As the platform grows in size, the richer the data engine becomes thus enabling more precise classifiers and future treatments.
Clinical Data:
Nash:
Proteases are important in the progression of fibrosis in NASH which is why it is logical that this is the company’s lead indication. Glympse is developing an injectable mixture of protease activity sensors (Glympse Bio Test System (GBTS-NASH)) that:
- Specifically detects the activity of proteases dysregulated in human NASH
- Is safe for human use
- Predicts NASH with fibrosis severity and monitor Drug treatment response in animal models of NASH
- Panel A: shows the NASH proteases that were originally upregulated, meaning increased responsiveness. From the F2 vs. F0-F1 there was a significant increase in gene expression as the disease progressed
- Panel B: shows that 11 NASH proteases were positively correlated with fibrosis stage
- Panel C: MMP2 and FAP are the two most correlated proteases that gradually increase with the fibrosis score
- Panel A: a binary classifier trained on the same 13 proteases as above accurately predicted F2+ from F0-F1 (AUROC=0.85; 95% CI 0.79–0.91)(Sensitivity=78.1, Specificity=79.7)
- Panel B: assigned correct histological score of 141 out of 179 samples
Sensitivity= ability of a test to correctly identify people with a disease
Specificity= ability of a test to correctly identify people without a disease
There is no therapeutic for NASH currently, and as new therapies move through the clinic and into the market, they will need a diagnostic to be able to diagnose patients to then be able to treat them with these new therapies.
Also, if you are someone who understands the clinical data at a deeper level, I would love to talk so I can work through questions I have. Feel free to DM on twitter.
Oncology:
The discovery of cancer at an early stage can improve outcomes, yet cancer detection thresholds for measuring the abundance of biomarkers produced by small tumors are biologically limited. Activity based biomarkers rely on the catalytic activity of enzymes (proteases) to amplify cancer-derived signals and allow detection of small tumors. Synthetic biomarkers can circulate in stealth but then activate at the site of disease potentially can identify tumors as small as 5mm in diameter.
The study used MMP9, which is a protease that is broadly dysregulated in solid cancers. MMP’s have been implicated in cancer cell invasion and metastasis for over 35 years. MMP9 is expressed to activate VEGF (Vascular endothelial growth factor, a protein responsible for blood vessel growth which is key in tumor growth) ligands during the angiogenic “switch” (process of new blood vessels now supplying tumors with nutrients needed to grow?) that occurs when tumors are 1–2mm in diameter; therefore, measuring MMP9 activity may allow detection of tumors smaller than the detection threshold of medical imaging.
This image is of tumor-bearing and healthy mice post administration of F1-PEG showing higher urine fluorescence in tumor-bearing mice.
Again, this is an area that I am particularly weak on and welcome any feedback that can help me learn and understand.
Market:
Nash:
Non-Alcoholic Steatohepatitis (NASH) is the company’s lead indication, and makes sense for multiple reasons. First, this disease effects the liver where a very high concentration of proteases happen to be located. Second, NASH effects roughly 16 million people within the US and 100 million people worldwide. Lastly, there are many difficulties with the current standard needle liver biopsy.
Oncology
Cancer impacts 15 million patients in the US and 50 million people worldwide. A majority of cancer cases are not found until the cancer has metastasized to other parts of the body. As was mentioned prior, there are many instances where tumors go undetected due to the inability of current technology. These synthetic biomarkers are capable of detecting tumors smaller than 5mm in diameter, thus creating a more proactive approach to cancer diagnosis that is currently unavailable.
The markets for both of these indications are quite large, especially if Glympse is able to transition to offering at-home diagnostic exams (oral or aerosol biomarkers and pregnancy test type devices to analyze).
Management:
Dr. Bhatia (MIT; Chair of Scientific Advisory Board) and Dr. Kwong (Georgia Tech/Emory) co-founded Glympse Bio. Dr. Bob Langer is also a board member.
The company is led by Dr. Caroline Loew, who brings over 20 years of experience having worked at companies such as BMS and Merck. The rest of the management team brings decades of experience from companies such as BMS, Merck, Next Generation Diagnostics at the Novartis Institutes of Biomedical Research, and Foundation Medicine.
Financing:
To date the company has raised ~$78MM. Most recently, Glympse raised a $46MM Series B led by Section 32 and Steve Kafka (Foundation Medicine) in July of 2020. Previously, the company raised a $22MM Series A led by Arch Venture Partners and LS Polaris Innovation Fund in October of 2018. It should be noted that Gilead also participated in the Series A giving them the opportunity to leverage this platform to develop treatments based off these new biomarkers.
With a number of blue chip investors on the cap table including the diagnostic experience of both Steve Kafka and Mike Pellini at Section 32, along with the cash position after last year’s raise, the company is in a great position to advance its pipeline towards commercialization. Given the current state of the capital markets, I would not be surprised to see an IPO within the next year or so assuming the IPO window stays open; Bruce Booth had a great post on this topic the other day Life Sci VC.
(Source: Glympse Bio Fundraising)
Summary:
Josh Wolfe has a mental model dubbed directional arrow of progress.
Apple Watch->Oura Ring/Whoop->Levels Health (continuous glucose monitor)-> Glympse biosensors
Each platform allows for continuous health monitoring of your basic health data points (heart rate/steps, sleep/recovery, which foods does your body respond best to). Not to mention, as you follow the directional arrows, you can see that each platform gets more proactive and advanced in terms of understanding the body’s biology and what’s going on. This further strengthens Glympse Bio’s position as a leader in creating a new standard of care for how we diagnose and treat disease. This can be seen maybe as a bit of a reach given that the first three are consumer platforms; however, each represents greater interest in one’s health and when you add that to Glympse’s platform which is capable of functioning like a pregnancy test, its not too extreme.
Mike Maples Jr. has a mental model called backcasting where you think of a possible future and work backwards to get to the breakthrough. One way to backcast is to look for technology inflections (ie. GPS on mobile phones becoming significantly more precise, which meant drivers and riders could be located more accurately through Lyft’s app). This can be applied to Glympse: Advances in nanomedicine are providing the ability to precisely control the behavior of nanoscale drugs and diagnostics. This inflection point will drive us to a future where we are able to detect disease before it becomes a problem, thus giving people a much healthier, better life.
Glympse Bio is one of my favorite private companies, and I thought it would only be right to have them as my first write-up as they are in my fantasy VC portfolio. I have structured my write-ups in a way that examines a company through a risk lens; each bolded headline (technology/pipeline, clinic/regulatory/ip, market, management, and financial) represents a potential risk to an investor and can show where the company needs to de-risked. That lens will serve as my foundation for all my write-ups, and I look to continue to iterate and get better in my analysis as I take more reps. The goal is to consistently build an open discussion each week centered around curiosity in the life sciences.
Questions:
- Does the sensitivity increase (decrease) as the number of proteases increase (decrease) in a given indication?
- Given that these biosensors can be delivered by needle, aerosol, or orally, is there any variance in efficacy between modalities?
- Is there greater complexity in developing biosensors that can be delivered orally or aerosol as compared to being injected intravenously?
- What proteins could the company explore aside from proteases?
Associated links and articles:
Dr. Bhatia Ted Talk (2015)
STAT Article (2020; paywalled)
