Among the novel oncology mechanisms that have let investors down CD47 looks particularly disappointing. Except for one company, that is: Forty Seven today sits on a $2bn valuation thanks to data presented at Ash last month suggesting that its lead asset, magrolimab, could be a serious contender in haematology.
True, this week’s unveiling of magrolimab data in colorectal cancer will have disappointed some, but expectations in solid tumours had generally been low. Armed with a $196m post-Ash equity raise Forty Seven now has a plan that could see magrolimab filed for myelodysplastic syndromes next year.
This would mark the company as a distinct outlier in CD47 inhibition. Celgene, once a leader, canned its phase I project, prompting Surface Oncology, currently 80% off its IPO price, to change tack and also ditch work on CD47; Trillium has kept the faith, but its shares have imploded (“Don’t eat me” competition finds Celgene discontinuation hard to digest, October 10, 2018).
It was magrolimab data at Ash that marked Forty Seven’s transformation, and the 333% gain saw the group become the best-performing stock over the conference period.
While some companies have tinkered with antibody design, and fretted over which end of the CD47 pathway to target, Forty Seven’s success might be down to something as simple as combining magrolimab with the chemotherapy azacytidine. The company argues that the combination is synergistic, and the Ash data seemed to back this up.
In 24 evaluable subjects with untreated intermediate to very high-risk myelodysplastic syndromes (MDS) the combo yielded a 92% overall response rate, including 12 complete remissions. In a similar population of 57 MDS patients Roche/Abbvie’s blockbuster-in-waiting Venclexta combined with azacytidine yielded a 77% ORR and CR rate of 39%.
In the second quarter Forty Seven plans to start Enhance, a phase III MDS study versus azacytidine alone.
Magrolimab also showed striking data in 14 first-line AML patients: 64% ORR, with nine CRs. Forty Seven also highlighted results in AML subjects with the TP53 mutation, suggestive of aggressive disease but present in only 5-10% of AML cases; of nine such subjects four had a complete and three a partial response.
While AML is an intractable haematological tumour type it has seen the entry of several new drugs. It is possible that Forty Seven will target TP53-positive disease, where no treatment is specifically indicated: for now it plans to enrol more TP53-positive subjects into its phase I study “to inform a potential registrational path”.
If these results showed magrolimab’s promise in haematology then solid tumours will be much harder to crack. On Saturday the Asco-GI conference will see the results of an Erbitux combo in colorectal cancer.
The abstract paints a gloomy picture: just two partial remissions, both in Kras wild-type disease, among 70 evaluable subjects. Still, analysts had low expectations for this readout, as well as for a separate Bavencio combo in ovarian cancer, due to be presented at the Asco-SITC immuno-oncology symposium on February 6-8.
More important is a separate pillar of Forty Seven’s initial registrational strategy, combining magrolimab with Rituxan in lymphoma. Here a pivotal third-line study is to begin in the current quarter, with initial data by the year end.
EvaluatePharma sellside consensus sees magrolimab generating $285m of revenue in 2024, virtually all of it in lymphoma, but these forecasts are derived from before the Ash data presentation.
It now seems likely that MDS will provide an initial route to market, and in magrolimab Forty Seven hopes to have found the elusive secret sauce.
|Forty Seven's magrolimab catalysts|
|Azacytidine combo||NCT03248479||ORR 92% (CR50%)||Data at Ash 2019|
|Azacytidine combo||Enhance||Vs azacytidine||Starts Q1 2020|
|BLA filing Q4 2021|
|Acute myelogenous leukaemia|
|Azacytidine combo||NCT03248479||ORR 64% (CR 41%)||Data at Ash 2019|
|Adding more TP53mut subjects||Data in 2020 to inform registrational plan|
|Erbitux combo||NCT02953782||3% ORR, all in Kras-wt||Data at Asco-GI|
|Bavencio combo||NCT03558139||Measures safety & ORR||Data at Asco-SITC, Feb 2020|
|Diffuse large B-cell lymphoma|
|Rituxan combo||Pivotal||3rd-line, single-cohort||Starts Q2 2020; initial data Q4 2020|
|Source: company announcements.|