RE:Biotechs fall after Roche trial failure.Evercore ISI analysts put out a note on Wednesday headlined: “I do NOT think TIGIT failed.”
As I posted earlier today, the hope was that by using both tiragolumab and Roche's PD-L1 checkpoint inhibitor Tecentriq, it might overcome immune suppression and restore the immune response.
The rationale for this hypothesis with anti-TIGIT advanced from the work of Dr. James Allision who was the co-receipient of the 2018 Nobel Prize in Physiology and Medicine for his discovery of the of the immunosuppresssant molecule CTLA-4 inhibitor while Dr. Tasku Honjo was awarded the prize for his discovery of the PD-1 molecule on T cells.
Dr. Allison is affiliated with MD Anderson.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7160651/
https://www.nature.com/articles/s41577-020-0306-5
However, genomic analyses has revealed that several factors and multiple signaling pathways are involved in the development of cancer and other complex disorders. To enhance the efficacy of the treatment, researchers have also developed their effective counterparts, bispecific antibodies which have the ability to bind to two different antigens simultaneously, which is why ONCY has discussed bispecifics in combination with CAR-T therapy.
https://www.biospace.com/article/roche-phase-iii-data-does-not-bode-well-for-anti-tigit-immunotherapies-/
That being said, ONCY's AWARE-1 study has demonstrated that pelareorep is complementary and synergistic with Roche's PD-L1 checkpoint inhibitor Tecentriq and there is appears to be good rationale for pelareorep to be synergistic with TIGIT + Tecentriq, thus further reducing Treg and further enhancing the innate and adaptive immune system for a durable and long lasting treatment effect, which was the initial intent of Roche's study.
The inability of Roche to reach one of the study's co-endpoints with TIGIT just serves to further open the door for ONCY's pelareorep with Roche's checkpoint inhibitor Tecentriq and now with their TIGIT checkpoint inhibitor tiragolumab.
That said Rcohe's TIGIT checkpoint inhibitor tiragolumab may be down, but not out.
RBC Capital Markets’ analyst Brian Abrahams correctly said any benefit of TIGIT co-administration could take longer to play out, which is not uncommon with immuno-oncology therapies.
So the setback today could be linked to the way Roche designed a statistical plan for the trial, analysts cautioned, suggesting that the study still had a chance of eventually demonstrating positive results - which points to the reason why ONCY has been proceeding cautiously with the execution of the AWARE-1 and Bracelet-1 studies in an effort to properly design its Phase III mBC study with pelareorep + PD-L1 checkpoint inhibitor (avelumab) .
https://financialpost.com/pmn/business-pmn/new-class-of-cancer-drugs-down-not-out-after-roche-trial-setback-analysts