[HN Gopher] Shasqi (YC W15) aims to make chemotherapy more power...
___________________________________________________________________
Shasqi (YC W15) aims to make chemotherapy more powerful and less
toxic
Author : mejiaoneto
Score : 64 points
Date : 2020-10-14 17:07 UTC (2 days ago)
(HTM) web link (www.forbes.com)
(TXT) w3m dump (www.forbes.com)
| panabee wrote:
| thanks very much for working on this.
|
| dumb question: if you can inject the biopolymer directly into the
| tumor, why can't you inject doxorubicin directly into the tumor?
| mft_ wrote:
| Interesting - congratulations for making it into phase I.
|
| Your technology requires localised injection of the biopolymer
| 'magnet'. Is the injection intratumoral? How
| difficult/specialised is this technique, and to what extent do
| you expect subtle differences here might influence the efficacy?
| mejiaoneto wrote:
| Thank you for your thoughts and question.
|
| There has been a recent wave of intratumoral approaches
| particularly for immunooncology (e.g. TLR, Sting, oncolytic
| viruses) and there are manuscripts in the scientific literature
| about the technical challenges and possibilities (https://jaman
| etwork.com/journals/jamanetworkopen/fullarticle...).
|
| So, to your question, yes it is specialized, but not
| particularly difficult. We have taken great care to leverage
| the learnings of those experts to minimize the challenges of
| interpatient variability.
|
| But we will only know for sure if our efforts where sufficient
| once the human clinical data comes back. For now I can say that
| our preclinical studies are highly encouraging.
| mmaunder wrote:
| I've been on Doxy and it nuked what I had, and as a patient I'd
| be extremely nervous about detoxifying the badass chemical that's
| supposed to kill the thing that was killing me. The side effects
| weren't bad enough for me to want to make it less potent. Also
| worth noting that it sounds like it wouldn't work for something
| diffuse like B cell non-hodgkins lymphoma.
|
| "Here's how Shasqi's treatment works: Say a patient has a tumor
| in her breast. The first step is to inject a biopolymer--
| naturally occurring molecules--into the tumor that essentially
| function as a magnet. Next, the patient will receive a modified
| version of the chemotherapy drug doxorubicin, which has been
| chemically "switched off" so that it's about 80 times less toxic.
| But once the drug gets to the tumor site, the biopolymer "magnet"
| pulls the drug in, causing a chemical reaction that switches the
| drug on to its full effect. The end result? Higher doses with
| fewer side effects (or at least that's what Shasqi is hoping the
| clinical trial will bear out.)"
| mejiaoneto wrote:
| Thank you for your comment. Congratulations on your positive
| response and recovery.
|
| Our goal is to enable the same response in others who may
| experience side effects and may have to forgo treatment because
| of it.
|
| Doxorubicin, also nicknamed red devil or red death, is
| notorious for its side effects. In addition to the bone marrow
| toxicity common to most chemotherapies, a person cannot receive
| more than 6 doses of doxorubicin in their lifetime without
| increasing their risk of heart failure. So when patients
| respond to doxorubicin, but more doses are needed, the patient
| and the doctors face a difficult choice: risk of death from the
| cancer or risk of cardiac failure. Shasqi is trying to change
| that equation for solid tumors. We are not focused on lymphomas
| yet.
| maxander wrote:
| Presumably, making it more targeted means they can use _more_ ,
| potentially to the point that the effect on the tumor would
| correspond to a lethal systemic dose using a course of normal
| doxorubicin. The patient wouldn't feel any better while
| undergoing the therapy in that case, but worse tumors could be
| successfully treated. The effect/toxicity ratio is the key
| factor in a lot of these kinds of drugs.
| mejiaoneto wrote:
| This is Jose, CEO of Shasqi. There are three firsts that Shasqi
| announced this morning: 1. First time click chemistry is used in
| humans. 2. First YC company to reach first-in-human clinical
| trials 3. First two patients dosed for SQ3370 in Shasqi's Phase 1
| clinical trial
|
| More info can be found here:
|
| https://www.shasqi.com/
|
| https://blog.ycombinator.com/shasqi-first-in-human-clinical-...
