We have an annu­al tra­di­tion at Kan­vas Bio, where we host an in-depth review of our research and devel­op­ment accom­plish­ments from the past year. We also out­line our mile­stones for the year ahead. We call it Sci­ence Day, and as Kan­vas Bio con­tin­ues to grow, it’s an impor­tant time for our team, part­ners and investors to come togeth­er, and col­lec­tive­ly assess the company’s momen­tum and goals. 

Fresh off the heels of our pre­sen­ta­tion at SITC – where we shared excit­ing new data that demon­strates that the micro­bio­me can have a clin­i­cal impact in can­cer treat­ment – this year’s Sci­ence Day focused on two major updates: 

1. A new micro­scope we’re devel­op­ing called the Kan­vas Spec­tral Light­sheet (KSL), which enables fun­da­men­tal­ly new insights into host-micro­bio­me inter­ac­tions and will accel­er­ate our pre­clin­i­cal development.
2. A new immuno-oncol­o­gy drug we’re design­ing called KAN-004, which tar­gets immune check­point inhibitor (ICI)-induced col­i­tis, and may allow can­cer patients to stay on ICI ther­a­py longer with improved response rates.

We spoke with mem­bers of our sci­en­tif­ic team to dive deep­er into how these two mile­stones bring us clos­er to achiev­ing some of our biggest goals and why they mat­ter more broad­ly. Read on for our conversation.

Drs. Kevin Keo­ma­nee-Dizon and Hao Shi on the KSL:

Q: Why are you devel­op­ing a new microscope?

A: The Kan­vas plat­form uses com­bi­na­to­r­i­al spec­tral bar­cod­ing to enable high­ly mul­ti­plexed spa­tial map­ping of gene expres­sion at sin­gle-cell res­o­lu­tion. Pre­vi­ous­ly, we used com­mer­cial­ly avail­able, con­fo­cal spec­tral micro­scopes for data acqui­si­tion relat­ed to host-micro­bio­me inter­ac­tions. With con­fo­cal micro­scopes, our plat­form can mea­sure 10⁵ micro­bial cells and 10³ host cells per tis­sue sec­tion, and observe local spa­tial het­ero­gene­ity across the tis­sue sec­tion. But this sam­pling strat­e­gy involves a small frac­tion of the spa­tial biol­o­gy in a tis­sue spec­i­men, mak­ing com­pre­hen­sive analy­sis across tis­sue sam­ples challenging. 

Light-sheet microscopy, which selec­tive­ly illu­mi­nates the focal plane of inter­est, can image live and trans­par­ent sam­ples (such as cul­tured cells and small organ­isms), pro­vid­ing good spa­tial res­o­lu­tion and fast imag­ing speed. But it’s lim­it­ed in cap­tur­ing large vol­umes at high spa­tial res­o­lu­tion, and very lim­it­ed in spec­tral capa­bil­i­ties. High­er through­put instru­ments exist, but they’ve pri­mar­i­ly been devel­oped for imag­ing the brain and gen­er­al­ly do not have spec­tral imag­ing. Cur­rent­ly, there’s no sin­gle instru­ment (com­mer­cial or aca­d­e­m­ic) that com­bines high spa­tial res­o­lu­tion, high sam­ple through­put and high spec­tral mul­ti­plex­ing capa­bil­i­ties, and this is what we need to con­tin­ue to advance our mis­sion of unlock­ing the pow­er of the microbiome.

Q: What makes the KSL different?

A: While exist­ing imag­ing modal­i­ties lim­it the vol­ume of tis­sue that can be mea­sured, the KSL enables spec­tral imag­ing across large sam­ple areas, at high spa­tial res­o­lu­tion, with a short turn­around time and in 3D. Our micro­scope images across mil­lime­ter-scale and beyond vol­umes at <1 day/​tissue, com­bin­ing sev­er­al inno­va­tions to address the chal­lenges of the sam­ple through­put, spa­tiotem­po­ral res­o­lu­tion, and spec­tral mul­ti­plex­i­ty of con­fo­cal and con­ven­tion­al light-sheet microscopy.

The KSL enables data acqui­si­tion rates at least 820-fold above any com­mer­cial­ly avail­able plat­form, and can gen­er­ate large datasets for our pro­pri­etary data­base. It also stands to enhance our ther­a­peu­tic man­u­fac­tur­ing capa­bil­i­ties. We’ve already inte­grat­ed our plat­form to achieve pre­cise ther­a­peu­tic strain iso­la­tion and opti­mize drug man­u­fac­tur­ing process­es by mea­sur­ing strain abun­dance and via­bil­i­ty. Using a con­fo­cal micro­scope, we can process hun­dreds of sam­ples per week, but with the KSL, we can process hun­dreds of sam­ples per day. This increased through­put will facil­i­tate the pre­cise con­struc­tion of live bio­ther­a­peu­tic prod­ucts (LBPs) and accel­er­ate our pre­clin­i­cal devel­op­ment.

