Bristol Myers Squibb (BMS) has agreed to co-develop and co-commercialize BioNTech’s cancer-fighting bispecific antibody candidate BNT327 across numerous solid tumor types through a collaboration that could generate up to $11.1 billion for the German next-generation immunotherapy developer, the companies said.
BNT327, a next-generation bispecific antibody targeting PD-L1 and VEGF-A, is under study in multiple ongoing trials with more than 1,000 patients treated to date—including potentially registrational global Phase III trials assessing the candidate as a first-line treatment in extensive stage small cell lung cancer (ES-SCLC) and non-small cell lung cancer (NSCLC). Also recruiting patients is a Phase III study assessing the bispecific antibody in untreated small-cell lung cancer (SCLC; NCT06712355).
According to the companies, preliminary data from those studies have shown promise for fighting cancer by targeting PD-L1 and VEGF-A with a single molecule across multiple tumor types.
By year’s end, a global Phase III trial evaluating BNT327 in triple negative breast cancer (TNBC) is expected to begin. Also planned are additional trials set to combine BNT327 with BioNTech’s antibody-drug conjugate candidates (ADCs). More than 20 clinical trials are currently ongoing or planned for BNT327 in more than 10 solid tumor indications, according to BioNTech.
BMS and BioNTech have agreed to jointly develop and commercialize BNT327 as both a monotherapy and as part of combinations with other drugs. The companies have the right to independently develop BNT327 in further indications and combinations as they wish, such as combinations of BNT327 with candidates form their own pipelines.
“Our deep experience and expertise in advancing and delivering groundbreaking immuno-oncology medicines positions BMS well to collaboratively realize the potential of BNT327, an asset with significant potential for transforming the standard of care for patients with solid tumors,” BMS Board Chair and CEO Christopher Boerner, PhD, said in a statement. “The science behind BNT327 and its leading clinical position in multiple hard-to-treat tumor types, further bolsters our pursuit of novel mechanisms and multiple modalities in oncology and enhances our growth trajectory.”
Ugur Sahin, MD, CEO and Co-Founder of BioNTech, stated that the collaboration will bolster his company’s focus on advancing what it deems high-impact, pan-tumor programs and combination strategies in oncology, with BNT327 complementing its antibody-drug conjugate programs and messenger RNA (mRNA)-based immunotherapies.
BioNTech—short for “Biopharmaceutical New Technologies”—emerged as a global drug developer when it partnered with Pfizer to co-develop the mRNA-based COVID-19 vaccine Comirnaty®. As SARS-CoV-2 evolved from pandemic to chronic disease, sales of the vaccine have waned in recent years, skidding from about $56.7 billion in 2022, to roughly $15.6 billion in 2023, to approximately $8.5 billion last year.
Oncology focus
As its COVID-19 vaccine sales have fallen, BioNTech has pivoted.
“Our focus remains on advancing high-impact, pan-tumor programs and combination strategies in oncology, with BNT327 complementing our antibody-drug conjugate programs and mRNA-based immunotherapies. We are dedicated to delivering truly transformative options for patients in need,” Sahin added.
BioNTech investors propelled a buying surge that sent the company’s share price jumping 18% Monday, to $113.10 from $95.81 at Friday’s closing bell. BMS shares inched up 1% to $48.79 from $48.28. On Tuesday, BioNTech shares rose another 2% to $115.64, while BMS shares dipped 1.4% to $48.09.
“We see this deal accelerating BNT327’s path to market and the ability to de-risk additional settings while providing BNTX non-dilutive capital to bolster the oncology pipeline,” Jessica Fye, a managing director and senior equity research analyst for J.P. Morgan, observed Monday in a research note. “While we acknowledge that OS [overall survival] HRs [hazard ratios] in the category have been less robust than for PFS [progression free survival] we see this deal as both further validating the asset and strengthening BNTX’s financial position and potential long-term outlook, and we continue to expect focus in the BNTX story to move beyond COVID and towards BNTX’s own pipeline updates.
