Launch HN: Matrubials (YC S21) Milk-derived therapeutics for infectious diseases

[ishishah]

Hi, I'm Ishita, cofounder of Matrubials (https://matrubials.com/). We are developing milk-derived therapeutics to address infectious diseases.

I have extensive experience in microbiology and infectious diseases in both academia and industry. Taken together, our founding team has ~100 years of combined experience in microbiology and ecology, food science and chemistry. My cofounders have previously founded other health companies with specialized products (eg. Evolve Biosystems and BCD Bioscience).

We have been focused on structure-function analysis of mammalian milk and the benefits individual components can bring to human health for about two decades. In recent years, we discovered peptides in milk that have selective antimicrobial activity, meaning that they know who the pathogens are, and essentially go after them fast for elimination while bypassing the "good" bugs, leaving them around to continue their jobs. That was the moment we decided we needed to bring these to the market.

One niche in the human body where the imbalance between the good and the bad is really bad, is the human vagina. We've been focusing on specific bacteria that reside in the normal human vagina and those that take over to cause disease. In particular, we hope to reduce the burden of bacterial vaginosis, which remains unresolved with current antibiotics. This is especially important because these infections tend to recur, and can lead to secondary infections and reproductive issues.

Antibiotic discovery is hard, technically and financially. To develop candidate molecules from early stage research to clinically viable products, with efficacy and safety that do better than current standard-of-care, is a major challenge. An opportunity like this one doesn't come around often so we're pretty excited about it.

Converting milk components into therapeutics- now isn't that a great hack? We think so! Happy to hear your thoughts and answer questions!

[nokcha]

Interesting! Are you planning to market your product(s) as a drug, a supplement (or other less-regulated category), or both? (E.g., some fish oil is marketed as a supplement, while other fish oil is marketed as an FDA-approved drug [1].)

>Taken together, our founding team has ~100 years of combined experience in microbiology and ecology, food science and chemistry.

Minor nitpick: Without knowing the size of your team, this sentence is really hard to make sense of. Having 100 people with 1 year of experience each is a lot less impressive than having 10 people with 10 years of experience each.

[1] https://slatestarcodex.com/2014/06/15/fish-now-by-prescripti...

[ishishah → nokcha]

Thank you for your comment. We are evaluating the best path forward based on safety dossier requirements for topical applications. Longer term, we envision that the product should be a prescription based.

Re your comment about founders' experience, we are four founders (three full time Professors, and a senior scientist), with academic and translational portfolio.

[robocat]

What happens if you discover an antibiotic/antimicrobial, your business succeeds in getting it used widely, and then the bacteria evolve antibiotic resistance?

Would that cause problems for the effectiveness of human milk in the general population?

(Also aside: perhaps fix the spelling mistake in the submission title!)

[ishishah → robocat]

Great question: The goal is to dramatically slow down the process of resistance by choice of molecules that are rapid in activity, and creative compositions.

Milk, as a whole will remain to be very effective, like it has been during the millions of years of mammalian evolution. The entire constellation of molecules present in milk (and still many unknowns) will allow for continued functionality (with many exclusive and redundant roles).

That spelling error you pointed out..argh!!! But thanks.

[kQq9oHeAz6wLLS]

Wait...so Minecraft was right? Use milk to get rid of bad effects!

[ishishah → kQq9oHeAz6wLLS]

:-)

[knuthsat]

Nice to see your focus on women's health. The amount of women with recurrent/embedded UTIs and other issues close to the vagina is enormous.

I was quite surprised to find out there are thousands of women suffering decade long issues with no help or just enormous, health devastating doses of antibiotics (multi-year long therapies).

There's been so many approaches over the years (I watched the d-mannose just explode in sales when previously there was none available) but they do not seem to work completely.

There are also small research groups trying to figure out what's happening but there's still no widely accepted therapies. For example, doctors from most EU contries would never prescribe the amount of antibiotics required for multi-year therapies.

It was also quite surprising to me, as a male, when I got my first UTI, they gave me quite a lot of antibiotics, but then when my wife complains about it, she gets silly advice (get pregnant, drink multivitamins, it's probably not UTI [until she starts having kidney infections or urinates blood]).

[ishishah → knuthsat]

Thanks! And I hear you, and recurrent & the secondary infections and the cyclic nature of it all are terrifying, to say the least, and the truth is also that in many cases, the recurrence is due to resistant bugs, that are just not eliminated by current care of Abx. Not to mention, some Abx when systemically administered, lead to major alterations in the gut microbiome as well. All in all, its not a good situation. I'm sorry to hear about your and your wife's infections, and hope we can contribute to reducing that burden somewhat for so many people.

[giantg2]

Sounds interesting. If I'm understanding this correctly, these peptides target a wide range of 'bad' pathogens. Does that include things other than bacteria?

What benefits do these peptides have over other emerging therapies, such as phages?

