31 abstracts, at least, should be presented at the coming ESMO 2019 meeting on therapies or products from European biotech companies in our universe. The meeting kicks off at the end of the week.
Faron managed to get a Late-Breaking Abstract spot (Faron says it was accepted as a Poster Discussion), which is quite rare for the European biotech companies in general. An update of the dose-escalation of the MATINS trial is expected. This trial tests a new kind of checkpoint inhibitor called bexmarilimab, targeting Clever-1, in monotherapy. This checkpoint blockade allows the repolarization of the M2 macrophages, who have an immunosuppressive role and thus a pro-tumoral activity, into M1 macrophages, who have an antitumoral activity, in addition to their regular job of antigen presentation. In April, at one of the low doses, the company reported 1 partial response with CEA level normalization, out of the 4 first patients. There was no other response in the 5 next patients, as per a new update released in July, but there was 1 stable disease with a CEA drop by 40%.
Innate Pharma will also have monalizumab featured in an oral presentation, but via an Investigator-Sponsored Trial called UPSTREAM, a biomarker-driven study. The data will be reported on the "I1 cohort". It is not clear what it refers to but it is likely that only monotherapy data of monalizumab will be available, as a combination with durvalumab was only initiated earlier this year.
PharmaMar will also have lurbinectedin showcased in an oral session, thanks to another Investigator-Initiated Study in Malignant Pleural Mesothelioma.
Mologen's IMPALA failed phase 3 trial of lefitolimod in mCRC will also be presented.
The other presentations are posters and "Trial in Progress" posters, with several efficacy updates like for 1134P, 1370P, 1210P or 1576P. 1201P could also disclose some efficacy data.
We will know that in a few hours since the abstract content for posters should be available from Monday 23th at 00:05 CET. For oral presentations, they will be available from Friday, 27th also at 00:05 CET. For Faron's LBA, we will have to wait for the beginning of the presentation that will occur in Barcelona on 28th.
Post meeting wrap-up
Good data were presented in STS for PharmaMar’s chemo agent Yondelis in combination with low-dose radiotherapy (n=27/ORR 56%/PFS-6 75%/1 related death though), in the TRASTS trial by the Spanish/French/Italian Sarcoma Research Groups. Yondelis is already approved in STS, but not in this combination regimen. Another IST led by the Swiss Group for Clinical Cancer Research provided data “supporting the evaluation of Zepsyre in a randomized phase III trial” in progressive MPM, where “no progress has been seen since 2005”, according one KOL (n=42/PFS 4.1mo/mOS 11mo). So, more supportive data for Zepsyre after a hit on SCLC earlier this year.
Still early (n=8) but interesting, Oryzon Pharma presented data of iadademstat -an LSD1 inhibitor- tested in relapsed ED-SCLC (CLEPSIDRA trial), in combination with chemo. The company claims an ORR of 75% but according to the waterfall plot and the individual data, the ORR is of 50% and the Clinical Benefit Rate is of 75%. Still remarkable, however the combination had significant hematological toxicities. Iadademstat toxicity profile in monotherapy (after “induction”) was much cleaner.
Transgene showcased dose-escalation data of their therapeutic vaccine TG4001 in HPV16-positive solid tumors (expressing HPV16 E6 and E7 oncoproteins), in combination with avelumab. Out of the 9 patients, 3 PR, 3 SD and 3 PD were observed, including 3 PR, 2 SD and 1 PD at the highest dose (RP2D). The most interesting point comes from the length of the partial responses, all superior to 12mo (one curve is tangent to the 30% tumor size reduction criteria as per RECIST, so it would strictly be a SD at last follow-up). Jus tafter the meeting, Transgene’s CEO said that the preparation of a pivotal trial could start now, while waiting for confirmation of these preliminary results in H1 2020.
Innate Pharma, on the cusp of a Nasdaq IPO, confirmed the interesting data for monalizumab (first-in-class anti-NKG2A mAb) and cetuximab combination in relapsed/metastatic HNSCC (n=40/ ORR 28%/OS-12 44%). These data triggered the option exercise of AstraZeneca last year for USD 100m, and Innate Pharma recently exercised its option to co-develop monalizumab in Europe. A transition into phase 3 in was announced last month (trial in HNSCC to start in 2020). The first dose-escalation data of another Innate Pharma’s program were also disclosed at ESMO. They concerned IPH5401, an anti-C5aR in which the company has high expectations, in combination with durvalumab. Beyond unimpressive ORR data (n=12, ORR=8%), 1 PR was observed in a HCC patient who progressed on nivolumab, and a long SD (>40wks) was observed in a NSCLC patient who also progressed on nivolumab. So “promising data” demonstrating that IPH5401 can contain or revert the acquired resistance to anti-PD1 checkpoint inhibitors.
Faron provided a deceptive update for bexmarilimab (first-in-class anti-Clever mAb). The company had disclosed 1 PR in CRC, among the first 3 patients enrolled in the MATINS dose-escalation trial earlier this year. This was matter to create at least curiosity if not interest, since this was observed in monotherapy in advanced solid tumors. No other response had been disclosed in further patients, despite improved immune biomarkers. In contrast to this promising signal, among the other 8 evaluable patients, no other tumor shrinkage was observed. Moreover, preclinical data discussed after the poster presentation underlined that the company’s strategy to combine bexmarilimab with anti-PD-(L)1s might not be a winning one, as the preclinical experiments exhibited lower anti-tumor effects when both agents were combined, compared to bexmarilimab alone. Faron will initiate a cohort expansion in CRC in the next few months.
Finally, on a more negative note, the data from Mologen’s failed phase 3 trial (IMPALA) in CRC for lefitolimod (TLR9 agonist) were even worse than one may have expected, compared to Standard of Care. Topline and few additional data were already disclosed in August, mainly on OS. But here, PFS with lefitolimod was statistically inferior to SOC. Some biomarkers translated an immune modulation. At least it was safe. The company is already heading to develop lefitolimod in combination, and the first "next-gen" TLR9 agonist from the Enandim family should enter the clinics around year end.
04/10/2019 update: links to posters and press releases added
05/10/2019 update: wrap-up added