Checking out Checkpoint
Checkpoint Therapeutics’ cosibelimab could become the ninth PD-(L)1 drug to reach the US market, but who will be around to launch it?
Checkpoint inhibitors, it seems, are two a penny. Investors met last month’s first approval of Incyte’s Zynyz, the eighth anti-PD-(L)1 MAb to reach the US, with barely a shrug; now brings the prospect of a US green light for the ninth such drug at a time when its maker risks no longer being financially solvent.
Step forward Checkpoint Therapeutics, a $45m microcap that stands a decent chance of having cosibelimab gain FDA approval by its January 2024 Pdufa date – about six months after its cash reserves run out. Understandably, a high priority for Checkpoint is finding a licensee willing to put up the cash for launch, the group tells Evaluate Vantage.
Cosibelimab has been filed for cutaneous squamous cell carcinoma (CSCC), and with no adcom planned “this is not a controversial review at all ... it should hopefully be smooth sailing”, says James Oliviero, Checkpoint’s chief executive. “Our plan is to launch the drug in the US ourselves or potentially with a partner” and potentially at a discount.
Behind such optimism sits the elephant in the room that Checkpoint, majority owned by Fortress Biotech, ended 2022 with just $12m in the bank. It recently raised another $6m, but last year burnt through $43m, and its annual SEC filing states: “There is substantial doubt about our ability to continue as a going concern. We do not believe that our cash [is] sufficient for the next 12 months.”
Ignoring Checkpoint’s financial problems cosibelimab might have something going for it. It is a fully human MAb, as well as being Fc-competent so it can engage NK as well as T cells.
And it is an anti-PD-L1, a property that Oliviero claims gives it fewer immune system-mediated toxicities than incumbents. Both of the currently approved checkpoint blockers for CSCC, Merck & Co’s Keytruda and Sanofi’s Libtayo, target PD-1.
Oliviero says that, while the metastatic CSCC market comprises 11,000 US patients, 60% are still treated with chemo because they are immunosuppressed, and thanks to cosibelimab’s PD-L1 mechanism these could be candidates for the Checkpoint drug. However, he admits that cosibelimab has yet to be studied in immunosuppressed CSCC patients.
Though Keytruda and Libtayo carry full approvals Checkpoint is confident that its drug can get the nod using overall response rate data, in its case 47%, in a single-cohort trial. At one point the company was boasting 51% ORR, based on investigator assessment, but this waned on central review and is now on a par with Libtayo’s on a cross-trial basis.
Though numerous attempts to undercut Keytruda on price have failed, most notably in the case of EQRX, Oliviero sees this too as an opportunity, and stresses that EQRX failed because its data were generated in China. “We’re looking to use pricing to potentially take market share.”
However, Checkpoint too has backed off somewhat. Two years ago it was still touting a 20-30% discount to peers, according to investor presentations, but now says that was before cosibelimab generated “best-in-class” data. “It’s unlikely that we’re going to be at a 20-30% discount, but I think ... we will be at some discount,” says Oliviero.
CSCC will at best be the only near-term indication for cosibelimab. Clinicaltrials.gov shows no other active studies, and Conterno, a phase 3 first-line NSCLC trial, was terminated when the war in Ukraine started. Conterno included numerous Russian hospitals, and it would have been too costly and taken too long to expand enrolment in other countries.
If that was one example of Checkpoint’s bad luck, a looming financial crunch could be another. Oliviero remains upbeat: “The drug is going to be there whether it’s us or somebody else running the show.”
|Some anti-PD-(L)1 laggards|
|Project||Company||Lead indication(s)||US status|
|Zynyz||Incyte||2nd-line Merkel cell carcinoma||Jul 2021 CRL for SCAC, approved Mar 2023 for Merkel|
|Cosibelimab||Checkpoint (Fortress)||Cutaneous squamous cell carcinoma||Filed (4 Jan 2024 Pdufa date, no adcom)|
|Balstilimab||Agenus||2nd-line cervical cancer||Filing pulled Oct 2021|
|Sintilimab||Lilly/Innovent||1st-line non-squam NSCLC||Mar 2022 CRL|
|Toripalimab||Coherus/Shanghai Junshi||1st & 3rd-line nasopharyngeal carcinoma||Filed (May 2022 CRL; new Pdufa date Dec 2022 missed because of Covid travel restrictions)|
|Penpulimab||Akeso/Sino||3rd-line nasopharyngeal carcinoma||Filed (Pdufa date likely missed because of Covid travel restrictions)|
|Tislelizumab||Novartis/Beigene||2nd-line oesophageal squamous cell carcinoma||Filed (Jul 2022 Pdufa date missed owing to Covid travel restrictions)|
|Sugemalimab||Cstone/EQRX||1st-line NSCLC||US plan to file for NSCLC abandoned|
|Envafolimab||Tracon/Alphamab/3D Medicines||1st-line biliary tract cancer||Ph3 trial ends Jan 2024 (delayed from Dec 2021)|
|Sasanlimab||Pfizer||Non-muscle-invasive bladder cancer||Ph3 trial ends Jun 2025 (delayed from Jun 2024)|
|Serplulimab||Shanghai Henlius/Fosun||1st-line SCLC||Ph3 trial vs Tecentriq ends Jun 2024|
|Zimberelimab||Arcus (via Wuxi/Gloriabio)||1st-line PD-L1+ve NSCLC||Ph3 trial ends Dec 2025|
|Cetrelimab (JNJ-63723283)||Johnson & Johnson||Muscle-invasive bladder cancer||Ph3 trial ends Dec 2026|
|Ezabenlimab (BI 754091)||Boehringer Ingelheim||Various, Lag3 & VEGF/Ang2 combos||Ph2 trial ends May 2024|
|Spartalizumab (PDR001)||Novartis||Melanoma||Failed Combi-I trial Aug 2020 and deprioritised|
|SCAC=squamous cell carcinoma of the anal canal; Source: Evaluate Vantage & clinicaltrials.gov.|