[ishishah → giantg2]

Thank you! Yes, absolutely. Some of our candidate peptides impact bacteria across the spectrum and we are in the process of evaluating effects on viruses, specifically because the vaginal infections predispose patients to other secondary viral infections, and increased rates of HIV acquisition. In terms of benefits over other emerging therapies, we are focused on the safety aspect to the host and importantly, selectivity (differentiation between pathogenic and commensal bacteria), so that return to homeostasis is fast(er). Btw, I'm a fan of phages. But per our particular application, we belive it is best to move a bit away from "precision" as vaginosis and the umbrella of secondary infections are polymicrobial to a great extent.

[giantg2 → ishishah]

Great, thanks!

[burlesona]

Very interesting! I imagine the challenges of a bio-tech startup are very different as compared to a software startup. What would you say are your biggest challenges getting your company off the ground?

[latenightcoding → burlesona]

Not author but I can tell you it's really hard if you don't have connections in pharma. Location is important, most biotech deals happen in the Bay Area and Boston. Medicinal chemists are not necessarily known for being eager to try out new things.

[ishishah → burlesona]

Thanks! Yes, I imagine that any industry with higher requirement of resources and de-risking of technology walk hand in hand with challenges. Getting off the ground challenge #1 is When?, #2 Funds? and #3 Determining precise timing to get to market?

[arrosenberg]

Interesting concept. Are you extracting existing compounds from the milk and concentrating them to a therapeutic dose, or are you using milk proteins as a scaffolding for synthesis?

Have you mapped out the mechanism of action by which the peptides are antimicrobial? How does it compare to antibiotics derived from fungi?

How scalable is this if it works as well as you hope it will? Is there a path to peptide synthesis without requiring milk as an input?

[ishishah → arrosenberg]

Thanks for your question. Our initial analysis was from a small batch of milk, separation from other components, and evaluating function. Subsequently, we have been getting them synthetically made, determining dose and therapeutic index, to scale, and without the need for milk from an animal source.

[DantesKite]

It would be remarkable seeing this technology applied to restoration of the gut microbiome.

It seems to be involved in so many autoimmune diseases.

Heavy antibiotic use also seems to irrevocably damage the diversity of gut bacteria, leaving individuals susceptible to a lot of health complications later down the line.

Anecdotally, I know raw kefir and Visbiome (a well-studied probiotic) has been very helpful for the restoration of the gut microbiome.

[ishishah → DantesKite]

Amen to that. Restoration of the gut microbiome is key to life-long health, starting with infancy, where colonization by the "right" beneficial bacteria is really important.

Infact, milk does a remarkable job with that. One example: diverse group of complex oligosaccharides present in milk and reaching the colon intact serve as food for the beneficial bacteria, allowing them to dominate the infant gut and present a wide array of benefits.

[chrisco255 → ishishah]

Does pasteurization mess with this effect at all? Is raw milk better?

[ishishah → chrisco255]

Hi! Pasteurization is not known to impact the structure or function of human milk oligosaccharides. But there are certain heat labile molecules that are impacted by it, and raw milk may retain those.

But there is a whole another story with raw milk and pathogenesis. If interested, check this article: https://pubmed.ncbi.nlm.nih.gov/32591006/

[matsemann → DantesKite]

Since peptides is mentioned, BPC-157 is popular for certain gut/digestive problems.

[Etheryte]

Please add a way to subscribe to further updates and/or a newsletter. Your work is highly interesting, but it's easy to lose track of everything you want to keep tabs on over the years.

[ishishah → Etheryte]

Thank you for that advice. I will work on that.

[henearkr]

Once you discovered interesting peptides, please consider mass-producing them with a bioreactor e.g. of modified yeasts.

Milk will be phased out because its carbon footprint is too heavy, so even if it will probably not disappear short-term, you cannot regard it as eternally a plentiful resource, and even right now it is starting to get a stench of non-politically correct (veganism, etc).

[ishishah → henearkr]

Yep. For us, production and scaling is/will continue to be COMPLETELY independent of donor milk.

[henearkr → ishishah]

This is marvelous!!

I sincerely wish you a great success!

[colechristensen → henearkr]

>Milk will be phased out because its carbon footprint is too heavy

It really won't. The food culture heritage of a large portion of the world won't be wiped out by an environmentalist/vegan dream. In the US there is a government finger on the scale which makes dairy quite inexpensive which might see a reduction, but carbon reduction is going to be primarily constrained to transportation and power generation.

You can have my cheese when you pry it from my cold dead fingers (unless you want some :) )

[henearkr → colechristensen]

Nah, lol :)

I just said it won't disappear, exactly for the reasons you quoted! (I know the subject, I come from a cheese-loving country)

But I'm still correct that it is less and less supported.

On the CO2e side, don't underestimate the sheer amount just from the cows.

[rnavara]

Huge congrats, Ishita - amazing to see all your progress!

[ishishah → rnavara]

Thank you! Long way to go, but the ride is fun.

[DanielBaum]

Love the idea and mission! Best of luck Ishita!

[ishishah → DanielBaum]

:-) Thanks!

[skulle16]

Congrats Ishita!

[ishishah → skulle16]

Thank you! We are all excited.

[simonebrunozzi]

Typo in the title: diesases -> diseases

Congrats on the launch!

[dang → simonebrunozzi]

Ouch how did we miss that. Fixed now. Thanks!