SEZ6

AbbVie is rejoining the likes of AstraZeneca, BioNTech, Gilead Sciences, GSK, Merck & Co. and Pfizer on a roster of pharma companies that have spent mightily to acquire ADC programs. The sizzling antibody-drug conjugate (ADC) field is at the center of another major life sciences deal.  This time, AbbVie is shelling out $10.1 billion in cash to acquire ImmunoGen, maker of the ovarian cancer treatment Elahere, which won accelerated approval from the FDA about a year ago. The acquisition accelerates AbbVie’s entry into the solid tumor space and strengthens the company’s oncology pipeline, CEO Rick Gonzalez said on a call Thursday. Establishing a strong presence in solid tumors has been a “strategic priority for AbbVie,” and ImmunoGen represents an “extremely compelling opportunity,” he said. With the buyout, AbbVie is rejoining the likes of AstraZeneca, BioNTech, Gilead Sciences, GSK, Merck & Co. and Pfizer on a list of pharma companies that have spent mightily to acquire ADC programs. By deal value, the proposed buyout ranks third among biopharma M&A transactions announced this year, trailing Pfizer’s $43 billion offer for another ADC giant, Seagen, and Merck’s $10.8 billion takeover of immunology company Prometheus. AbbVie was actually one of the earliest Big Pharma companies to identify ADCs as a promising field. Back in 2011, when AbbVie was still part of Abbott, the company paid $8 million upfront to Seagen (then called Seattle Genetics) to utilize the latter’s ADC technology on a single cancer target. Now, ImmunoGen could give AbbVie a chance to clear its ADC reputation after another of its deals in the space turned into a flop. AbbVie's first large ADC play came in 2016 when the company put down $5.8 billion to acquire Stemcentrx. But the crown jewel of the deal, DLL3-targeted ADC Rova-T, failed multiple small cell lung cancer trials until AbbVie eventually admitted defeat and scrapped the entire program in 2019. Rova-T was one of the most notable failures of the ADC field, and the setback disrupted AbbVie’s plan to move into solid tumors. This time, AbbVie is getting an ADC that’s already on the market. An FRα-directed ADC, Elahere was approved by the FDA in November 2022 as a treatment for advanced ovarian cancer that’s resistant to platinum chemotherapy. Earlier this year, the drug’s MIRASOL confirmatory trial was hailed at a landmark success. In the study, Elahere became the first medicine to show an overall survival benefit in platinum-resistant ovarian cancer. The drug is expected to generate around $500 million in sales in 2024, and Wall Street analysts on average projected about $2 billion in peak sales at the end of the decade, according to Barclays. To reach that threshold, Elahere will need to move into earlier lines of treatment later this decade. Trials are ongoing to test Elahere—either by itself or with bevacizumab—in FRα-high, platinum-sensitive ovarian cancer. And AbbVie plans to explore adding Elahere to either bevacizumab or PARP inhibitors in the first-line maintenance setting, with phase 3 studies expected to begin in 2024 and 2025, respectively. AbbVie made the ImmunoGen announcement just as the company’s own c-Met ADC candidate telisotuzumab-vedotin (Teliso-V) showed a 35% response rate in EGFR wild type, advanced nonsquamous non-small cell lung cancer. With the mid-stage results, AbbVie is preparing to seek accelerated approval with the FDA. Tapping more than four decades of ADC experience from ImmunoGen will likely make AbbVie a formidable player in the ADC space, William Blair analysts said in a Thursday note. AbbVie’s infrastructure, combined with ImmunoGen’s know-how, could help further entrench Elahere in ovarian cancer and expedite development of the biotech’s pipeline, the analysts said. ImmunoGen’s clinical assets include IMGN-151, an anti-FRα follow-on to Elahere with the potential to move beyond ovarian cancer. The biotech also has an anti-CD123 ADC in phase 2 testing for a rare blood cancer called blastic plasmacytoid dendritic cell neoplasm. Within oncology, blood cancer is AbbVie’s home turf. Together with Johnson & Johnson, AbbVie sells the BTK inhibitor Imbruvica, which has lately come under pressure from competitor drugs from AstraZeneca and BeiGene. Besides Teliso-V, AbbVie’s internal ADC pipeline remains in early-stage development. It includes a c-Met follow-up coded ABBV-400, two anti-SEZ6 candidates, ABBV-011 and ABBV-706, as well as drugs targeting B7-H3, CD19 and LRRC15. During AbbVie’s third-quarter earnings call, CEO Rich Gonzalez said the company opted to prioritize internal ADC work instead of pursuing a transaction with Daiichi Sankyo, which counts AZ and Merck as partners. That comment came in response to a question about Daiichi and Merck's megablockbuster ADC deal from the prior week. “The reality is we believe we have what we need with [ABBV-400],” Gonzalez said. “We believe that platform—and we own that platform, we've developed it internally—would give us everything that we need in that area,” Gonzalez added.  AbbVie expects the ImmunoGen deal to close in the middle of 2024.  Meanwhile, the U.S. Federal Trade Commission has recently adopted a more aggressive stance on biopharma M&A deals. The antitrust agency is currently taking a closer look at Pfizer’s Seagen buy. The ImmunoGen deal “would have no overlap from an FTC standpoint, based on our portfolio and our market presence,” Gonzalez said Thursday.

