Bristol makes its radiopharma move

The radiopharmaceutical sector is fast becoming one of the hottest in biotech, with Bristol Myers Squibb last week agreeing to pay $4.1bn for RayzeBio, a group that only went public in September. 

The deal follows Lilly’s $1.4bn move for Point Biopharma, which finally went through last week, and several large deals from Novartis, the early big pharma trendsetter. Both recent acquisitions illustrate the importance of manufacturing in this field: Point had long made much of its capabilities here, while RayzeBio is completing construction of a facility that is expected to come online in the first half of 2024.

This wasn't Bristol’s only big deal of the festive period: in December it also bought the schizophrenia player Karuna for $14.0bn, after spending $4.8b on Mirati in October. 

Actinium

With RayzeBio, Bristol reckons it’s getting in on the next generation of radiopharmaceuticals, which could help explain why it paid so much more than Lilly did for Point. RayzeBio is focused on actinium-based projects; alpha emitters such as actinium are said to be more potent than beta emitters like lutetium, around which the current crop of radioconjugates are based.

Point’s lead project, PNT2002, which recently succeeded but underwhelmed in the pivotal Splash trial in prostate cancer, employs lutetium, as do Novartis’s Lutathera and Pluvicto. 

Point does have actinium-based projects in development, PNT2001 (targeting PSMA) and PNT2004 (against FAP-α), but both are at the preclinical stage.

Somatostatin receptor 2

RayzeBio’s lead asset, meanwhile, is RYZ101, which targets somatostatin receptor 2 (SSTR2), said to be overexpressed in gastroenteropancreatic neuroendocrine tumours (GEP-NETs) and extensive-stage small-cell lung cancer.

Last year the group began enrolling into the phase 3 portion of the Action-1 trial, in SSTR-positive GEP-NETs patients who have progressed on Lutathera; data are expected late 2025 or early 2026. At ESMO 2023, phase 1b data from that study found a 29% overall response rate among 17 patients receiving RYZ101. 

RayzeBio has highlighted a 13% ORR in Lutathera’s registrational trial, Netter-1, and also said it hoped to move RYZ101 into earlier lines of therapy. Bristol will also gain RYZ801, which targets glypican-3 and is being developed for hepatocellular carcinoma. This project is in IND-enabling studies, along with an unnamed asset targeting CA9, for renal cell cancer.

Competition

Other groups with clinical-stage alpha emitters include Fusion Pharmaceuticals, Telix, Perspective Therapeutics (formerly Isoray), RadioMedix, AdvanCell and Artbio.

Like RayzeBio, Perspective and privately held RadioMedix are targeting SSTR. The latter’s Alphamedix is in a phase 2 trial in NETs, with data expected in mid-2024, while Perspective is carrying out a phase 1/2 study of its agent, 212Pb-VMT-α-NET. 

Others are looking at another well-validated target, PSMA, with prostate cancer the main focus. The furthest ahead appears to be Fusion, whose FPI-2265 is in the phase 2 Tatcist trial in castration-resistant patients, including those naive to radiopharmaceuticals or those who have progressed on Pluvicto.

Telix is slightly behind with TLX592, in phase 1; that group is also developing a beta emitter for prostate cancer, TLX591. Two private companies are also active here, with AdvanCell recently starting dosing in a phase 1/2 trial of ADVC001, and Artbio promising further development of its lead project, AB001, when it completed an upsized $90m series A round last month; an early phase 1 trial of that project is listed as completed.

Any investors hoping that these groups might also tempt a buyer would do well to keep in mind what big pharma is looking for, which according to Truist analysts includes projects in or close to pivotal trials, and radioisotope supply, preferably in house. 

Notable deals involving radiopharmaceuticals

Source: OncologyPipeline.