Interesting early results from Genocea, a microcap ($70M market cap) with a poster presentation at ASCOMeeting Library | GEN-009, a neoantigen vaccine containing ATLAS selected neoantigens, to generate broad sustained immunity against immunogenic tumor mutations and avoid inhibitory peptides.https://meetinglibrary.asco.org/record/188863/abstract<< Results:The 40 doses given across patients have induced only mild local discomfort and no DLT. Vaccination has generated immune responses against 99% of administered peptides, with both CD8+ and CD4+ responses in ex vivo fluorospot assays. To date, no patients have developed recurrent disease. Broad immunity develops as early as Day 29 and is sustained for over 12 months. Immune response against individual peptides is correlated with peptide concentration (OR = 1.26, p=0.0001) but not with other classifiers such as GRAVY index (Grand Average of Hydropathy), tumor type, injection site or sex. The Inhibigen burden prior to treatment again correlates with disease progression. >>
Interesting!Though I encourage caution on all things intra-tumoral injection related. Many have tried, most if not all have been unsuccessful for one reason or another.
Are you familiar with Gritstone’s neoantigen platform, EDGE? I’m trying to understand the differences between Genocea and Gritstone.Both are early stage (Phase 1/2) with lead candidates
I’m trying to understand the differences between Genocea and Gritstone.The Genocea platform is based on a functional readout of each candidate neoantigen, and classifies each as inhibitory or stimulatory based on the patients own T cells. Obviously, they would select only stimulatory antigens for treatment. OTOH, the Edge platform is based on selection of candidate antigens through predictive algorithms based on physical biochemistry of peptide and molecules on antigen presenting cells. As such, it is agnostic on the issue of whether or not a given peptide is stimulatory or inhibitory. Cosmid
encourage caution on all things intra-tumoral injectionIt was lost on me that the treatment was intra-tumoral. Can someone verify? Also, were pure peptides used for treatment or were these conjugated to a carrier or delivered with an adjuvant? Cosmid
I didn’t pick up that it was intra-tumoral, reviewed limited info I have and returned to ask Fuma to explain.The ASCO poster presentation looks interesting: https://static1.squarespace.com/static/5ad0dd36aa49a1a3dfa66...
If I understood correctly, the peptides were delivered with an adjuvant (ICLC / Hiltonol)
Sorry, I misspoke. I had only briefly looked at the initial post, and now having looked at the website and researched a bit, below are my thoughts.-On first glance, the concept is intriguing. (no, its not intra-tumoral, I have just always associated "neoantigen" with intra-tumoral injections - my fault). .... though this is likely incredibly time and money intensive. And while that in and of itself shouldnt be a hinderance, well... there is a huge barrier to all of this:- the FDA. They, understandably, probably want an air-tight manufacturing process and any minute changes to the process may result in months / years of setbacks. I like the concept, and it *seems* simple enough, but its probably incredibly complex. and this *might* be where the world takes us (and/or the "off the shelf" "precision therapy" market), but then the question is, can it be genocea? To which I have to ask, can it be? So, to me, I tend to be risk averse in biotech and try not to hit home runs, but rather doubles. There are ALOT of things that go into the scrap heap in biotech. As a matter of personal preference, I wait for published clinical trial data to suggest clinical / real world success before I jump in. While this limits my multi-multi-multi baggers, it also minimizes my chances of utter failure and losing a large fraction of my investment. To me, I dont even bother playing the game of "just a small portion of my portfolio" with super small phase 1 trial companies. I give 1-2% of my port to companies with a proven P2 trial that can expand past their initial indicated market with a few (maybe 2-3ish) other drugs in development. So with that....-Penny stocks are hard to swallow for me. Strike 1.-proven track record. kind of; decent data as ASCO this year, promising, but VERY early. Ball 1 / foul ball.-As for track record, I see they have been public since 2014ish. Looks like they were developing a herpes vaccine that was suddenly shelved after completing P3 trials. So, they can develop something clinically (maybe) but cant market it (bad business sense / doesnt make sense for the world financially?). Theyve only recently gone into oncology. I dont like companies that hope focus from one field to another, and have not proven much in their "current" target field yet have been in business for years. Strike 2.I understand the excitement, but I would be *very* cautious. Interesting idea to keep an eye on, but not for me right now. I like coming to the plate with a 2-0 count rather than 1-2 :PCheers.
I think you are being too kind Fuma. IMO, the abstract shows nothing other than a dose-dependent relationship between peptide concentration and immune response. This validates what has been known for decades. The problem with peptide immunization has never been immune response, but clinical response despite the appearance of immunity. They state there was no disease progression in the 8 patients, but given most patients received either chemo or some form of blockade, it’s impossible to attribute this to vaccination. With that said, their categorization of peptides as inhibigens or stimulatory is very interesting scientifically. Their website takes a veiled swipe at Edge by claiming that they “know” what peptides are effective while others guess. Of course this is nonsense as it presupposes outcomes of trials yet to be done. But this does set up an interesting competition between the two platforms. Genocea in the camp that peptides derived from neoantigens are engendered with a binary (and presumably fixed) property of being either inhibitors or stimulators. Edge, otoh, would assume that a given peptide could be either, depending on physiological context. If I were a granting agency I would love to fund something like a comparison between the two because it addresses a very critical scientific question. As an investment? Not for me. Cosmid (no position)
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