Pictured: AbbVie headquarters in California/iStock, Michael Vi AbbVie has terminated its license and collaboration agreement with I-Mab, the Maryland- and Shanghai-based biotech announced in an SEC filing posted Friday. As a result, I-Mab will regain the global rights to develop and commercialize all CD47 compounds covered by the deal, including the monoclonal antibody lemzoparlimab. The termination will take effect on Nov. 20, 2023 and will not affect the $200 million in upfront and milestone payments that I-Mab had already received from AbbVie. According to I-Mab’s SEC document, AbbVie is pulling away from the partnership as a “strategic decision,” though a prior program discontinuation also factored into its decision. AbbVie and I-Mab first entered into their global agreement in September 2020. For an upfront payment of $180 million and the promise of up to $1.74 billion in success-based milestones, AbbVie earned exclusive rights—outside of the greater China area—to develop and commercialize lemzoparlimab. The deal also allowed for potential future targets using I-Mab’s CD47 molecules. In August 2022, however, AbbVie ended two Phase Ib trials of lemzoparlimab, one in myelodysplastic syndrome (MDS) and another in acute myeloid leukemia. The partners gave no specific reason for discontinuing these studies, though I-Mab said that it was not triggered by “specific or unexpected safety concerns.” At the time, the companies were studying lemzoparlimab in combination with azacytidine and AbbVie’s chronic lymphocytic leukemia drug Venclexta (venetoclax tablets). The partners also amended their collaboration then, which still had the potential for up to nearly $1.3 billion in development, regulatory and sales milestones for I-Mab. Despite losing a powerhouse partner, I-Mab will continue its development of lemzoparlimab. According to the company’s SEC filing, the investigational antibody is in a Phase III registrational study in combination with azacytidine for high-risk MDS in China. The company will also continue analyzing data from the candidate’s development program to assess future opportunities for it. If approved, lemzoparlimab could become a first-in-class CD47 antibody for hematologic malignancies in China, I-Mab said. For AbbVie, dropping the I-Mab partnership comes just days after it chose not to exercise its exclusive licensing option for Harpoon Therapeutics’ TriTAC candidate HPN217, which is in a Phase I trial for multiple myeloma. Last month, AbbVie also cut two early-stage oncology assets from its developmental pipeline. The first, ABBV-011, was an anti-SEZ6 antibody-drug conjugate (ADC) being trialed for relapsed or refractory lung cancer. The second dropped asset was ABBV-647, a Pfizer-partnered ADC targeting the PTK7 protein for the potential treatment of solid tumors. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.

Update: AbbVie headquarters building in California/iStock, Michael Vi AbbVie has removed two early-stage antibody-drug conjugates in an update to its pipeline webpage, suggesting that the company is terminating the development of these candidates, Endpoints News reported Thursday. The company appears to have dropped ABBV-011 and the Pfizer-partnered ABBV-647, both in Phase I development for cancer targets. BioSpace was not able to determine exactly when the pipeline changes happened, but according to the Wayback Machine—a digital archive of the internet—these two assets were still on AbbVie’s webpage as late as Aug. 19 but have since been removed. BioSpace has reached out to AbbVie for comment but the company was not immediately available. ABBV-011 is an antibody-drug conjugate (ADC) targeting SEZ6, a cell surface protein commonly highly expressed in neuroendocrine tumors but typically present in low levels in healthy tissues, according to AbbVie’s website. The investigational ADC carries the toxic calicheamicin payload, which has already been used in two FDA-approved ADCs. AbbVie was evaluating ABBV-011 either as a monotherapy or in combination with the company’s own budigalimab, a PD-1 inhibitor, for the treatment of relapsed or refractory small cell lung cancer. During the 2023 Annual Meeting of the American Society of Clinical Oncology (ASCO), held in June, AbbVie presented Phase I data for ABBV-011, demonstrating that the candidate had encouraging efficacy, eliciting an overall response rate of 25% with a median duration of 4.2 months. AbbVie’s second discontinued candidate, ABBV-647, is also known as cofetuzumab pelidotin and is an investigational ADC designed to target the PTK7 protein. The candidate carries the payload Aur0101, an auristatin microtubule inhibitor, and was being developed for solid tumors. The company in February 2020 had also launched a Phase Ib trial of cofetuzumab pelidotin in recurrent non-small cell lung cancer. AbbVie presented its methodology for this trial in 2021, during that year’s annual ASCO meeting. Cofetuzumab pelidotin was first discovered and developed by Stemcentrx, which debuted in September 2015. The company partnered with Pfizer for the development of the candidate, before it was eventually bought by AbbVie in 2016. AbbVie’s Wednesday pipeline update stands in contrast to an industry trend of growing preference for ADC therapeutics in cancer. Last month, ImmunoGen signed a multi-target license and option deal with ImmunoBiochem to develop first-in-class ADCs, though the partners declined to reveal specific financial details. The month before that, Eli Lilly bought European biotech Emergence Therapeutics, gaining access to its anti-Nectin-4 ADC assets. In March 2023, Pfizer made one of the biggest investments in the ADC space so far with its announced $43 billion acquisition of cancer-focused Seagen. If the deal goes through, it will provide Pfizer’s cancer business with four approved treatments and nearly a dozen promising candidates. Tristan Manalac is an independent science writer based in Metro Manila, Philippines. He can be reached at tristan@tristanmanalac.com or tristan.manalac@biospace.com.