Fye’s discussion of OS alluded to last week’s mixed results for Summit Therapeutics’ ivonescimab plus platinum-doublet chemotherapy in the Phase III HARMONi trial (NCT05184712) in a form of NSCLC. Ivonescimab-chemo reduced the risk of disease progression or death by 48% vs. placebo-chemo—but showed only a “positive trend” in overall survival without achieving a statistically significant benefit, Summit acknowledged.
“While OS missed stat. sig [statistical significance] at current data maturity, the PFS-to-OS correlation for Ivo[nescimab] still trended in the right direction,” suggesting better results for PD-(L)1xVEGF therapies vs. VEGF inhibitors alone, Jefferies equity analyst Akash Tewari noted.
“We think having the optionality to combine w/ different assets (i.e., ADCs) will be key to winning across different tumor types, making this more of a LC [large capital] pharma game,” Tewari wrote.
Entering the race
Especially for BMS, a large-cap pharma that Tewari noted now enters the race to develop a combination PD-L1/VEGF-A treatment ahead of Pfizer and Merck & Co., and ahead of the 2028 loss of exclusivity for BMS’ current best-selling drug, cancer-fighting Opdivo® (nivolumab).
Pfizer on May 20 agreed to pay 3SBio $1.25 billion upfront and up to $4.8 billion in milestone payments for ex-China rights to the Chinese biopharma’s PD-L1/VEGF inhibitor SSGJ-707. Merck in December closed on an exclusive global license to develop, manufacture and commercialize LM-299, a PD-1/VEGF bispecific antibody from LaNova Medicines, with Merck agreeing in return to pay LaNova $588 million upfront and up to $2.7 billion in milestone payments.
As a result, the BMS-BioNTech collaboration “looks like win-win for both parties,” Tewari concluded.
Daina M. Graybosch, PhD, senior managing director, immuno-oncology, and a senior research analyst with Leerink Partners, commented that BMY adds breadth to the pipeline of established and novel assets to combine with BNT327, including ADCs like their EGFR x HER3 ADC, BL-B01D1—which had promising data updates at this ASCO—and immuno-oncology assets like their anti-CCR8 and anti-CTLA-4, ipilimumab.
More importantly, Graybosch said, BMY brings depth and breadth of clinical trial development strategic and operational expertise to the partnership with BioNTech.
“BioNTech’s relative naïveté in late-stage oncology development was a major risk prior to this deal, in our view. The deal also reinforces our confidence in BioNTech’s management team’s ability to make incisive business decisions that spread risk, preserve their balance sheet, and protect their organization to grow internal capabilities pragmatically,” Graybosch wrote Monday in a research note.
Business acumen and leadership
“We often hear the bear case from investors that they worry about investing in a company lead by physician scientists,” Graybosch added. “While we agree with this as a general risk, BioNTech’s CEO, Uğur Şahin, and his senior management team have repeatedly shown business acumen and strong leadership that negates the criticism.”
BNT327 combines PD-L1 checkpoint inhibition designed to restore T cells’ ability to recognize and destroy tumor cells with VEGF-A inhibition. This is intended to prevent the tumor from growing and proliferating by reversing the tumor’s immuno-suppressive effect in its microenvironment and cutting off the blood and oxygen supply that feeds tumor cells. By targeting PD-L1 on tumor cells in order to localize anti-VEGF activity within the tumor microenvironment, BNT327 aims to enhance therapeutic precision and minimize systemic exposure.
By helping normalize blood vessels at the tumor site, improving delivery and potential effectiveness of combination therapies, BioNTech reasons, BNT327 could potentially emerge as a backbone therapy across a variety of solid tumors.
BMS agreed to pay BioNTech $1.5 billion upfront and $2 billion total in non-contingent anniversary payments through 2028. These tax-deductible charges will be recorded as acquired in-process research and development (IPR&D) expenses, with the $1.5 billion being incurred in the current second quarter. In addition, BMS also agreed to pay BioNTech up to $7.6 billion in payments tied to achieving development, regulatory, and commercial milestones.
BioNTech and BMS will share joint development and manufacturing costs 50:50, subject to specified exceptions, as well as global profits and losses from the collaboration.
“We are impressed by the innovation that BioNTech has achieved to date, and we look forward to partnering to accelerate existing clinical trials and time to market, while expanding the number of potential indications,” Boerner added.