|
| https://en.wikipedia.org/wiki/Click_chemistry
| xiphias2 wrote:
| Hi Jose, thanks very much for working on this!
|
| My girlfriend had breast cancer twice already, and actually I
| was quite scared that she told me that she would almost rather
| die thank go through chemotherapy again, it was so bad for her
| (she's been through more than 15 operations, but she doesn't
| care about that). Currently it looks that she can't ever stop
| taking anti-estrogen drugs ever in her life even though it has
| lots of side effects.
|
| My question is: most of the drugs fail at one of the trials
| with much more than 90% probability. What is the chance you
| give your drug to be succeeding, and how did you get failure
| rate probability under that 90%? Also what's plan B?
| mejiaoneto wrote:
| Sorry to hear about your girlfriend. I have heard those
| feelings as well. They are not uncommon. The probability of
| success changes as you move further in the development. Below
| there is a link for a booklet that talks about the general
| pharma odds in page 53.
|
| In our particular case, we took a known chemotherapeutic
| agent called doxorubicin. It has been used for the last 40
| years in about a dozen types of tumors (include certain types
| of breast cancer).
|
| The problem is that 3 out of every 4 patients end up major
| side effects to their immune system (e.g. neutropenia), but
| even worse, you can only take about 6 doses in your whole
| life, otherwise your risk for cardiac damage increases very
| rapidly. It is known colloquially as red death and red devil,
| because of its red color.
|
| Using that drug as the starting block for our approach
| improves our probability of success and helps us know what to
| expect in terms of side effects.
| MayeulC wrote:
| Congratulations, reaching that stage is very impressive and
| could be life-changing to a lot of people.
|
| > CEO Dr. Jose M. Mejia Oneto, who has a PhD in organic
| chemistry and trained as a medical doctor
|
| As an electronics PhD student with a growing interest in
| medical applications of my skills, how does one go about
| training as a medical doctor? Are there shortcuts one can take
| if not intending to practice? Though at this point, it seems to
| me that recognition/credentials is a bit orthogonal to building
| up knowledge.
| RandallBrown wrote:
| As far as I understand, that means they went to medical
| school.
|
| A quick google search shows that Dr. Jose M. Mejia Oneto went
| to the University of Minnesota and did their residency at UC
| Davis. All this was done after their PhD in Chemistry from
| Emory.
|
| I don't know if there's any other way to get medical training
| that will give you any level of authority or respect other
| than medical school (or related profession like PA or Nurse)
| mejiaoneto wrote:
| That is an interesting question. Thank you for sharing.
| Indeed, I was a chemistry PhD before going to medical school.
| Unfortunately, there are no easy shortcuts that I know of.
| Interestingly it is a bit unpredictable if somebody will
| practice medicine or not when they go to do an MD or MD/PhD.
| MayeulC wrote:
| Thank you for your answer. After nine-ish years of higher
| education, I'm not sure I want to double down on that. Not
| right away, at least.
|
| Another option is to learn on the side, and ask actual
| doctors to confirm/infirm theories and assess feasibility,
| but without credentials, it's easy to get dismissed...
| ihnorton wrote:
| If you are interested in medical devices, at least in the US
| there are hospital-based postdoc positions which will hire
| some engineering PhDs even w/out specifically medical thesis
| focus (as you are coming from ferroelectrics: potentially MRI
| or robotics research). In such a position there is a lot of
| opportunity to attend medical lectures, and also ideally to
| shadow MDs in clinic, observe procedures, and sit in on case
| reviews.
|
| There are also various 1-2 year MS degree programs, often
| called "MS in biomedical sciences", which can function as a
| bridge into medical careers. Some are designed to prepare for
| MD or other professional school, while others have a focus on
| broader background (variety of subjects like anatomy,
| physiology, and pharmacology).
