BioNTech SE

Available data favor BNT327, but there are reasons to question whether the apparent edge is real. \n BioNTech has shown why it made small cell lung cancer (SCLC) a priority for its PD-L1xVEGF-A bispecific. The biotech linked BNT327 to a median overall survival (OS) of 16.8 months in a Chinese phase 2 trial, suggesting the drug candidate could set a new benchmark in a market served by AstraZeneca and Roche.Once SCLC, which accounts for about 14% of lung cancer cases, spreads too far for surgery or radiation therapy, patients typically receive chemotherapy. In recent years, Roche and AstraZeneca have won FDA approvals to give checkpoint inhibitors, Tecentriq and Imfinzi, respectively, in combination with chemo as a first-line treatment for extensive-stage SCLC.BioNTech is betting BNT327 can improve on the incumbents. Shortly after paying $800 million to take full control of BNT327, the biotech began a phase 3 trial to test the bispecific in combination with chemo in patients with previously untreated extensive-stage SCLC.Friday, researchers presented phase 2 data on the combination at the European Lung Cancer Congress (ELCC). As of the December cutoff, 48 patients in the open-label, single-arm trial had completed at least one tumor evaluation. Median OS was 16.8 months, and 72.7% of patients were alive after 12 months.  Talking on an earnings call earlier this month, BioNTech executives named Tecentriq plus chemotherapy as the standard of care in the setting and the IMpower133 trial that supported FDA approval of Roche’s combination as the benchmark. Median OS on the Tecentriq combination in Roche’s phase 3 trial was (PDF) 12.3 months. AstraZeneca’s Imfinzi came to market with (PDF) a median OS of 13 months.The available OS data favor BNT327, but there are reasons to question whether the bispecific’s apparent edge over Tecentriq and Imfinzi is real. Cross-trial comparisons can be unreliable, particularly when, as in this case, a single-country, single-arm study of just 48 patients is being pitted against randomized global trials that each enrolled more than 400 people. BioNTech is barreling toward a readout that will give a truer picture of how BNT327 performs in SCLC, with enrollment of the first of a planned 439 phase 3 patients now underway at a handful of sites across the U.S. That study is enrolling previously untreated patients, but the company has also generated phase 2 data in the second-line population. Researchers provided an update on the second-line trial at ELCC. BioNTech saw a median OS of 14.3 months and median duration of response (DOR) of 5.6 months in 65 evaluable patients. Amgen won FDA approval for its DLL3-targeting bispecific Imdelltra after reporting (PDF) a median DOR of 9.7 months in a trial of 99 patients, 74% of whom had previously taken a checkpoint inhibitor. The median DOR for BNT327 was 11.5 months in immunotherapy-naive patients.  A phase 3 trial of BNT327 plus chemotherapy in second-line patients is underway in China, but BioNTech has made first-line opportunities the focus of its global studies. The biotech has started phase 3 trials of the bispecific in first-line SCLC and non-small cell lung cancer and is preparing to start a first-line study in triple-negative breast cancer. The multipronged pivotal program is part of BioNTech’s broader attempt to capitalize on its status as a front-runner in one of the hottest areas of oncology R&D. BioNTech is running or planning phase 1/2 trials to show whether BNT327 pairs well with TROP2, HER2, HER3 and B7H3 antibody-drug conjugates, and its longer-term road map includes studies with bispecifics, cell therapies and other ADCs. BioNTech’s commitment to the candidate reflects evidence that PD-(L)1xVEGF-A bispecifics can replace drugs such as Merck & Co.’s Keytruda as the backbone of cancer combinations and succeed in indications where conventional checkpoint inhibitors have failed. Akeso raised such hopes when its bispecific beat Keytruda last year, triggering a surge in R&D activity and dealmaking in the process. 