Q: How will the KSL ben­e­fit the broad­er sci­en­tif­ic community?

A: We believe the scale of data acqui­si­tion enabled by KSL will have a trans­for­ma­tive impact on micro­bio­me research. For exam­ple: In can­cer, rare cells often form small nich­es that dri­ve ther­a­py resis­tance, and in micro­bi­ol­o­gy, rare species can pro­found­ly influ­ence ecosys­tems by play­ing key roles in spe­cial­ized bio­log­i­cal process­es. Inter­ac­tions between rare cells are sta­tis­ti­cal­ly uncom­mon, mak­ing them chal­leng­ing to study, and cur­rent meth­ods (such as using lentivi­ral vec­tor sys­tems to label cell types) are cum­ber­some and time-con­sum­ing. The KSL can cap­ture these cell inter­ac­tions with unprece­dent­ed sen­si­tiv­i­ty and scale, while also archiv­ing the data. This enables hypoth­e­sis test­ing to be con­duct­ed in the time it takes to query our pro­pri­etary data­base, as opposed to the months or years typ­i­cal­ly required for syn­thet­ic biol­o­gy experiments.

Drs. Jeb Berle­man and Lee Swem on KAN-004: 

Q: What indi­ca­tion does your new drug target?

A: KAN-004 is a com­plex LBP that tar­gets ICI-induced col­i­tis. ICI col­i­tis is the most com­mon immune-relat­ed adverse event seen in sin­gle-agent can­cer immunother­a­py treat­ment and the increased use of dual-ICI reg­i­mens is broad­en­ing this patient pop­u­la­tion. Patients suf­fer­ing from ICI col­i­tis are often forced to put their ICI treat­ment on hold, which unfor­tu­nate­ly allows their can­cer to progress. 

Our longer term goal is that the suc­cess of KAN-004 in the ICI-induced col­i­tis patient pop­u­la­tion will lead to expand­ing to oth­er relat­ed indi­ca­tions, includ­ing treat­ment of all immune relat­ed adverse events (irAEs) asso­ci­at­ed with can­cer immunother­a­py and even beyond oncol­o­gy to ulcer­a­tive col­i­tis and Crohn’s disease. 

Q: How does KAN-004 dif­fer from exist­ing treatments?

A: Over-the-counter treat­ments, such as Lop­eramide or fiber sup­ple­ments, may help some, but they aren’t par­tic­u­lar­ly potent. Steroids like Pred­nisone are anoth­er com­mon treat­ment, but as immuno­sup­pres­sants, they bring a high risk of com­pli­ca­tions, such as infec­tion and/​or can­cer pro­gres­sion. Plus, there are many con­di­tions where treat­ment with steroids isn’t safe, such as Type I Dia­betes and oth­er autoim­mune diseases.

Fecal micro­bio­ta trans­plants (FMTs) are a trans­for­ma­tive ther­a­py for ICI col­i­tis, and we see an oppor­tu­ni­ty to make them even more effec­tive by replac­ing the fecal com­po­nent with a com­plex LBP com­mu­ni­ty. In doing so, KAN-004 will offer mul­ti­ple safe­ty and purifi­ca­tion steps, and more con­sis­tent prod­uct and sup­ply, all while main­tain­ing the ben­e­fits of a diverse, com­plex con­sor­tium. Also, KAN-004 will be avail­able oral­ly, as opposed to FMT’s deliv­ery via colonoscopy. 

Q: How will KAN-004 impact ICI ther­a­py overall? 

A: To start, reduc­ing col­i­tis symp­toms will improve patients’ over­all health. Next, while steroids are often the first line of treat­ment, as many as 30 – 45% of patients who resume ICI ther­a­py after steroid treat­ment expe­ri­ence col­i­tis again – indi­cat­ing that while steroids may alle­vi­ate symp­toms, they don’t address the under­ly­ing cause. Instead, hav­ing a safe and well-tol­er­at­ed micro­bio­me treat­ment that restores key func­tions of the gut micro­bio­me may be the key to durable res­o­lu­tion of col­i­tis symp­toms and long term suc­cess­ful ICI therapy. 

Pre-clin­i­cal stud­ies of KAN-004 show improved response to ICI ther­a­py in mouse mod­els. These data are com­pelling, in par­tic­u­lar because KAN-004 micro­bio­me ther­a­py has the poten­tial to increase sys­temic immune response to tumors, while reduc­ing local inflam­ma­tion in the gut. We expect that suc­cess­ful results for KAN-004 can resolve col­i­tis symp­toms, with the poten­tial to allow patients to stay on ICI longer and improve ICI ther­a­py response rates.