| mejiaoneto wrote:
| In addition, for those who are interested in learning more,
| here are two pre-print manuscripts that we submitted this week.
|
| This one talks about the effect of our therapy on local and
| distant tumors:
|
| https://www.biorxiv.org/content/10.1101/2020.10.13.337899v1
|
| This other one talks about the potential applications of the
| CAPAC platform and the versatility of our chemistry approach:
|
| https://doi.org/10.26434/chemrxiv.13087715.v1
| evmar wrote:
| My layman's understanding of chemo is that it's meant to be
| systemic: surgeries and radiation are targeted at the tumor
| itself, while chemo is meant to hopefully wipe out cells that
| have reached other parts of the body.
|
| But the description from this article suggests they're trying to
| make the chemo more targeted to the site of the tumor. That seems
| to counteract what I had understood to be the point of chemo.
|
| Can you explain? (In case it wasn't obvious from the above, I
| have low knowledge in this area.)
| mft_ wrote:
| Your impression that chemo is only valuable for metastatic
| cancer is mistaken.
|
| Chemo is effectively a poison that poisons the tumour faster
| than the rest of the body; the tumour's cells are more
| susceptible to the poison than normal cells because they're
| reproducing faster. As such, it doesn't matter whether the
| tumour is large or small, localised or metastatic. It's given
| systemically simply because of the nature of the drugs in
| question - because that's generally how we get drugs into the
| body. Local administration of drugs is rare, and chemo
| especially so.
| rubatuga wrote:
| Chemo can be both curative or palliative. This means it can be
| used to cure the cancer, or simply prolong the life of a
| patient. Chemo can also be used in combination with surgical or
| used alone. Just because chemo affects most dividing cells
| doesn't mean it is not a curative treatment. Targeted chemo
| therapies have less side effects and can be tolerated at higher
| doses.
| evmar wrote:
| I think all of the things you just wrote are true, but I
| don't see how they answer the question I asked... ?
| mejiaoneto wrote:
| 1. Cancer is characterized as local tumor, locoregional or
| distant (metastasis). 2. Our approach can certainly help
| patients with local or locoregional disease. 3. As we have
| presented in multiple cancer conferences, our approach
| seems to also help with distant disease, because by
| focusing more powerful therapy to the tumor, sparing the
| rest of your body, we give the body the opportunity to
| recognize the tumor as foreign and fight it. https://cancer
| res.aacrjournals.org/content/80/16_Supplement/...
| https://www.biorxiv.org/content/10.1101/2020.10.13.337899v1
| tomerico wrote:
| It's not uncommon to use chemo treatment to shrink the growth
| prior to removal.
| mejiaoneto wrote:
| Historically, and probably the mainstream hypothesis, is that
| you need chemo to be systemic in order to take care of
| micrometastatic disease (tumors that you cannot see). However,
| with the advent of immunooncology (IO) therapies (drugs that
| help your body recognize the tumor) and the benefits of having
| chemo + IO drugs is challenging that dogma. Certain chemo drugs
| are known to trigger an immune response. Having a technology
| that gives intense amount of chemo at the tumor and without
| diminishing the persons immune system. Our technology opens the
| door to have this effect in humans. We have seen those effects
| in mice studies and presented the results in cancer
| conferences.
| evmar wrote:
| Thanks so much for answering! I think what I'm trying to
| understand is why you'd want to target chemicals if other
| options like surgery also are targeted. Is the application
| then for tumors that are hard to remove surgically?
| jcims wrote:
| Surgery is not a great option. It's incredibly invasive,
| it's risky, it costs valuable time to schedule, it's
| expensive and at the point where you're metastatic it's not
| curative in any way.
|
| I haven't read the article, but if you can integrate this
| with regular chemo cadence to amplify effects at certain
| locations it seems like a no brainer.
| cogburnd02 wrote:
| For a moment--just reading the title--I thought this had
| something to do with 'Shaq' O'Neill.
___________________________________________________________________
(page generated 2020-10-16 23:00 UTC)