BioNTech has highly encouraging survival data for its bispecific antibody combining checkpoint blockade with VEGF-A inhibition as a first-line treatment for a serious form of lung cancer. And if the drug can maintain a similar level of efficacy in larger trials in the future, the company believes it could become the standard of care in this setting. The data are an interim cut from an open-label Phase 2 trial in China assessing BioNTech’s bispecific, known as BNT327, plus chemo as a first-line therapy in the most aggressive type of lung cancer — extensive stage small cell lung cancer (ES-SCLC). They were presented Friday at the European Lung Cancer Congress in Paris. At the cut-off date of Dec. 20, 48 patients had undergone at least one tumor evaluation. Among this group, median overall survival (mOS) was not mature, but 72.7% of treated patients survived for one year. “We only had one-third of OS events at the time of data cutoff,” Özlem Türeci, BioNTech’s chief medical officer, told Endpoints News . “With standard of care, the median OS is around 12 months in first-line, and we see a 12-month OS rate of 72%, which means that we most likely will also see a median OS effect once the data is mature.” Another OS cutoff will hit around the end of this year, she said. Leerink analysts wrote in a note last week that the 12-month survival rate is about 20 percentage points above “relevant benchmarks.” In a comparable Phase 3 trial , 45% of ES-SCLC patients taking Keytruda plus chemo lived for a year. In another study, this time for Roche’s PD-1 inhibitor Tecentriq and its VEGF blocker Avastin plus chemo, the one-year survival rate was 56%. The PD-(L)1xVEGF mechanism, as it is known, has been white-hot since May , when Summit Therapeutics announced that its similar bispecific was more effective in non-small cell lung cancer than Merck’s previously unassailable PD-1 blocker Keytruda. In ES-SCLC, however, BioNTech is way out in front as far as PD-(L)1xVEGF bispecifics are concerned. It is the only company conducting “registration-intending advanced clinical trials in small cell lung cancer,” Türeci said. BioNTech also said that progression-free survival (PFS) was 6.9 months in the mid-stage trial for BNT327. According to BioNTech, median PFS in this setting is less than six months with currently available treatment options. Türeci called this “a significant and clinically meaningful increase.” BioNTech’s bispecific yielded a confirmed objective response rate of 85.4%, and 87.5% including unconfirmed responses. A Phase 1b trial for Summit’s bispecific, ivonescimab, paired with chemo in first-line ES-SCLC demonstrated an ORR of 80%. BNT327’s safety looked acceptable, though 86% of patients had a grade 3 or higher treatment-related adverse event. The most common events were neutrophil count decrease (90%), anemia (80%), white blood cell count decrease (76%) and platelet count decrease (62%). There were no treatment-related deaths, but 6% of patients discontinued treatment due to treatment-related events. It’s crucial for BioNTech to ensure the impressive results can be replicated in larger, global studies, since clinical data obtained solely in China is generally not regarded as approvable by US regulators. “There’s no reason why there should be a difference between those data packages” in China-based and global trials, Türeci said. An international Phase 2 trial is currently testing two doses of the bispecific in first- and second-line ES-SCLC. Those data, which could come later this year, are particularly important since they will be the first results from a global trial of BNT327. They should be followed by the first international Phase 3 readout for the asset in 2028, also in ES-SCLC. The latter is using a Tecentriq-chemo regimen, one of the current first-line treatment standards, as its control. To preserve data integrity, no interim cuts from this Phase 3 trial will be released, according to Türeci. The full results could emerge in three years or so, and a successful trial would enable BioNTech to file the drug in Europe and the US. More importantly, Türeci said that if the BNT327 arm beats the Tecentriq arm, BioNTech’s drug could become the front-line therapy of choice in ES-SCLC. BNT327 came from the China-based biotech Biotheus, which BioNTech initially partnered with before buying outright for $800 million in November . If BNT327 does go all the way, this deal will have been a very smart move.

+Plus, news about Autolus, MacroGenics and BlissBio: Akeso bispecific looks promising in cervical cancer: The China-based biotech said Friday that all patients in a Phase 3 cervical cancer trial responded to treatment with a bispecific antibody called cadonilimab. The addition of the PD-1xCTLA-4 bispecific on top of chemoradiotherapy in the COMPASSION-18 study generated complete and partial response rates of 84.8% and 15.2%, respectively. Median PFS was not reached, but the 12-month PFS rate was 74.9%. Cadonilimab is already approved in China for patients with recurrent or metastatic cervical cancer who have not responded to platinum-based chemotherapy. — Elizabeth Cairns Pulmatrix to divest assets ahead of merger: The biotech will seek buyers for three of its pipeline programs as well as its iSPERSE platform technology. Pulmatrix in November agreed to a reverse merger with Cullgen, which was expected to close this month but is now set to close in the first half of 2025. — Max Gelman BioNTech’s option for Autolus CAR-T fizzles out: The German biotech allowed its option to lapse for AUTO1/22, a CAR-T cell therapy in Phase 1 trials for childhood acute lymphoblastic leukemia. Back in February 2024 , BioNTech paid $50 million in cash and bought $200 million of Autolus’ shares in a deal that granted it access to AUTO1/22. The deal also covered AUTO6NG, a programmed T-cell therapy in early trials in neuroblastoma, and Aucatzyl, which has since been approved for an aggressive form of leukemia. BioNTech declined to exercise its time-limited option to AUTO1/22 because of a pipeline prioritization , and it lapsed Feb. 8. — Elizabeth Cairns MacroGenics shelves prostate cancer ADC: The company had to stop dosing prostate cancer patients in a Phase 2 trial of its antibody-drug conjugate, called vobramitamab duocarmazine, in July . On Thursday , it said it would shut down all development and seek a partner for the product, which targets the tumor antigen B7-H3 and delivers a cytotoxic duocarmycin payload. MacroGenics said the results of the trial do not justify any more investment; in the patients treated before dosing was halted, mature median radiographic progression-free survival was 9.5 months with the lower dose and 10 months with the higher. — Elizabeth Cairns BlissBio to proceed with ADC on its own: Eisai had signed an option deal in 2023 to advance a BlissBio program called BB-1701, but last month said in its third-quarter earnings that it would no longer do so. Instead, BlissBio will develop BB-1701 on its own. Eisai had been partnered with liquid biopsy company Angle on development plans, and now Angle is planning to work with BlissBio. — Max Gelman