Scancell founder says the company is ready to commercialise novel medicines to counteract cancer. Watch the video here.
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Anyone know where to find the abstracts on Tyk2? Due to be published today but nothing on the SAR or AACR websites.
RMM this is the link, but no abstracts until yet!
https://eventpilotadmin.com/web/page.php?page=Session&project=AACR19MT&id=p439
Thanks Fadec - might be that we have to wait until the US wakes up!
RMM - 'The full text of the regular abstracts will be posted online at 4:30 p.m. ET on Wednesday, Oct. 16. ......which I think is 2030
https://www.aacr.org/Meetings/Pages/MeetingDetail.aspx?EventItemID=184&DetailItemID=1079
Thanks Krone. Plenty of time to get back from the city, have dinner and wait.....
Here is the abstract
Author(s): John Reader1, Nicole Williams2, James Bojdo2, Jenny Worthington2, Tim Mitchell2
1Sareum Ltd; 2Axis Bio
Background: TYK2 (tyrosine kinase 2) is a member of the Janus family of non-receptor tyrosine kinases and has been shown to play an important role in the signalling of type I interferons, as well as IL-12 and IL-23, via phosphorylation of downstream STATs. The TYK2/STAT1/BCL-2 pathway is implicated in the survival of leukemic cells in a proportion of T-ALL cases. It has been reported that STAT3 signalling in both the tumor, and microenvironment, is critical in shifting the balance from IL-12, a central cytokine in antitumor and antiviral immunity, to potentially pro-carcinogenic IL-23 production. Furthermore there is increasing evidence that chronic tumor interferon signalling leads to multigenic T cell exhaustion and resistance to immune checkpoint blockade. Additionally, TYK2 has been suggested to play a key role in CTLA-4 STAT3 signal transduction in B cell lymphomas and in melanoma associated B cells. We have previously reported on SAR-20347, a 1,3-oxazole-4 carboxamide, which is an orally bioavailable potent and selective inhibitor of TYK2, which causes tumor regression in in vivo models of T-ALL, and which has shown striking reductions in STAT phosphorylation downstream of IFNa signalling, and IFN? production in response to IL-12 both in vitro and in vivo. Here we report the effects of SAR-20351, an orally bioavailable optimised analog of SAR-20347, on tumor cell viability and components of the tumor microenvironment in immunocompetent mouse models. Method A range of syngeneic tumor models were used to establish SAR-20351 efficacy as both a monotherapy and in combination with standards of care. FACS analysis was used to identify immune cell sub-populations within tumor tissue and measure PD-1 and PD-L1 expression levels on appropriate cell types. Result Reduced tumor growth was observed following SAR-20351 treatment as a monotherapy in the Panc02, CT26, MC38, B16F10, Renca and A20 models, and in combination with 5-FU or anti-CTLA-4 in the colon CT26 model. Similar effects were seen in the MC38 model when SAR-20351 was combined with 5-FU and in the Renca model when SAR-20351 was combined with everolimus. To elucidate mechanism of action in these models, tumors were grown in immunocompetent and immunodeficient animals and efficacy compared. Increased efficacy of SAR-20351 in an immunocompetent background compared to immunodeficient animals indicated immunotherapy as a mechanism of action. FACS analysis identified reduced myeloid and Treg cell infiltration in tumor tissue and reduced PD-1 expression was observed on TIL and TAMs, indicative of a less-exhausted phenotype. SAR-20351 was seen to reduce levels of PD-L1 expression by tumor cells, and reversed the increase in PD-L1 levels induced by certain chemotherapy or targeted agents.
Continues
Part 2
Reduction of pTYK2, pSTAT3 and cMYC was observed in B cells derived from the A20 model. No changes in animal bodyweight or behavior, and no significant differences in complete blood counts and blood chemistry parameters following treatment with SAR-20351 demonstrated that treatment was well-tolerated during these studies. Conclusion The TYK2 inhibitor, SAR-20351 results in significant control of solid tumor growth and the mechanism of action involves immunotherapy, with reductions in myeloid and Treg cell infiltration in a range of tumor models.
GLA
Hi All - interesting comment from TM in the RNS
“ We are delighted to be presenting at this important international cancer conference and engaging with interested parties from the many leading pharma and biotech companies that attend this event."
GLA
Game on and orally administrable against most which are injection based.
Hi Ahfam
I also think that based on the abstract details we could be classed as in ‘late preclinical’ which is the sweet spot in SAR’s business model for licensing......coming together nicely and every day you get to present at such a prestigious and notable forum.
GLA
I'm hoping that they are already engaging with 'interested parties' and getting the data out to potential licencees. If its as good as suggested then there's no reason to wait until the end of the month. I'm quietly optimistic.
I think it's quite obvious that with Tyk2/Jaks being such a hot topic now, that the majors will be all over the data and have a close eye all those presenting as AACR. It's a major cancer conference anyone who has anything to show to improve the fight against cancer will be presenting something and anyone in the business of commercialising and bringing in billions for shareholder and the like will be watching if not present.
Some presentation for three and a half hours.
I hope it goes well ????
Its not a 3.5 hrs presentation. Tim will get a slot in the 3.5 hr session. He'll probably get 20-30 mins but that's enough to put out the store. It's what happens behind the scenes that matters.
I see that makes more sense
It did seem a long time
Cheers